Assessment of Regional Pediatric Computed Tomography Dose Indices in Tamil Nadu.
The aim of this article is to assess Tamil Nadu pediatric computed tomography (CT) diagnostic reference levels (DRLs) by collecting radiation dose data for the most commonly performed CT examinations. This work was performed for thirty CT scanners installed in various parts of the Tamil Nadu region. The patient cohort was divided into two age groups: <1 year, and 1-5 years. CT dose indices were measured using a 10 cm3 pencil ion chamber with pediatric head and body polymethyl methacrylate phantoms. Dose data such as volumetric CT dose index (CTDIv) and dose length product (DLP) on a minimum of twenty average-sized pediatric patients in each category were recorded to calculate a mean site CTDIv and DLP value. The rounded 75th percentile was used to calculate a pediatric DRL for each hospital, and then region by compiling all results. Data were collected for 3600 pediatric patients. Pediatric CT DRL for two age groups: <1 year (CTDIv and DLP of head [20 mGy, 352 mGy.cm], chest [7 mGy, 120 mGy.cm] and abdomen [12 mGy, 252 mGy.cm]), and 1-5 years (CTDIv and DLP of head [38 mGy, 505 mGy.cm], chest [8 mGy, 132 mGy.cm] and abdomen [14 mGy, 270 mGy.cm]) for select procedures have been calculated. Proposed pediatric DRLs of CTDIv and DLP for head procedure were lower, and for chest and abdomen procedures were higher than European pediatric DRLs for both age groups.


Carrier-mediated transport of uridine diphosphoglucuronic acid across the endoplasmic reticulum membrane is a prerequisite for UDP-glucuronosyltransferase activity in rat liver.
UDP-glucuronosyltransferases (EC 126.96.36.199) is an isoenzyme family located primarily in the hepatic endoplasmic reticulum (ER) that displays latency of activity both in vitro and in vivo, as assessed respectively in microsomes and in isolated liver. The postulated luminal location of the active site of UDP-glucuronosyltransferases (UGTs) creates a permeability barrier to aglycone and UDP-GlcA access to the enzyme and implies a requirement for the transport of substrates across the ER membrane. The present study shows that the recently demonstrated carrier-mediated transport of UDP-GlcA across the ER membrane is required and rate-limiting for glucuronidation in sealed microsomal vesicles as well as in the intact ER of permeabilized hepatocytes. We found that in both microsomes and permeabilized hepatocytes a gradual inhibition by N-ethylmaleimide (NEM) of UDP-GlcA transport into the ER produced a correspondingly increasing inhibition of 4-methylumbelliferone glucuronidation. That NEM selectively inhibited the UDP-GlcA transporter, without affecting intrinsic UGT activity, was demonstrated by showing that NEM had no effect on glucuronidation in microsomes or hepatocytes with permeabilized ER membrane. Additional evidence that UDP-GlcA transport is rate-limiting for glucuronidation in sealed microsomal vesicles as well as in the intact ER of permeabilized hepatocytes was obtained by showing that gradual selective trans-stimulation of UDP-GlcA transport by UDP-GlcNAc, UDP-Xyl or UDP-Glc in each case produced correspondingly enhanced glucuronidation. Such stimulation of transport and glucuronidation was inhibited completely by NEM, which selectively inhibited UDP-GlcA transport.


Subcutaneous fluid administration and the hydration of older people.
Hypodermoclysis, or the subcutaneous administration of fluids, is a method of rehydration that is not routinely used in the UK. Yet it is a simple and effective method of fluid administration for individuals with mild-to-moderate dehydration, especially for the frail and elderly (Sasson and Shvartzman, 2001). Subcutaneous infusion is an alternative route of parenteral administration. It provides a number of advantages over the intravenous route for those individuals unable to tolerate enteral fluids, as it is associated with fewer complications, as well as a wider range of infusion sites. This makes it particularly advantageous for frail and/or older patients requiring low-volume hydration in the community setting. This article discusses indications and contraindications for subcutaneous infusions, as well as patient assessment, placement, securement and potential complications.


Apalutamide for the treatment of prostate cancer.
Five new agents have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer, including two targeting androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide). Recognition that these tumors remain driven by androgen receptor signaling has prompted clinical evaluation of these agents at earlier states in the prostate cancer disease continuum, along with the continued development of new agents targeting this pathway. Areas covered: This article focuses on apalutamide, a next-generation nonsteroidal antiandrogen, with current literature queried in PubMed/Medline. A narrative review strategy describes studies from engineering of the compound through to a 5-year outlook. Expert commentary: In the phase III SPARTAN study, apalutamide significantly improved metastasis-free survival in patients with nonmetastatic castration-resistant prostate cancer - the first treatment approved by the US Food and Drug Administration for this indication. Phase III studies are under way to determine the clinical benefit of apalutamide in other disease states. Given the multiplicity of prostate cancer treatment options now available, there is a need to maximize individual patient benefit through the development and validation of predictive biomarkers of sensitivity to drugs that can be used in real time to determine the optimal sequence and combinations of treatments for patients in need.


Accessory gene regulator (Agr) functionality in Staphylococcus aureus derived from lower respiratory tract infections.
Characterization of Staphylococcus aureus clinical isolates derived from lower respiratory tract infections (LRTIs), and correlation between the functionality of the accessory gene regulator (Agr) and genotypic and phenotypic characteristics, clinical variables and clinical outcome. S aureus isolates derived from LRTIs and control groups (nasal carriage and bacteraemia) were genotyped using StaphyType DNA microarray. Agr activity was evaluated using the CAMP synergistic haemolysis assay and the Vesicle Lysis Test (VLT). Discordant strains were analysed by quantitative reverse-transcriptase real-time PCR (qRT-PCR). Agr was functional in 79.7% and 84.5% of strains according to the CAMP and VLT assays respectively. Higher concordance with RNAIII expression measured by qRT-PCR was observed with the VLT assay (76.2%) compared with the CAMP assay (23.8%). No statistically significant differences were observed in Agr functionality between the study groups, nor the phenotypical/genotypical bacterial characteristics. No association between increased mortality/respiratory complications and Agr function was observed. Agr activity was high (82.2%) in isolates from LRTIs suggesting the importance of this global regulator in lower respiratory tract colonisation and infection. However, equally high Agr activity was observed in isolates derived from nasal carriage and bacteraemia, contradictory to previous observations. Agr functionality measured by the VLT assay was superior to CAMP assay.


Informed consent: do we achieve it? What are the elements that help create it?
Informed consent is a complex concept, it raises issues which involve ethical, moral and legal debates. This paper is intended to explore the elements of informed consent and to give guidance to those in the process of gaining consent from patients. The process should be seen as a partnership between the multidisciplinary team and the patient.


Blueprints for Connection: A Meta-Organizational Framework for Layering Theory, Philosophy, and Praxis Within Continuing Education in the Health Professions.
As a field, Continuing Professional Development (CPD) lies at the intersection of many disciplines. Tensions can occur as scholars from fields ranging from education to quality improvement seek to advance the practices and workplaces of health care professionals. Owing to the diversity of people working to affect change within the field of CPD, it remains a very challenging space to collaborate and understand the various philosophies, epistemologies, and practice of all those within the field.In this article, the authors have proposed a meta-organizational framework for how we might re-examine theory, application, and practice within the field of CPD. It is their belief that this proposal might inspire others to reflect on how we can cultivate and invite diverse scientists and scholars using a range of theories to add to the fabric of the field of CPD.


[A surgical treatment method in syringomyelia].
The author provides pathogenetic evidence for surgical treatment of syringomyelia. Based on the experience gained with surgical treatment of syringomyelia, gives a critical assessment of the hydrodynamic theory of the formation of intraspinal cavities. Provides the data obtained during examination of 127 patients suffering from genuine syringomyelia with the aid of cystography and NMR tomography. The communicating and non-communicating disease pattern were established. The short- and long-term results of surgical treatment were elucidated in 109 patients operated on. It is assumed that derangement of hydrodynamics plays a definite part in the disease pathogenesis. The hydrodynamic alterations include not only circulatory disorders but also have the signs of general functional insufficiency of the CSF system. The surgical treatment method is aimed at the correction of the hydrodynamic alterations, being one of the constituent parts in the whole complex of treatment measures for syringomyelia.


Examining communication and assertiveness as predictors of condom use: implications for HIV prevention.
The current study explored the relationship between communication and assertiveness in general and sexual contexts and examined each construct's differential ability to predict reported condom use among college students. The results suggest that the constructs are positively related to each other, but general communication does not predict sexual assertiveness. Although sexual assertiveness is a better predictor of condom use than general assertiveness, general communication, and sexual communication, it needs to be considered within the context of other variables (e.g., normative beliefs regarding condom use). HIV prevention programs and models of health behavior should incorporate individual characteristics such as sexual assertiveness. The results of this study suggest that sexual assertiveness, social norm perceptions of condom use, self-efficacy for HIV prevention, and condom attitudes are among the critical variables that should be examined in an integrated model of sexual health behavior.


Long-term lower extremity prosthetic costs in children with traumatic lawnmower amputations.
To evaluate prosthetic costs of pediatric lawnmower amputations; to see if reducing the incidence of pediatric lawnmower amputations could result in significant cost savings; and to consider if a cost analysis could be useful to implement more safety features (voluntarily or legislatively). Pediatric lawnmower amputees from 1980 to 2000 were reviewed to determine age at time of injury, level of amputation, number of prostheses, and lifetime per prosthesis. A standard prosthetic program beginning at amputation and ending at age 18 years was constructed. An aggregate cost was calculated according to the proportion of amputation levels. The cost burden for prosthetic care was estimated from the statistics of US pediatric lawnmower injuries. Referral pediatric orthopedic center. Fifty-three lower extremity amputees with 58 lower extremity amputations at a mean +/- SD age of 4.7 +/- 2.5 years were reviewed. The percentage of amputee children injured by riding lawnmowers was 80%; the percentage injured by riding lawnmowers engaged in reverse was 39%. Prosthetic costs from the time of injury to the age of 18 years range from 73,140 dollars to 116,040 dollars per single lower extremity amputation. With 600 to 650 new childhood amputations per year due to lawnmowers, the new annual burden for prosthetic costs thus ranges from 43.88 to 75.42 million dollars, or (600)(73,140 dollars) to (650)(116,040 dollars). Further encouragement of lawnmower manufacturers to install improved safety devices (such as those to disengage power while in reverse mode of operation), new research on improved safety measures, and continued promotion of educational campaigns regarding the dangers of children being around and/or operating riding lawnmowers and garden tractors should be pursued. This will result in significant cost savings as well as incalculable health savings.


