Ultrastructural identification of the hemopoietic inductive microenvironment in the human embryonic liver.
Reciprocal interaction between the hemopoietic organ stromal cells and the cells of the granulocytic, megakaryocytic and erythrocytic series in the human liver obtained from 109 embryos 28 to 49 days after ovulation and 76 fetuses from 8 to 22 weeks of gestation were investigated by light and electron microscopy. The close association of stromal cells with immature cells of the three series was confirmed under the electron microscope and a presumptive HIM (hemopoietic inductive microenvironment) was visualized. A majority of immature erythroblasts intruded into the cytoplasm of the hepatocytes, so the presumptive hemopoietic stem cell types II and IV are undoubtedly differentiated into cells of the erythroid line by contact with hepatocytes at a certain stage of maturation. Granulopoiesis developed among the reticular cells around the ductus venosus--or large arteries in hepatic parenchyma--and the cells of the granulocytic series were enclosed by thin cytoplasmic projections of mesenchymal cells. Neither erythropoiesis nor megakaryopoiesis was noted here. Therefore the compartments composed of one or more reticular cells around the ductus venosus or large arteries seem to have a capacity to regulate the differentiation of the presumptive hemopoietic stem cells type IV into cells of the granulocytic series. This differentiation of presumptive hemopoietic stem cell types II and IV into the megakaryocytic series is belived to be induced by the presence of the microenvironments that consist of foci of a few reticular cells in the hepatic parenchyma, as immature cells of megakaryocytic lineage were encircled by the cytoplasmic projection of one or more reticular cells among hepatocytes. Erythroblastic islets are concluded to be a kind of HIM, where erythroblasts loosely adhere to the central macrophages and undergo mitoses and maturation.


PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants.
Plasminogen activator inhibitor-1 (PAI-1) plasma levels have been consistently related to a polymorphism (4G/5G) of the PAI-1 gene. The renin-angiotensin pathway plays a role in the regulation of PAI-1 plasma levels. An insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been related to plasma and cellular ACE levels. In 1032 employees (446 men and 586 women; 22 to 66 years old) of a hospital in southern Italy, we investigated the association between PAI-1 4G/5G and the ACE I/D gene variants and plasma PAI-1 antigen levels. None of the individuals enrolled had clinical evidence of atherosclerosis. In univariate analysis, PAI-1 levels were significantly higher in men (P<.001), alcohol drinkers (P<.001), smokers (P=.009), and homozygotes for the PAI-1 gene deletion allele (4G/4G) (P=.012). Multivariate analysis documented the independent effect on PAI-1 plasma levels of body mass index (P<.001), triglycerides (P<.001), sex (P<.001), PAI-1 4G/5G polymorphism (P=.019), smoking habit (P=.041), and ACE I/D genotype (P=.042). Thus, in addition to the markers of insulin resistance and smoking habit, gene variants of PAI-1 and ACE account for a significant portion of the between-individual variability of circulating PAI-1 antigen concentrations in a general population without clinical evidence of atherosclerosis.


A single tRNA (guanine)-methyltransferase from Tetrahymena with both mono- and di-methylating activity.
A tRNA (guanine-2) methyltransferase has been purified to homogeneity from the protozoan Tetrahymena pyriformis. The enzyme methylates purified E. coli tRNAs which have a guanine residue at position 26 from the 5' end; it also methylates tRNA prepared from the m22G- yeast mutant trm 1. This methyltransferase is therefore equivalent to the guanine methyltransferase 2mGII found in mammalian extracts. The purified 2mGII from Tetrahymena is capable of forming both N2-methylguanine and N22-dimethylguanine on a single tRNA isoaccepting species; under conditions of limiting tRNA or long reaction times the predominant product is dimethylguanine. Analysis of the products formed under varying reaction conditions suggests that dimethylguanine formation is a two step process requiring dissociation of the enzyme-monomethylated tRNA intermediate.


Cost estimation of a school-based intervention for improving HIV/AIDS risk perception among secondary school adolescents in Enugu State, Nigeria.
Early sexual debut is common in Nigeria and increases HIV risk among adolescents. About 152,000 adolescents are living with HIV. Lack of knowledge and appropriate sexual reproductive health services are some factors responsible. This paper estimated the cost of secondary school-based HIV/AIDS intervention for schools in Enugu State, Nigeria. The rationale for estimation is to avoid unaffordable and ineffective interventions. The cost was estimated between March to October 2019 for schools in urban and rural areas with population of 1595 students. The cost estimation was aided through UNAID proposed guideline. The estimation was done by classifying intervention into cost of training, cost of services and cost of commodities. The cost was estimated at $5954. The estimated cost in urban is lesser than that of rural. This estimated cost of intervention may inform stakeholders with the knowledge of cost implications to avoid unaffordable school-based HIV interventions in Enugu State, Nigeria.


Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply.
Folic acid fortification in the United States became mandatory January 1, 1998, to reduce the occurrence of neural tube defects (NTDs). We evaluated the impact of folic acid fortification on orofacial clefts using United States birth certificate data for 45 states and the District of Columbia. Prevalence ratios (PRs) were calculated comparing orofacial cleft prevalence among births prefortification (1/1990-12/1996) and postfortification (10/1998-12/2002), based on fortification status at conception. The JoinPoint Regression Program and exponentially weighted moving average charts (EWMA) were used to assess the timing of any statistically significant changes in prevalence. Data were stratified by maternal race/ethnicity, age, smoking, and timing of prenatal care. Orofacial clefts declined following folic acid fortification (PR=0.94; 95% CI: 0.92-0.96). The EWMA chart flagged a significant decrease in the fourth quarter of 1998. The JoinPoint graph had one change in slope, with a significant quarterly percent change (-0.34) between 1996 and 2002. The decline in orofacial clefts occurred in non-Hispanic Whites but not other racial/ethnic groups, nonsmokers but not women who reported smoking during pregnancy, and women who received prenatal care in the first trimester but not women who began receiving care later in pregnancy. Folic acid fortification in the United States was associated with a small decrease in orofacial cleft prevalence, with the timing of the decline consistent with the introduction of fortification. The decline is much smaller than that observed for NTDs, but nonetheless suggests an additional benefit of this public health intervention.


Epitope design of L1 protein for vaccine production against Human Papilloma Virus types 16 and 18.
Cervical cancer accounts for about two-thirds of all cancer cases linked etiologically to Human Papilloma Virus (HPV). 15 oncogenic HPV types can cause cervical cancer, of which HPV16 and HPV18 combinedly account for about 70% of it. So, effective epitope design for the clinically relevant HPV types 16 and 18 would be of major medical benefit. Here, a comprehensive analysis is carried out to predict the epitopes against HPV types 16 and 18 through "reverse vaccinology" approach. We attempted to identify the evolutionarily conserved regions of major capsid protein (L1) as well as minor capsid protein (L2) of HPV and designed epitopes within these regions. In this study, we analyzed about 49 and 27 sequences of HPV L2 and L1 proteins respectively. Since we found that the intertype variability of L2 is higher than for L1 proteins, our analysis was emphasized on epitopes of L1 of HPV types 16 and 18. We had selected HLA-A*0201, DRB1*1501, DQB1*0602, DRB1*0401 and DQB1*0301 alleles for the prediction of T cell epitopes of L1 of HPV 16 and 18. Finally, we reported that predicted epitope sequences EEYDLQFIFQLCKITLTA, and RHGEEYDLQFIFQLCKITLTA of L1 protein of HPV 16, and LPDPNKF, PETQRLVWAC, PVPGQYDA, YNPETQRLVWAC, DTGYGAMD, PVPGQYDATK, KQDIPKVSAYQYRVFRV, RDNVSVDYKQTQLCI and YSRHVEEYDLQFIF of L1 protein of HPV 18 could be therapeutic tools for vaccine design against HPV.


Reversal effects of several Ca(2+)-entry blockers, neuroleptics and local anaesthetics on P-glycoprotein-mediated vincristine resistance of L1210/VCR mouse leukaemic cell line.
The ability of several Ca(2+)-entry blockers, neuroleptics and local anaesthetics to depress the P-glycoprotein-mediated resistance to vincristine was studied in vitro using the L1210/VCR cell line. This cell line was obtained by long-term adaptation of the L1210 mouse leukaemic cell line on vincristine and showed an overexpression of P-glycoprotein and accompanying multidrug resistance (MDR) which was defined as a cell resistance to several cytostatics such as vincristine, vinblastine and actinomycin D. Efficiency of the drugs applied to reverse this resistance was as follows: for Ca(2+)-entry blockers: verapamil (VER) > or = galopamil (GAL) > flunarizine (FLU) >> diltiazem (DIL) > nimodipine (NIM) > or = nifedipine (NIM); for neuroleptics: trifluoperazine (TFP) > chlorpromazine (CHP) > thioridazine (TRD) > perphenazine (PER); for local anaesthetics: carbanilate-Ca7 > cinchocaine (CIN) >> carbanilate-Ca3 > articaine (ART) > carbanilate CAO > lidocaine (LID). Quaternary cabanilate derivatives (Ca7Q and Ca3Q) with permanent positive charge were found to be unable to reverse the vincristine resistance of L1210/VCR cells. No reasonable correlation between the ability of calcium-entry blockers (DIL, VER, GAL, NIF, NIM and FLU) to reduce the viability of L1210/VCR cells growing in the medium supplemented with vincristine and their reported affinity to the L-type of calcium channel was observed. On the other hand, significant positive correlations were observed between both the inhibitory action of local anaesthetics on propagation of action potential in rat sciatic nerve and the ability of drugs to interact with calmodulin and the ability of the respective drug to reverse the resistance of L1210 cells to vincristine.


Uses and abuses of sodium bicarbonate in the neonatal intensive care unit.
Despite the lack of evidence for its effectiveness in the treatment of acid-base disturbances in critically ill patients of all ages, and despite several lines of evidence that indicate it might be dangerous, bicarbonate therapy is used routinely in many neonatal intensive care units. The justification for the persistent use of this controversial therapy comes from a variety of sources, many based more in philosophy than in science. Clinicians contemplating the use of bicarbonate therapy should consider what they expect the intervention to accomplish and what evidence exists that their therapeutic objective will be met. Without rigorous scientific support for this therapy, it should be considered of unproven value and, therefore, experimental.


