Rapid Growth of the World Population and Its Socioeconomic Results.
This article is mainly devoted to the study of socioeconomic opportunities and problems that may arise from the growth of the world's population. The article identifies the reasons for the increase in world population and analyzes the factors influencing on the process. The article examines the impact of changes on the world's demographics on socioeconomic development. As a result, the characteristics of possible problems were investigated and evaluated. The study analyzes the issues of demographic change in the world population, the current situation, and opportunities of the world economy in accordance with population statistics and its growth rate. The main purpose of the study is to determine the causes of world population growth, analyze the current demographic situation, and determine and assess the forecast of future growth dynamics. The study discusses, analyzes, and evaluates the problems that can be caused by the growth of the world's population. The main problem we raise in the study is the mismatch between the rapid growth of the world's population and the socioeconomic security of the people. That is, if the issue of socioeconomic security is not resolved, the growth of the world's population would be a global social problem.


Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer patients.
Polymorphisms in xenobiotic metabolizing enzymes have been implicated in inter-individual and inter-ethnic differences in cancer susceptibilty. Several studies have indicated an association between variant alleles of the human CYP1A1, CYP2E1 and GSTM1 genes and lung cancer. Activity of microsomal epoxide hydrolase (HYL1) has also been associated with lung cancer, and 2 variant alleles causing amino acid substitutions have been described. We have investigated genetic polymorphisms of the CYP1A1, CYP2E1, GSTM1 and HYL1 genes in 76 Chinese lung cancer patients and 122 healthy Chinese subjects. The allele frequency of the CYP1A1*2B allele was 0.21 among lung cancer patients and 0.20 in the reference group, whereas the corresponding values for the CYP1A1*2A allele were 0.34 and 0.36. The CYP2E1*5B and CYP2E1*6 alleles were less frequent among the cancer patients (0.20 and 0.22) compared with healthy subjects (0.25 and 0.26). The frequency distribution of the HYL1*2 allele was 0.49 among lung cancer patients and 0.42 in the reference group, and the corresponding frequencies for the HYL1*3 allele were 0.13 and 0.10. The homozygous GSTM1*0 genotype was found in 64% of lung cancer patients and in 66% of healthy subjects. Among heavy smokers, the frequency was 73%. The differences in the distribution of variant CYP1A1, CYP2E1 and GSTM1 alleles in lung cancer patients and healthy controls were not statistically significant. Our results indicate that the polymorphisms investigated are of minor importance as genetic susceptibility markers for lung cancer in this population. An increased risk for lung cancer in subjects carrying the HYL*3 allele was observed and suggests that polymorphism in this gene might possibly be a susceptibility factor in the Chinese population.


Preconditioning beef cattle for long-duration transportation stress with rumen-protected methionine supplementation: A nutrigenetics study.
In general, beef cattle long-distance transportation from cow-calf operations to feedlots or from feedlots to abattoirs is a common situation in the beef industry. The aim of this study was to determine the effect of rumen-protected methionine (RPM) supplementation on a proposed gene network for muscle fatigue, creatine synthesis (CKM), and reactive oxygen species (ROS) metabolism after a transportation simulation in a test track. Angus × Simmental heifers (n = 18) were stratified by body weight (408 ± 64 kg; BW) and randomly assigned to dietary treatments: 1) control diet (CTRL) or 2) control diet + 8 gr/hd/day of top-dressed rumen-protected methionine (RPM). After an adaptation period to Calan gates, animals received the mentioned dietary treatment consisting of Bermuda hay ad libitum and a soy hulls and corn gluten feed based supplement. After 45 days of supplementation, animals were loaded onto a trailer and transported for 22 hours (long-term transportation). Longissimus muscle biopsies, BW and blood samples were obtained on day 0 (Baseline), 43 (Pre-transport; PRET), and 46 (Post-transport; POST). Heifers' average daily gain did not differ between baseline and PRET. Control heifer's shrink was 10% of BW while RPM heifers shrink was 8%. Serum cortisol decreased, and glucose and creatine kinase levels increased after transportation, but no differences were observed between treatments. Messenger RNA was extracted from skeletal muscle tissue and gene expression analysis was performed by RT-qPCR. Results showed that AHCY and DNMT3A (DNA methylation), SSPN (Sarcoglycan complex), and SOD2 (Oxidative Stress-ROS) were upregulated in CTRL between baseline and PRET and, decreased between pre and POST while they remained constant for RPM. Furthermore, CKM was not affected by treatments. In conclusion, RPM supplementation may affect ROS production and enhance DNA hypermethylation, after a long-term transportation.


Postpartum surveillance of bacteriuria in term vaginal deliveries.
This study examined the prevalence of bacteriuria in early postpartum period after term vaginal delivery in Trinidad, West Indies. Asymptomatic bacteriuria occurred in 58 (34.5%) of 168 patients tested. The prevalence of bacteriuria was significantly higher in non-catheterized patients than in catheterized patients and occurred more commonly in patients who were 20 to 29 years old and who were primigravida rather than multigravida. Forty-four patients had a history of urinary tract infection; 18 (40.9%) of these patients had positive urine cultures. Although 10 patients had a vaginal discharge in the late third trimester, none presented with postpartum bacteriuria. Because of the high prevalence of postpartum bacteriuria and the potential to progress to pyelonephritis and chronic renal disease, quantitative urine cultures for all postnatal patients and curative treatment for all positive cultures are recommend.


Increased production of interleukin 4 in children with simple idiopathic nephrotic syndrome.
Sera and peripheral blood mononuclear cells (PBMC) were collected from 42 children with simple idiopathic nephrotic syndrome (INS) aged from 1.5 to 14 years and 28 age and sex-matched healthy children. The levels of IgE in serum and interleukin 4 (IL-4) in supernatant of PHA-activated PBMC were tested by ELISA. A significantly high incidence of allergic diseases was noted in INS children and their first-degree relatives, and there was a close association between atopy and INS. Besides, the levels of IgE and IL-4 were increased in nephrotic state (P < 0.001 both). IgE normal and IL-4 slightly lower in remission state (P < 0.2, P < 0.01 respectively). A positive correlation was noticed between IL-4 and IgE, and between IL-4 and 24-hour proteinuria (r = 0.472, r = 0.562; P < 005, P < 0.01 respectively). These showed a close association between atopy and INS. Both IL-4 and IgE, the important mediators in atopy, showed abnormal change in patients. The increased IL-4 production of T cells might account for the elevated serum IgE level. IL-4 may have a pathogenetic role in INS, but it still remains speculative.


The physical functional capacity of frail elderly persons undergoing ambulatory rehabilitation is related to their nutritional status.
To estimate the prevalence of malnutrition in frail elders undergoing rehabilitation and the association between their nutritional status and physical function. Observational study of new participants undergoing ambulatory rehabilitation. Two Geriatric Day Hospitals (GDH) in Montreal, Quebec. 121 women and 61 men. Evaluation of nutritional status, body composition and physical function. The nutritional status was assessed with a composite index based on anthropometric measurements and serum albumin, as well as using the Mini Nutritional Assessment (MNA) questionnaire. Patients were classified as well-nourished, having mild/at risk of malnutrition or malnourished. Body composition was estimated by bioimpedance and handgrip strength and gait speed by standard methods. 13% of patients were found to be mildly malnourished, whereas 6% were malnourished. Malnourished patients were older and had worse cognition, lower BMI, and % body fat (all p<0.05). Malnourished patients and those with mild malnutrition had lower weight, triceps skinfold thickness, muscle and fat mass (all, p<0.003). Handgrip strength was different according to the nutritional status (p=0.034) and correlated with muscle mass (r=0.65, p<0.001). MNA classified 53% of patients as being at risk whereas 3% were malnourished and it correlated with gait speed (r=0.26, p=0.001). There is a high prevalence of patients in GDH at risk or with mild malnutrition. Being malnourished was associated with worse physical performance, which suggests that a nutritional intervention may be of benefit in improving their physical function.


Overview of the actions of glucocorticoids on the immune response: a good model to characterize new pathways of immunosuppression for new treatment strategies.
Glucocorticoids have been used for over 50 years in the treatment of inflammatory and autoimmune diseases and in preventing graft rejection. Today, knowledge of their molecular, cellular, and pharmacological properties allows a better understanding of glucocorticoid-mediated immunosuppression. Glucocorticoids exert both negative and positive effects with a dynamic and bi-directional spectrum of activities on various limbs and components of the immune response. They modulate genes involved in the priming of the innate immune response, while their actions on the adaptive immune response are to suppress cellular (Th1) immunity and promote humoral (Th2) immunity. Interestingly, glucocorticoids can also induce tolerance to specific antigens by influencing dendritic cell maturation and function and promoting the development of regulatory high IL-10-producing T cells. The ex vivo therapeutic use of glucocorticoids could therefore represent an adjuvant treatment to cell therapy in autoimmune diseases, avoiding the long-term deleterious adverse effects of glucocorticoids. Thus, the panoramic view of glucocorticoid actions on the immune system provides an interesting model for characterizing important biological pathways of immunosuppression.


Identifying health system value dimensions: more than health gain?
Publicly funded health system reforms increasingly require the evaluation of competing programmes. However, programmes are made of multi-dimensional attributes of value (where value refers to latent expectations of health system improvement). This paper identifies the design, implementation and validation of a methodology to elicit health system values to guide health care priority setting. The exercise suggests that the proposed methodology is suitable for eliciting and validating health system values, and its findings show that pursuing health gain alone does not fully capture the dimensions of health system value. More specifically, we identify a list of health system values (elicited by both potential and actual users) and classify them in terms of process-related values (e.g., shorter waiting lists, greater choice, etc.) and improvements in health system equity in addition to value derived from health gain.