Bma-LAD-2, an Intestinal Cell Adhesion Protein, as a Potential Therapeutic Target for Lymphatic Filariasis.
Lymphatic filariasis is a debilitating disease that afflicts over 70 million people worldwide. It is caused by the parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Despite substantial success, efforts to eliminate LF will likely require more time and resources than predicted. Identifying new drug and vaccine targets in adult filariae could help elimination efforts. This study's aim was to evaluate intestinal proteins in adult Brugia malayi worms as possible therapeutic targets. Using short interfering RNA (siRNA), we successfully targeted four candidate gene transcripts: Bma-Serpin, Bma-ShTK, Bma-Reprolysin, and Bma-LAD-2. Of those, Bma-LAD-2, an immunoglobulin superfamily cell adhesion molecule (IgSF CAM), was determined to be essential for adult worm survival. We observed a 70.42% knockdown in Bma-LAD-2 transcript levels 1 day post-siRNA incubation and an 87.02% reduction in protein expression 2 days post-siRNA incubation. This inhibition of Bma-LAD-2 expression resulted in an 80% decrease in worm motility over 6 days, a 93.43% reduction in microfilaria release (Mf) by day 6 post-siRNA incubation, and a dramatic decrease in (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Transmission electron microscopy revealed the loss of microvilli and unraveling of mitochondrial cristae in the intestinal epithelium of Bma-LAD-2 siRNA-treated worms. Strikingly, Bma-LAD-2 siRNA-treated worms exhibited an almost complete loss of pseudocoelomic fluid. A luciferase immunoprecipitation system assay did not detect anti-Bma-LAD-2 IgE in the serum of 30 LF patients, indicating that LF exposure does not result in IgE sensitization to this antigen. These results indicate that Bma-LAD-2 is an essential protein for adult Brugia malayi and may be an effective therapeutic target. IMPORTANCE Brugia malayi is a parasitic nematode that can cause lymphatic filariasis, a debilitating disease prevalent in tropical and subtropical countries. Significant progress has been made toward eliminating the disease. However, complete eradication may require new therapeutics such as drugs or a vaccine that kill adult filariae. In this study, we identified an immunoglobulin superfamily cell adhesion molecule (Bma-LAD-2) as a potential drug and vaccine candidate. When we knocked down Bma-LAD-2 expression, we observed a decrease in worm motility, fecundity, and metabolism. We also visualized the loss of microvilli, destruction of the mitochondria in the intestinal epithelium, and loss of pseudocoelomic fluid contents after Bma-LAD-2 siRNA treatment. Finally, we demonstrated that serum from filaria-infected patients does not contain preexisting IgE to Bma-LAD-2, which indicates that this antigen would be safe to administer as a vaccine in populations where the disease is endemic.


Correlations, agreement and utility of frailty instruments in prevalent haemodialysis patients: baseline cohort data from the FITNESS study.
Frailty is associated with poor outcomes for haemodialysis patients, but its prevalence is uncertain due to heterogeneous definitions. The aim of this study was to compare and contrast prevalence and features of commonly used frailty instruments in a British haemodialysis cohort. The FITNESS (Frailty Intervention Trial iN End-Stage patientS on haemodialysis) study recruited adults aged ≥18 years after informed consent, with ≥3 months haemodialysis exposure and no hospital admission within 4 weeks unless for dialysis access. Study participants were clinically phenotyped with frailty instruments including the Frailty Index (FI), Frailty Phenotype (FP), Edmonton Frailty Scale (EFS) and Clinical Frailty Scale (CFS), alongside comprehensive baseline data collection of biochemical, clinical and social characteristics. Between 12 January 2018 and 18 April 2019, 485 haemodialysis patients were recruited. Baseline demographics were median age 63 years, male sex 58.6% and non-White ethnicity 42.1%. Prevalence of frailty was high; 41.9% of participants were frail by FP, 63.3% by FI, 50.2% by EFS and 53.8% by CFS. Female gender was associated with increased frailty, with no independent association observed with age or ethnicity. While correlation between frailty instruments was strong, intraclass correlation coefficient for frailty agreement was 0.628 (95% confidence interval 0.585-0.669) and only weak agreement between instrument pairs. Frailty is highly prevalent among haemodialysis patients regardless of criteria used. However, our data suggest caution when interpreting heterogenous definitions of frailty for haemodialysis patients as they are not interchangeable. Consensus agreement on the optimal frailty definition for haemodialysis patients must balance ease of use with predictive ability for adverse outcomes before determining clinical application.


Effects of maternal parity on response of human myometrium to oxytocin and ergometrine in vitro.
The aim of this study was to compare the effects of oxytocin and ergometrine on the intrinsic contractile parameters of human uterine smooth muscle at term between primiparous and multiparous women. Myometrial biopsies were obtained from women undergoing planned caesarean section at term. The biopsies were dissected into eight uniform strips and mounted in tissue baths for isometric recording. The strips were challenged with increasing concentrations of oxytocin and ergometrine. Parameters of contractile activity, including mean contractile force (MCF) and maximum amplitude of contractions (MAMP) were recorded and analysed. Results were compared between primiparous (Group 1) and multiparous (Group 2) women. Myometrial biopsies were obtained from n = 11 donors (88 tissue strips), of which n = 5 were Group 1 and n = 6 were Group 2. In relation to oxytocin, the MAMP value observed was significantly greater in Group 2 than in Group 1 (151 ± 18mN vs 67 ± 14mN, P < 0.01). Regarding ergometrine, the MCF response was greater in Group 2 samples (24 ± 10 mN) than that in Group 1 (18 ± 2mN) (P < 0.05). Our findings highlight that women in a first pregnancy have a decreased response to both oxytocin and ergometrine in an in vitro setting when compared with women in a subsequent pregnancy, and this may have clinical implications regarding the management of postpartum haemorrhage in this cohort.


NSs protein of rift valley fever virus induces the specific degradation of the double-stranded RNA-dependent protein kinase.
Rift Valley fever virus (RVFV) continues to cause large outbreaks of acute febrile and often fatal illness among humans and domesticated animals in Africa, Saudi Arabia, and Yemen. The high pathogenicity of this bunyavirus is mainly due to the viral protein NSs, which was shown to prevent transcriptional induction of the antivirally active type I interferons (alpha/beta interferon [IFN-alpha/beta]). Viruses lacking the NSs gene induce synthesis of IFNs and are therefore attenuated, whereas the noninducing wild-type RVFV strains can only be inhibited by pretreatment with IFN. We demonstrate here in vitro and in vivo that a substantial part of the antiviral activity of IFN against RVFV is due to a double-stranded RNA-dependent protein kinase (PKR). PKR-mediated virus inhibition, however, was much more pronounced for the strain Clone 13 with NSs deleted than for the NSs-expressing strain ZH548. In vivo, Clone 13 was nonpathogenic for wild-type (wt) mice but could regain pathogenicity if mice lacked the PKR gene. ZH548, in contrast, killed both wt and PKR knockout mice indiscriminately. ZH548 was largely resistant to the antiviral properties of PKR because RVFV NSs triggered the specific degradation of PKR via the proteasome. The NSs proteins of the related but less virulent sandfly fever Sicilian virus and La Crosse virus, in contrast, had no such anti-PKR activity despite being efficient suppressors of IFN induction. Our data suggest that RVFV NSs has gained an additional anti-IFN function that may explain the extraordinary pathogenicity of this virus.


[Burnout syndrome in medical residents at the General Hospital of Durango, México].
The burnout syndrome is commonly spread among health workers and students, due to the excessive demands they feel on their workspaces. Depersonalization, emotional exhaustion and personal accomplishment are the areas assessed. To determine the prevalence of burnout syndrome in medical residents at the General Hospital of Durango; a descriptive, prolective, cross-sectional study was designed and applied to residents of different specialties of the General Hospital of Durango who agreed to participate, the "Maslach Burnout Inventory" was applied. We surveyed 116 residents, 43.1 % (50) women and 56.89 % (66) men. The overall prevalence was 89.66 % (95 % CI: 82.63- 94.54). Affected in a single area the 48.28 % (95 % CI: 38.90-57.74), in two areas the 35.34 % (95 % CI: 26.69-44.76) and in the three areas 6.03 % (95 % CI: 2.46-12.04). Stratified by areas, high emotional exhaustion was 41.38 % (95 % CI: 32.31-50.90), high depersonalization in 54.31 % (95 % CI: 44.81-63.59), and low personal accomplishment 41.38 % (95 % CI: 32.31-50.90). The prevalence is higher than the reported. The most frequently affected is depersonalization, followed by emotional exhaustion and finally the personal accomplishment. In the areas of Gynecology and obstetrics, Internal medicine, Pediatrics and Orthopedics, the 100 % of the residents are affected.


Core-shell structured PtRu nanoparticles@FeP promoter with an efficient nanointerface for alcohol fuel electrooxidation.
In this study, a bottleneck was overcome for direct alcohol fuel cells using state-of-the-art PtRu catalysts for alcohol fuel oxidation. Herein, a core-shell structured PtRu catalyst system based on the emerging promoter FeP was developed that showed excellent catalytic performance for the oxidation of alcohol fuels. The surface spectrometric analysis and morphology observation confirmed the formation of a nanointerface of the PtRu shell and FeP core hybrid catalyst (PtRu@FeP), and efficient ligand effects and electronic effects were found to result from the noble metal active sites and adjacent promoter in the core-shell structure. The facile formation of oxygen-containing species and the strong electronic effects could activate the Pt active sites, leading to high catalytic performance. High anti-CO poisoning ability was found for this catalyst system when compared with the case of the benchmark commercial PtRu/C catalyst (110 mV less and 60 mV less as evaluated by the peak and onset potentials for CO oxidation, respectively). The PtRu@FeP catalysts also exhibited much higher catalytic activity and stability when compared with commercial and home-made PtRu/C catalysts; specifically, the peak current density of the PtRu@FeP 1 : 1 catalyst was about 2 and 3 times higher than those of the commercial PtRu/C catalyst and home-made PtRu/C for the oxidation of the alcohol fuels methanol and ethanol; moreover, high catalytic efficiency, improved by 2 times, was found, as expressed by the specific activity. Excellent catalytic stability as evaluated by 1000 cycles of cyclic voltammetry measurements was also demonstrated for the PtRu@FeP catalysts. The high catalytic performance could be attributed to the intimate nanointerface contact of the core-shell structured PtRu shell over the FeP core via a bi-functional catalytic mechanism and electronic effects based on the ligand effect in this catalyst system. The current study is a significant step to increase the PtRu catalytic performance via nanointerface construction by a core-shell structure on a novel promoter for direct alcohol fuel cells.