Immunohistochemical detection of p53 protein in borderline and malignant serous ovarian tumors.
The p53 suppressor gene protein expression was studied with immunoperoxidase staining in 61 serous tumors of the ovary. Twenty four (53%) of the 45 histologically malignant tumors were positive for p53, whereas neither the six benign nor the 10 tumors of borderline malignancy showed positive staining, except for one borderline tumor with atypia and increased mitotic activity. Therefore, p53 immunostaining may have diagnostic value in discriminating between borderline and malignant serous ovarian tumors. Malignant ovarian tumors with negative staining for p53 were associated with a 67% 3-year crude survival rate as compared with only an 18% 3-year survival rate if p53 staining was positive (p = 0.002). In a multivariate analysis, the p53 staining was the most important prognostic factor, with a relative risk of 4.2 (95% confidence interval, 1.8-9.9) followed by the FIGO stage (2.1, 1.3-3.5). We conclude that immunohistochemical p53 suppressor gene protein expression analysis has both diagnostic and prognostic value.


Effect of Flumorph on F-Actin Dynamics in the Potato Late Blight Pathogen Phytophthora infestans.
Oomycetes are fungal-like pathogens that cause notorious diseases. Protecting crops against oomycetes requires regular spraying with chemicals, many with an unknown mode of action. In the 1990s, flumorph was identified as a novel crop protection agent. It was shown to inhibit the growth of oomycete pathogens including Phytophthora spp., presumably by targeting actin. We recently generated transgenic Phytophthora infestans strains that express Lifeact-enhanced green fluorescent protein (eGFP), which enabled us to monitor the actin cytoskeleton during hyphal growth. For analyzing effects of oomicides on the actin cytoskeleton in vivo, the P. infestans Lifeact-eGFP strain is an excellent tool. Here, we confirm that flumorph is an oomicide with growth inhibitory activity. Microscopic analyses showed that low flumorph concentrations provoked hyphal tip swellings accompanied by accumulation of actin plaques in the apex, a feature reminiscent of tips of nongrowing hyphae. At higher concentrations, swelling was more pronounced and accompanied by an increase in hyphal bursting events. However, in hyphae that remained intact, actin filaments were indistinguishable from those in nontreated, nongrowing hyphae. In contrast, in hyphae treated with the actin depolymerizing drug latrunculin B, no hyphal bursting was observed but the actin filaments were completely disrupted. This difference demonstrates that actin is not the primary target of flumorph.


The Year in Review: Anesthesia for Congenital Heart Disease 2019.
This review focuses on the literature published from January 2019 to February 2020 that is of interest to anesthesiologists taking care of children and adults with congenital heart disease. Five themes are addressed during this time period, and 59 peer-reviewed articles are discussed.


Evaluation of QuantiFERON-TB Gold-Plus in Health Care Workers in a Low-Incidence Setting.
Although launched in 2015, little is known about the accuracy of QuantiFERON-TB Gold-Plus (QFT-Plus) for diagnosis of latent M. tuberculosis infection (LTBI). Unlike its predecessor, QFT-Plus utilizes two antigen tubes to elicit an immune response from CD4+ and CD8+ T lymphocytes. We conducted a cross-sectional study in low-risk health care workers (HCWs) at a single U.S. center to compare QFT-Plus to QuantiFERON-TB Gold in-tube (QFT). A total of 989 HCWs were tested with both QFT and QFT-Plus. Risk factors for LTBI were obtained from a questionnaire. QFT-Plus was considered positive if either antigen tube 1 (TB1) or TB2 tested positive, per the manufacturer's recommendations, or if both TB1 and TB2 tested positive, using a conservative definition. Results were compared using Cohen's kappa and linear regression, respectively. Agreement of QFT with QFT-Plus was high, at 95.6% (95% confidence interval [CI], 94.3 to 96.9; kappa, 0.57). The majority of discordant results between QFT and QFT-Plus TB1 (84.8%) and QFT and QFT-Plus TB2 (88.6%) fell within the range of 0.2 to 0.7 IU/ml. The positivity rate in 626 HCWs with no identifiable risk factors and no self-reported history of positive LTBI tests was 2.1% (CI, 1.0 to 3.2) and 3.0% (CI, 1.7 to 4.3) with QFT and QFT-Plus, respectively. A conservative definition of a QFT-Plus-positive result yielded a positivity rate of 1.0% (CI, 0.2 to 1.7; P value of 0.0002 versus QFT-Plus and 0.07 versus QFT). On follow-up testing, of 11 HCWs with discordant QFT-Plus results, 90.9% (10/11) had a negative QFT result. The QFT-Plus assay showed a high degree of agreement with QFT in U.S. HCWs. A conservative interpretation of QFT-Plus eliminated nearly all nonreproducible positive results in low-risk HCWs. Larger studies are needed to validate the latter finding and to more clearly define conditions under which a conservative interpretation can be used to minimize nonreproducible positive results in low-risk populations.


Auditing in intensive care: comparison of two tools.
This article addresses some of the practical aspects of auditing in the intensive care setting by comparing two audit tools. An overview of each tool is provided together with a description of how it was used. Recommendations for auditing in intensive care are given.


Comparison of Maternal and Neonatal Outcomes among COVID-Positive Pregnant Women Affected in Second and Third Waves in a Dedicated COVID Hospital in Amritsar.
With the emergence of new mutated variants of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), we have witnessed three waves of coronavirus disease (COVID) with varying severity, complication, and outcome in Punjab. The physiological changes of pregnancy make mother more vulnerable for severe infection. Current study is aimed at comparison of maternal and neonatal outcomes of COVID-positive pregnant women in second and third waves. This was a retrospective observational single-center study conducted at a dedicated COVID hospital in Punjab, India. Records of all COVID-positive pregnant women admitted from January to June 2021 and from January to February 2022 were reviewed. The demographic details, severity of symptoms, maternal and fetal complications, outcomes, and mortality were noted. There were 220 COVID-positive pregnant patients in the second wave and 65 in third wave. The majority of patients belonged to the age group of 20-34 years (57.73% in the second wave and 70.77% in the third wave). Maternal deaths and severity of disease increased with increasing age of the mother, that is, 6.7% in <35 years and 13.95% in >35 years age group (RR = 2.058, P value = 0.1248). Also, the maternal deaths increased with increasing parity (RR = 2.00, P value = 0.2380). The majority of the study subjects were in the third trimester, with 77.73% in the second wave and 90.77% in the third wave. The majority of the patients in both the waves were asymptomatic or had mild symptoms. In the COVID second wave, 10.91% pregnant patients had moderate COVID symptoms and 8.18% had severe COVID symptoms, whereas none presented with moderate or severe symptoms in the third wave. Eighteen maternal deaths (8.18%) were seen during the COVID second wave, whereas no maternal death occurred in the third COVID wave. 100% of these deaths were because of COVID. Need of oxygen supplementation and intensive care unit admission had statistically significant association with maternal mortality. In the third COVID wave, the morbidity and mortality were significantly reduced. This could be a result of wide-spread vaccination, new strain of COVID, or both. In spite of this, the pregnancy complications such as pre-term birth, IUGR, and IUD were significant. Hence, pregnancies complicated by COVID should be considered as a high risk and closely monitored.


[Restoration and maintenance of sinus rhythm in patients with atrial fibrillation. New pharmacological approaches].
Atrial fibrillation is the most frequent cardiac arrthythmia in adults and its prevalence is increasing with age. Therefore, the importance of an adequate therapy is an increasing challenge, in particular considering the demographic shift towards an aging population. Current antiarrhythmic drug therapies for the conversion of atrial fibrillation and the maintenance of sinus rhythm are limited by efficacy, tolerance and safety of the currently available agents. Therefore, a primary goal is to develop effective antiarrhythmic drugs with as little as possible side effects. The following review describes new promising drug therapy approaches to atrial fibrillation that may overcome some of the limitations of current therapies.


G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation State.
G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and serve as primary targets of approximately one-third of currently marketed drugs. In particular, adenosine A1 receptor (A1 AR) is an important therapeutic target for treating cardiac ischemia-reperfusion injuries, neuropathic pain, and renal diseases. As a prototypical GPCR, the A1 AR is located within a phospholipid membrane bilayer and transmits cellular signals by changing between different conformational states. It is important to elucidate the lipid-protein interactions in order to understand the functional mechanism of GPCRs. Here, all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method were performed on both the inactive (antagonist bound) and active (agonist and G-protein bound) A1 AR, which was embedded in a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) lipid bilayer. In the GaMD simulations, the membrane lipids played a key role in stabilizing different conformational states of the A1 AR. Our simulations further identified important regions of the receptor that interacted distinctly with the lipids in highly correlated manner. Activation of the A1 AR led to differential dynamics in the upper and lower leaflets of the lipid bilayer. In summary, GaMD enhanced simulations have revealed strongly coupled dynamics of the GPCR and lipids that depend on the receptor activation state. © 2019 Wiley Periodicals, Inc.


Comprehensive Genomic Profiling of Rare Tumors: Routes to Targeted Therapies.
Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcomes for patients with rare tumors. This study aims to discover opportunities for use of targeted therapies already approved for routine use in patients with rare tumors. Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiological data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal were compared with that of the Chinese population for targetable genomic alterations (TGAs). TGAs were defined as mutations of ALK, ATM, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, FGFR1,2,3, KIT, MET, NF1, NTRK1,2,3, PIK3CA, PTEN, RET, and ROS1 with level 1 to 4 of evidence according to the OncoKB knowledge database. Genomic data of 4,901 patients covering 63 subtypes of rare tumor from cBioPortal were used as the western cohort. The Chinese cohort was comprised of next generation sequencing (NGS) data of 1,312 patients from across China covering 67 subtypes. Forty-one subtypes were common between the two cohorts. The accumulative prevalence of TGAs was 20.40% (1000/4901) in cBioPortal cohort, and 53.43% (701/1312) in Chinese cohort (p < 0.001). Among those 41 overlapping subtypes, it was still significantly higher in Chinese cohort compared with cBioPortal cohort (54.1%% vs. 26.1%, p < 0.001). Generally, targetable mutations in BRAF, BRCA2, CDKN2A, EGFR, ERBB2, KIT, MET, NF1, ROS1 were ≥3 times more frequent in Chinese cohort compared with that of the cBioPortal cohort. Cancer of unknown primary tumor type, gastrointestinal stromal tumor, gallbladder cancer, intrahepatic cholangiocarcinoma, and sarcomatoid carcinoma of the lung were the top 5 tumor types with the highest number of TGAs per tumor. The incidence of TGAs in rare tumors was substantial worldwide and was even higher in our Chinese rare tumor population. Comprehensive genomic profiling may offer novel treatment paradigms to address the limited options for patients with rare tumors.