The role of plasma arachidonic acid metabolites in the pathogenesis and the prognosis of Henoch-Schönlein purpura.
Henoch-Schönlein Purpura (HSP) involve small vessel inflammation. Arachidonate biochemical pathways play an important role in the pathogenesis of vascular inflammation. The aim of this study was to investigate the change in the ratio of plasma arachidonic acid metabolites in the patients with HSP and evaluate the association between clinical activity and prostanoid activity in the acute phase of HSP. Plasma prostaglandin E2 (PGE2)-like activities were found to be 7.2 +/- 0.8 ng/ml in control group (n = 12) while it was 5.3 +/- 0.6 ng/ml in the patients with HSP (n = 12). Plasma leukotriene C4 (LTC4)-like activities were found to be 16.0 +/- 1.1 ng/ml in control while it was 30.9 +/- 4.3 ng/ml in the patients. The differences of LTC4-like activities and the LTC4/PGE2 ratios between the HSP patients and the controls were significant (p < 0.01, p < 0.001 respectively), but no significant difference was found in PGE2-like activities. Plasma LTC4-like activity and LTC4/PGE2 ratio were also significantly increased in the patients with high clinical score (p < 0.05, p < 0.02 respectively). These results suggested that not only cyclooxygenase products but also LTs may play an important role in vascular inflammation. Therefore LTC4/PGE2 ratio must be taken into consideration in the pathogenesis and the prognosis of HSP.


Heterogeneity Signs on Noncontrast Computed Tomography Predict Hematoma Expansion after Intracerebral Hemorrhage: A Meta-Analysis.
Hematoma expansion (HE) is related to clinical deterioration after intracerebral hemorrhage (ICH) and noncontrast computed tomography (NCCT) signs are indicated as predictors for HE but with inconsistent conclusions. We aim to clarify the correlations of NCCT heterogeneity signs with HE by meta-analysis of related studies. PubMed, Embase, and Cochrane library were searched for eligible studies exploring the relationships between NCCT heterogeneity signs (hypodensity, mixed density, swirl sign, blend sign, and black hole sign) and HE. Poor outcome and mortality were considered as secondary outcomes. Odds ratio (OR) and its 95% confidence intervals (CIs) were selected as the effect size and combined using random effects model. Fourteen studies were included, involving 3240 participants and 435 HEs. The summary results suggested statistically significant correlations of heterogeneity signs with HE (OR, 5.17; 95% CI, 3.72-7.19, P < 0.001), poor outcome (OR, 3.60; 95% CI, 1.98-6.54, P < 0.001), and mortality (OR, 4.64; 95%, 2.96-7.27, P < 0.001). Our findings suggested that hematoma heterogeneity signs on NCCT were positively associated with the increased risk of HE, poor outcome, and mortality rate in ICH.


Distribution and elimination of [2-14C]amino-3,8-dimethylimidazo [4, 5-f] quinoxaline in mice. Analysis by whole animal autoradiography.
1. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a potent bacterial promutagen and carcinogen, formed when beef is cooked. In mammals, MeIQx is metabolized and activated by liver enzymes, but induces tumours in both hepatic and extrahepatic tissues. 2. Intravenous administration of [14C]MeIQx and whole animal autoradiography has been employed to examine the disposition of MeIQx. Within 10 min, radiolabel was distributed throughout body tissue. Liver levels of radioactivity rapidly rose and remained elevated in comparison to other tissues, throughout the period of study (4 d). 3. At early time points radioactivity accumulated in the stomach, kidney and salivary glands then later in the intestine. Radioactivity was rapidly eliminated from the majority of tissues although did persist in liver and intestines throughout the duration of the study, probably due to covalently bound material. No radioactivity could be detected in the central nervous system, thus neither MeIQx nor its metabolites cross the blood-brain barrier to any significant extent. 4. The rapid elimination of radioactivity from the tissues is in good agreement with the time course of excretion of MeIQx. Irrespective of the route of administration (i.v., i.p., p.o.), a substantial proportion of the labelled material is excreted within 24 h and is present in both urine and faeces in similar quantities. 5. Thus MeIQx is extensively bioavailable, is distributed throughout body tissue and, although the majority is quickly cleared, some remains bound to liver and intestine.


Knowledge, Attitude And Practice Of Common Cold And Its Management Among Doctors Of Pakistan.
Antibiotic misuse for upper respiratory tract infections such as the common cold is widespread in clinical practice. Excessive prescription of antibiotics by doctors has resulted in increased antimicrobial resistance. This led to our objective of determining the percentage of doctors in Pakistan prescribing antibiotics for the treatment of common cold and to know about their knowledge in preventing the spread of this disease. It was a cross-sectional descriptive study, conducted in 9 cities of Pakistan including Rawalpindi, Islamabad, Peshawar, Lahore, Karachi, Faisalabad, Sargodha, Multan and D.G. Khan over a period of 03 months -from October to December, 2013. Questionnaire regarding the disease spread and its treatment was distributed among 300 randomly selected doctors in nine cities of Pakistan from both public and private sector. Eighteen percent of the doctors prescribe antibiotics for common cold. Only 113 (37.7%) doctors correctly responded that mean incubation period for common cold was 1-2 days. Two hundred and nine (69.7%) answered correctly that cold weather increases susceptibility to common cold. Only 84 (28%) responded correctly by choosing that regular and frequent hand-washing with good quality soaps was the most effective way to prevent spread of this disease in day-to-day life. Antibiotics are being prescribed for treatment of common cold by a large proportion of doctors. There is insufficient knowledge among our doctors regarding the factors which aggravate or alleviate common cold symptoms as well as the methods by which these infections can be prevented.


The social reality of the imaginary audience: a grounded theory approach.
Traditional approaches to understanding the imaginary audience are challenged in this study. Three hundred sixty-one British schoolchildren (aged 14 and 15 years) were asked to express their worries and concerns, using grounded theory methodology. Qualitative responses were collated and coded according to emerging categories, with "what other people think" identified as the central concern. In particular, the findings are used to critique Elkind's (1967) theory of adolescent egocentrism. Data presented in this study suggest that adolescents worry about what other people think because there are real personal and social consequences. Such concerns are seen as being based in social reality and are not imaginary as Elkind suggested. In conclusion, new methodologies which place young people at the center of the analysis are advocated.


Zero-point energy conservation in classical trajectory simulations: Application to H2CO.
A new approach for preventing zero-point energy (ZPE) violation in quasi-classical trajectory (QCT) simulations is presented and applied to H2CO "roaming" reactions. Zero-point energy may be problematic in roaming reactions because they occur at or near bond dissociation thresholds and these channels may be incorrectly open or closed depending on if, or how, ZPE has been treated. Here we run QCT simulations on a "ZPE-corrected" potential energy surface defined as the sum of the molecular potential energy surface (PES) and the global harmonic ZPE surface. Five different harmonic ZPE estimates are examined with four, on average, giving values within 4 kJ/mol-chemical accuracy-for H2CO. The local harmonic ZPE, at arbitrary molecular configurations, is subsequently defined in terms of "projected" Cartesian coordinates and a global ZPE "surface" is constructed using Shepard interpolation. This, combined with a second-order modified Shepard interpolated PES, V, allows us to construct a proof-of-concept ZPE-corrected PES for H2CO, V eff, at no additional computational cost to the PES itself. Both V and V eff are used to model product state distributions from the H + HCO → H2 + CO abstraction reaction, which are shown to reproduce the literature roaming product state distributions. Our ZPE-corrected PES allows all trajectories to be analysed, whereas, in previous simulations, a significant proportion was discarded because of ZPE violation. We find ZPE has little effect on product rotational distributions, validating previous QCT simulations. Running trajectories on V, however, shifts the product kinetic energy release to higher energy than on V eff and classical simulations of kinetic energy release should therefore be viewed with caution.


High-efficiency water-window x-ray generation from nanowire array targets irradiated with femtosecond laser pulses.
We demonstrate the high-efficiency generation of water-window soft x-ray emissions from polyethylene nanowire array targets irradiated by femtosecond laser pulses at the intensity of 4×1019 W/cm2. The experimental results indicate more than one order of magnitude enhancement of the water-window x-ray emissions from the nanowire array targets compared to the planar targets. The highest energy conversion efficiency from laser to water-window x-rays is measured as 0.5%/sr, which comes from the targets with the longest nanowires. Supported by particle-in-cell simulations and atomic kinetic codes, the physics that leads to the high conversion efficiency is discussed.


Genotyping-Guided Discovery of Persiamycin A From Sponge-Associated Halophilic Streptomonospora sp. PA3.
Microbial natural products have been a cornerstone of the pharmaceutical industry, but the supply of novel bioactive secondary metabolites has diminished due to extensive exploration of the most easily accessible sources, namely terrestrial Streptomyces species. The Persian Gulf is a unique habitat for marine sponges, which contain diverse communities of microorganisms including marine Actinobacteria. These exotic ecosystems may cradle rare actinomycetes with high potential to produce novel secondary metabolites. In this study, we harvested 12 different species of sponges from two locations in the Persian Gulf and isolated 45 symbiotic actinomycetes to assess their biodiversity and sponge-microbe relationships. The isolates were classified into Nocardiopsis (24 isolates), Streptomyces (17 isolates) and rare genera (4 isolates) by 16S rRNA sequencing. Antibiotic activity tests revealed that culture extracts from half of the isolates displayed growth inhibitory effects against seven pathogenic bacteria. Next, we identified five strains with the genetic potential to produce aromatic polyketides by genotyping ketosynthase genes responsible for synthesis of carbon scaffolds. The combined data led us to focus on Streptomonospora sp. PA3, since the genus has rarely been examined for its capacity to produce secondary metabolites. Analysis of culture extracts led to the discovery of a new bioactive aromatic polyketide denoted persiamycin A and 1-hydroxy-4-methoxy-2-naphthoic acid. The genome harbored seven gene clusters involved in secondary metabolism, including a tetracenomycin-type polyketide synthase pathway likely involved in persiamycin formation. The work demonstrates the use of multivariate data and underexplored ecological niches to guide the drug discovery process for antibiotics and anticancer agents.