Complications of Nd:YAG laser posterior capsulotomy.
A number of ocular complications are seen to be associated with the use of Nd:YAG laser for posterior capsulotomy after cataract surgery. We have outlined possible hazards to the cornea, trabecular meshwork, vitreous and intraocular lenses and have discussed their consequences. It would appear that the degree of severity of complications is related to the pulse energy used upon the capsule.


Similarities and differences between excessive exercising anorexia nervosa patients compared with DSM-IV defined anorexia nervosa subtypes.
This study describes anorexia nervosa (AN) patients who use excessive exercise for weight management and how this behaviour relates to the classical Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) sub-grouping of AN. The study compared 428 clinical AN patients with 119 age and gender-matched controls. The AN cases were initially dichotomised according to DSM-IV subtype criteria into restricting (RAN; N=198) and binge-purge (BPAN; N=230) anorexia. The psychometric instruments were chosen to reflect key features concerning the diagnosis of eating disorders and characteristics of eating and food behaviour and included the 26-item Eating Attitude Test (EAT-26), Three Factor Eating Questionnaire (TFEQ), Dutch Eating Behaviour Questionnaire (DEBQ), Eysenck Personality Inventory (EPI) and Rosenberg Self-Esteem scale (RSE). Structured clinical interviews (1) were carried out in order to identify the subgroup of patients who use excessive exercise in order to facilitate weight control (EAN). The three groups (RAN, BPAN, EAN) did not differ in measures of current age, current body mass index, age of onset of AN and measures of restrained eating. However, significant differences were observed on EAT-26, DEBQ emotional and external factors, TFEQ disinhibition and hunger factors, EPI extraversion and neuroticism, and self-esteem. The EAN were similar to the RAN on the majority of variables but showed significant differences on extraversion, neuroticism, self-esteem and disease pathology (EAT-26). Compared with BPAN, EAN had lower disease pathology (EAT-26 scores), scored higher on the EPI extraversion scale, lower on the neuroticism scale and had greater self-esteem. The EAN also displayed significantly lower emotional and external eating (DEBQ) than BPAN and significantly lower disinhibition and hunger scores (TFEQ). These data suggest that EAN group display a mixed profile of characteristics resembling both BPAN and RAN. When EAN are defined as a separate group they appear to be phenotypically more similar to RAN than BPAN on this particular profile of variables. However when DSM-IV criteria are applied they are almost exclusively classified as BPAN. This outcome suggests that EAN do constitute an identifiable group that can be distinguished from RAN and BPAN. Consequently it is likely that the behaviour of excessive exercising should be considered as clinically relevant on the outcome of treatment.


Hemodynamic effects of morphine and nalbuphine in acute myocardial infarction.
Hemodynamic effects of morphine and the new narcotic analgesic, nalbuphine, were compared in a randomized, double-blind study in 15 patients with acute myocardial infarction (11 men and four women, average age 56.2 yr) and normal group mean hemodynamic function. During a 1-hr evaluation the hemodynamic effects were small but there were changes in several parameters. Morphine reduced heart rate (78 to 72 bpm, p less than 0.01) and diastolic and mean arterial pressures (69 to 64 mm Hg, p less than 0.05; and 91 to 84 mm Hg, p less than 0.05); nalbuphine was associated with a decrease in heart rate (82 to 72 bpm, p less than 0.01), decrease in cardiac index, which remained within the normal range (3.16 to 2.75 l/min/m(2), p less than 0.01), and an increase in systemic vascular resistance (1,204 to 1,461 dynes . sec . cm(-5), p less than 0.05). Neither drug altered systolic arterial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, stroke index, stroke work index, or pulmonary vascular resistance. Echocardiographic assessment revealed diminution of left ventricular mean velocity of circumferential fiber shortening after nalbuphine (1.26 to 1.08 circ/sec, p less than 0.05). Both drugs induced small reductions in respiratory rate and arterial pH and increases in PAO2. There were no changes in PaO2. Because of the absence of clinically important deleterious effects on cardiac pump function, nalbuphine merits further investigation as an analgesic in acute myocardial infarction.


[Epidemiologic study of birth weight from birth certificates].
Based on the fact that there is evidence of an association between low birth weight and neonatal and infant morbi-mortality, the World Health Organization considered birth weight as the main isolated factor associated with infant's survival. A study was undertaken to identify risk factors associated with low birth weight, using epidemiological and demographic variables present on the Birth Certificates, the source of data for the System of Information on Newborn Infants of the Brazilian Ministry of Health, for the purpose of motivating the use and the analysis of data currently generated in hospitals. The distribution, by birth weight, of 14,784 single hospital newborn infants from five cities of the State of S. Paulo, Brazil, in an observation period of six months (1992), was analysed. Statistical analysis was based on point estimates (average, median and standard deviation) measures of association and confidence intervals (95%) of the prevalence ratios. The highest proportion (10.4%) of low birth weight infants (weight less than 2,500 g) occurred in Itararé, the city with the highest infant mortality rate in the State, the overall proportion being 7.5%. Significant statistical associations between low birth weight and sex (female), gestational age (less than 37 weeks), mother's age (adolescent and 35 or more years of age) and parity were detected. The use of Birth Certificates in epidemiological and public health studies is highly recommended because of their validity, great importance and high coverage.


Predictors, Neuroimaging Characteristics and Long-Term Outcome of Severe European Tick-Borne Encephalitis: A Prospective Cohort Study.
Tick-borne encephalitis (TBE) still represents a considerable medical and health economic problem in Europe and entails a potential threat to travellers. The aim of this study was to characterise the conditions of severe TBE by precisely recording its clinical variants, the related neuroimaging features, and the variant-specific long-term outcome and by identifying predictors for severe courses. A cohort of 111 TBE patients (median age 51, range 17-75 years; 42% females) was analysed prospectively. Data were acquired from the department of neurology, University Hospital Heidelberg, and the infectious diseases registry of the Robert-Koch institute Berlin. Neurological status was ascertained by protocol at admission and discharge and the degree of disability was scored using the modified RANKIN Scale (mRS; clinical score addressing neurological disability, range from 0, healthy to 6, dead) at admission and at follow-up. Follow-up examination was conducted by means of a telephone interview. To identify independent predictors for severe TBE and functional outcome, modelled logistic regression was performed. MRI changes were correlated with infection variants. To assess alpha-motor neuron injury patterns, we used high-resolution magnetic resonance neurography (hrMRN). Analyses were performed at the Department of Neurology, University Hospital, University of Heidelberg from April 2004 through September 2014. Acute course: 3.6% of patients died during the acute infection. All patients with a lethal course suffered from meningoencephaloradiculitis (MER, 14.4% of the cohort), which is associated with a significantly higher risk of requiring intensive care (p = 0.004) and mechanical ventilation (p<0.001) than menigoencephalitis (ME, 27.9% of the cohort). At admission, both MER and ME groups were severely affected, with the MER group having a statistically higher mRS score (median of 5 in the MER groups versus 4 in the ME group; p<0.001). Long-term outcome: outcome for MER was considerably worse (median mRS = 4) than for ME (mRS = 1, p<0.0001) and meningitis (mRS = 0, 57.7% of the cohort). advanced age (p<0.001) and male gender (p = 0.043) are independent risk factors for a severe infection course. Furthermore, we identified pre-existing diabetes mellitus (p = 0.024) as an independent risk factor for MER. In MER, alpha-motor neuron injury accounts for the poor prognosis confirmed by hrMRN. These data provide critical information for neurologists and other health professionals to use in evaluating TBEV patients who live in or travel to endemic areas. This information can be used to classify clinical presentation and estimate infection-associated complications and individual prognosis. Furthermore, the risk for severe, disabling infections in older patients should prompt general practitioners to recommend and encourage vaccination to those patients living in or travelling to endemic areas.


Biological and clinical implications of cancer stem cells in primary brain tumors.
Despite therapeutic advances, glioblastoma multiforme (GBM) remains a lethal disease. The infiltrative nature of this disease and the presence of a cellular population resistant to current medical treatments account for the poor prognosis of these patients. Growing evidence indicates the existence of a fraction of cancer cells sharing the functional properties of adult stem cells, including self-renewal and a greater ability to escape chemo-radiotherapy-induced death stimuli. Therefore, these cells are commonly defined as cancer stem cells (GBM-SCs). The initial GBM-SC concept has been challenged, and refined according to the emerging molecular taxonomy of GBM. This allowed to postulate the existence of multiple CSC types, each one driving a given molecular entity. Furthermore, it is becoming increasingly clear that GBM-SCs thrive through a dynamic and bidirectional interaction with the surrounding microenvironment. In this article, we discuss recent advances in GBM-SC biology, mechanisms through which these cells adapt to hostile conditions, pharmacological strategies for selectively killing GBM-SCs, and how novel CSC-associated endpoints have been investigated in the clinical setting.


[Recurrent disseminated infundibulofolliculitis].
A white male patient with disseminated, pruritic, follicular papules on the skin is reported. Histologically, an inflammatory infiltration around the infundibulum, perifollicular oedema and spongiosis of the follicular epithelium were demonstrated. The lesions failed to respond to therapy. On the basis of the clinical and histological findings, we suggest that this is a case of disseminated and recurrent infundibulofolliculitis, which was first described by Hitch and Lund in 1968.