The effect of dietary habits and socioeconomic status on the prevalence of iron deficiency in children of northern Greece.
Despite encouraging reports concerning the declining prevalence of iron deficiency, this easily preventable disorder is still an existing problem in presumably developed regions. To evaluate the prevalence of iron deficiency and relevant anemia in children residing in Northern Greece and to study possible associations. 3,100 children aged 8 months to 15 years were evaluated. Socioeconomic status was determined based on the parents' profession and place of residence. Nutrition habits were also evaluated. The incidence of iron deficiency was found to be 14% and that of iron deficiency anemia was 2.9%, with a higher prevalence in children younger than 2 years of age. The place of residence was the most significant factor in relation to the development of iron depletion in the children studied. Additional independent factors were revealed to be breast-feeding, meat-containing meal consumption and the consumption of non-home-cooked meals. Iron deficiency remains prevalent in Northern Greece, mainly affecting the vulnerable toddler group. Nutritional iron deficiency is still a severe public health problem even in what are considered to be developed regions. An improvement of dietary habits and an upgrading of semiurban areas should contribute substantially to decreasing the prevalence of iron depletion in Greek children.


Identifying interventions that promote belt-positioning booster seat use for parents with low educational attainment.
Many parents with low educational attainment prematurely graduate their children to seat belt restraint rather than use belt-positioning booster seats. This study aimed to identify interventions that promoted booster seat use among this population. This multi-site study used focus groups to elicit contributing factors to booster seat non-use, which informed subsequent intervention development. A first phase (10 focus groups, N = 117) identified parents' perceived barriers, benefits, and threats relating to belt-positioning booster seats. These findings were used to identify existing and create new interventions. A second phase (20 focus groups, n = 171) elicited parent's reactions to these interventions and provided parents with belt-positioning booster seats and education on their use. Follow-up interviews were conducted six weeks later. Lack of education and fear of injury were the primary barriers to belt-positioning booster seat use. Parents were motivated by interventions that provided them with clear, concrete messaging relating to use. Parents favored the intervention that presented a real story detailing a child's severe injury that could have been prevented with appropriate restraint. At follow-up, parents credited this intervention with motivating booster seat use most often. Although parent's cited their child's lack of comfort and non-compliance as barriers to use, they were not as motivated by interventions that addressed these barriers. Effective intervention programs can be created by identifying and addressing factors that contribute to a population's intention to use belt-positioning booster seats. In addition, successful programs must utilize messages that motivate the target population by addressing their perceived threats to booster seat non-use.


Essential Oil Composition of Five Thymus Species from Bulgaria.
In this study, the essential oil composition of five Thymus species, belonging to Sect. Hyphodromi (A. Kerner) Halácsy - Thymus atticus Čelak., T. leucotrichus Halácsy, T. striatus Vahl, T. zygioides Griseb. and T. perinicus (Velen.) Jalas. was studied by GC/MS/FID. T. atticus, T. leucotrichus, and T. striatus were characterized by high amounts of sesquiterpenoids (57.7, 78.9 and 79.7 %, respectively) with β-caryophyllene and caryophyllene oxide as the main constituents. Aromatic compounds (61.2 %) were the most abundant group in T. zygioides essential oil, with thymol (51.2 %) as the principal component. The essential oil from the endemic species T. perinicus contained almost equal amounts of monoterpenoids (37.8 %) and aromatic compounds (36.0 %) with borneol (17.9 %) and thymol (20.9 %) as the major components. The obtained results revealed the existence of new chemotypes of T. atticus (caryophyllene oxide/β-caryophyllene), T. leucotrichus (β-caryophyllene/elemol/germacrene D) and T. striatus (β-caryophyllene/germacrene D/caryophyllene oxide). The essential oil content of endemic T. perinicus is reported for the first time. Principal component analysis (PCA) and cluster analysis (CA) were used to investigate the variations in the essential oils of different Thymus species from Sect. Hyphodromi (A. Kerner) Halácsy.


The influence of the parental environment on sexual maturation in male mice.
Experiments were designed to examine the influence of either one or both parents on the sexual maturation of male mice. A pregnant female and an adult vasectomized male were housed together and, at delivery, the litter was reduced to 6 pups, 3 of each sex. After weaning, mother, foster-father or both, stayed in cohabitation with their pups until sacrifice. The results showed that: (1) the permanent presence of one or both parents did not affect either testicular growth or the age at first fertile matings. (2) in maturing males (30-40 days), seminal vesicle growth was accelerated by the presence of the mother, inhibited by the presence of the foster-father. (3) in maturing males, the presence of one or both parents lowered plasma testosterone levels. On the opposite, in 90-day-old males, the same conditions increased testosterone levels. These results indicate that only the endocrine function of the testis is affected by the parental environment. The effects are age-dependent.


Triethylammonium hydrogen fumarate.
In crystals of the title compound, the hydrogen fumarate anions form one-dimensional chains through an O-H.O hydrogen bonding along the c and (a+b)/2 directions. There are three sites of the hydrogen fumarate, two of which have an inversion centre.


Functional roles of two novel P450 genes in the adaptability of Conogethes punctiferalis to three commonly used pesticides.
Introduction: Insect cytochrome P450 (CYP450) genes play important roles in the detoxification and metabolism of xenobiotics, such as plant allelochemicals, mycotoxins and pesticides. The polyphagous Conogethes punctiferalis is a serious economic pest of fruit trees and agricultural crops, and it shows high adaptability to different living environments. Methods: The two novel P450 genes CYP6CV1 and CYP6AB51 were identified and characterized. Quantitative real-time PCR (qRT-PCR) technology was used to study the expression patterns of the two target genes in different larval developmental stages and tissues of C. punctiferalis. Furthermore, RNA interference (RNAi) technology was used to study the potential functions of the two P450 genes by treating RNAi-silenced larvae with three commonly used pesticides. Results: The CYP6CV1 and CYP6AB51 genes were expressed throughout various C. punctiferalis larval stages and in different tissues. Their expression levels increased along with larval development, and expression levels of the two target genes in the midgut were significantly higher than in other tissues. The toxicity bioassay results showed that the LC50 values of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin on C. punctiferalis larvae were 0.2028 μg/g, 0.0683 μg/g and 0.6110 mg/L, respectively. After treating with different concentrations of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin (LC10, LC30, LC50), independently, the relative expressions of the two genes CYP6CV1 and CYP6AB51 were significantly induced. After the dsRNA injection, the expression profiles of the two CYP genes were reduced 72.91% and 70.94%, respectively, and the mortality rates of the larvae significantly increased when treated with the three insecticides independently at LC10 values. Discussion: In the summary, after interfering with the CYP6CV1 and CYP6AB51 in C. punctiferalis, respectively, the sensitivity of C. punctiferalis to chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin was significantly increased, indicating that the two CYP6 genes were responsible for the adaptability of C. punctiferalis to the three chemical insecticides in C. punctiferalis. The results from this study demonstrated that CYP6CV1 and CYP6AB51 in C. punctiferalis play crucial roles in the detoxification of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin.


A Study of the Epidemiology, Clinical, and Phenotypic Characteristics of Inflammatory Bowel Disease in the Northen-Central Region of Saudi Arabia.
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is becoming increasingly prevalent in Saudi Arabia. However, there is limited data on the characteristics and manifestations of IBD in this population. This study aimed to establish a multi-center database of patients with IBD in the Qassim region of Saudi Arabia to better understand the demographics, prevalence, and manifestations of IBD in this population. This retrospective study included patients diagnosed with IBD at three healthcare facilities in the Qassim region of Saudi Arabia. The patient's demographic and clinical characteristics, disease location and behavior, age at diagnosis, medication use, related surgeries, and extraintestinal manifestations were recorded based on the Montreal classification. A total of 257 patients with IBD were included in the study, of which 126 had UC and 131 had CD. Of the 257 patients with IBD, 134 (52.2%) were male and 123 (47.8%) were female. The mean age of patients with CD and UC were 28.74 (range 15-67) and 38.79 (range 15-75) years, respectively. There was a significant difference between all age groups (p < 0.005), with more patients aged over 40 years being diagnosed with UC. UC was most commonly classified as left-sided UC (E2) (60; 47.6%), while the most common location of CD was the ileocolon (L3) (76; 58%). Non-stricturing and non-penetrating CD was the most common behavior (B1) (70; 53.8%). Approximately one-third of the patients with Crohn's disease developed perianal disease (70; 27.2%), with fistulizing Crohn's being the most prevalent manifestation (40; 30.5%), followed by abscess formation (10; 7.6%) and fissures (9; 6.8%). The most common extraintestinal manifestation was arthropathy (15; 5.8%). Significant p-values were detected for UC and CD (p = 0.036). This study provides crucial insights into the demographics, patterns, and manifestations of IBD in Saudi Arabia. The findings highlight the need for improved diagnosis, management, and treatment strategies for IBD in this population. The establishment of a multi-center database will help to facilitate future research and improve patient care in Saudi Arabia.


Direct effects of estradiol and progesterone on pituitary graft gonadotrophs and their differential response to median eminence extract.
The direct effects of median eminence extract (MEE), estradiol (E) or progesterone (P) or combinations of these hormone preparations on the structure of the adenohypophysis and its secretion of gonadotrophins were examined in female rats bearing pituitary homografts obtained from long-term ovariectomized (LTO) donors. Preliminary investigation had shown that the pars distalis of LTO animals retained large numbers of hypertrophied gonadotrophs for several weeks even when homografted under the kidnay capsule of hypophysectomized recipients. Homografts from vehicle-treated controls contained many gonadotrophs at 24 days. Treatment with E or P resulted in complete disappearance of gonadotrophs at 24 days, but not at 10 days. E produced depletion of gonadotrophs even in the presence of MEE, while P + MEE treatment resulted in retention of gonadotrophs. In general, ovarian morphology correlated well with changes in pituitary cytology. These results suggest that the ability of MEE to stimulate release (and probably synthesis) of gonadotrophic hormones depends on the steroid sensitization of pituitary tissue and the differential effect of E and P on gonadotrophin release in the presence of MEE.