Interfacial interaction track of amorphous solid dispersions established by water-soluble polymer and indometacin.
The present work studied interfacial interactions of amorphous solid dispersions matrix of indometacin (IMC) that established using PVP K30 (PVP) and PEG 6000 (PEG) by focusing on their interaction forces and wetting process. Infrared spectroscopy (IR), raman spectroscopy, X-ray photoelectron spectra and contact angle instrument were used throughout the study. Hydrogen bond energy formed between PEG and IMC were stronger than that of PVP and IMC evidenced by molecular modeling measurement. The blue shift of raman spectroscopy confirmed that hydrogen bonding forces were formed between IMC and two polymers. The contact angle study can be used as an easy method to determine the dissolution mechanism of amorphous solid dispersions through fitting the profile of contact angle of water on a series of tablets. It is believed that the track of interfacial interactions will certainly become powerful tools to for designing and evaluating amorphous solid dispersions.


Variation in the enteric distribution of cryptosporidia in acquired immunodeficiency syndrome.
Clinical observation suggests that the natural history of intestinal cryptosporidiosis in patients with acquired immunodeficiency syndrome varies greatly. The relation between clinical, small-bowel functional, and nutritional status and the intestinal distribution of the organism was studied in 41 patients who had acquired immunodeficiency syndrome and cryptosporidiosis and who had undergone both proximal small-bowel and colonic biopsies. Two patterns of enteric cryptosporidiosis were identified: severe clinical disease with malabsorption in patients with cryptosporidia in proximal small-bowel biopsy specimens (61% of cases) and less severe clinical disease in patients with cryptosporidia only in the colon or stool (39% of cases). Patients with cryptosporidia in proximal small-bowel biopsy specimens had small-bowel crypt hyperplastic villous atrophy, lamina propria inflammatory infiltrates, poorer D-xylose absorption, greater weight loss, and shorter survival and more often needed intravenous hydration or hyperalimentation. Patients with cryptosporidia in the small-bowel villi only had less severe disease than those with cryptosporidia in the small-bowel crypts. In conclusion, the anatomic distribution of intestinal cryptosporidia in patients with acquired immunodeficiency syndrome varies, and this variation may explain differences in clinical course. Cryptosporidial infection of the proximal small bowel correlates with mucosal injury, malabsorption, dehydration, weight loss, and shortened survival.


Electron-hole plasma induced band gap renormalization in ZnO microlaser cavities.
We report electron-hole plasma (EHP) lasing in hexagonal ZnO microrods and thin nanobelts. Under the excitation of 325 nm line femtosecond pulsed laser, ultraviolet whispering-gallery mode (WGM) lasing was observed from hexagonal ZnO microrods. When EHP was formed at high excitation energy density, the center wavelength of the WGM lasing band presented a redshift from 387.5 nm to 397.5 nm, and the full width of half maximum (FWHM) of the WGM lasing band increased from 2.5 nm to 7 nm. Each lasing mode showed obvious blueshift and broadening. Such lasing characteristics were attributed to the band gap renormalization (BGR) due to the high carrier concentration at the EHP condition. In addition, EHP Fabry-Perot (F-P) mode lasing from thin ZnO nanobelt was also observed and discussed. According to the phenomenological BGR calculation with including the carrier density dependent screening effect, the values of the band gap of ZnO at different excitation energy densities were obtained, which agree well with the experimental results.


[Influenza in global aspect].
Due to a high ability to change, the influenza virus is still a danger for humans. The outbreak of the next influenza pandemic is very probable. The disturbing events that occurred in Hong Kong in 1997 and in the beginning of 2003 confirmed such a possibility. Every year in Poland influenza causes from several hundred thousands to several millions of cases of infections. All over the world the annual number of influenza cases amounts to approximately 100 millions and from 0.5 million to 1 million patients die due to influenza. The most severe threat is connected with post-influenza complications that are the cause of death after influenza infection. The only one effective method of prophylaxis against influenza and its complications is vaccination. Moreover, since 1999 new anti-influenza drugs are available: oseltamivir (Tamiflu) and zanamivir (Relenza). They are effective for treatment or for treatment and prophylaxis of infections caused by influenza virus type A and also type B. The efficacy of these drugs depends on appropriate diagnosis. Due to this fact laboratory diagnostics of respiratory infections is so important and crucial. It should be emphasised that clinical symptoms of infection may indicate influenza even if the disease is caused by other viral or bacterial pathogen.


Incidence of toxoplasmosis in pregnant women in the city of Malmö, Sweden.
The incidences of latent and primary Toxoplasma gondii infections in pregnant women were studied using stored sera from 4,351 women delivered in the city of Malmö, Sweden in 1982 and 1983. Infants born to mothers with signs of primary infection (seroconversion or specific IgM in sera collected during pregnancy) were studied with regard to serological evidence of congenital infection (specific IgM in cord serum). Sera were tested for specific IgG antibodies by direct agglutination test and enzyme-linked immunosorbent assay, and for specific IgM by immunosorbent assay. 40% of the women were seropositive at delivery. Seroconversion (change from negative to positive serological status) was demonstrated in 12 pregnant women and specific IgM in the first postconceptional serum sample (indicating infection in the first trimester or in the last year(s) before conception) in another 17. The incidence of primary maternal infection was calculated to 4-6:1,000 deliveries. Among the 29 infants born to mothers with seroconversion or, alternatively, IgM in the first postconceptional sample, 6 had laboratory signs of congenital infection. One of the 6 had a positive toxoplasma isolation test in autopsy material and 5 had a clearly positive IgM value in cord serum. The real incidence of congenital infection in this material is unknown since IgM might be absent or sparse in cord serum in spite of congenital infection. The noticeable prevalence of maternal toxoplasmosis in Malmö calls for further incidence studies in Sweden.


Encounters with indigenous patients in Australian general practice.
The BEACH program, a continuous national study of general practice activity in Australia, gives an overview of consultations with indigenous patients. Between 1998 and 2003, general practitioners recorded 5476 consultations with people who identified themselves as being of Aboriginal and/or Torres Strait Islander origin. These accounted for approximately 1% of total BEACH encounters for the 5 year period. In this article we compare 'indigenous encounters' with total BEACH encounters. This provides a backdrop against which articles in this issue of Australian Family Physician can be further considered.


Structural Phase Transition of Multilayer VSe2.
Vanadium diselenide (VSe2), a member of the transition metal dichalcogenides (TMDs) family, is emerging as a promising two-dimensional (2D) candidate for the electronic and spintronic device with exotic properties including charge/spin density wave and ferromagnetism. The bulk crystal VSe2 exists in a crystallographic form of 1T-phase with metallic behavior. In this paper, we report a structural phase transition of multilayer VSe2 from 1T to 2H through annealing at 650 K, accompanying a metal-insulator transition. We observe that the 2H-phase is more thermodynamically favorable than the 1T-phase at 2D.


Viability thresholds and the penumbra of focal ischemia.
The classic concept of the viability thresholds of ischemia differentiates between two critical flow rates, the threshold of electrical failure and the threshold of membrane failure. These thresholds mark the upper and lower flow limits of the ischemic penumbra which is thought to suffer only functional but not structural injury. Recent studies of the functional and metabolic disturbances suggest a more complex pattern of thresholds. At declining flow rates, protein synthesis is inhibited at first (at a threshold of about 0.55 ml/gm/min), followed by a stimulation of anaerobic glycolysis (at 0.35 ml/gm/min), the release of neurotransmitters and the beginning disturbance of energy metabolism (at about 0.20 ml/min), and finally the anoxic depolarization (< 0.15 ml/gm/min). The penumbra, as defined by the classic flow thresholds, does not remain viable for extended periods. Since viability of the tissue requires maintenance of energy-dependent metabolic processes, penumbra is redefined as a region of constrained blood supply in which the energy metabolism is preserved. Imaging of the penumbra by combining autoradiographic cerebral blood flow measurements with bioluminescent images of adenosine triphosphate (ATP) demonstrates a gradual expansion of the infarct core (in which ATP is depleted) into the penumbra until, after a few hours, the penumbra has disappeared. It is suggested that the limited survival of the penumbra is due to periinfarct depolarizations, which result in repeated episodes of tissue hypoxia, because the increased metabolic workload is not coupled to an adequate increase of collateral blood supply. This explains pharmacological suppression of periinfarct depolarizations lowering the threshold of metabolic disturbances and reducing the volume of the ischemic infarct.


Coordinate induction and activation of metalloproteinase and ascorbate depletion in structural luteolysis.
Structural luteolysis was found decades ago to be induced by PRL in the hypophysectomized rat, but the mechanisms of this process are unknown. To gain information on mechanisms of luteal involution, we developed an animal model that circumvented complex surgery and provided ample tissue for analyses. Gonadotropin-synchronized ovulation and luteinization were induced in immature rats, followed by treatment with ergot alkaloid and PRL. PRL-induced structural luteolysis, as shown by loss of luteal weight, protein, and DNA after pretreatment with ergot alkaloid, was evident after 36 h. Ascorbic acid depletion was rapid, severe, and lasting in luteal tissue during structural luteolysis, but lipid peroxidation or depletion of vitamin E was not evident. PRL treatment of animals with functional corpora lutea did not induce luteal involution. Significantly, after natural functional luteolysis occurred, PRL was highly effective in inducing structural luteolysis. Thus, either natural or ergot-induced functional luteolysis permitted the luteolytic expression of PRL. A greater depletion of protein than DNA was seen during PRL-induced structural luteolysis and was associated with a significant increase in neutral caseinase activity in luteal extracts. Caseinase activity was markedly reduced by calcium chelators and profoundly inhibited by the chelator orthophenanthroline; only slightly reduced activity was seen with serine, aspartate, or cysteine proteinase inhibitors. These findings implicate metalloproteinase (MMP) as the relevant caseinase that was increased during structural luteolysis. The major proteinase identified by zymography had apparent sizes of 72 and 66 kilodaltons (kDa), and slight but detectable activity was also seen at 92 and 84 kDa. Organomercurial treatment caused a major shift of the 72-kDa band to 66 kDa and the 92-kDa band to 84 kDa, confirming MMP-2 and MMP-9 by activation of latent activity of each MMP, respectively. Structural luteolysis caused a significant increase in the activated 66-kDa form and the latent 72-kDa form of MMP-2, which occurred before a loss of luteal weight or protein. As MMP-2 degrades collagen (type IV) in basement membranes, we conclude that an early event in PRL-induced structural luteolysis is the degradation of extracellular matrix. This conclusion is further emphasized by the marked and lasting depletion of ascorbic acid, a vitamin long known to serve an essential role in collagen synthesis.