Effect of honey bee venom on lewis rats with experimental allergic encephalomyelitis, a model for multiple sclerosis.
Multiple sclerosis (MS) is a progressive and autoimmune neurodegenerative disease of the central nervous system (CNS). This disease is recognized through symptoms like inflammation, demyelination and the destruction of neurological actions. Experimental allergic encephalomyelitis (EAE) is a widely accepted animal model for MS. EAE is created in animals by injecting the tissue of myelin basic protein (MBP), CNS, or myelin oligodendrocyte glycoprotein (MOG) along with the adjuvant. EAE and MS are similar diseases. Honey Bee venom (Apis mellifera) contains a variety of low and high molecular weight peptides and proteins, including melittin, apamin, adolapin, mast cell degranulating peptide and phospholipase A2. Bee venom (BV) could exert anti-inflammatory and antinociceptive effects on the inflammatory reactions. The guinea pig spinal cord homogenate (GPSCH) is with the Complete Freund's Adjuvant (CFA), consisting of 1 mg/mL Mycobacterium tuberculosis. It was used for inducting EAE in Lewis rats for creating the MS model. The hematoxylin and eosin and luxol fast blue methods were used respectively in analyses of inflammation and detection of demyelination in the central nervous system. Furthermore, the ELISA and the high performance liquid chromatography (HPLC) were used for the assessment of tumor necrosis factor alpha (TNF-α) and nitrate in rats serum. In this study, we indicated that the treatment of EAE with Bee venom decreased the symptoms of clinical disorder, pathological changes, inflammatory cell infiltration, demyelination in the central nervous system, level of serum TNF-α, and the serum nitrates in rat EAE induced through GPSCH.


Social relationships and hypertension in late life: evidence from a nationally representative longitudinal study of older adults.
Social relationships are widely understood to be important for sustaining and improving health and longevity, but it remains unclear how different dimensions of social relationships operate through similar or distinct mechanisms to affect biophysiological markers of aging-related disease over time. This study utilized longitudinal data on a nationally representative sample of older adults from the National Social Life, Health, and Aging Project (2005-2011) to examine the prospective associations between social integration and social support and change in systolic blood pressure (SBP) and hypertension risk over time. Although both social relationship dimensions have significant physiological impacts, their relative importance differs by outcome. Low social support was predictive of increase in SBP, whereas low social integration was predictive of increase in risk of hypertension. The different roles of relationship characteristics in predicting change in physiological outcomes suggest specific biophysiological stress response and behavioral mechanisms that have important implications for both scientific understandings and effective prevention and control of a leading chronic condition in late life.


Mammalian embryo culture media: now and into the future.
For over 70years, since the culture of the first mammalian embryo in vitro , scientists have undertaken studies to devise and optimise media to support the manipulation and culture of gametes and embryos. This area of research became especially active in the late 1970s onwards following the successful birth of the first human in vitro fertilised embryo. This review summarises some of the key advances in mammalian embryo culture media over time based on a greater understanding of the biochemical milieu of the reproductive tract. It highlights how learnings from studies in mice and agricultural species have informed human culture media compositions, in particular the inclusion of albumin, growth factors, cytokines, and antioxidants into contemporary culture media formulations, and how these advances may then in turn help to inform and guide development of in vitro culture systems used in other arenas, in particular agriculture. Additionally, it will highlight how the introduction of new technologies, such as timelapse, can influence current trends in media composition and usage that may see a return to a single step medium.


Childhood warts: an update.
Warts are benign intraepidermal neoplasms that are caused by infection with human papillomavirus and commonly affect children and adolescents. The 4 most common types of cutaneous warts are common warts, plantar warts, flat warts, and genital warts. Although they rarely pose a serious health problem, warts can result in physical impairment and psychosocial discomfort. A variety of treatment modalities are employed to treat these growths in children.


Methyl jasmonate upregulates biosynthetic gene expression, oxidation and conjugation of polyamines, and inhibits shoot formation in tobacco thin layers.
The effect of methyl jasmonate (MJ) on de novo shoot formation and polyamine metabolism was investigated in thin layer explants of tobacco (Nicotiana tabacum L. cv. Samsun). A relatively low concentration of MJ (0.1 microM) enhanced explant fresh weight, but had no effect on the final number of shoots per explant while higher concentrations (1 and 10 microM) significantly inhibited organogenesis. The histological study revealed that, with increasing concentrations of MJ, the formation of meristemoids and shoot domes declined and the incidence of cell hypertrophy increased. In explants cultured with 0.1, 1 or 10 microM MJ, the endogenous levels of free putrescine, spermidine and spermine generally declined compared with controls, after 7 and 15 d. Perchloric acid-soluble conjugated polyamines accumulated dramatically during culture, but much more so in the presence of MJ than in controls. Acid-insoluble conjugated spermidine alone increased in response to the elicitor. Activities of the putrescine biosynthetic enzymes arginine decarboxylase (ADC, EC 18.104.22.168) and ornithine decarboxylase (ODC, EC 18.104.22.168) in the soluble fraction of MJ-treated explants displayed up to 3-fold increases relative to control explants. However, the most relevant increases in these enzyme activities occurred in the particulate fraction. The activity of S:-adenosylmethionine decarboxylase (SAMDC, EC 184.108.40.206), an enzyme involved in spermidine and spermine biosynthesis, was also stimulated by exposure to MJ. Northern analyses revealed MJ-induced, generally dose-dependent, increases in the mRNA levels of all three enzymes. Diamine oxidase (DAO, EC 22.214.171.124) activity was stimulated by MJ mainly in the cell wall fraction. The upregulation of polyamine metabolism is discussed in relation to the morphogenic behaviour of MJ-treated explants.


Suprascapular nerve decompression for treatment of neuropathy in a bucking bull.
A 3-year-old 639-kg (1,406-lb) American bucking bull was examined because of a 4-day history of right forelimb lameness that began after the bull sustained an injury to the right shoulder region while exiting the chute during a rodeo. A 10 × 10-cm soft tissue swelling was present over the right shoulder region. Ultrasonographically, the contour of the scapular spine, bicipital bursa, bicipital tendon, and greater tubercle of the humerus appeared unremarkable; the swelling appeared to be a hematoma overlying the distal aspect of the scapula. No external wounds, palpable joint effusion, or swellings were noted on examination of the distal portions of the limbs. The bull developed atrophy of the supraspinatus and infraspinatus muscles with lateral abduction of the shoulder joint when walking. Electromyography revealed decreased innervation to the supraspinatus and infraspinatus muscles consistent with suprascapular neuropathy. The suprascapular nerve was surgically decompressed by removing the entrapping hematoma and periosteum and performing a notch resection of the scapula; dexamethasone (40 mg) was administered prior to closure. The bull was discharged 5 days after surgery; no lameness was evident at the time of discharge. The owner was instructed to restrict the bull to a stall or small pen for 6 weeks. Four months after surgery, the muscle atrophy had substantially improved, and the bull returned to bucking. Findings suggested that suprascapular neuropathy can develop in bulls secondary to injury and that suprascapular nerve decompression may improve nerve function, muscle atrophy, and gait.


Identification of cicatricial pemphigoid antigens.
The nature of skin antigens defined by antibodies in patients with cicatricial pemphigoid was studied with use of the 1 mol/L of sodium chloride split skin technique and Western immunoblot analysis. Antibodies in the serum samples of three of seven patients with cicatricial pemphigoid reacted to the epidermal side of 1 mol/L of sodium chloride split skin, and antibodies in the serum sample of one patient reacted to the dermal side. With Western immunoblot analysis, three patients had antibodies to antigens in the epidermal extracts of skin. The antibodies reacted in all patients to a 160-kd antigen and in one patient to an additional 230-kd antigen. These two antigens are similar in molecular weight to the 230-kd major bullous pemphigoid antigen and to the 160-kd minor bullous pemphigoid antigen. However, while the basement membrane zone antibodies present in cicatricial pemphigoid were most often directed to the 160-kd antigen, those present in 38 patients with bullous pemphigoid reacted most often (in 34 patients [89%]) to the 230-kd antigen. None of the serum samples reacted to antigens in dermal extracts that contained the epidermolysis bullosa acquisita antigen. These results indicate that the basement zone membrane antibodies present in cicatricial pemphigoid are directed in part to epidermal antigens that are similar in molecular weight to bullous pemphigoid antigens. However, the frequency of reactions to different basement membrane zone antigens differs in the two diseases, which may account for the clinical differences between the two conditions.


Myxococcus xanthus fibril appendages are essential for excitation by a phospholipid attractant.
Isolated (A-motile) Myxococcus xanthus cells glide over solid surfaces and display excitation, a suppression of direction reversals, when presented with phosphatidylethanolamine (PE) purified from its own membranes or synthetic dilauroyl PE and dioleoyl PE. Although the mechanism of PE signal transduction is unknown, we hypothesized that M. xanthus might use surface-associated factors to detect exogenous PE to prevent endogenous lipids from self-stimulating the sensory system. Peritrichous protein and polysaccharide appendages called fibrils were correlated with dilauroyl PE excitation. Wild-type cells treated with Congo red, an inhibitor of fibril assembly, and mutants defective in fibril biosynthesis showed an elevated reversal period, which suggested that fibrils regulate the gliding motor. Furthermore, the loss of fibrils resulted in loss of excitation to dilauroyl PE but not dioleoyl PE. Restoration of fibril production to these mutants restored the dilauroyl PE response. In addition, the dif cytoplasmic signal transduction system and starvation conditions were required for dilauroyl PE excitation. The chemically specific nature of the response and the dependence on the dif system suggests that fibrils define a novel sensory organelle whose evolution may have been necessary to prevent autostimulation by endogenous membrane lipids. Because the hydrophobic nature of dilauroyl PE would be inaccessible to periplasmic chemosensors, we suggest that fibrils act as extracellular signal transducers to probe surfaces for insoluble chemical signals.


Resolving dynamics of acoustic phonons by surface plasmons.
We show that the dynamics of acoustic phonons generated by femtosecond impulsive optical excitation can be clearly resolved by a surface plasmon technique, with enhanced sensitivity orders of magnitude higher than regular optical probe measurements. Our calculations confirm that the enhanced sensitivity is an intrinsic property of the surface plasmon probe. Therefore, the surface plasmon technique is a promising tool to detect small signal changes in optical and mechanical properties on a microscopic scale.