Competency-based nursing in a rehabilitation setting.
The success of achieving a competency-based rehabilitation nursing practice is shared in this article. An education day provided a comprehensive approach to ensure that practicing staff nurses stay abreast of the knowledge and skills necessary to provide quality patient care. This article details the decision-making process, competency development, strategies, and evaluation of the competency program. Formal documentation of competency testing is an asset for follow-up and accreditation review.


Physiological differences in professional basketball players as a function of playing position and level of play.
The aim of this investigation is to evaluate the physical and physiological characteristics of different first (ProA) and second division (ProB) professional basketball players, and to relate them to playing position and level of play. A total of 58 players were divided into ProA and ProB groups and were assessed for physical characteristics, maximal treadmill test and a 30 s all-out test. The sample included 22 centers, 22 forwards and 14 guards. Centers were significantly taller and heavier (203.9+/-5.3 cm and 103.9+/-12.4 kg) than forwards (195.8+/-4.8 cm and 89.4+/-7.1 kg) and guards (185.7+/-6.9 and 82+/-8.8 kg) and also had higher body fat percentages than the other groups. Forwards were also significantly taller than guards. Centers presented a lower maximal aerobic velocity (kmxh-1) than guards (15.5+/-1.2 vs 16.8+/-1.5, P<0.05) on the maximal treadmill test and a lower maximal velocity (rpm) than forwards (156.5+/-18.4 vs 170.3+/-18.3, P<0.05) on the 30 s all-out test. VO2max (mlxmin-1xkg-1) was significantly lower for ProA (53.7+/-6.7) compared to ProB (56.5+/-7.7) players and the fatigue index on the 30 s all-out test was higher for the ProA group (P<0.05). Many physical differences, most notably size, exist between players as a function of their playing position. But these differences have no relationship to the level of play of professional players. General aerobic capacity is fairly homogeneous between playing position and level of play, even if there are observable VO2max differences due to inter-individual profiles. On the other hand, anaerobic capacity seems to be a better predictor of playing level even though it is not clear whether such capacity comes from specific training in ProA, or from an initial selection criteria.


Siamese KG-LSTM: A deep learning model for enriching UMLS Metathesaurus synonymy.
The Unified Medical Language System, or UMLS, is a repository of medical terminology developed by the U.S. National Library of Medicine for improving the computer system's ability of understanding the biomedical and health languages. The UMLS Metathesaurus is one of the three UMLS knowledge sources, containing medical terms and their relationships. Due to the rapid increase in the number of medical terms recently, the current construction of UMLS Metathesaurus, which heavily depends on lexical tools and human editors, is error-prone and time-consuming. This paper takes advantages of the emerging deep learning models for learning to predict the synonyms and non-synonyms between the pairs of biomedical terms in the Metathesaurus. Our learning approach focuses a subset of specific terms instead of the whole Metathesaurus corpus. Particularly, we train the models with biomedical terms from the Disorders semantic group. To strengthen the models, we enrich the inputs with different strategies, including synonyms and hierarchical relationships from source vocabularies. Our deep learning model adopts the Siamese KG-LSTM (Siamese Knowledge Graph - Long Short-Term Memory) in the architecture. The experimental results show that this approach yields excellent performance when handling the task of synonym detection for Disorders semantic group in the Metathesaurus. This shows the potential of applying machine learning techniques in the UMLS Metathesaurus construction process. Although the work in this paper focuses only on specific semantic group of Disorders, we believe that the proposed method can be applied to other semantic groups in the UMLS Metathesaurus.


Palladium-Catalyzed Cross-Coupling of Silyl Electrophiles with Alkylzinc Halides: A Silyl-Negishi Reaction.
We report the first example of a silyl-Negishi reaction between secondary zinc organometallics and silicon electrophiles. This palladium-catalyzed process provides direct access to alkyl silanes. The delicate balance of steric and electronic parameters of the employed DrewPhos ligand is paramount to suppressing isomerization and promoting efficient and selective cross-coupling.


Endoparasites in dogs diagnosed at the Veterinary Teaching Hospital (VTH)-University of Bologna, combined with clinicopathological results. A long-term retrospective secondary data study.
Humans and dogs commonly share the same domestic environment. Europe, and Italy specifically, have a substantial and growing dog population. Potentially zoonotic parasites may be harbored even by dogs receiving regular veterinary care. Thus, transmission of zoonotic or potentially zoonotic parasites to owners and their families should not be underestimated. Frequently, endoparasite infections occur as a subclinical infection and clinicopathological alterations have been documented including anemia, hypoalbuminemia, and eosinophilia. The aim of this large retrospective secondary data study was to analyze coprological endoparasite results and putative risk factors obtained from owned dogs, through a 9-year-period (2011-2019). Possible associations between diagnosed endoparasites and sex, age, seasonality, and year of examination were evaluated. Additionally, parasitological diagnoses were combined to complete blood count parameters and biochemical profiles, when available, to check for any possible hematological alteration from parasitism. A total of 1,972 dogs were evaluated for endoparasites using common fecal diagnostic tests over a 9-year period. The overall proportion of endoparasite-positive animals was 10%. The most common endoparasites detected were Cystoisospora spp. (3%), Toxocara canis (2.8%), Giardia duodenalis (1.6%), and Trichuris vulpis (1.2%). Of these parasites detected, Toxocara poses the greatest zoonotic risk, while Giardia species are considered to have a low potential to be zoonotic. There was no significant diagnostic trend across the years through the study period. Dogs were more frequently diagnosed endoparasite-positive when young and during cold seasons compared to the baselines of mature dogs and warm seasons. The clinicopathological profiles indicated that parasitized dogs had mild hematological alterations. The frequency of detected potentially zoonotic endoparasites in this study highlights that the risk should not be underestimated. Parasitic infection was found to be mostly dependent on age and season. Having this information may help clinicians to develop anthelmintic protocols to reduce the risk of transmission.


Intestinal carcinogenesis and dietary fibers: the influence of cellulose or Fybogel chronically given after exposure to DMH.
This study was initiated to analyze the effect of a) two characterized vegetal fibers [i.e., a polysaccharide (cellulose) and a mucilaginous substance (Fybogel)], which were b) added at two concentrations (5% and 15% wt/wt), c) as constituents of low (5% wt/wt) and high (20% wt/wt) fat isocaloric diets d) given chronically to rats one week after the administration of 1,2-dimethylhydrazine (DMH); DMH had previously been injected once a week for 15 weeks to induce intestinal carcinogenesis. The dietary consumption, the body weight, and the fecal outflow showed a similar and regular evolution for the rats of all experimental groups; the exception was those receiving the 20% lipids-15% Fybogel diet. That specific diet caused a decrease in body weight concomitant with an increase in dietary consumption and in fecal outflow. The variation in fecal outflow depended on fat and fiber concentrations. The mucilage was more degraded, in absolute and relative amount, than was cellulose when this polysaccharide was included at a 20% lipid diet. Concerning the effect of these two fibers on intestinal carcinogenesis, Fybogel showed an anticarcinogenic property, whereas cellulose did not. The inhibitory activity of Fybogel was on the incidence of intestinal and colonic tumors as well as on the colonic tumor yield. Moreover, it slowed down the rate of colonic formation.


Neanderthals in central Asia and Siberia.
Morphological traits typical of Neanderthals began to appear in European hominids at least 400,000 years ago and about 150,000 years ago in western Asia. After their initial appearance, such traits increased in frequency and the extent to which they are expressed until they disappeared shortly after 30,000 years ago. However, because most fossil hominid remains are fragmentary, it can be difficult or impossible to determine unambiguously whether a fossil is of Neanderthal origin. This limits the ability to determine when and where Neanderthals lived. To determine how far to the east Neanderthals ranged, we determined mitochondrial DNA (mtDNA) sequences from hominid remains found in Uzbekistan and in the Altai region of southern Siberia. Here we show that the DNA sequences from these fossils fall within the European Neanderthal mtDNA variation. Thus, the geographic range of Neanderthals is likely to have extended at least 2,000 km further to the east than commonly assumed.


Percutaneous Drainage of a Rapidly Enlarging Simple Ovarian Cyst in the Third Trimester.
Persistent adnexal masses increase the risk of pregnancy complications including cyst rupture, ovarian torsion, and labor obstruction. Treatment options include observation, surgical excision, and early first or second trimester drainage. Our case represents the most advanced gestational age for intervention with percutaneous drainage. A 32-year old G3P1102 at 29.2 weeks gestation presented with left lower quadrant pressure, right abdominal fullness, and left uterine displacement. She had a right, simple-appearing ovarian cyst, which had increased in size from previous ultrasounds to 12.8 × 13.4 × 15.7 cm. Ultrasound-guided percutaneous drainage with pigtail catheter placement removed 1.2 L serous green fluid. Fluid culture was negative and cytology showed no evidence of malignancy. The pigtail catheter was removed at 31.2 weeks because of pain at the surgical site and significant cyst regression. The cyst resolved and she delivered via uncomplicated vaginal delivery at term. A few case reports describe first and second trimester percutaneous or transvaginal drainage of symptomatic ovarian cysts as a less invasive approach than surgical excision. However, our case suggests drainage of a simple-appearing cyst as an alternative treatment option in the third trimester when the risk of preterm labor and fetal complications with surgical intervention is at its highest.


Sources of pancreatic pathogens in acute pancreatitis in cats.
The source(s) of pancreatic pathogens is uncertain, although the colon is usually implicated. We studied whether pathogens may spread from different sites in a feline model of the disease. Acute pancreatitis was induced using a standard technique and a distinctive clinical strain of Escherichia coli as the marker bacterium. E. coli were placed in the colon, gall bladder, main pancreatic duct, or obstructed renal pelvis of control cats (no pancreatitis) and acute pancreatitis cats. Pancreases were colonized from each source, whether or not pancreatitis was present. The pancreatic colonization rate was greater in acute pancreatitis only when E. coli had been placed in the colon. In conclusion, E. coli may spread to the pancreas from different sources. The high rate of pancreatic colonization in both control and inflamed glands suggested that, clinically, bacteria may spread to the pancreas more frequently than is currently thought.