A Systematic Review of the Methods of Diagnostic Accuracy Studies of the Afirma Gene Expression Classifier.
The Afirma® Gene Expression Classifier (GEC) risk stratifies The Bethesda System for the Reporting of Thyroid Cytopathology class III/IV (indeterminate) thyroid nodules (ITNs) as suspicious for malignancy or benign. Several authors have published studies describing the diagnostic accuracy of the GEC. However, the quality of these methods has not been rigorously examined. In this study, MEDLINE and EMBASE were searched for studies published between January 1, 2010, and June 30, 2016, examining the sensitivity, specificity, negative predictive value, and positive predictive value of the GEC. The Quality of Diagnostic Accuracy Studies 2 was customized to evaluate the methods of included studies in each of four domains: nodule selection, index test execution, reference standard assignment, and flow and timing. Signaling questions were used to identify sources of potential bias in calculation of diagnostic accuracy, and issues of applicability were assessed. Three panelists applied the Quality of Diagnostic Accuracy Studies 2 tool to each study included, and divergence was resolved in conference. In 12 studies evaluated, the most common methodologic flaw was lack of reference standard diagnosis assignment to un-excised GEC-benign ITNs. Exclusion of these ITNs from the analyses resulted in unreliable estimates of specificity and negative predictive value. Other flaws identified included restriction to ITNs that had already been selected for referral for thyroidectomy or lobectomy. Future studies should define and assign a "true negative" label to GEC-benign nodules that do not develop malignant signs or symptoms during a pre-specified period of follow-up, and these nodules should be included in calculations of diagnostic accuracy.


Selective autophagy inhibition through disruption of the PIK3C3-containing complex I.
The PIK3C3/VPS34-containing phosphatidylinositol 3-kinase (PtdIns3K) initiation complex (complex I) is necessary for macroautophagy/autophagy initiation and is comprised of PIK3R4/VPS15-PIK3C3/VPS34-BECN1-ATG14, while the endosomal trafficking complex (complex II) is necessary for vesicle trafficking and is comprised of PIK3R4/VPS15-PIK3C3/VPS34-BECN1-UVRAG. This composition difference was exploited to identify novel and specific autophagy inhibitors that disrupted the BECN1-ATG14 protein-protein interaction, without affecting vesicle trafficking. A cellular NanoBRET assay was implemented to identify these inhibitors, and one compound was able to successfully disrupt the BECN1-ATG14 interaction and inhibit autophagy, with limited impact on vesicle trafficking. These results reveal the first protein-protein interaction inhibitor targeting the autophagy initiation machinery and demonstrate the viability of targeting protein-protein interactions for the discovery of autophagy-specific modulators.


Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases.
A number of human diseases have been shown to be associated with mutation in the genes encoding leucine-rich-repeat (LRR)-containing proteins. They include 16 different LRR proteins. Mutations of these proteins are associated with 19 human diseases. The mutations occur frequently within the LRR domains as well as their neighboring domains, including cysteine clusters. Here, based on the sequence analysis of the LRR domains and the known structure of LRR proteins, we describe some features of different sequence variants and discuss their adverse effects. The mutations in the cysteine clusters, which preclude the formation of sulfide bridges or lead to a wrong paring of cysteines in extracellular proteins or extracellular domains, occur with high frequency. In contrast, missense mutations at some specific positions in LRRs are very rare or are not observed at all.


Iterative Indirect Immunofluorescence Imaging (4i) on Adherent Cells and Tissue Sections.
Highly multiplexed protein measurements from multiple spatial scales using fluorescence microscopy recently emerged as a powerful way to investigate tumor microenvironments in biomedicine and the multivariate nature of complex systems' interactions. A range of methods for this exist, which either rely on directly labeling the primary antibody with oligonucleotides/rare metals or employing methods to remove fluorescence for cyclic acquisition. Here, we describe a protocol that uses off-the-shelf primary and secondary antibodies without further need for modification and only commonly available chemical reagents. The method harnesses the observation that antibodies can crosslink to bound epitopes during light exposure, thus preventing elution. By utilizing a simple oxygen radical scavenging buffer during imaging and by blocking free sulfhydryl groups before antibody incubation, the presented method can employ comparably mild conditions to remove bound antibodies from epitopes, which preserves sample integrity. Thus, with the stated minor modifications, it allows for a standard immunofluorescence imaging protocol in cyclic fashion, currently permitting staining of up to ~80 unique epitopes.


Disordered voluntary cough as freezing phenomenon in parkinsonism.
[Purpose] In patients with parkinsonism, the precise mechanism of impaired voluntary cough remains poorly understood. This study used the flow-volume curve to clarify whether disordered voluntary cough reflects the freezing phenomenon. [Subjects and Methods] Case 1 was a 58-year-old female who had been suffering from progressive supranuclear palsy-pure akinesia with gait freezing. Case 2 was a 59-year-old female who had advanced juvenile parkinsonism. The subjects were asked to take a deep inspiration to the total lung capacity and then cough more than five times through the face mask into the spirometer without intervening inspirations between the coughing efforts. [Results] Hesitation in cough initiation (case 2), decreased peak cough flow (case 1), and rounding of the first spike (cases 1 and 2) were observed. In addition, movements of the spike wave at a lower lung volume became progressively smaller and faster (cases 1 and 2). [Conclusion] These clinical manifestations in our patients are similar to those observed in the freezing phenomenon. However, to date, the concept of cough freezing has been underrecognized in clinical practice. From the present study, it could be hypothesized that the freezing phenomenon can occur in voluntary cough as well as in gait, speech, and writing.


Probabilistic risk analysis and game theory.
The behavioral dimension matters in Probabilistic Risk Analysis (PRA) since players throughout a system incur costs to increase system reliability interpreted as a public good. Individual strategies at the subsystem level generally conflict with collective desires at the system level. Game theory, the natural tool to analyze individual-collective conflicts that affect risk, is integrated into PRA. Conflicts arise in series, parallel, and summation systems over which player(s) prefer(s) to incur the cost of risk reduction. Frequently, the series, parallel, and summation systems correspond to the four most common games in game theory, i.e., the coordination game, the battle of the sexes and the chicken game, and prisoner's dilemma, respectively.


Acute Pancreatitis in Children.
Acute pancreatitis has become a common general pediatric condition with an increasing incidence over the past 2 decades. It presents with nonspecific complaints of abdominal pain, vomiting, and nausea. Therefore, it is crucial to have it on the differential diagnosis, as it requires prompt treatment and has the potential to become life-threatening. Although pancreatic rest, antiemetics, analgesia, and hydration remain the mainstay of treatment, a new perspective on fluid management, early enteral nutrition, and opioid use has evolved. This review identifies gaps in management awareness and provides understanding on long-term implications of acute and recurrent pancreatitis. This article also reviews the epidemiology, diagnostic criteria, imaging and procedural modalities, common causes, management, and complications of acute pancreatitis and is geared toward the general pediatric hospitalist. [Pediatr Ann. 2021;50(8):e330-e335.].


[Correction of a deformity of the upper lip after primary plastic surgery of bilateral cleft lip].
The author describes a method of reparative operation intended for bringing down the prolabium as a skin-muscle flap on two feeding vascularized pedicles with simultaneous plasty of the defect of the lining of the intermaxilla with a flap of the mucosa from the prolabium. The posterior wall of the upper lip and entrance to the mouth were formed by shifting the lateral fragments of the lip to the center. The red border defect was also eliminated at the expense of the same tissues. In order to avoid complications it is necessary not to make thinner the skin of the nose septum which was used for the elongation of prolabium and to suture the edges of the orbicular muscle of the mouth with tension. The method was used in 438 patients and gave good results.


Diverse changes in shipping emissions around the Western Pacific ports under the coeffect of the epidemic and fuel oil policy.
The Western Pacific Ocean (the WPO), as one of the busiest shipping areas in the world, holds a complex water traffic network. In 2020, the International Maritime Organization (IMO) low-sulfur fuel regulations were implemented globally, while the COVID-19 outbreak influenced shipping activities together. This study aimed to assess the combined impact of epidemics and low-sulfur fuel policies on ship emissions, as well as their environmental effects on the WPO. The ship emission model based on the Automatic Identification System (AIS) data was applied to analyze the monthly emission variations during 2018-2020. It was found that the epidemic had obvious diverse influences on the coastal ports in the WPO. Overall, shipping emissions declined by 15 %-30 % in the first half of 2020 compared with those in 2019 due to the COVID-19 lockdown, whereas they rebounded in the second half as a result of trade recovery. The pollutants discharged per unit of cargo by ships rose after the large-range lockdown. China's multiphase domestic emission control areas (DECAs) and the IMO global low-sulfur fuel regulation have greatly reduced SO2 emissions from ships and caused them to "bypass and come back" to save fuel costs around emission control areas from 2018 to 2020. Based on satellite data and land-based measurements, it was found that the air quality over sea water and coastal cities has shown a positive response to changes in ship-emitted NOx and SO2. Our results reveal that changes in shipping emissions during typical periods, depending on their niches in the complex port traffic network, call for further efforts for cleaner fuel oils, optimized ECA and ship lane coordination in the future. Shipping related air pollutions during the later economic recovery also needs to be addressed after international scale standing-by events.