Role of nitric oxide in the acquisition and expression of apomorphine- or morphine-induced locomotor sensitization.
In the present study, the effects of L-arginine, a nitric oxide (NO) precursor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on apomorphine- or morphine-induced locomotor sensitization in male albino mice were investigated. Our data showed that subcutaneous (s.c.) injection of apomorphine (2-10 mg/kg) or morphine sulphate (5-50 mg/kg) significantly increased locomotor behaviour in a dose-dependent manner. Intraperitoneal (i.p.) administration of L-arginine (100 mg/kg) increased locomotor activity, whereas L-NAME (20 mg/kg) decreased it. L-Arginine and L-NAME increased and decreased apomorphine- or morphine-induced locomotions, respectively. The locomotor behavioural response was enhanced in mice pretreated with apomorphine (2 mg/kg, daily x3 days) or morphine (10 mg/kg, daily x3 days) alone, indicating that sensitization had developed. Administration of L-arginine 30 min before each of three daily doses of apomorphine or morphine increased the development of sensitization, while administration of L-NAME 30 min before each of three daily doses of apomorphine or morphine decreased the acquisition of sensitization induced by apomorphine or morphine. Administration of L-arginine significantly increased and L-NAME significantly and dose-dependently decreased the expression of both apomorphine- and morphine-induced sensitization. The results indicate that NO may be involved in the acquisition and expression of apomorphine- or morphine-induced sensitization.


First Report of Pestalotiopsis chamaeropis Causing Leaf Spot on Eurya nitida in China.
Eurya nitida Korth. belonging to the family Theaceae is an evergreen shrub or small tree and is usually used as a very important ornamental tree and nectar source plant (Khan et al. 1992; Ma et al. 2013). It also has high medicinal values with the treatment of rheumatoid arthritis, diarrhea, innominate inflammatory of unknown origin, ulcer fester and traumatic hemorrhage (Park et al. 2004). In October 2020, symptoms of leaf spot were observed on E. nitida in Meiling Scenic Spot of Nanchang, Jiangxi Province, China (28.78°N, 115.83°E). We surveyed about 300 m2 of the mountain area which holds about 100 trees of E. nitida scattered naturally near the waterside or regularly planted on either side of the mountain road. Most of the infected plants were observed from humid environments or waterside, with 15~20% disease incidence, and the disease severity on a plant basis was determined to be 25% to 30%, depending on the field. Sixty infected leaves were collected from 20 individual trees which have the same symptoms. The symptoms on infected leaves appeared as tiny circular spots that gradually enlarged into brown circular necrotic lesions and then became a light gray with brown borders and black acervuli at the later stages of the disease. Ten leaves of infected tissues randomly selected from collected sixty infected leaves were cut into 4 mm2 pieces, and surface disinfected with 75% ethanol for 30s and 1% hypochlorite for 1 min, rinsed three times with sterile water, plated on potato dextrose agar (PDA), and incubated at 25°C in the dark for 5 to 7 days. Five isolates with similar morphological characteristics were obtained. Colonies developed copious white aerial mycelium covering the entire Petri dish area after 7 to 10 days. Conidiogenous cells were discrete, hyaline, and smooth. Conidia were fusiform, ellipsoid, 4-euseptate and ranged from 21.86 to 29.80 × 5.95 to 9.80 µm. Apical cells were hyaline with 2 to 3 unbranched, tubular apical appendages (mostly 3); basal cell was hyaline, obconic with a truncate base; three median cells doliiform to subcylindrical, brown. The morphological characteristics of all isolates matched features described for Pestalotiopsis chamaeropis Maharachch., K.D. Hyde & Crous (Maharachchikumbura et al. 2014). Two single representatives (JAUCC L001-1 and JAUCC L002) were used for molecular identification, which were verified based on the amplification of DNA sequences of internal transcribed spacer region (ITS) gene and translation elongation factor 1 alpha (TEF1-α) gene, using the primers ITS4/ITS5 (White et al. 1990) and EF1-526F/EF1-1567R (Rehner and Buckley 2005), respectively. The sequenced loci (GenBank accession nos. ITS: MW845761, MW828589 and TEF1-α: MW838967, MZ292464) exhibited over 99% homology with P. chamaeropis strain CBS 186.71 in GenBank (GenBank accession nos. KM199326 and KM199473), confirming the morphological identification. Phylogenetic reconstruction was generated by using the maximum likelihood (ML) method based on the Kimura 2-parameter model, with bootstrap nodal support for 1000 pseudoreplicates in MEGA software, version 7.0. The result showed that our isolates were clustered together with P. chamaeropis at 99% bootstrap values. Based on morphological characteristics and molecular phylogenetic analysis, the isolates were identified as P. chamaeropis. The pathogenicity of one representative isolate (JAUCC L001-1) was tested indoor by inoculating the top leaves of six healthy E. nitida plants. Three plants with three leaves were punctured with flamed needles and sprayed with a conidial suspension (1 × 106 conidia/ml), and other three plants wounded inoculated with mycelial plugs (5 × 5 mm3). Mock inoculations were used as controls with sterile water and non-infested PDA plugs on three leaves each. Treated plants were incubated in an artificial climate box with high relative humidity at 25 °C. After 10 days, symptoms on all wounded inoculated plants were similar to those previously observed with distinct tiny circular spots, whereas no symptoms appeared on inoculated plants. Pestalotiopsis chamaeropis was re-isolated from symptomatic tissues but not from the mock-inoculated plants, and its identity was confirmed by morphological characteristics and molecular data, which confirmed Koch's postulates. Pestalotiopsis chamaeropis was previously reported as the causal agent of leaf blight diseases on Camellia sinensis in China (Chen et al. 2020), Pieris japonica in Japan (Nozawa et al. 2019) and Prostanthera rotundifolia in Australia (Azin et al. 2015). To our knowledge, this is the first report of P. chamaeropis causing a leaf spot disease on E. nitida in China, and this disease may be more widespread than the sampled location. This finds is beneficial to the better protection of E. nitida, a widespread medicinal and nectar source plant with high economic value.


Enhanced cartilage regeneration by icariin and mesenchymal stem cell-derived extracellular vesicles combined in alginate-hyaluronic acid hydrogel.
Osteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs. MSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo. EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers. The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.


HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1.
The transporter associated with antigen processing (TAP), which is composed of two subunits (TAP1 and TAP2) that have different biochemical and functional properties, plays a key role in peptide loading and the cell surface expression of HLA class I molecules. Three cases of HLA class I deficiency have previously been shown to result from the absence of a functional TAP2 subunit. In the present study, we analyzed two cases displaying not only the typical lung syndrome of HLA class I deficiency but also skin lesions, and found these patients to be TAP1-deficient. This defect leads to unstable HLA class I molecules and their retention in the endoplasmic reticulum. However, the absence of TAP1 is compatible with life and does not seem to result in higher susceptibility to viral infections than TAP2 deficiency. This work also reveals that vasculitis is often observed in HLA class I-deficient patients.


Understanding Heterogeneity in the Impact of Public Preschool Programs.
We examine the North Carolina Pre-K (NC Pre-K) program to test the hypothesis that observed variation in effects resulting from exposure to the program can be attributed to interactions with other environmental factors that occur before, during, or after the pre-k year. We examine student outcomes in 5th grade and test interaction effects between NC's level of investment in public pre-k and moderating factors. Our main sample includes the population of children born in North Carolina between 1987 and 2005 who later attended a public school in that state, had valid achievement data in 5th grade, and could be matched by administrative record review (n = 1,207,576; 58% White non-Hispanic, 29% Black non-Hispanic, 7% Hispanic, 6% multiracial and Other race/ethnicity). Analyses were based on a natural experiment leveraging variation in county-level funding for NC Pre-K across NC counties during each of the years the state scaled up the program. Exposure to NC Pre-K funding was defined as the per-4-year-old-child state allocation of funds to a county in a year. Regression models included child-level and county-level covariates and county and year fixed effects. Estimates indicate that a child's exposure to higher NC Pre-K funding was positively associated with that child's academic achievement 6 years later. We found no effect on special education placement or grade retention. NC Pre-K funding effects on achievement were positive for all subgroups tested, and statistically significant for most. However, they were larger for children exposed to more disadvantaged environments either before or after the pre-k experience, consistent with a compensatory model where pre-k provides a buffer against the adverse effects of prior negative environmental experiences and protection against the effects of future adverse experiences. In addition, the effect of NC Pre-K funding on achievement remained positive across most environments, supporting an additive effects model. In contrast, few findings supported a dynamic complementarity model. Instrumental variables analyses incorporating a child's NC Pre-K enrollment status indicate that program attendance increased average 5th grade achievement by approximately 20% of a standard deviation, and impacts were largest for children who were Hispanic or whose mothers had less than a high school education. Implications for the future of pre-k scale-up and developmental theory are discussed.


Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression.
Post-stroke depression (PSD) is a common complication after stroke. Ganoderic acid A (GAA), one of the main bioactive Ganoderma triterpenoids, exerts preventive and therapeutic effects in many diseases. However, the function of GAA in PSD has not been well studied. PSD model was established via stimulating rats with chronic unpredictable mild stress stimulations (CUMS) after middle cerebral artery occlusion (MCAO). Rats were treated with GAA before CUMS. Depressive-like behaviors were investigated by body weight alteration, open field test (OFT), and sucrose preference test (SPT). Neuronal damage was evaluated by hematoxylin and eosin (HE) staining and Western blotting. Inflammation was detected by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Microglial polarization was analyzed via qRT-PCR and Western blotting. The extracellular signal-regulated kinase (ERK)/cAMP-response element-binding protein (CREB) pathway was analyzed by Western blotting, and inactivated by the inhibitor PD98059 (PD). GAA attenuated PSD-induced depressive-like behaviors in rats. GAA mitigated PSD-induced neuronal damage and reduced BDNF and NGF levels in the cerebral hippocampus. GAA weakened PSD-induced inflammatory response in the cerebral hippocampus. GAA prevented pro-inflammatory (M1) polarization and promoted anti-inflammatory (M2) polarization, as indicated by decreased iNOS and CD86 levels and increased Arg-1 and CD206 levels. GAA restored the PSD-induced inactivation of the ERK/CREB pathway. GAA regulated M1/M2 microglial polarization by activating the ERK/CREB pathway. GAA alleviated the depressive-like behaviors and brain inflammation in PSD rats, indicating its potential for PSD therapy.


lncRNA799/TBL1XR1/ZEB1 Axis Forms a Feedback Loop to Promote the Epithelial-Mesenchymal Transition of Cervical Cancer Cells.
Cervical cancer is a common malignancy among women worldwide. Long non-coding RNAs (lncRNAs) are frequently involved in the pathogenesis of cervical cancer. Therefore, the present study aimed to investigate the potentials of lncRNA799 in cervical cancer. mRNA and protein expression were detected by reverse transcription-quantitative polymerase chain reaction and Western blot analysis, respectively. Cellular functions were assessed using CCK-8, wound healing and transwell analysis. The binding potential of zinc finger E-box-binding homeobox 1 (ZEB1) on the promoter of lncRNA799 was predicted utilizing the JASPAR database, and was then verified by luciferase and chromatin immunoprecipitation (ChIP) assays. Furthermore, the gene interactions were assessed using RNA immunoprecipitation and co-immunoprecipitation assays. The results demonstrated that lncRNA799 was upregulated in cervical cancer cells. However, lncRNA799 deficiency suppressed the proliferation and epithelial-mesenchymal transition of cervical cancer cells. Furthermore, lncRNA799 could interact with eukaryotic translation initiation factor 4A3 to maintain the mRNA stability of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) and promote the interaction between ZEB1 and TBL1XR1. Additionally, the results showed that ZEB1 could transcriptionally activate lncRNA799. Taken together, the present study suggested that the lncRNA799/TBL1XR1/ZEB1 axis could form a positive feedback loop in cervical cancer and could be, therefore, considered as a potential therapeutic strategy for cervical cancer.