Classic Tower of Hanoi, Planning Skills, and the Indian Elderly.
Elderly populations are vulnerable to age-related cognitive decline. Planning, a frontal lobe function, is reported to be affected in the elderly population. There is a paucity of studies which assessed planning skills in the elderly Indian population. The present study aimed to examine the utility of the classic Tower of Hanoi in the assessment of planning skills of elderly Indian subjects. A total of 215 (60 of whom were females, all aged 55-80 years) cognitively normal elders and 24 patients with mild Alzheimer's disease were recruited. All subjects provided informed consent and their planning skills were assessed using the classic Tower of Hanoi. Performance at each level was measured by the total time taken to solve, number of moves to solve, and the number of rule violations. Receiver operating characteristic curve analysis was exploratively performed to test the utility of the Tower of Hanoi in differentiating patients with mild Alzheimer's disease from those who were cognitively normal. Performance measures of cognitively normal group steeply worsened with increasing complexity. With receiver operating characteristic curve analysis, patients with mild Alzheimer's disease were poorly differentiated from cognitively normal group according to their Tower of Hanoi performance. The Tower of Hanoi test is of limited value for the assessment of planning skills in the Indian elderly population. There is a need to modify and develop a suitable neuropsychology tool to assess the planning skills of elderly Indian subjects and further validate it.


School Breakfast Policy Is Associated with Dietary Intake of Fourth- and Fifth-Grade Students.
Breakfast skipping has been associated with obesity. Schools have adopted breakfast policies to increase breakfast participation. Recently, there have been concerns that students in schools where breakfast is served in the classroom may be eating two breakfasts--one at home and one at school--thereby increasing their risk of excessive energy intake and weight gain. The study objective was to compare the prevalence of not eating breakfast, eating breakfast at home or school only, and eating double breakfasts (home and school) by students in schools with distinct breakfast policies and evaluate the relationship of breakfast policy to energy intake and diet quality. Baseline data were collected in 2011-2012 as part of a cluster randomized controlled trial to evaluate the effectiveness of a school-based intervention to promote fruit and vegetable intake and physical activity in low-resource elementary schools in California. Participants were 3,944 fourth and fifth graders from 43 schools, 20 served breakfast in the cafeteria before school, 17 served breakfast in the classroom at the start of school, and 6 served "second chance" breakfast (in the cafeteria before school and again at first recess). As part of a secondary data analysis, differences in school and individual characteristics by school breakfast policy were assessed by χ(2) test of independence or analysis of variance. Associations between school breakfast policy and breakfast eating patterns were assessed. Outcomes included calorie intake at breakfast, total daily calorie intake, and diet quality as measured by the Healthy Eating Index 2010. Control variables included student race/ethnicity, grade, and language spoken at home, and clustering of students by school. Breakfast in the classroom was associated with fewer students not eating breakfast (P<0.001), but more eating breakfast at both home and school (P<0.001). Students in the breakfast in the classroom group did not have higher mean energy intakes from breakfast or higher daily energy intakes that were higher than other breakfast policy groups. The breakfast in the classroom group had higher overall diet quality (P=0.01). No evidence was found to support discontinuation of breakfast in the classroom policy on the basis of concerns that children will eat excess calories.


Discs-Large and Strabismus are functionally linked to plasma membrane formation.
During early embryogenesis in Drosophila melanogaster, extensive vesicle transport occurs to build cell boundaries for 6,000 nuclei. Here we show that this important process depends on a functional complex formed between the tumour suppressor and adaptor protein Discs-Large (Dlg) and the integral membrane protein Strabismus (Stbm)/Van Gogh (Vang). In support of this idea, embryos with mutations in either dlg or stbm displayed severe defects in plasma membrane formation. Conversely, overexpression of Dlg and Stbm synergistically induced excessive plasma membrane formation. In addition, ectopic co-expression of Stbm (which associated with post-Golgi vesicles) and the mammalian Dlg homologue SAP97/hDlg promoted translocation of SAP97 from the cytoplasm to both post-Golgi vesicles and the plasma membrane. This effect was dependent on the interaction between Stbm and SAP97. These findings suggest that the Dlg-Stbm complex recruits membrane-associated proteins and lipids from internal membranes to sites of new plasma membrane formation.


Computed tomography of thoracic and lumbar spine injuries.
CT scans of 73 patients with acute thoracic/lumbar spine injuries from T3 to L5 were reviewed. Injuries were classified as burst fractures (48), fracture-dislocations (ten), wedge compression fractures (11), and seatbelt-type injuries (four). Thirty-one (42%) had motor deficits due to spinal cord or nerve root damage. Such neurologic deficits were present in all patients with fracture-dislocations, and 60% of those with burst fractures. Seven patients, four initially normal, developed progressive neurologic impairment early after injury. Burst fractures, one with dislocation, were the spinal injury associated with each progressive deficit. Burst fractures at T12 or L1 with 50% or more decrease of the mid-sagittal neural canal diameter had a significant risk of neurologic involvement, and of progressive deficit. CT scans demonstrate vertebral column damage well, and help identify those patients at risk of acute neurologic compromise.


Neonatal oxytocin and vasopressin manipulation alter social behavior during the juvenile period in Mongolian gerbils.
Oxytocin and vasopressin are important modulators of a wide variety of social behaviors, and increasing evidence is showing that these neuropeptides are important organizational effectors of later-life behavior as well. We treated day-old gerbil pups with oxytocin, vasopressin, an oxytocin receptor antagonist, a vasopressin V1a receptor antagonist, or saline control, and then measured received parental responsiveness during the early postnatal period and juvenile social behavior during weaning. Neonatal vasopressin treatment enhanced sociality in males, but not females, at both developmental time points. When pups were individually placed outside the nest, parents were more responsive to male pups treated with vasopressin compared with littermates, and vasopressin treated male pups exhibited increased play with littermates as juveniles. These results show that vasopressin during very early life can enhance social interactions throughout early development.


Proteins from eight eukaryotic cytochrome P-450 families share a segmented region of sequence similarity.
Proteins from eight eukaryotic families in the cytochrome P-450 superfamily share one region of sequence similarity. This region begins 275-310 amino acids from the amino terminus of each P-450, continues for approximately 170 residues, and ends 35-50 amino acids before the carboxyl terminus. The region can be divided into four domains of sequence similarity, each possessing its own pattern of invariant, conserved, and variable amino acids. The four domains are 56, 20, 59, and 28 residues long and are connected by three shorter segments of limited sequence similarity. The number of residues in these short segments varies with the P-450 protein but ranges from 0 to 20 residues. Consensus sequences based on these similarities can be used to determine whether the sequence of an unidentified peptide resembles that expected for a P-450. Sequence similarities between proteins sometimes reflect constraints imposed by the requirements of a common function. The fourth domain of the P-450s, for example, contains an invariant cysteine that provides the axial thiolate ligand to the heme iron. Other relationships between the four domains and P-450 function can be examined by in vitro mutagenic procedures that alter the conserved amino acids or modify the distance between domains.


Preferences of Coptotermes formosanus Shiraki and Coptotermes gestroi (Wasmann) (Blattodea: Rhinotermitidae) among Three Commercial Wood Species.
The Formosan subterranean termite, Coptotermes formosanus Shiraki, and the Asian subterranean termite, Coptotermes gestroi (Wasmann), are both pests of wood in service in Hawaii and Florida. We conducted a laboratory study using method modified from those described in standard E1-09 of the American Wood Protection Association (AWPA 2009) to assess the termite resistance of three commercially available wood species used in regions of the USA where both termite species occur: Douglas fir, Pseudotsuga menziessii, southern yellow pine, Pinus spp. and redwood, Sequoia sempervirens. A multiple-choice (three-choice) assay was used for four weeks (28 days) in order to simulate field conditions of food choice and assess termite feeding preferences under 28 °C and 72-80% RH. 400 termites (360 workers: 40 soldiers) were released into each test jar. Five replicates and two controls of each wood species were used with each termite species. Termite mortality was recorded at the end of the test; and wood wafers were oven-dried and weighed before and after termite exposure to determine the mass loss due to termite feeding, and rated visually on a 0 (failure) to 10 (sound) scale. There were significant differences in mean mass loss values among the three wood species and between two termite species. The mean mass loss value for redwood was significantly lower than Douglas fir and southern yellow pine with both termite species. However, C. formosanus showed increased feeding on Douglas fir and southern yellow pine compared to C. gestroi.


The Role of Copper Chaperone Atox1 in Coupling Redox Homeostasis to Intracellular Copper Distribution.
Human antioxidant protein 1 (Atox1) is a small cytosolic protein with an essential role in copper homeostasis. Atox1 functions as a copper carrier facilitating copper transfer to the secretory pathway. This process is required for activation of copper dependent enzymes involved in neurotransmitter biosynthesis, iron efflux, neovascularization, wound healing, and regulation of blood pressure. Recently, new cellular roles for Atox1 have emerged. Changing levels of Atox1 were shown to modulate response to cancer therapies, contribute to inflammatory response, and protect cells against various oxidative stresses. It has also become apparent that the activity of Atox1 is tightly linked to the cellular redox status. In this review, we summarize biochemical information related to a dual role of Atox1 as a copper chaperone and an antioxidant. We discuss how these two activities could be linked and contribute to establishing the intracellular copper balance and functional identity of cells during differentiation.


FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress.
Retinal pigment epithelial (RPE) cells that underlie the neurosensory retina are essential for the maintenance of photoreceptor cells and hence vision. Interactions between the RPE and their basement membrane, i.e. the inner layer of Bruch's membrane, are essential for RPE cell health and function, but the signals induced by Bruch's membrane engagement, and their contributions to RPE cell fate determination remain poorly defined. Here, we studied the functional role of the soluble complement regulator and component of Bruch's membrane, Factor H-like protein 1 (FHL-1). Human primary RPE cells adhered to FHL-1 in a manner that was eliminated by either mutagenesis of the integrin-binding RGD motif in FHL-1 or by using competing antibodies directed against the α5 and β1 integrin subunits. These short-term experiments reveal an immediate protein-integrin interaction that were obtained from primary RPE cells and replicated using the hTERT-RPE1 cell line. Separate, longer term experiments utilising RNAseq analysis of hTERT-RPE1 cells bound to FHL-1, showed an increased expression of the heat-shock protein genes HSPA6, CRYAB, HSPA1A and HSPA1B when compared to cells bound to fibronectin (FN) or laminin (LA). Pathway analysis implicated changes in EIF2 signalling, the unfolded protein response, and mineralocorticoid receptor signalling as putative pathways. Subsequent cell survival assays using H2O2 to induce oxidative stress-induced cell death suggest hTERT-RPE1 cells had significantly greater protection when bound to FHL-1 or LA compared to plastic or FN. These data show a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identifies a novel interaction that has implications for ocular diseases such as age-related macular degeneration.