Generalizable items of quantitative and qualitative cornerstones for personnel requirement of physicians in anesthesia.
Anesthesiologists perform a broad spectrum of tasks. However, in many countries, there is no legal basis for personnel staffing of physicians in anesthesia. Also, the German diagnosis related groups system for refunding does not deliver such a basis. Thus, in 2006 a new calculation base for the personnel requirement that included an Excel calculation sheet was introduced by the German Board of Anesthesiologists (BDA) and the German Society of Anesthesiology and Intensive Care Medicine (DGAI), and updated in 2009 and 2015. Oriented primarily to organizational needs, in 2015, BDA/DGAI defined quantitative and qualitative cornerstones for personnel requirement of physicians in anesthesia, especially reflecting recent laws governing physician's working conditions and competence in the field of anesthesia, as well as demands of strengthened legal rights of patients, patient care and safety. We present a workload-oriented model, integrating core working hours, shift work or standby duty, quality of care, efficiency of processes, legal, educational, controlling, local, organizational and economic aspects for calculating personnel demands. Auxiliary tables enable physicians to calculate personnel demands due to differing employee workload, non-patient oriented tasks and reimbursement of full-equivalents due to parental leave, prohibition of employment, or long-term illness. After 10 years of experience with the first calculation tool, we report the generalizable key aspects and items of a necessary calculation tool which may help physicians to justify realistic workload-oriented personnel staffing demands in anesthesia. A modular, flexible nature of a calculation tool should allow adaption to the respective legal and organizational demands of different countries.


Inducible Clindamycin Resistance among Clinical Isolates of Staphylococcus aureus from Sub Himalayan Region of India.
Clindamycin is an alternative antibiotic in the treatment of Staphylococcus aureus (S.aureus) infections, both in infections by methicillin susceptible and resistant (MSSA and MRSA) strains. The major problem of use of clindamycin for staphylococcal infections is the presence of inducible clindamycin resistance that can lead to treatment failure in such infections. To determine inducible and constitutive clindamycin resistance among clinical isolates of S. aureus in a tertiary care centre of sub Himalayan region of India. A total of 350 isolates of S. aureus from various clinical samples were subjected to routine antibiotic sensitivity testing by Kirby Bauer disc diffusion method. Methicillin resistance was detected by cefoxitin (30μg) disc. All isolates were subjected to inducible clindamycin resistance was by Clinical Laboratory Standards Institute (CLSI) recommended D test. Among 350 S.aureus isolates, 82 (23.42%) were MRSA and 268 (76.57%) were MSSA. Erythromycin resistance was detected in 137 (39.14%) isolates. Erythromycin resistance in MRSA and MSSA was 71.6% and 29.36% respectively. Overall clindamycin resistance was seen in 108 (30.85%) isolates. Constitutive MSLB phenotype predominated (29.62% MRSA; 13.38% MSSA) followed by iMLSB (28.39% MRSA; 9.29% MSSA) and MS phenotypes (13.58% MRSA; 6.69%MSSA). Both inducible and constitutive clindamycin resistance was significantly higher (p=0.00001, 0.0008 respectively) in methicillin resistant strains than in methicillin susceptible strains. The present study gives a magnitude of clindamycin resistance among clinical isolates of S. aureus from this region of the country. Our study recommends routine testing of inducible clindamycin resistance at individual settings to guide optimum therapy and to avoid treatment failure.


Precise Construction and Growth of Submillimeter Two-Dimensional WSe2 and MoSe2 Monolayers.
Currently, as shown by large-scale research on two-dimensional materials in the field of nanoelectronics and catalysis, the construction of large-area two-dimensional materials is crucial for the development of devices and their application in photovoltaics, sensing, optoelectronics, and energy generation/storage. Here, using atmospheric-pressure chemical vapor deposition, we developed a method to regulate growth conditions according to the growth mechanism for WSe2 and MoSe2 materials. By accurately controlling the hydrogen flux within the range of 1 sccm and the distance between the precursor and the substrate, we obtained large-size films of single atomic layers with thicknesses of only about 1 nm. When growing the samples, we could not only obtain a 100 percent proportion of samples with the same shape, but the samples could also be glued into pieces of 700 μm and above in size, changing the shape and making it possible to reach the millimeter/submillimeter level visible to the naked eye. Our method is an effective method for the growth of large-area films with universal applicability.


Proper Distal Placement of Tibial Nail Improves Rate of Malalignment for Distal Tibia Fractures.
We hypothesize that the anatomic center of the distal tibia is just lateral and anterior to the center of the distal tibia articular surface in the coronal and sagittal planes, respectively, and that placement of the nail along this axis results in improved rates of malalignment when treating distal tibia fractures. Retrospective study. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. One Level I and one Level II trauma center. Two hundred three distal tibia fractures treated with intramedullary nailing (IMN) (primary cohort) whose main fracture line extended within 5 cm of the plafond to evaluate the rate of malalignment with distal nail placement. Additionally, we retrospectively reviewed a secondary cohort of 15 patients with proximal tibia fractures treated with intramedullary nailing for evaluation of passive anatomic distal nail position. Primary malalignment ≤5 degrees on the anteroposterior (AP), mortise, and lateral planes were evaluated in distal tibia fractures on perioperative radiographs. Primary Cohort: 85 patients met inclusion criteria for evaluation in the coronal plane. Overall malalignment in the coronal plane was 17.6%. There was a 2.9% (1/34) fracture malalignment rate when the nail was placed lateral to the center of the joint versus 27.5% (14/51) when placed medial to the center of the joint, with all occurring in valgus. This achieved statistical significance (P = 0.04). Correlation was highest when measuring the trajectory on mortise view using the talus as reference point. When evaluating the sagittal plane, there were 64 patients that met inclusion criteria with a 48% malalignment rate. Malalignment was greatest when the nail was placed in the anterior quadrant 100% (4/4), versus 50% (22/44) in the anterior middle, and 31.3% (5/16) in the posterior middle quadrant. This achieved statistical significance (P = 0.05). No nails were placed in the most posterior quadrant. Secondary Cohort: 15 patients met inclusion criteria for distal nail placement. The position of the nail in the coronal plane was measured on both the anteroposterior and mortise ankle radiographs using both the plafond and talus as a reference, whereas sagittal nail placement was measured on the lateral ankle radiographs. In the coronal plane, the mean passive distal position of the nail when referenced from the lateral cortex was 45.2% of the tibia plafond and 45.5% the width of the talus, or just lateral to the center of each. In the sagittal plane, passive nail placement was 40% the sagittal width of the joint measured from the anterior cortex, or just anterior to the center of the joint. This is the first patient series that defines optimal tibial nail placement in the treatment of distal tibia fractures. Distal placement of the nail just lateral to the center of the talus and plafond, or along mechanical axis of the tibia, results in significantly reduced rates of malalignment on the coronal plane when compared to nail placement medial to the center of the talus or plafond. Fluoroscopic judgment of distal nail trajectory was improved on the mortise view using the talus as a reference when compared to using the anteroposterior view. On the sagittal plane, anatomic passive nail placement is just anterior to the center of the plafond. However, nonanatomic nail placement just posterior to the center of the plafond had a lower incidence of malalignment compared with nails placed anterior to the center of the plafond. Further study of appropriate nail positioning on the sagittal plane is needed.


[Fournier's gangrene].
Fournier's gangrene is a necrotizing fasciitis of the genital and scrotal region due to infectious process. The gangrene is rare. Most cases are diagnosed in elderly patients with immunodeficiency, especially in diabetics or alcoholics. Currently a primary infection focus can be revealed in about 95% cases. The nidus is usually located in the genitourinary tract, lower gastrointestinal tract or skin. Fournier's gangrene is a mixed infection caused by both aerobic and anaerobic bacterial flora. The development and progression of the gangrene is often fulminating and can rapidly cause multiple organ failure and death. Early surgical debridement of necrotic tissues and antibiotics are fundamental in the treatment of Fournier's gangrene. Despite of advanced management mortality is still high and averages 20-30%.


Membranes with rotating motors.
We study collections of rotatory motors confined to two-dimensional manifolds. These systems show a nontrivial collective behavior since the rotational motion leads to a repulsive hydrodynamic interaction between motors. While for high rotation speed motors might exhibit crystalline order, they form at low speed a disordered phase where diffusion is enhanced by velocity fluctuations. These effects should be experimentally observable for motors driven by external fields and for dipolar biological motors embedded into lipid membranes in a viscoelastic solvent.


Potential use of mucins as biomaterial coatings. II. Mucin coatings affect the conformation and neutrophil-activating properties of adsorbed host proteins--toward a mucosal mimic.
In continuation of our recent fractionation and characterization study on mucins of bovine salivary (BSM), porcine gastric (PGM), and human salivary (MG1) origin, this study evaluates the effect of mucin precoating on the conformation and neutrophil-activating properties of host proteins adsorbed to a polyethylene terephthalate-based model biomaterial. Microscopy combined with assays for the neutrophil releases of reactive oxygen species and human neutrophil lipocalin showed that mucin precoating greatly reduced the strong immune-response normally induced by adsorbed immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), respectively. A similar finding was made for the proinflammatory fibrinogen. Although the total uptakes of these proteins depended on the mucin surface concentration, a detailed composite analysis suggested the fraction of surface-exposed protein to be a stronger determinant of coating performance. The unexpectedly low neutrophil activation showed by composites containing near-monolayer concentrations of exposed IgG and sIgA, respectively, suggested that these act synergistically with mucin on the surface. In support of this hypothesis, quartz crystal microbalance with dissipation monitoring measurements revealed that a preadsorbed BSM layer stabilizes IgG through complexation on a polymeric model surface. Our findings link well to the complex in vivo situation and suggest that functional mucosal mimics can be created in situ for improved biomaterials performance.