Genome-Wide Copy Number Variations Using SNP Genotyping in a Mixed Breed Swine Population.
Copy number variations (CNVs) are increasingly understood to affect phenotypic variation. This study uses SNP genotyping of trios of mixed breed swine to add to the catalog of known genotypic variation in an important agricultural animal. PorcineSNP60 BeadChip genotypes were collected from 1802 pigs that combined to form 1621 trios. These trios were from the crosses of 50 boars with 525 sows producing 1621 piglets. The pigs were part of a population that was a mix of ¼ Duroc, ½ Landrace and ¼ Yorkshire breeds. Merging the overlapping CNVs that were observed in two or more individuals to form CNV regions (CNVRs) yielded 502 CNVRs across the autosomes. The CNVRs intersected genes, as defined by RefSeq, 84% of the time - 420 out of 502. The results of this study are compared and contrasted to other swine studies using similar and different methods of detecting CNVR. While progress is being made in this field, more work needs to be done to improve consistency and confidence in CNVR results.


Effects of fruit and vegetable consumption on inflammatory biomarkers and immune cell populations: a systematic literature review and meta-analysis.
Inflammation is associated with an increased risk of a range of chronic diseases. A diet high in fruit and vegetables may help to reduce inflammation, as fruit and vegetables are rich sources of antioxidants and other biologically active substances, which may improve immune function. To summarize the evidence, we executed a systematic review and meta-analysis examining the effects of fruit and/or vegetable intake on inflammatory biomarkers and immune cells in humans with different diseases and conditions. Electronic databases including PubMed, Cochrane, CINAHL, and EMBASE were systematically searched up to March 2018. Eighty-three studies were included. Of these, 71 (86%) were clinical trials, and 12 were observational studies (n = 10 cross-sectional and n = 2 cohort). Amongst the observational research, n = 10 studies found an inverse association between intakes of fruit or vegetables and inflammatory biomarkers. Similarly, the majority of the intervention studies (68%, n = 48) reported beneficial effects of fruit or vegetable intake on ≥1 biomarker of systemic or airway inflammation. A meta-analysis of included studies showed that fruit or vegetable intake decreased circulating levels of C-reactive protein and tumor necrosis factor-α (P < 0.05) and increased the γδ-T cell population (P < 0.05). In conclusion, this review suggests that higher intakes of fruit and vegetables lead to both a reduction in proinflammatory mediators and an enhanced immune cell profile.


Association between occupational exposure to irritant agents and a distinct asthma endotype in adults.
The biological mechanisms of work-related asthma induced by irritants remain unclear. We investigated the associations between occupational exposure to irritants and respiratory endotypes previously identified among never asthmatics (NA) and current asthmatics (CA) integrating clinical characteristics and biomarkers related to oxidative stress and inflammation. We used cross-sectional data from 999 adults (mean 45 years old, 46% men) from the case-control and familial Epidemiological study on the Genetics and Environments of Asthma (EGEA) study. Five respiratory endotypes have been identified using a cluster-based approach: NA1 (n=463) asymptomatic, NA2 (n=169) with respiratory symptoms, CA1 (n=50) with active treated adult-onset asthma, poor lung function, high blood neutrophil counts and high fluorescent oxidation products level, CA2 (n=203) with mild middle-age asthma, rhinitis and low immunoglobulin E level, and CA3 (n=114) with inactive/mild untreated allergic childhood-onset asthma. Occupational exposure to irritants during the current or last held job was assessed by the updated occupational asthma-specific job-exposure matrix (levels of exposure: no/medium/high). Associations between irritants and each respiratory endotype (NA1 asymptomatic as reference) were studied using logistic regressions adjusted for age, sex and smoking status. Prevalence of high occupational exposure to irritants was 7% in NA1, 6% in NA2, 16% in CA1, 7% in CA2 and 10% in CA3. High exposure to irritants was associated with CA1 (adjusted OR aOR, (95% CI) 2.7 (1.0 to 7.3)). Exposure to irritants was not significantly associated with other endotypes (aOR range: 0.8 to 1.5). Occupational exposure to irritants was associated with a distinct respiratory endotype suggesting oxidative stress and neutrophilic inflammation as potential associated biological mechanisms.


Aurora-A inhibitor synergistically enhances the inhibitory effect of anlotinib on hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a highly malignant tumor with a global prevalence. In addition to the existing clinical guidelines, the effectiveness of anlotinib and Aurora-A inhibitors in treating HCC has also been demonstrated. However, Anlotinib, as an anti-angiogenesis therapy, has shown significant benefits in clinical trials but is limited by its single-agent treatment and the development of drug resistance. Aurora-A inhibitors are currently being tested in clinical trials but have limited efficacy. Combination therapy may offer clear advantages over monotherapy in this context. In this study, we used HCC cell lines to investigate whether the combination of the two drugs could enhance their individual strengths and mitigate their weaknesses, thereby providing greater clinical benefits both in vitro and in vivo. Our findings confirmed that the Aurora-A inhibitor alisertib and anlotinib exhibited a time-dose-dependent inhibitory effect on HCC cells. In vitro cytological experiments demonstrated that the combination of the two drugs synergistically inhibited cell proliferation, invasion, and metastasis, while promoting cell apoptosis. Furthermore, we identified the underlying molecular mechanism by which the combination of the Aurora-A inhibitor alisertib and anlotinib inhibited HCC through the inhibition of the NF-ĸB signaling pathway. In summary, we have demonstrated the effectiveness of combining anlotinib with an Aurora-A inhibitor, which expands the potential applications of anlotinib in the clinical treatment of HCC in the future.


How to best manage time interaction with patients? Community pharmacist workload and service provision analysis.
Primary health care disease management models are rooted in multidisciplinary participation; however, implementation of services is lagging behind desires and predictions. Barriers like workload and lack of demand have been described. The aim of this research is to observe the workload and work patterns of Portuguese community pharmacists, and relate it with the demand of pharmaceutical services. A time-and-motion observational study was performed to describe community pharmacists' workload in a sample of four pharmacies in the metropolitan Lisbon area. A reference list of activities to be observed was developed by reviewing other studies of community pharmacy work. This study took place during a weekday's 8-h shift, focusing on pharmacists' activities. Data to be collected included the type and duration of the activity, who performed it and where. To estimate the demand of pharmaceutical care services, "thematic-patient scenarios" were developed. These scenarios were based on the defined daily dose and package size of the most consumed medicines in Portugal, combined with data obtained from the four pharmacies' information systems on the day the observational study took place. Between 67.0% and 81.8% of the registered activities were pharmacist-patient interactions. These interactions summed 158.44 min, with a mean duration of 3.98 min per interaction. On average, participant pharmacies' professionals handled 4.2 prescriptions and 0.9 over-the-counter (OTC) consultations per hour. About one third of the day was spent performing administrative and non-differentiated tasks. About 54.92 min were registered as free time, 50% of which were "micro pauses" with 1 min or less. The most dispensed therapeutic subgroup was antihypertensive drugs, while the dispensation of antidiabetics was characterized by a high number of packages sold per interaction. From the developed scenarios, one can estimate that a chronic patient may visit the pharmacy 4-9 times per year, depending on the condition presented. Workload results are very similar to findings from studies in other countries, which may be an indication of uniformity of community pharmacy practice across countries. The amount of time a pharmacist has at the counter to interact with a patient during a year renders disease management or therapeutic management non-viable. Also, the perception of "lack of time," many times reported as a barrier for service provision, must be called into question, since substantial available time was found. However, to turn this available time into usable time, redesign of work processes and new role definition are necessary. Both better management and new communication channels should be developed to address this gap and increase patient follow-up services.


The needs of older people with mental health problems according to the user, the carer, and the staff.
Individual assessment of needs has been recognised as the most appropriate way to allocate health and social care resources. These assessments, however, are often made by the staff or by a carer who acts as an advocate for the user themselves. Little is known about how these proxy measures compare to how individual patients perceive their own needs. The aim of this study was to measure and compare ratings of need for older people with mental health problems by the older person themselves, their carer, and an appropriate staff member. One-hundred and one older people were identified from various mental health services and 87 users, 57 carers, and 95 staff were interviewed using the Camberwell Assessment of Need for the Elderly (CANE) to identify met and unmet needs. Users identified significantly fewer of their needs (5.5) than either staff (8.1) or carers (8.3) did, but this difference was accounted for by people with dementia reporting less needs. Users identified fewer psychological or social needs (e.g. daytime activities, company, or carer distress) than staff or carers did. The average Kappa indicating level of agreement between staff and user was 0.52, between user and carer was 0.53, and between carer and user was 0.58. This showed only a fair level of reliability between different ratings of need. User perspectives should be given a high priority when assessing individual needs. Fears that assessment of need would be unduly time-consuming or would simply reflect individual demands should be allayed. A user-based assessment will assist healthcare providers to prioritise needs according to what the user themselves consider to be most important, beneficial, and acceptable to them. Reliance solely on assessment by staff or carers may not lead to the most equitable or appropriate use of services.