Atrial selective effects of intravenously administered vernakalant in conscious beagle dogs.
Vernakalant is a relatively atrial-selective antiarrhythmic drug approved for the conversion of recent onset atrial fibrillation in Europe and is under regulatory review in the United States. In this study, we examined the effects of intravenously administered vernakalant (5, 10, and 20 mg/kg) on blood pressure, heart rate, and the electrocardiogram in conscious male beagle dogs and compared them with those of orally administered dl-sotalol (32 mg/kg). Vernakalant had no consistent dose-dependent effects on the heart rate or mean arterial pressure. Although vernakalant inhibits I(Kr), it tended to decrease the QTc interval but only at the top dose and later time points. The most striking effect of vernakalant on the electrocardiogram was a dose-dependent and selective slowing of atrial conduction (P-wave duration), with no effect on ventricular conduction (QRS duration). In contrast, treatment with dl-sotalol resulted in a marked and statistically significant prolongation of PR and QTc intervals with no effect on QRS or P-wave duration, consistent with its known class II and III antiarrhythmic actions. These results provide further evidence that vernakalant is unlikely to alter ventricular refractoriness or conduction at plasma concentrations in excess of those necessary for conversion of atrial fibrillation to sinus rhythm in patients.


T cell metabolism in metabolic disease-associated autoimmunity.
This review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoimmunity. Multiple therapeutic approaches using existing pharmaceuticals are possible from a rationale in which T cell metabolism forms the hub in dampening the T cell component of autoimmunity in metabolic diseases. Future research into the effects of a metabolically aberrant micro-environment on T cell metabolism and its potential as a therapeutic target for immunomodulation could lead to novel treatment strategies for metabolic disease-associated autoimmunity.


[Acute kidney failure. Non-invasive diagnosis of acute kidney failure in operative intensive care patients].
Acute renal failure is a common and severe complication in ICU. Renal laboratory examinations like creatinine and urea are late signs of renal dysfunction: Most of the functional abilities are reduced and there is no time for therapeutical interventions. The aim of this study was to find some earlier sensitive parameters of renal dysfunction and the order of appearance, the cause of acute renal failure and the value of the measured parameters. After agreement of the local ethic committee, 21 patients of the ICU were investigated. They were divided into two groups: 1st (n = 14) with no signs of renal dysfunction and were regarded as control group and 2nd (n = 7) were examined until the beginning of acute renal failure. For five days the glomerular filtration rate, proteinuria (immunoglobulin G, Tamm-Horsfall protein, alpha-1- and beta-2 microglobulin, lysozyme), the brush border enzymes angiotensinase A and the lysosomal enzyme N-acetyl-beta-d-glucosaminidase were daily measured and compared with clinical standards like the excretion of albumin, the clearances of creatinine and urea and the fractional excretion of sodium. Both groups were comparable with respect to drug therapy, APACHE-II-score (with the exception of the last day before ARF), and infusion therapy. There were differences in tubular functions between the 2 groups. Patients developing renal insufficiency showed an increased excretion of alpha-1-microglobulin, and decreased excretions of Tamm-Horsfall-protein, angiotensinase A as well as a low renal blood flow. Significant differences were also detectable in glomerular functions (glomerular filtration rate), albumin, and immunoglobulin G. Only a short time interval (1 to 2 days) between tubular and glomerular damage were detectable in patients with renal insufficiency. Renal failure must be due to circulatory problems because of the nearly simultaneous increase of tubular and glomerular parameters after RPF decreased. The parameters alpha 1-microglobulin, angiotensinase A and Tamm-Horsfall-protein gave early indications for the acute renal failure. They showed satisfactory sensitivity and specificity, but the positive predictive value was poor.


The currency and completeness of specialized databases of COVID-19 publications.
Several specialized collections of COVID-19 literature have been developed during the global health emergency. These include the WHO COVID-19 Global Literature Database, Cochrane COVID-19 Study Register, CAMARADES COVID-19 SOLES, Epistemonikos' COVID-19 L-OVE, and LitCovid. Our objective was to evaluate the completeness of these collections and to measure the time from when COVID-19 articles are posted to when they appear in the collections. We tested each selected collection for the presence of 440 included studies from 25 COVID-19 systematic reviews. We sampled 112 journals and prospectively monitored their websites until a new COVID-19 article appeared. We then monitored for 2 weeks to see when the new articles appeared in each collection. PubMed served as a comparator. Every collection provided at least one record not found in PubMed. Four records (1%) were not in any of the sources studied. Collections contained between 83% and 93% of the primary studies with the WHO database being the most complete. By 2 weeks, between 60% and 78% of tracked articles had appeared. Our findings support the use of the best performing COVID-19 collections by systematic reviews to replace paywalled databases.


Mitochondrial DNA analysis of the bark beetle predator Thanasimus dubius F. (Coleoptera: Cleridae) reveals regional genetic differentiation.
The checkered beetle, Thanasimus dubius F., is an important predator of scolytid bark beetles that attack conifers. Relatively few studies exist that have addressed the population genetics of predatory beetles, especially those with potential as biological control agents. This study was conducted to investigate the population genetics of T. dubius across a large part of its range in the eastern United States. A 464-base pair portion of the mitochondrial cytochrome c oxidase subunit I was sequenced for 85 individuals resulting in 60 haplotypes. Analysis of molecular variance was conducted on the resulting haplotypes for all populations and as a hierarchical analysis between populations defined as broad-scale northern and southern groups. Results indicate a significant overall Phi ST = 0.220 (P < 0.001) for all populations with the hierarchical analysis revealing that this significant Phi ST is due to structuring of the populations between northern and southern regions (Phi CT = 0.388, P < 0.009). The observed genetic structure is possibly due to the discontinuous distribution of pine trees, which act as hosts for the prey of T. dubius, which has occurred historically in the central region of the United States that has been covered by prairie.


Thoracic neuroblastoma presenting as a cystic hygroma.
A case of thoracic neuroblastoma with extension into the supraclavicular fossa is described. By physical examination and ultrasound the patient was thought to have a cystic hygroma with mediastinal extension. A 'cystic' neck mass may be the initial presentation of a mediastinal neuroblastoma.


Limitations of interview-based risk assessment of RF exposure from appliances.
This study was conducted to assess the quality of interview-based exposure estimates obtained in a large epidemiologic case-control study: The Northern Germany Leukemia and Lymphoma Study (1997-2002) (NLL). The NLL used standardized, face-to-face, computer-assisted interviews to record subjects' lifetime use of radiofrequency (RF)-emitting appliances such as cellular telephones, cordless telephones, baby monitors, and television headphones. Exposure assessment comprised 3 levels of precision: ever use, gross vs. net appliance-years, and lifetime cumulative exposure hours. In the current study, the authors analyzed data from 3041 interviews of NLL controls, representing an age-stratified random sample of the general populations of 6 counties in Northern Germany. Weighted kappa coefficients for gross vs. net appliance-years for men were 0.59 (95% confidence interval [CI] = 0.46, 0.71) for baby monitors and 0.98 (95% CI = 0.97, 0.99) for cordless phones; for women, the coefficients were 0.68 (95% CI = 0.56, 0.79) and 0.97 (95% CI = 0.94, 0.98), respectively. Weighted kappa values were considerably lower when net appliance-years and lifetime cumulative exposure hours were compared. Study results demonstrated that interview information on use of RF-emitting appliances, when measured at different levels of precision, can result in misclassification and biased risk estimates.


Heterologous expression of ApGSMT2 and ApDMT2 genes from Aphanothece halophytica enhanced drought tolerance in transgenic tobacco.
The glycine-methylation biosynthetic pathway of glycinebetaine (GB) has been investigated, but only a few studies on GB accumulation in transgenic higher plants have utilized this pathway. In this study, two methyltransferase genes named ApGSMT2 and ApDMT2, encoding proteins catalyzing GB biosynthesis from glycine, were cloned from a relative strain of Aphanothece halophytica. The potential roles of ApGSMT2 and ApDMT2 in GB synthesis were first examined in transgenic Escherichia coli, which had increased levels of GB and improved salt tolerance. Then ApGSMT2 and ApDMT2 were transferred into tobacco. Compared with transgenic tobacco expressing betA, transgenic tobacco co-expressing ApGSMT2 and ApDMT2 accumulated more GB and exhibited enhanced drought resistance with better germination performance, higher relative water content, less cell membrane damage and better photosynthetic capacity under drought stress. We concluded that the ApGSMT2 and ApDMT2 genes cloned in this study will be very useful for engineering GB-accumulating transgenic plants with enhanced drought resistance.


Gel Electrolytes with Polyamidopyridine Dendron Modified Talc for Dye-Sensitized Solar Cells.
Organic-inorganic hybrid layered materials are proposed as additives in a quasi-solid gel electrolyte for dye-sensitized solar cells. Talcs could provide a low-cost and environmentally friendly, as well as abundant, option as gelators. Here, talcs were prepared by functionalizing an organotalc with three polyamidopyridine dendron generations, PAMPy-talc-Gn (n = 1, 2 and 3). PAMPy dendrons grow parallel to the lamellae plane and form an organized structure by intermolecular interactions. In addition, polyiodide-dendron charge-transfer complexes were prepared onto the organotalc by adsorption of iodine. In this work, the effect of the dendron generation of PAMPy-talc and the influence of polyiodide intercalation on solar cell performance and stability were investigated. The best results were reached with the use of lowest-generation PAMPy-talc (η = 4.5 ± 0.3%, VOC = 710 ± 19 mV, Jsc = 10.4 ± 0.9 mA cm-2, and FF = 61 ± 2%): 15% higher efficiency compared to similar liquid devices. While some previously studied talcs illustrate very strong absorption of the iodide from the electrolyte, in the case of PAMPy-talc such interfering effects were absent: In a 1000 h light soaking test, the PAMPy-talc cells both with and without polyiodide intercalation demonstrated stable performances. Furthermore, the color analysis of the electrolyte indicated that the color of the electrolyte remained stable after an initial period of stabilization, which is a good indication of the compound being stable and not absorbing charge carriers from the electrolyte. The performance and stability results indicate that PAMPy-talc has potential as a gelling method for electrolytes for dye solar cells.