POCT: An Inherently Ideal Tool in Pediatric Laboratory Medicine.
Point of care testing (POCT) is important in the provision of timely laboratory test results and continues to gain specific appreciation in the setting of pediatric healthcare. POCT platforms offer several advantages compared to central laboratory testing, including improved clinical outcomes, reduced time to diagnosis, length of stay, and blood volume requirements, as well as increased accessibility. These advantages are most pronounced in acute care settings such as pediatric emergency departments, intensive care units, and in remote settings, wherein rapid patient assessment and prognostication is essential to patient outcomes. The current review provides an overview and critical discussion of the evidence supporting clinical implementation of POCT systems in pediatric clinical decision-making, including but not limited to the diagnosis of viral and bacterial infection, identification of critical glucose and electrolyte dysregulation, and prognostication of post-operative inpatients. Important considerations for test result reporting and interpretation are also discussed, including analytical concordance between POCT systems and central laboratory analyzers as well as availability of pediatric reference intervals for key analytes on POCT systems. Notably, a paucity of evidence-based pediatric reference intervals for test interpretation for critical care parameters on POCT platforms is highlighted, warranting further study and unique consideration prior to clinical implementation.


Thioether Coordination Chemistry for Molecular Imaging of Copper in Biological Systems.
Copper is an essential element in biological systems. Its potent redox activity renders it necessary for life, but at the same time, misregulation of its cellular pools can lead to oxidative stress implicated in aging and various disease states. Copper is commonly thought of as a static cofactor buried in protein active sites; however, evidence of a more loosely bound, labile pool of copper has emerged. To help identify and understand new roles for dynamic copper pools in biology, we have developed selective molecular imaging agents for this metal, drawing inspiration from both biological binding motifs and synthetic model complexes that reveal thioether coordination as a general design strategy for selective and sensitive copper recognition. In this review, we summarize some contributions, primarily from our own laboratory, on fluorescence- and magnetic resonance-based molecular-imaging probes for studying copper in living systems using thioether coordination chemistry.


Group interactions during space missions.
Previous anecdotal reports from space and results from space simulation studies on Earth have suggested that the group interactions of crewmembers during space missions can be problematic in ways that can negatively affect crew safety and the accomplishment of mission goals. To assess the interpersonal environment of space crewmembers, we used a set of standard questionnaires that were completed by 5 astronauts, 8 cosmonauts, and 58 American and Russian mission control personnel who participated in the Shuttle/Mir Program. Although we did not find strong evidence supporting predicted decrements in tension and cohesion during the second half of the missions, we did find that both crewmembers and mission control personnel displaced unpleasant emotions to monitoring personnel outside of their group. We also found significant differences between Americans and Russians in terms of measures of satisfaction with their interpersonal and work environments. These findings suggest a number of countermeasures to help future space crews deal with potential maladaptive group interactions. These countermeasures address issues at the time of selection, during prelaunch training, during the mission itself, and after the crew returns to Earth.


Simulation of the gyroid phase in off-lattice models of pure diblock copolymer melts.
Particle-based molecular simulations of pure diblock copolymer (DBC) systems were performed in continuum space via dissipative particle dynamics and Monte Carlo methods for a bead-spring chain model. This model consisted of chains of soft repulsive particles often used with dissipative particle dynamics. The gyroid phase was successfully simulated in DBC melts at selected conditions provided that the simulation box size was commensurate with the gyroid lattice spacing. Simulations were concentrated at conditions where the gyroid phase is expected to be stable which allowed us to outline approximate phase boundaries. When more than one phase was observed by varying simulation box size, thermodynamic stability was discerned by comparing the Helmholtz free energy of the competing phases. For this purpose, chemical potentials were efficiently simulated via an expanded ensemble that gradually inserts/deletes a target chain to/from the system. These simulations employed a novel combination of Bennett's [J. Comput. Phys. 22, 245 (1976)] acceptance-ratio method to estimate free-energy differences and a recently proposed method to get biasing weights that maximize the number of times that the target chain is regrown. The analysis of the gyroid nodes revealed clear evidence of packing frustration in the form of an (entropically) unfavorably overstretching of chains, a phenomenon that has been suggested to provide the structural basis for the limited region of stability of the gyroid phase in the DBC phase diagram. Finally, the G phase and nodal chain stretching were also found in simulations with a completely different DBC particle-based model.


iStent versus iStent inject implantation combined with phacoemulsification in open angle glaucoma.
To compare the outcomes of iStent vs. iStent inject implantation combined with phacoemulsification. This single center retrospective comparative case series included subjects with open angle glaucoma who underwent iStent or iStent inject implantation combined with phacoemulsification with ≥1 year follow-up. The main outcome measures were in-group and between-group changes in intraocular pressure (IOP) and medication number, proportion of eyes that achieved IOP ≤15 mmHg, and surgical success defined as 20% IOP reduction from baseline at 6/12 months. Univariate/multivariate regression analyses were done to identify predictors of surgical failure. One hundred ninety-seven eyes of 148 patients were included (122 iStent, 75 iStent inject). Both groups achieved significant IOP and medication reduction at months 6/12 (P < 0.05). At month 6, IOP was significantly lower in iStent inject vs. iStent eyes (P = 0.003), but the difference was insignificant by month 12 (P = 0.172). Medication number was comparable in both groups at months 6/12 (P > 0.05). More iStent inject eyes achieved IOP ≤15 mmHg at month 6 (P = 0.003) and 12 (P = 0.047). Surgical success was comparable in both groups at months 6/12 (P > 0.05). Kaplan-Meier survival analysis showed similar cumulative rate of surgical failure at year-1 in both groups (P = 0.644). The multivariate model identified older age (P = 0.017) and lower baseline IOP (P = 0.002) as the strongest predictors of surgical failure. Compared to iStent, iStent inject achieved lower IOP at month 6 and higher proportion of eyes achieved IOP ≤15 mmHg at month 6/12. However, surgical success was similar in both groups. Predictors of surgical failure were older age and lower baseline IOP rather than the stent type.


Competing values among criminal justice administrators: The importance of substance abuse treatment.
This study applied latent class analysis (LCA) to examine heterogeneity in criminal justice administrators' attitudes toward the importance of substance abuse treatment relative to other programs and services commonly offered in criminal justice settings. The study used data collected from wardens, probation and/or parole administrators, and other justice administrators as part of the National Criminal Justice Treatment Practices survey (NCJTP), and includes both adult criminal and juvenile justice samples. Results of the LCA suggested that administrators fell into four different latent classes: (1) those who place a high importance on substance abuse treatment relative to other programs and services, (2) those who place equal importance on substance abuse treatment and other programs and services, (3) those who value other programs and services moderately more than substance abuse treatment, and (4) those who value other programs and services much more than substance abuse treatment. Latent class membership was in turn associated with the extent to which evidence-based substance abuse treatment practices were being used in the facilities, the region of the country in which the administrator worked, and attitudes toward rehabilitating drug-using offenders. The findings have implications for future research focused on the impact that administrators' attitudes have on service provision as well as the effectiveness of knowledge dissemination and diffusion models.


A unique case of segmental vasal atresia.
We report a case of a 2-year-old boy who presented with an empty left scrotum. Clinical examination revealed a left palpable undescended testis. During orchidopexy, segmental atresia of the vas deferens was found, and microsurgical repair was carried out. Segmental vasal atresia is an extremely rare condition and is infrequently diagnosed, especially in the pediatric age group. This is the first reported case of segmental vasal atresia without an association with cystic fibrosis.


T-REX: a web server for inferring, validating and visualizing phylogenetic trees and networks.
T-REX (Tree and reticulogram REConstruction) is a web server dedicated to the reconstruction of phylogenetic trees, reticulation networks and to the inference of horizontal gene transfer (HGT) events. T-REX includes several popular bioinformatics applications such as MUSCLE, MAFFT, Neighbor Joining, NINJA, BioNJ, PhyML, RAxML, random phylogenetic tree generator and some well-known sequence-to-distance transformation models. It also comprises fast and effective methods for inferring phylogenetic trees from complete and incomplete distance matrices as well as for reconstructing reticulograms and HGT networks, including the detection and validation of complete and partial gene transfers, inference of consensus HGT scenarios and interactive HGT identification, developed by the authors. The included methods allows for validating and visualizing phylogenetic trees and networks which can be built from distance or sequence data. The web server is available at: www.trex.uqam.ca.


Bimodality in the transverse fluctuations of a grafted semiflexible polymer and the diffusion-convection analogue: an effective-medium approach.
Recent Monte Carlo simulations of a grafted semiflexible polymer in 1+1 dimensions have revealed a pronounced bimodal structure in the probability distribution of the transverse (bending) fluctuations of the free end, when the total contour length is of the order of the persistence length [G. Lattanzi, Phys. Rev E 69, 021801 (2004)]. In this paper, we show that the emergence of bimodality is related to a similar behavior observed when a random walker is driven in the transverse direction by a certain type of shear flow. We adapt an effective-medium argument, which was first introduced in the context of the sheared random-walk problem [E. Ben-Naim, Phys. Rev. A 45, 7207 (1992)], in order to obtain a simple analytic approximation of the probability distribution of the free-end fluctuations. We show that this approximation captures the bimodality and most of the qualitative features of the free-end fluctuations. We also predict that relaxing the local inextensibility constraint of the wormlike chain could lead to the disappearance of bimodality.


Personal development: a lifelong journey.
This article explores critical aspects of career and personal development, in particular the importance of a lifelong commitment to reflective practice. It focuses on the key questions: Where have I been? Where am I now? and Where do I want to be? Specific approaches discussed include journal writing and collegial small group work.