Obesity and asthma morbidity in a community-based adult cohort in a large urban area: the Chicago Initiative to Raise Asthma Health Equity (CHIRAH).
Urban minority populations experience increased rates of obesity and increased asthma prevalence and severity. Objective. The authors sought to determine whether obesity, as measured by body mass index (BMI), was associated with asthma quality of life or asthma-related emergency department (ED)/urgent care utilization in an urban, community-based sample of adults. This is a cross-sectional analysis of 352 adult subjects (age 30.9 +/- 6.1, 77.8% females, forced expiratory volume in one second (FEV(1))% predicted = 87.0% +/- 18.5%) with physician-diagnosed asthma from a community-based Chicago cohort. Outcome variables included the Juniper Asthma Quality of Life Questionnaire (AQLQ) scores and health care utilization in the previous 12 months. Bivariate tests were used as appropriate to assess the relationship between BMI or obesity status and asthma outcome variables. Multivariate regression analyses were performed to predict asthma outcomes, controlling for demographics, income, depression score, and beta-agonist use. One hundred ninety-one (54.3%) adults were obese (BMI > 30 kg/m(2)). Participants with a higher BMI were older (p = .008), African American (p < .001), female (p = .002), or from lower income households (p = .002). BMI was inversely related to overall AQLQ scores (r = -.174, p = .001) as well as to individual domains. In multivariate models, BMI remained an independent predictor of AQLQ. Obese participants were more likely to have received ED/urgent care for asthma than nonobese subjects (odds ratio [OR] = 1.8, p = .036). In a community-based sample of urban asthmatic adults, obesity was related to worse asthma-specific quality of life and increased ED/urgent care utilization. However, compared to other variables measured such as depression, the contribution of obesity to lower AQLQ scores was relatively modest.


Sensorineural Hearing Loss After Teprotumumab Therapy for Thyroid Eye Disease: A Case Report.
Teprotumumab is a fully human IgG1 monoclonal antibody against insulin-like growth factor-1 receptor (IGF-1R). It has been approved by the FDA to treat thyroid eye disease (TED) by reducing extraocular muscle and orbital fat volume. In clinical trials, hearing loss was noted as a side effect in 7 to 12% of patients, but no formal audiometric investigations of these patients were reported. Furthermore, the FDA and manufacturer offer no formal guidelines for audiometric monitoring. This case report is the first to describe sensorineural hearing loss (SNHL) in a patient undergoing treatment with teprotumumab. A 77-year-old woman presenting with bilateral SNHL after treatment with teprotumumab therapy for TED. Audiometric testing was performed due to worsening and prolonged SNHL after subsequent teprotumumab infusions. Word recognition scores, pure tone average. Audiometry after discontinuation of therapy showed moderate to moderate-severe SNHL with word recognition scores of 64% in the right ear and 68% in the left ear. There are currently no formal guidelines for routine audiograms before, during, and after infusion of teprotumumab. Given that such guidelines exist for ototoxic medications such as gentamicin and cisplatin, we strongly encourage audiometric monitoring for patients undergoing treatment with teprotumumab.


Adequacy of diabetes care for older U.S. rural adults: a cross-sectional population based study using 2009 BRFSS data.
In the U.S. diabetes prevalence estimates for adults ≥ 65 years exceed 20%. Rural communities have higher proportions of older individuals and health disparities associated with rural residency place rural communities at risk for a higher burden from diabetes. This study examined the adequacy of care received by older rural adults for their diabetes to determine if older rural adults differed in the receipt of adequate diabetes care when compared to their non-rural counterparts. Cross-sectional data from the 2009 Behavioral Risk Factor Surveillance Survey were examined using bivariate and multivariate analytical techniques. Logistic regression analysis revealed that older rural adults with diabetes were more likely to receive less than adequate care when compared to their non-rural counterparts (OR = 1.465, 95% CI: 1.454-1.475). Older rural adults receiving less than adequate care for their diabetes were more likely to be: male, non-Caucasian, less educated, unmarried, economically poorer, inactive, a smoker. They were also more likely to: have deferred medical care because of cost, not have a personal health care provider, and not have had a routine medical check-up within the last 12 months. There are gaps between what is recommended for diabetes management and the management that older individuals receive. Older adults with diabetes living in rural communities are at greater risk for less than adequate care when compared to their non-rural counterparts. These results suggest the need to develop strategies to improve diabetes care for older adults with diabetes and to target those at highest risk.


Assessment of stigma in patients with cystic fibrosis.
Research that explores stigma in Cystic Fibrosis (CF) is limited. Productive cough, repeated lung infections, and periods of serious illness requiring hospitalizations are among common symptoms of CF. These symptoms may cause a negative perception by others. We developed a CF-specific Stigma Scale and tested its psychometric properties. We conducted a focus group with 11 participants including adult patients with CF (n = 5) and their informal caregivers (n = 6). The thematic content of the focus group was analyzed to find key themes. We developed a CF-specific Stigma Scale and assessed its psychometric properties in a 3-month prospective cohort study of adult CF outpatients (n = 45). Stigma emerged as consistent concern for people living and caring for those with CF, affecting both patients' lives and health through the focus group. Using the newly developed CF Stigma scale, the mean baseline score was 16.6 (SD = 4.5, Range = 10-25). The CF Stigma Scale demonstrated robust psychometric properties: 1) Internal consistency: α = 0.79; 2) Mean inter-item correlation: 0.30 with good test-retest reliability; 3) Convergent validity: Positive associations with depression, severity of CF symptoms and anxiety; negative associations with validated quality of life scores were observed. Stigma is measurable and significantly impacts the lives of CF patients. Further research should investigate the role of stigma in patients living with CF.


Generative models of cortical oscillations: neurobiological implications of the kuramoto model.
Understanding the fundamental mechanisms governing fluctuating oscillations in large-scale cortical circuits is a crucial prelude to a proper knowledge of their role in both adaptive and pathological cortical processes. Neuroscience research in this area has much to gain from understanding the Kuramoto model, a mathematical model that speaks to the very nature of coupled oscillating processes, and which has elucidated the core mechanisms of a range of biological and physical phenomena. In this paper, we provide a brief introduction to the Kuramoto model in its original, rather abstract, form and then focus on modifications that increase its neurobiological plausibility by incorporating topological properties of local cortical connectivity. The extended model elicits elaborate spatial patterns of synchronous oscillations that exhibit persistent dynamical instabilities reminiscent of cortical activity. We review how the Kuramoto model may be recast from an ordinary differential equation to a population level description using the nonlinear Fokker-Planck equation. We argue that such formulations are able to provide a mechanistic and unifying explanation of oscillatory phenomena in the human cortex, such as fluctuating beta oscillations, and their relationship to basic computational processes including multistability, criticality, and information capacity.


Hemodynamic instability during carotid angioplasty and stenting-relationship of calcified plaque and its characteristics.
During carotid angioplasty and stenting (CAS), hemodynamic instability (HDI) can occur, possibly causing post-procedural ischemic complications. The goal of this study was to investigate the risk factors of HDI focusing on characteristics of plaque. Thirty nine CAS patients were retrospectively evaluated for HDI. Prolonged HDI that lasted over 30 minutes was analyzed in relation to characteristics of calcified plaque. Nineteen (48.7%) patients had HDI. Ten of the 19 had both bradycardia and hypotension, and nine had only bradycardia. All bradycardia was treated well with a transcutaneous temporary cardiac pacemaker. But eight patients presented with prolonged hypotension in spite of recovery of bradycardia. Calcified plaque was a related factor associated with HDI (odds ratio, 8.571; 95% confidence interval, 1.321-55.62; p=0.024). Extensive and eccentric type calcified plaques were associated with prolonged hypotension (p=0.04, and p=0.028, respectively). The calcification of plaque is a predictable factor of HDI during CAS, and its extensive and eccentric calcified plaques may be related to prolonged HDI.


Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs.
In this study we aimed to clarify the role of endothelin in arterial pressure regulation during anaesthesia with increasing concentrations of sevoflurane (1-3 MAC) and compare it with those of vasopressin and angiotensin. After an awake control period, on different days, six dogs underwent each of the following four interventions: sevoflurane anaesthesia alone (1-3 MAC), sevoflurane after block of either endothelin receptors using tezosentan (3 mg kg(-1) followed by 3 mg kg(-1) h(-1)), vasopressin V(1a) receptors using [d(CH(2))(5)Tyr(Me(2))]AVP (40 micro g kg(--1)) or angiotensin receptors using losartan (6 mg kg(-1) h(-1)). Plasma concentrations of endothelin, big endothelin, vasopressin and renin were measured. Effects of sevoflurane in the presence and absence of the respective receptor block were analysed and compared using analysis of variance for repeated measures (ANOVA followed by Fisher's PLSD (protected least significant difference) (P<0.05)). Mean arterial pressure decreased in a dose-dependent manner with sevoflurane during all interventions. At 1 MAC, this decrease was greatest during angiotensin receptor block (mean (SEM), -41 (3) mm Hg), intermediate during vasopressin and endothelin receptor block (-31 (4) and -30 (2) mm Hg respectively), and least during sevoflurane alone (-24 (3) mm Hg). The course of systemic vascular resistance mirrored the course of arterial pressure, while cardiac output did not differ between groups. Plasma concentrations of endothelin, big endothelin and renin did not change during any intervention, whereas vasopressin concentration increased from approximately 0.5 to 40 ng litre(-1) at 3 MAC as arterial pressure decreased in all groups. At 1 MAC, angiotensin attenuated the decrease in arterial pressure during sevoflurane anaesthesia more than endothelin and vasopressin. However, at higher MAC only vasopressin was specifically activated to partly compensate for the arterial pressure decrease.


Translational regulation of Arabidopsis XIPOTL1 is modulated by phosphocholine levels via the phylogenetically conserved upstream open reading frame 30.
In Arabidopsis thaliana, XIPOTL1 encodes a phosphoethanolamine N-methyltransferase with a central role in phosphatidylcholine biosynthesis via the methylation pathway. To gain further insights into the mechanisms that regulate XIPOTL1 expression, the effect of upstream open reading frame 30 (uORF30) on the translation of the major ORF (mORF) in the presence or absence of endogenous choline (Cho) or phosphocholine (PCho) was analysed in Arabidopsis seedlings. Dose-response assays with Cho or PCho revealed that both metabolites at physiological concentrations are able to induce the translational repression of a mORF located downstream of the intact uORF30, without significantly altering its mRNA levels. PCho profiles showed a correlation between increased endogenous PCho levels and translation efficiency of a uORF30-containing mORF, while no correlation was detectable with Cho levels. Enhanced expression of a uORF30-containing mORF and decreased PCho levels were observed in the xipotl1 mutant background relative to wild type, suggesting that PCho is the true mediator of uORF30-driven translational repression. In Arabidopsis, endogenous PCho content increases during plant development and affects root meristem size, cell division, and cell elongation. Because XIPOTL1 is preferentially expressed in Arabidopsis root tips, higher PCho levels are found in roots than shoots, and there is a higher sensitivity of this tissue to translational uORF30-mediated control, it is proposed that root tips are the main site for PCho biosynthesis in Arabidopsis.