Validation and Extension of the Prolonged Mechanical Ventilation Prognostic Model (ProVent) Score for Predicting 1-Year Mortality after Prolonged Mechanical Ventilation.
Prognostic models can inform management decisions for patients requiring prolonged mechanical ventilation. The Prolonged Mechanical Ventilation Prognostic model (ProVent) score was developed to predict 1-year mortality in these patients. External evaluation of such models is needed before they are adopted for routine use. The goal was to perform an independent external validation of the modified ProVent score and assess for spectrum extension at 14 days of mechanical ventilation. This was a retrospective cohort analysis of patients who received prolonged mechanical ventilation at the University of Iowa Hospitals. Patients who received 14 or more days of mechanical ventilation were identified from a database. Manual review of their medical records was performed to abstract relevant data including the four model variables at Days 14 and 21 of mechanical ventilation. Vital status at 1 year was checked in the medical records or the social security death index. Logistic regressions examined the associations between the different variables and mortality. Model performance at 14 to 20 days and 21+ days was assessed for discrimination by calculating the area under the receiver operating characteristic curve, and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. A total of 180 patients (21+ d) and 218 patients (14-20 d) were included. Overall, 75% were surgical patients. One-year mortality was 51% for 21+ days and 32% for 14 to 20 days of mechanical ventilation. Age greater than 65 years was the strongest predictor of mortality at 1 year in all cohorts. There was no significant difference between predicted and observed mortality rates for patients stratified by ProVent score. There was near-perfect specificity for mortality in the groups with higher ProVent scores. Areas under the curve were 0.69 and 0.75 for the 21+ days and the 14 to 20 days cohorts respectively. P values for the Hosmer-Lemeshow statistics were 0.24 for 21+ days and 0.22 for 14 to 20 days. The modified ProVent model was accurate in our cohort. This supports its geographic and temporal generalizability. It can also accurately identify patients at risk of 1-year mortality at Day 14 of mechanical ventilation, but additional confirmation is required. Further studies should explore the implications of adopting the model into routine use.


HGR-Net: Hierarchical Graph Reasoning Network for Arbitrary Shape Scene Text Detection.
As a prerequisite step of scene text reading, scene text detection is known as a challenging task due to natural scene text diversity and variability. Most existing methods either adopt bottom-up sub-text component extraction or focus on top-down text contour regression. From a hybrid perspective, we explore hierarchical text instance-level and component-level representation for arbitrarily-shaped scene text detection. In this work, we propose a novel Hierarchical Graph Reasoning Network (HGR-Net), which consists of a Text Feature Extraction Network (TFEN) and a Text Relation Learner Network (TRLN). TFEN adaptively learns multi-grained text candidates based on shared convolutional feature maps, including instance-level text contours and component-level quadrangles. In TRLN, an inter-text graph is constructed to explore global contextual information with position-awareness between text instances, and an intra-text graph is designed to estimate geometric attributes for establishing component-level linkages. Next, we bridge the cross-feed interaction between instance-level and component-level, and it further achieves hierarchical relational reasoning by learning complementary graph embeddings across levels. Experiments conducted on three publicly available benchmarks SCUT-CTW1500, Total-Text, and ICDAR15 have demonstrated that HGR-Net achieves state-of-the-art performance on arbitrary orientation and arbitrary shape scene text detection.


Interorgan communication networks in the kidney-lung axis.
The homeostasis and health of an organism depend on the coordinated interaction of specialized organs, which is regulated by interorgan communication networks of circulating soluble molecules and neuronal connections. Many diseases that seemingly affect one primary organ are really multiorgan diseases, with substantial secondary remote organ complications that underlie a large part of their morbidity and mortality. Acute kidney injury (AKI) frequently occurs in critically ill patients with multiorgan failure and is associated with high mortality, particularly when it occurs together with respiratory failure. Inflammatory lung lesions in patients with kidney failure that could be distinguished from pulmonary oedema due to volume overload were first reported in the 1930s, but have been largely overlooked in clinical settings. A series of studies over the past two decades have elucidated acute and chronic kidney-lung and lung-kidney interorgan communication networks involving various circulating inflammatory cytokines and chemokines, metabolites, uraemic toxins, immune cells and neuro-immune pathways. Further investigations are warranted to understand these clinical entities of high morbidity and mortality, and to develop effective treatments.


Hepatocyte nuclear factor-1alpha modulates pancreatic beta-cell growth by regulating the expression of insulin-like growth factor-1 in INS-1 cells.
Maturity-onset diabetes of the young type 3 (MODY3) is characterized by impaired insulin secretion. Heterozygous mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha are the cause of MODY3. Transgenic mice overexpressing dominant-negative HNF-1alpha mutant in pancreatic beta-cells and HNF-1alpha knockout mice are animal models of MODY3. These mice exhibit defective glucose-stimulated insulin secretion and have reduced beta-cell mass and beta-cell proliferation rate. Here we examined the effect of HNF-1alpha on beta-cell proliferation by overexpressing a human naturally occurring dominant- negative mutation P291fsinsC in INS-1 cells under the control of doxycycline-induction system. INS-1 cells overexpressing P291fsinsC showed apparent growth impairment. The proliferation rate estimated by [(3)H]thymidine incorporation was significantly reduced in P291fsinsC-expressing INS-1 cells compared with noninduced or wild-type HNF-1alpha-overexpressing INS-1 cells. Growth inhibition occurred at the transition from G1 to S cell cycle phase, with reduced expression of cyclin E and upregulation of p27. cDNA array analysis revealed that the expression levels of IGF-1, a major growth factor for beta-cells, and macrophage migration inhibitory factor (MIF), a cytokine expressed in pancreatic beta-cells, were reduced in P291fsinsC-HNF-1alpha-expressing INS-1 cells. Although MIF seemed to have proliferative function, blockade of MIF action by anti-MIF antibody stimulated INS-1 cell proliferation, excluding its direct role in the growth impairment. However, addition of IGF-1 to P291fsinsC-expressing INS-1 cells rescued the growth inhibition. Our data suggest that HNF-1alpha is critical for modulating pancreatic beta-cell growth by regulating IGF-1 expression. IGF-1 might be a potential therapeutic target for the treatment of MODY3.


The impact of reclassifying moderate CKD as a coronary heart disease risk equivalent on the number of US adults recommended lipid-lowering treatment.
The Third National Cholesterol Education Program Adult Treatment Panel (ATP-III) guidelines recommend consideration of lipid-lowering therapy at lower low-density lipoprotein cholesterol levels (>or=100 mg/dL [>or=2.59 mmol/L]) for adults with coronary heart disease risk equivalents. Chronic kidney disease is associated with increased coronary heart disease risk but is not included as a risk equivalent in these guidelines. The impact of including moderate chronic kidney disease (estimated glomerular filtration rate, 30 to 59 mL/min/1.73 m(2) [0.50 to 0.98 mL/s]) as a coronary heart disease risk equivalent on the percentage and number of US adults with chronic kidney disease recommended lipid-lowering therapy was estimated by using data from the Third National Health and Nutrition Examination Survey. Of adults with moderate chronic kidney disease, 53.0% had a history of coronary heart disease or a risk equivalent, 24.7% reported a history of myocardial infarction or stroke, 17.7% had diabetes, 9.6% had angina, and 26.9% had a 10-year coronary heart disease risk greater than 20%. Using current ATP-III guidelines, lipid-lowering therapy is recommended for 61.4% of adults with moderate chronic kidney disease. If moderate chronic kidney disease was reclassified as a coronary heart disease risk equivalent, this percentage would increase to 87.7%, representing an increase in number of adults with moderate chronic kidney disease recommended lipid-lowering treatment from 4.5 to 6.5 million adults. This analysis shows that a majority of adults with moderate chronic kidney disease have coronary heart disease or risk equivalents. Nonetheless, a substantially greater proportion of US adults with moderate chronic kidney disease would be recommended lipid-lowering therapy through its reclassification as a coronary heart disease risk equivalent.


Using Web-based reporting systems to evaluate health promotion: the experience of two statewide HIV prevention programs.
While Web-based reporting systems are becoming more common in public health for disease surveillance and for tracking interventions such as immunizations, their use for program evaluation is relatively new. This article describes two Web-based reporting systems developed to enable local agencies that conduct health promotion activities to enter process and outcome data for their own use, as well as for analysis by researchers and funders. The systems support the three major uses of evaluation: accountability, program improvement, and generating knowledge for the field. Annually, these programs obtain evaluation information on thousands of clients and individual and group sessions. Developing and introducing the Web-based systems was time-consuming and required significant State Health Department and local agency resources. Involvement of end users in the development process was critical to creating responsive systems that were accepted by staff in local agencies. Staff members from grantee agencies responded well to systems, as evidenced by high rates of user compliance (over 90%) and positive reactions (over 80%) on anonymous surveys. Concerns about resistance from contractors to use of the system, based on fears about breaches in client confidentiality or concerns about the difficulty in using the technology, were not borne out.


Low-carbohydrate diet induces metabolic depression: a possible mechanism to conserve glycogen.
Long-term studies have found that low-carbohydrate diets are more effective for weight loss than calorie-restricted diets in the short term but equally or only marginally more effective in the long term. Low-carbohydrate diets have been linked to reduced glycogen stores and increased feelings of fatigue. We propose that reduced physical activity in response to lowered glycogen explains the diminishing weight loss advantage of low-carbohydrate compared with low-calorie diets over longer time periods. We explored this possibility by feeding adult Drosophila melanogaster a standard or a low-carbohydrate diet for 9 days and measured changes in metabolic rate, glycogen stores, activity, and body mass. We hypothesized that a low-carbohydrate diet would cause a reduction in glycogen stores, which recover over time, a reduction in physical activity, and an increase in resting metabolic rate. The low-carbohydrate diet reduced glycogen stores, which recovered over time. Activity was unaffected by diet, but metabolic rate was reduced, in the low-carbohydrate group. We conclude that metabolic depression could explain the decreased effectiveness of low-carbohydrate diets over time and recommend further investigation of long-term metabolic effects of dietary interventions and a greater focus on physiological plasticity within the study of human nutrition.