Genetics of Familial and Sporadic Pancreatic Cancer.
In the previous decade, comprehensive genomic analyses have yielded important insights about the genetic alterations that underlie pancreatic tumorigenesis. Whole-exome and whole-genome sequencing of pancreatic ductal adenocarcinomas have confirmed the critical driver genes altered in the majority of pancreatic cancers, as well as identified numerous less frequently altered driver genes, and have delineated cancer subgroups with unique biological and clinical features. It is now appreciated that pancreatic susceptibility gene alterations are often identified in patients with pancreatic cancer without family histories suggestive of a familial cancer syndrome, prompting recent efforts to expand gene testing to all patients with pancreatic cancer. Studies of pancreatic cancer precursor lesions have begun to elucidate the evolutionary history of pancreatic tumorigenesis and to help us understand the utility of biomarkers for early detection and targets to develop new therapeutic strategies. In this review, we discuss the results of comprehensive genomic characterization of pancreatic ductal adenocarcinoma and its precursor lesions, and we highlight translational applications in early detection and therapy.


Information management: considering adolescents' regulation of parental knowledge.
Employing Goffman's [(1959). The presentation of self in everyday life. New York: Doubleday and Company] notion of impression management, adolescents' conveyance of information about their whereabouts and activities to parents was assessed employing two methodologies. First, a two-wave panel design with a sample of 121 adolescents was used to test a model of information management incorporating two forms of information regulation (lying and willingness to disclose), adolescents' perception of their parents' knowledge about their activities, and adolescent misconduct. Path analysis was used to examine the model for two forms of misconduct as outcomes: substance use and antisocial behaviours. Fit indices indicate the path models were all good fits to the data. Second, 96 participants' responses to semi-structured questions were analyzed using a qualitative analytic technique. Findings reveal adolescents withhold or divulge information in coordination with their parents, employ impression management techniques, and try to balance safety issues with preservation of the parent-adolescent relationship.


Predictive value of serum β2-microglobulin in cardiac valve calcification in maintenance hemodialysis patients.
Cardiac valve calcification (CVC) is associated with adverse cardiovascular events. We studied the risk factors of CVC in maintenance hemodialysis (MHD) patients and the value of serum β2-microglobulin (β2-MG) levels in predicting the incidence of CVC. β2-MG is a middle molecular weight toxin. In recent years, researchers found that elevated blood β2-MG was associated with coronary, thoracic, and abdominal aortic calcifications with significant correlations. β2-MG has been emerging as a strong biomarker for cardiovascular mortality in uremic patients but its role in CVC is not well studied. This study looked specifically at CVC occurrence in relation to β2-MG for MHD patients. Patients who underwent MHD for more than 3 months in the First People's Hospital of Nantong City from November 2012 to November 2019 with complete available data were included in the study. The patients were divided into the CVC group and the non-CVC group. The general information and clinical laboratory indicators of the patients were collected in a retrospective manner. We analyzed the risk factors for developing CVC in MHD patients using binary logistic regression method. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value of β2-MG for predicting CVC. The decision tree (DT) method was used to classify and explore the probability of CVC in patients with MHD. The β2-MG in the CVC group was significantly higher than that in the non-CVC group (t=6.750, P<0.001). Multivariate binary logistic regression analysis showed that gender, age, serum β2-MG, and hemodialysis (HD) adequacy (Kt/V urea) were independent risk factors for CVC in MHD patients. ROC analysis showed that a β2-MG value of 25 µg/L was the best cut-off point for predicting CVC in MHD patients. According to binary logistic regression analysis, the β2-MG ≥25 µg/L group was 3.39 times more likely to develop CVC than the β2-MG <25 µg/L group [odds ratio (OR), 3.39; 95% confidence interval (CI), 1.63-7.06; P=0.001]. The DT model determined that serum β2-MG ≥25 µg/L and age >69 years were important determinants for predicting CVC in MHD patients. Serum β2-MG in MHD patients has a positive correlation with the severity and occurrence of CVC.


Disruption of laminin in the peripheral nervous system impedes nonmyelinating Schwann cell development and impairs nociceptive sensory function.
The mechanisms controlling the differentiation of immature Schwann cells (SCs) into nonmyelinating SCs is not known. Laminins are extracellular matrix proteins critical for myelinating SC differentiation, but their roles in nonmyelinating SC development have not been established. Here, we show that the peripheral nerves of mutant mice with laminin-deficient SCs do not form Remak bundles, which consist of a single nonmyelinating SC interacting with multiple unmyelinated axons. These mutant nerves show aberrant L1 and neural cell adhesion molecule (N-CAM) expression pattern during development. The homophilic and heterophilic interactions of N-CAM are also impaired in the mutant nerves. Other molecular markers for nonmyelinating SCs, including Egr-1, glial fibrillary acidic protein, and AN2/NG2, are all absent in adult mutant nerves. Analysis of expression of SC lineage markers demonstrates that nonmyelinating SCs do not develop in mutant nerves. Additionally, mutant mice are insensitive to heat stimuli and show a decreased number of C-fiber sensory neurons, indicating reduced nociceptive sensory function. These results show that laminin participates in nonmyelinating SC development and Remak bundle formation and suggest a possible role for laminin deficiency in peripheral sensory neuropathies.


Public and private health insurance: stacking up the costs.
Some proposals to expand health insurance coverage for people with low incomes are based on expansions of public programs, such as Medicaid or the State Children's Health Insurance Program (SCHIP), while others rely on the use of tax subsidies for individuals to purchase private insurance. Analyses of data from the 2005 Medical Expenditure Panel Survey indicate that total medical spending is much lower when coverage is provided by Medicaid or SCHIP than it is when coverage is provided by private insurance. Public insurance is particularly advantageous from the consumer's perspective because associated out-of-pocket spending is far lower.


[Derivation of germ cells from mouse embryonic stem cells in culture].
Mouse embryonic stem cells derive from the inner cell mass of the blastocyst and give rise to the three primitive embryonic layers, which later will form all the different tissue types of an adult. Embryonic stem cells are thus defined as totipotent cells. In vitro, these cells can give rise to all the somatic cells. Different laboratories have now shown that cultured embryonic stem cells can also differentiate into germline cells. By using the transcription factor Oct-4 as a tool for the visualization of germ cells, it has been shown the derivation of oocytes from mouse embryonic stem cells. These works should contribute to various areas, including therapeutic cloning which associates nuclear transfer and selective production of a specific cell type.


Comparison of single-agent androgen suppression for advanced prostate cancer.
Gonadotropin-releasing hormone (GnRH) agonists are the agents of choice for achieving androgen suppression in men with advanced prostate cancer. The GnRH agonists that have been developed and marketed for prostate cancer are leuprolide, goserelin, triptorelin, and histrelin. So far, there have been few randomized studies directly comparing these single-agent therapies; however, the literature and the data on file with the Food and Drug Administration suggest that triptorelin may be more reliable than leuprolide in maintaining castration levels of serum testosterone. The clinical significance of this benefit remains to be proven.


The Effect of Smoking on Spinal Cord Healing Following Surgical Treatment of Cervical Myelopathy.
Retrospective cohort. The purpose of this study was to compare outcomes of surgical treatment of cervical myelopathy between smokers and nonsmokers as assessed by the Nurick score. The harmful effects of smoking on healing have been well established. However, the effect of smoking on postoperative outcomes for cervical myelopathy has not been specifically evaluated. The medical records of 212 patients who underwent surgery for cervical spondylotic myelopathy were reviewed. Inclusion criteria were the diagnosis of cervical spondylotic myelopathy with a Nurick score, surgical intervention, and at least 2 years of follow-up. The patients were categorized into 2 groups according to smoking status and stratified according to pack years and packs per day. Age at presentation, sex, preoperative and postoperative Nurick score, duration of symptoms preoperatively, duration of follow-up, procedure performed, surgical approach, number of levels fused, diabetes status, cocaine use, ethanol use, preoperative magnetic resonance imaging signal change, and whether the patient belonged to the Veterans Administration (VA) were recorded. Analysis was done using simple linear regression and multiple regression. Univariate analysis demonstrated a postoperative improvement in nonsmokers of 1.53 points on the Nurick scale compared with 0.6 points in smokers (P < 0.001). There is a progressive decrease in improvement as the number of pack years and packs per day increase (P < 0.001). There is a greater improvement in Nurick score with greater (worse) preoperative score but only in patients with fewer than 25 pack years. Smoking status is not associated with preoperative Nurick score. Smoking status is associated with poor improvement in Nurick score after surgical treatment of cervical myelopathy. Smoking may have a directly toxic effect on the intrinsic healing capability of the spinal cord, particularly beyond 25 pack years. 3.


Enhancing the Antitumor Immunity of T Cells by Engineering the Lipid-Regulatory Site of the TCR/CD3 Complex.
The engagement of the T-cell receptor (TCR) by a specific peptide-MHC ligand initiates transmembrane signaling to induce T-cell activation, a key step in most adaptive immune responses. Previous studies have indicated that TCR signaling is tightly regulated by cholesterol and its sulfate metabolite, cholesterol sulfate (CS), on the membrane. Here, we report a novel mechanism by which CS modulates TCR signaling through a conformational change of CD3 subunits. We found that the negatively charged CS interacted with the positively charged cytoplasmic domain of CD3ε (CD3εCD) to enhance its binding to the cell membrane and induce a stable secondary structure. This secondary structure suppressed the release of CD3εCD from the membrane in the presence of Ca2+, which in turn inhibited TCR phosphorylation and signaling. When a point mutation (I/A) was introduced to the intracellular immunoreceptor tyrosine-based activation motifs (YxxI-x6-8-YxxL) of CD3ε subunit, it reduced the stability of the secondary structure and regained sensitivity to Ca2+, which abolished CS-mediated inhibition and enhanced the signaling of the TCR complex. Notably, the I/A mutation could be applied to both murine and human TCR-T cell therapy to improve the antitumor efficacy. Our study reveals insights into the regulatory mechanism of TCR signaling and provides a strategy to functionally engineer the TCR/CD3 complex for T cell-based cancer immunotherapy.