B lymphocyte differentiation induced by lipopolysaccharide. II. Response of fetal lymphocytes.
Cultures of mouse fetal liver and spleen, stimulated by bacterial lipopolysaccharide, gave rise to plasma cells staining for IgM, IgG2, IgG1, and IgA. Cells containing Igm and IgG2 were found in cultures from 17-day fetuses, coincident with the appearance of B lymphocytes bearing cell-surface IgM. IgG1- and IgA-containing cells were induced in cultures from 19-day fetuses and 1-day-old mice. The capacity to give rise to immunoglobulin-secreting cells of all classes preceded the development of a significant proliferative response to LPS; the proportions of cells staining for each class reached adult values by 1 day of age whereas the proliferative response did not mature until 3 weeks.


Recognition of protein coding genes in the yeast genome at better than 95% accuracy based on the Z curve.
The Z curve is a three-dimensional space curve constituting the unique representation of a given DNA sequence in the sense that each can be uniquely reconstructed from the other. Based on the Z curve, a new protein coding gene-finding algorithm specific for the yeast genome at better than 95% accuracy has been proposed. Six cross-validation tests were performed to confirm the above accuracy. Using the new algorithm, the number of protein coding genes in the yeast genome is re-estimated. The estimate is based on the assumption that the unknown genes have similar statistical properties to the known genes. It is found that the number of protein coding genes in the 16 yeast chromosomes is </=5645, significantly smaller than the 5800-6000 which is widely accepted, and much larger than the 4800 estimated by another group recently. The mitochondrial genes were not included into the above estimate. A codingness index called the YZ score (YZ OE [0,1]) is proposed to recognize protein coding genes in the yeast genome. Among the ORFs annotated in the MIPS (Munich Information Centre for Protein Sequences) database, those recognized as non-coding by the present algorithm are listed in this paper in detail. The criterion for a coding or non-coding ORF is simply decided by YZ > 0.5 or YZ < 0.5, respectively. The YZ scores for all the ORFs annotated in the MIPS database have been calculated and are available on request by sending e-mail to the corresponding author.


Energy Transfer Dynamics in an RC-LH1-PufX Tubular Photosynthetic Membrane.
Light absorption and the subsequent transfer of excitation energy are the first two steps of the photosynthetic process, carried out by protein-bound pigments, mainly bacteriochlorophylls (BChls), in photosynthetic bacteria. BChls are anchored in light-harvesting (LH) complexes, such as light-harvesting complex I (LH1), which directly associates with the reaction center (RC), forming the RC-LH1 core complex. In Rhodobacter sphaeroides, RC-LH1 core complexes contain an additional protein, PufX, and assemble into dimeric RC-LH1-PufX core complexes. In the absence of light-harvesting complexes II, the former complexes can aggregate into a helically ordered tubular photosynthetic membrane. We examined the excitation transfer dynamics in a single RC-LH1-PufX core complex dimer using the hierarchical equations of motion for dissipative quantum dynamics that accurately, yet computationally costly, treat the coupling between BChls and their protein environment. A widely employed description, generalized Förster theory, was also used to calculate the transfer rates of the same excitonic system in order to verify the accuracy of this computationally cheap method. Additionally, in light of the structural uncertainties in the Rhodobacter sphaeroides RC-LH1-PufX core complex, geometrical alterations were introduced in the BChl organization. It is shown that the energy transfer dynamics is not affected by the considered changes in the BChl organization, and that generalized Förster theory provides accurate transfer rates. An all-atom model for a tubular photosynthetic membrane is then constructed on the basis of electron microscopy data, and the overall energy transfer properties of this membrane are computed.


Detection of occult cardiac invasion by two dimensional echocardiography in patients with bronchial carcinoma.
Cardiac invasion by bronchial carcinoma may prevent successful resection but may be undetected before operation. In a retrospective analysis of 100 consecutive thoracotomies nine patients had unsuspected cardiac invasion by tumour. A prospective study of preoperative two dimensional echocardiography was therefore undertaken in patients with bronchial carcinoma who had no clinical evidence of cardiac tumour. Comparison with anatomical findings was possible in 65 patients in whom an echocardiogram of suitable quality had been obtained. There was one false negative among 55 negative echocardiograms and three false positives among 10 positive echocardiograms; non-malignant pericardial disease accounted for the echocardiographic finding in one of the latter. The predictive value of a negative test was 98%, and the predictive value of a positive test was highest (80%) if the echocardiogram suggested atrial invasion.


CD4+ T cells dominate the leukocyte infiltration response initiated by intra-dermal injection of phytohemagglutinin into growing feathers in chickens.
Phytohemagglutinin (PHA) is commonly used to evaluate cell-mediated immunocompetence. In chickens, PHA is typically injected intra-dermally (i.d.) into the skin (e.g., wing web, wattle, or footpad), and the tissue swelling response is monitored, whereby the extent of tissue swelling positively relates to the individual's cell-mediated immune system capabilities. Although i.d. injected PHA was shown to stimulate mononuclear cell and basophil infiltration to the site of injection, reports on temporal, qualitative, and quantitative aspects of the local cutaneous PHA response are limited. The objective of this study was to use the growing feather (GF) as a cutaneous test site to assess and monitor the type and relative amounts of leukocytes present in the pulp of PHA-injected GF. For this study, male, non-vaccinated Light-brown Leghorn chickens reared at the Arkansas Experiment Station Poultry Health Laboratory were used. At 9 wk of age, the dermis of 20 18-day-old regenerating GF was injected with 10 μL of either PBS diluent or 300 μg/mL PHA-P (5 chickens per treatment). GF were collected from each chicken before (zero) and at 0.25, 1, 2, 3, 4, 5, and 7 d post injection. At each time point, one GF was collected for immunofluorescent staining of pulp cell suspensions and leukocyte population analysis by flow cytometry, and another GF for histological analysis. Histological analysis confirmed participation of granulocytes and mononuclear cells, primarily lymphocytes, in the cutaneous PHA response. As revealed by flow cytometric cell population analysis, T cells, especially CD4+ T cells, constituted the major portion of the mononuclear cell infiltrate. Levels of CD4+ T cells were greatly elevated in PHA-injected GF within 6 h and remained elevated throughout the 7-day examination period. γδ T cells, CD8+ T cells, and B cells also infiltrated in response to PHA although at lower levels and with different time-course patterns from CD4+ T cells. The dominant presence of CD4+ T cells at the site of PHA injection further affirms this polyclonal response as an indicator of cell-mediated immunity.


Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia.
Neuroinflammation contributes to many neurologic disorders including Alzheimer's disease, multiple sclerosis, and stroke. Microglia is brain resident myeloid cells and have emerged as a key driver of the neuroinflammatory responses. MicroRNAs (miRNAs) provide a novel layer of gene regulation and play a critical role in regulating the inflammatory response of peripheral macrophages. However, little is known about the miRNA in inflammatory activation of microglia. To elucidate the role that miRNAs have on microglial phenotypes under classical (M1) or alternative (M2) activation under lipopolysaccharide ('M1'-skewing) and interleukin-4 ('M2a'-skewing) stimulation conditions, we performed microarray expression profiling and bioinformatics analysis of both mRNA and miRNA using primary cultured murine microglia. miR-689, miR-124, and miR-155 were the most strongly associated miRNAs predicted to mediate pro-inflammatory pathways and M1-like activation phenotype. miR-155, the most strongly up-regulated miRNA, regulates the signal transducer and activator of transcription 3 signaling pathway enabling the late phase response to M1-skewing stimulation. Reduced expression in miR-689 and miR-124 are associated with dis-inhibition of many canonical inflammatory pathways. miR-124, miR-711, miR-145 are the strongly associated miRNAs predicted to mediate anti-inflammatory pathways and M2-like activation phenotype. Reductions in miR-711 and miR-124 may regulate inflammatory signaling pathways and peroxisome proliferator-activated receptor-gamma pathway. miR-145 potentially regulate peripheral monocyte/macrophage differentiation and faciliate the M2-skewing phenotype. Overall, through combined miRNA and mRNA expression profiling and bioinformatics analysis we have identified six miRNAs and their putative roles in M1 and M2-skewing of microglial activation through different signaling pathways.


Benign mesenchymal liver hamartoma in an adult male: a case report and review of the literature.
Mesenchymal hamartoma of the liver is an uncommon benign lesion seen almost exclusively in children younger than two years of age. The first case was reported in 1903, and until now fewer than 200 cases have been reported. A 38-year-old male complaining of dull subcostal pain lasting for almost 10 months was found on abdominal ultrasound to have a focal lesion of the liver. He was referred to our Unit where imaging procedures (ultrasound and computed tomography) revealed a solid lesion, 8 centimeters in diameter, located in the IVb and V segments of the liver. There were no clear margins between the lesion and the gallbladder wall. Alpha-fetoprotein and carcinoembryonic antigen were within normal limits and carbohydrate antigen 19-9 was minimally elevated. There was no evidence of metastatic disease. Ultrasound-guided biopsy of the lesion was done and pathology report of a biopsy specimen suggested that the tumor was probably a benign mesenchymal hamartoma. The patient underwent a formal bi-segmentectomy (IVb and V segments) with cholecystectomy. Definitive pathology report confirmed the diagnosis of a benign mesenchymal hamartoma.


A head-to-head comparison of SCRalyze and Ledalab, two model-based methods for skin conductance analysis.
Model-based analysis of skin conductance responses (SCR) can furnish less noisy estimates of sympathetic arousal (SA) than operational peak scoring approaches, as shown in previous work. Here, I compare two model-based methods for analysis of evoked (stimulus-locked) SCR, implemented in two software packages, SCRalyze and Ledalab, with respect to their sensitivity in recovering SA. Four datasets are analysed to compare predictive validity, i.e. the sensitivity to distinguish pairs of SA states that are known to be different. SCRalyze was significantly better able than Ledalab to recover this known difference in four out of five tested contrasts and comparable in the remaining one. SCRalyze performed significantly better than conventional analysis in all contrasts. I conclude that the model-based method engendered in SCRalyze is currently the best available approach to provide robust and sensitive estimates of sympathetic arousal.