Ventilatory effects of a propofol infusion using a method to rapidly achieve steady-state equilibrium.
The ventilatory effects of a propofol infusion were studied in 10 females premedicated with atropine and nine with papaveretum and atropine. The infusion, at a rate of 20 mg kg-1 h-1 for 5 min, reducing to 12 mg kg-1 h-1 for 10 min and then 6 mg kg-1 h-1 thereafter, was known to produce a steady-state plasma propofol concentration for 20-25 min after 25 min from commencement. Minute ventilation, tidal volume, frequency and response to breathing carbon dioxide were measured before the infusion and during the steady-state period. Propofol decreased minute ventilation to 56% and 46% (P less than 0.01) of their mean control values in the atropine and papaveretum groups, respectively. Mean tidal volume was decreased to 41-44% (P less than 0.02) by propofol, but a tachypnoea observed in the atropine group during the infusion was absent in the papaveretum group. Propofol alone had no effect on the slopes of the carbon dioxide response curves but did produce a shift to the right (P less than 0.05). Following papaveretum premedication the minute ventilation-carbon dioxide response curve slope, was decreased to 55% of its mean control volume value by the infusion, but this failed to reach statistical significance.


Should I stay or should I go? Cadherin function and regulation in the neural crest.
Our increasing comprehension of neural crest cell development has reciprocally advanced our understanding of cadherin expression, regulation, and function. As a transient population of multipotent stem cells that significantly contribute to the vertebrate body plan, neural crest cells undergo a variety of transformative processes and exhibit many cellular behaviors, including epithelial-to-mesenchymal transition (EMT), motility, collective cell migration, and differentiation. Multiple studies have elucidated regulatory and mechanistic details of specific cadherins during neural crest cell development in a highly contextual manner. Collectively, these results reveal that gradual changes within neural crest cells are accompanied by often times subtle, yet important, alterations in cadherin expression and function. The primary focus of this review is to coalesce recent data on cadherins in neural crest cells, from their specification to their emergence as motile cells soon after EMT, and to highlight the complexities of cadherin expression beyond our current perceptions, including the hypothesis that the neural crest EMT is a transition involving a predominantly singular cadherin switch. Further advancements in genetic approaches and molecular techniques will provide greater opportunities to integrate data from various model systems in order to distinguish unique or overlapping functions of cadherins expressed at any point throughout the ontogeny of the neural crest.


Low-dose chenodiol to prevent gallstone recurrence after dissolution therapy.
Chenodiol is a safe and effective agent for the medical dissolution of gallstones in selected patients; however, after dissolution and cessation of treatment, gallstones recur. This study was done to determine the recurrence rate after successful medical treatment and cessation of chenodiol therapy; compare the efficacy and safety of low-dose chenodiol, as compared to placebo, for prophylaxis against recurrence; and identify factors predictive of recurrence. In a randomized, double-blind fashion, 53 patients with gallstone dissolution received either chenodiol, 375 mg/d, or placebo, for at least 2 years. Standardized oral cholecystograms were done at 6 months, 1 year, and then yearly thereafter. Routine laboratory testing was done every 6 months. The cumulative rate of recurrence (life-table) was 27% in patients followed for up to 3.5 years. Chenodiol, 375 mg/d, was ineffective in preventing the recurrence of gallstones. No demographic, clinical, roentgenographic, or biochemical characteristics were predictive of recurrence.


Afferent and peripheral control of muscle fiber properties during gravitational unloading.
The present paper covers two series of the experiment studies performed in attempt to analyze the support-triggered cellular mechanisms, controlling the maintenance of tonic muscle fiber characteristics. Exposure to 7 day dry immersion induced significant decline of the human soleus single fiber peak isometric tension and the Ca(2+)-sensitivity of myofibrils. 30-40% losses of the relative content of titin and nebulin were found after immersion. The application of the plantar support stimulation device prevented all these alterations. In the second experimental series the treatment of hindlimb suspended rats with the Ca(2+)-binding agent (EGTA) allowed to prevent or attenuate all the above mentioned unloading-induced soleus fiber alterations. Thus it is concluded that resting Ca2+ accumulation in the unloaded fibers may be among the mechanisms involved in the changes of fiber properties during unloading.


Hinge location and apical drill holes in opening wedge high tibial osteotomy: A finite element analysis.
At the time of medial opening wedge high tibial osteotomy (HTO) to realign the lower limb and offload medial compartment knee osteoarthritis, unwanted fractures can propagate from the osteotomy apex. The aim of this study was to use finite element (FE) analysis to determine the effect of hinge location and apical drill holes on cortical stresses and strains in HTO. A monoplanar medial opening wedge HTO was created above the tibial tuberosity in a composite tibia. Using the FE method, intact lateral hinges of different widths were considered (5, 7.5, and 10 mm). Additional apical drill holes (2, 4, and 6 mm diameters) were then incorporated into the 10 mm hinge model. The primary outcome measure was the maximum principal strain in the cortical bone surrounding the hinge axis. Secondary outcomes included the force required for osteotomy opening, minimum principal strain, and mean cortical bone stresses (maximum principal/minimum principal/von Mises). Larger intact hinges (10 mm) were associated with higher cortical bone maximum principal strain and stress, lower minimum principal strain/stress, and required greater force to open. Lateral cortex strain concentrations were present in all scenarios, but extended to the joint surface with the 10 mm hinge. Apical drill holes reduced the mean cortical bone maximum principal strain adjacent to the hinge axis: 2 mm hole 6% reduction; 4 mm 35% reduction; and 6 mm 55% reduction. Incorporating a 4-mm apical drill hole centered 10 mm from the intact lateral cortex maintains a cortical bone hinge, minimizes cortical bone strains and reduces the force required to open the HTO; thus improving control.


[Rapid diagnosis in microbiology, present and future (lecture)].
The authors analyze present-day rapid laboratory methods that are helpful in the diagnosis of various critical states in infectious diseases. Currently the immunologic and other than immunologic methods for visual detection of corpuscular antigens, soluble antigens in clinical material are the best rapid methods easy to perform. Methods with DNA probes are a promising alternative of these methods.


Effect of lithium metal on the chemical status of glutathione (GSH) present in whole blood (especially in plasma and cytosolic fraction in human blood).
Lithium remains a mainstay in the acute and prophylactic treatment of bipolar affective disorder. It is used in the augmentation of antidepressant treatment and, less frequently, in the augmentation of antipsychotic treatment of schizophrenia. It is reported to have specific anti-suicidal effects. Thus the effect of Lithium was interesting to study on the glutathione (GSH) level in vivo conditions. Ellman's method has been used to see the effect of lithium on glutathione (GSH) level in whole blood. The time dependent effect of Lithium on the chemical status of glutathione (GSH) was determined in the whole blood (Plasma and cytosolic fraction) of human. The concentration of Glutathione was drastically decreased. The decrease in the glutathione level was concentration and time of interaction dependent, probably due to oxidation of glutathione (GSH) to corresponding disulphide (GSSG). In this paper the effect of Lithium on the Thiol/GSH level was discussed in vitro, which in principal may present a model of in vivo reaction.


[Clinical investigation of delayed graft function recovery following renal transplantation].
To investigate the etiology and therapy of delayed graft function (DGF) recovery in renal transplant recipients. The clinical data were retrospectively analyzed in 15 renal recipients with DGF. All the 15 patients received hemodialysis along with pulse treatment against acute rejection (AR), or immunosuppressant adjustment, or in situ retransplantation after the resection of the original transplanted kidney according to different etiological factors. Among the 15 patients, 8 developed AR, 5 showed acute renal tubular necrosis (ATN), 1 had grafting-associated renal vein embolism and 1 had acute cyclosporine nephrotoxication. The renal function recovered within 10 to 35 days after transplantation without complication during the follow-up period (0.5-3.0 years). DGF is a common complication after kidney transplantation mainly due to the occurrence of AR and ATN. Good prognosis is expected if etiology-oriented therapy is performed properly and promptly.


Supporting Pediatric Patients and Their Families at the End of Life: Perspectives From Bereaved Parents.
Cancer remains the leading cause of death by disease for children in the United States. It is imperative to optimize measures to support patients and families facing the end of a child's life. This study asked bereaved parents to reflect on their child's end-of-life care to identify which components of decision-making, supportive services, and communication were helpful, not helpful, or lacking. An anonymous survey about end-of-life experiences was sent to families of children treated at a single institution who died of a malignancy between 2010 and 2017. Twenty-eight surveys were returned for a 30.8% response rate. Most of the bereaved parents (61%) reported a desire for shared decision-making; this was described by 52% of families at the end of their child's life. There was a statistically significant association between how well death went and whether the parental perception of actual decision-making aligned with desired decision-making (P = .002). Families did not utilize many of the supportive services that are available including psychology and psychiatry (only 22% used). Respondents felt that additional services would have been helpful. Health care providers should strive to participate in decision-making models that align with the preferences of the patient and family and provide excellent communication. Additional resources to support families following the death of a child should be identified for families or developed and funded if a gap in available services is identified.


Wisdom in Context.
Philosophers and psychological scientists have converged on the idea that wisdom involves certain aspects of thinking (e.g., intellectual humility, recognition of uncertainty and change), enabling application of knowledge to life challenges. Empirical evidence indicates that people's ability to think wisely varies dramatically across experiential contexts that they encounter over the life span. Moreover, wise thinking varies from one situation to another, with self-focused contexts inhibiting wise thinking. Experiments can show ways to buffer thinking against bias in cases in which self-interests are unavoidable. Specifically, an ego-decentering cognitive mind-set enables wise thinking about personally meaningful issues. It appears that experiential, situational, and cultural factors are even more powerful in shaping wisdom than previously imagined. Focus on such contextual factors sheds new light on the processes underlying wise thought and its development, helps to integrate different approaches to studying wisdom, and has implications for measurement and development of wisdom-enhancing interventions.