A comparative study of herpes simplex infections in renal transplant and leukemic patients.
Herpes simplex virus (HSV) reactivation and lesion formation were studied in 68 renal transplant recipients and 30 leukemic patients. Antibody titers to HSV were determined, and seropositive patients were examined three times weekly for up to one month. Surveillance cultures were taken for oral HSV, and HSV culture and cytology were done for all oral lesions found. In a smaller number of patients, immune responses were determined. HSV reactivation was similar in the transplant and leukemic groups (46.8% vs. 50%), but a significant difference in the incidence of HSV lesion formation was noted between the two groups. Of the transplant patients in whom HSV reactivated, 31.8% developed HSV lesions; of leukemic patients in whom HSV reactivated, 100% developed HSV lesions. Differences in the incidence of formation of HSV lesions in these groups of immunosuppressed patients suggest that reactivation of HSV and formation of HSV lesions may involve different mechanisms. Low levels of antibody-dependent cellular cytotoxicity were noted in leukemic patients and may contribute to increased formation of HSV lesions in this group.


[The endothelium injuries caused by homocysteine and treatmental effects of Tongxinluo powder].
To observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected. Healthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected. Compared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P < 0.01), the format and percentage that capillary dilated declined significantly (P < 0.05), after treatment with Tongxinluo powder, the effect of Ach on isolated rat thoracic aorta in vitro was improved obviously (p < 0.01), and the format and percentage that capillary dilated were increased compared with model group; comparing with the control group, the level of Ang II and ET, TXA2 in plasm increased obviously (P < 0.05, P < 0.01), while the content of PGI2 depressed manifestly (P < 0.05), at the same time, both content of NO and activity of SOD, (GSH-PX declined obviously (P < 0.001, P < 0.05). After treatment with Tongxinluo powder, the level of ET, AngII and TXA2 reduced significantly in different degree (P < 0.01), while the content of PGI2 appeared stepping up notably (P < 0.01), and both activity of SOD and NO level increased obviously (P < 0.01, P < 0.05). (1) The high homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.


Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells.
Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.


Modulation of the enzymatic activity of papain by interdomain residues remote from the active site.
The two main catalytic residues Cys25 and His159 of the monomeric cysteine protease papain are located on different walls of a cleft formed by two domains. This topology suggests a possible relationship between relative domain organization and catalytic mechanism. The effect on enzymatic parameters of structural modifications at various locations of the two-domain interface of papain was examined by individual or double replacements by Ala of pairs of interacting residues. Most modifications had no effect on enzyme activity. However, the enzyme's substrate turnover (kcat) decreased following simultaneous alteration of the two most conserved residues, forming an apolar contact located 15 A away from the active site. The pH activity profile of the double mutant was unchanged, indicating a conserved ionization state of the active site thiolate-imidazolium ion pair. This state is strongly dependent on the distance separating the two residues, thus suggesting that the active site geometry has not been significantly altered. Efficient enzymatic activity in papain requires more than a correct active site geometry and is influenced by domain packing properties in a region remote from the active site.


Localization of regulatory peptides in the male urogenital apparatus of domestic equidae: a comparative immunohistochemical study in Equus caballus and Equus asinus.
An immunohistochemical study was carried out on specimens of testis, excurrent duct including the male accessory glands and urethra in its various tracts in the horse and the donkey, in order to localize nine regulatory peptides. Immunoreactivities were tested by means of Labelled Strept Avidin-Biotin (LSAB) method. The study has shown that Equine male genitalia are supplied by many peptide immunoreactive nerves containing NPY-, VIP-, leu- and met-Enkephalin-, Substance P-, CGRP- and Bombesin/GRP-like peptides, each of them having a characteristic distribution pattern. These neurotransmitters were localized in nerve fibers running in the connective tissue or in contact with the smooth muscle cells, as well as in sub- and intraepithelial nerve terminals, and in perivascular nerve fibers. In addition, leu- and met-Enkephalin-like-immunoreactive endocrine cells were shown in the bulbourethral gland of the horse. In both species it was evident that an extensive utilization of NPY and VIP exists. A contingent of NPY- and VIP-ir nerve fibers may have an intrinsic origin. The other regulatory peptides tested show a characteristic distribution pattern, limited to some organs and peculiar to each of the two species of Equidae. Differences observed comparing E. caballus and E. asinus might be related to the species-specific balance of the accessory neurotransmitters which in turn accompany adrenergic innervation. In both species it is noteworthy the complete absence of any regulatory peptide in the testis, with the exception of the perivascular localization of NPY-ir nerve fibers.


Perceived Racism and Demographic, Mental Health, and Behavioral Characteristics Among High School Students During the COVID-19 Pandemic - Adolescent Behaviors and Experiences Survey, United States, January-June 2021.
Perceived racism in school (i.e., a student's report of being treated badly or unfairly because of their race or ethnicity) is an important yet understudied determinant of adolescent health and well-being. Knowing how perceived racism influences adolescent health can help reduce health inequities. CDC's 2021 Adolescent Behaviors and Experiences Survey (ABES), an online survey of a probability-based, nationally representative sample of U.S. public- and private-school students in grades 9-12 (N = 7,705), was conducted during January-June 2021 to assess student behaviors during the COVID-19 pandemic. CDC analyzed data from ABES to measure perceived racism and the extent to which perceptions of racism are associated with demographic, mental health, and behavioral characteristics. Mental health and behavioral characteristics analyzed included mental health status; virtual connection with others outside of school; serious difficulty concentrating, remembering, or making decisions; and feeling close to persons at school. Demographic characteristics analyzed included sex, race and ethnicity, and grade. Prevalence of perceived racism and associations between perceived racism and demographic, mental health, and behavioral characteristics are reported overall and stratified by race and ethnicity. Approximately one third (35.6%) of U.S. high school students reported perceived racism. Perceived racism was highest among Asian (63.9%), Black (55.2%), and multiracial students (54.5%). Students who reported perceived racism had higher prevalences of poor mental health (38.1%); difficulty concentrating, remembering, or making decisions (44.1%); and not feeling close to persons at school (40.7%). Perceived racism was higher among those students who reported poor mental health than those who did not report poor mental health during the pandemic among Asian (67.9% versus 40.5%), Black (62.1% versus 38.5%), Hispanic (45.7% and 22.9%), and White students (24.5% versus 12.7%). A better understanding of how negative health outcomes are associated with student experiences of racism can guide training for staff and students to promote cultural awareness and antiracist and inclusivity interventions, which are critical for promoting safe school environments for all students.


[Mechanism of rejection of islet of Langerhans xenografts].
For immediately vascularised xenografts, the presence of preformed antibodies associated with the activation of the complement induces a hyperacute humoral rejection in discordant combinations. For neovascularised xenografts, such as the islets of Langerhans, the absence of an initial vascularisation prevents the acute humoral rejection and there is some evidence to suggest that the rejection is cell mediated. To analyse the influence of species response to cellular transplantation, we compared the functional outcome and the immunohistochemical analysis of concordant and discordant xenotransplated islets with allotransplanted islets of Langerhans. In the concordant xenotransplantation experiment, rat (Sprague Dawley) purified islets (N = 600) were transplanted under the kidney capsule of streptozotocin diabetic mice. In the discordant experiment, purified human islets (N = 1000), in the allotransplantation model Balb mouse islets (N = 600) were transplanted under the kidney capsule of C57BL/6 mice. Daily blood glucose levels were monitored until rejection occurred (blood glucose > 11 mMol/L) and kidney biopsies were taken every second day for immunohistological examination. In allotransplanted mice, rejection occurred after a mean of 15 +/- 4 days, in concordant xenotransplanted mice after a mean of 10 +/- 3 days and in the discordant xenotransplanted mice after a mean of 8 +/- 1 days. The immunohistological analysis showed in both xenotransplantation models a deposit of IgM and C3 surrounding the grafted cells, starting at day 1 and persisting until rejection, associated with the presence of Mac-1 positive cells. The intensity of the humoral response was moderate to important in the concordant group, but very strong and unchanged until rejection in the disconcordant group. An invasion with CD4+ and CD8+ cells started between day 4 and 6 in both groups, progressively increasing until rejection. In the allotransplantation model, no humoral response was detectable and the cellular response started between day 10 and 12 after transplantation. We conclude, that a cellular response is involved in the rejection process of both concordant and discordant xenotransplanted islets of Langerhans. Compared to an allotransplantation model, the humoral response does not destroy the function of transplanted islets, but could trigger or accelerate the cell-mediated response.


Characterization of a new murine cellular DNA polymerase.
A new DNA polymerase (peak A) has been identified in the high-speed pellet fraction of two subclones of nonvirus producing Balb/3T3 cells. The activity is associated with a molecule of approximately 70,000 molecular weight and chromatographs in two systems like the mouse type-C viral reverse transcriptase and a similar enzyme from the high-speed pellet fraction of a virus producing Balb/3T3 subclone, S(2)Cl(3). Comparable quantities of peak A are present in both nonvirus infected (A31) and mouse sarcoma virus transformed nonproducer (KA31) subclones. Virus producing cells contain 10-20 times more peak A polymerase activity. A31 and KA31 peak A are comparably inhibited by anti-mouse type C virus reverse transcriptase IgG but to a lesser degree than S(2)Cl(3) peak A or authentic viral reverse transcriptase. They can also be differentiated from the latter two enzymes by template preference studies. KA31 peak A can be distinguished from three other KA31 DNA polymerases (R-DNA polymerase and DNA polymerase N and C), and thus appears to be a new species of cellular DNA polymerase.