Delayed spontaneous alternation in Purkinje cell degeneration mutant mice.
Purkinje cell degeneration (pcd) mutant mice lose cerebellar Purkinje cells. It was found that pcd mice, contrary to normal mice, did not alternate spontaneously at any of 3 inter-trial intervals (15 s, 3 or 6 min). Deficits in spontaneous alternation are typical of animals with brain damage in areas important in spatial learning. Results are discussed in terms of a role for the cerebellum in spatially mediated behavior and behavioral inhibition.


CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification.
CD19 regulates constitutive and antigen receptor-induced signaling thresholds in B lymphocytes through its unique cytoplasmic domain. Herein, we demonstrate a novel molecular mechanism where interactions between CD19 and Lyn amplify basal and antigen receptor-induced Src family kinase activation. Lyn expression was required for CD19 tyrosine phosphorylation in primary B cells. Experiments with purified proteins demonstrated that CD19-Y513 was Lyn's initial phosphorylation and binding site. This led to processive phosphorylation of CD19-Y482, which recruited a second Lyn molecule, allowing for transphosphorylation and amplification of Lyn activation. In vivo, CD19 deficiency impaired, and CD19 overexpression enhanced, Lyn kinase activity. Thus, CD19 functions as a specialized adapter protein for the amplification of Src family kinases that is crucial for intrinsic and antigen receptor-induced signal transduction.


Cognitive predictors of reactive and proactive aggression in a forensic sample: A comparison with a non-clinical sample.
This study aimed at examining cognitive predictors of reactive and proactive aggression in a forensic-psychiatric (n = 80) and a non-clinical sample (n = 98; Brugman et al., 2015). Three different cognitive predictors were incorporated: (1) attentional bias towards aggressive stimuli (measured with Emotional Stroop task) and towards angry faces (measured with a visual search task); (2) interpretation biases (measured with Aggressive Interpretative Bias Task (AIBT) and a vignette task), and (3) implicit self-aggression association (measured with a Single-Target Implicit Association Task). To measure aggression, the Reactive-Proactive Aggression Questionnaire (RPQ) and the Taylor Aggression Paradigm (TAP) were used. An automatic self-aggression association positively predicted proactive aggressive behavior on the TAP in both samples. Furthermore, this self-aggression association predicted, increased self-reported proactive aggression (RPQ) in the forensic sample only. Pain, injury, and danger interpretations reported on the vignettes, negatively predicted self-reported proactive aggression in both samples. A stronger aggressive interpretation bias on the AIBT predicted more reactive aggressive behavior (TAP) in the non-clinical sample only. Taken together, findings show both common and distinct mechanisms in reactively vs. proactively driven aggressive behavior.


Merging Directed C-H Activations with High-Throughput Experimentation: Development of Iridium-Catalyzed C-H Aminations Applicable to Late-Stage Functionalization.
Herein, we report an iridium-catalyzed directed C-H amination methodology developed using a high-throughput experimentation (HTE)-based strategy, applicable for the needs of automated modern drug discovery. The informer library approach for investigating the accessible directing group chemical space, in combination with functional group tolerance screening and substrate scope investigations, allowed for the generation of reaction application guidelines to aid future users. Applicability to late-stage functionalization of complex drugs and natural products, in combination with multiple deprotection protocols leading to the desirable aniline matched pairs, serve to demonstrate the utility of the method for drug discovery. Finally, reaction miniaturization to a nanomolar range highlights the opportunities for more sustainable screening with decreased material consumption.


In vitro effect of dopamine and pimozide on human chorionic gonadotropin secretion.
In human placental explants cultured in vitro, dopamine inhibited human chorionic gonadotropin (hCG) secretion into the culture media. In the control flasks, the level of hCG secretion was 751 +/- 215 mIU/gm of tissue. When 1 mM of dopamine was added, hCG levels decreased to 321 +/- 57.6 mIU/gm of tissue (n = 6, P less than 0.1)--5 and 10 mM of dopamine significantly inhibited hCG secretion. In contrast, 1 mM of pimozide enhanced hCG secretion by 1.8-fold compared to control levels (1,707 +/- 343 versus 3,117 +/- 0.005). This in vitro effect on hCG is similar to the effect of dopamine and pimozide on hCS secretion by placental explants.


Balloon angioplasty for disruption of tunneled dialysis catheter fibrin sheath.
Management of failing tunneled hemodialysis catheters, sometimes the only vascular access for hemodialysis, presents a difficult problem. In spite of various techniques having been developed, no consensus has been reached about the preferred technique, associated with the longest catheter patency. We report disruption of the fibrin sheath covering dysfunctional tunneled hemodialysis catheter by means of angioplasty, followed by over guidewire catheter exchange. Following the procedure, the catheter placed in the recovered lumen of the vessel presented correct function. The described procedure allowed maintenance of vascular access in our patient. Additionally, dilatation of the concomitant central vein stenosis opens an option for another attempt for arteriovenous fistula creation.


Toxoplasma gondii: in vivo and in vitro studies of a mutant resistant to arprinocid-N-oxide.
The anticoccidial drug arprinocid and arprinocid-N-oxide, a metabolite produced in vivo, blocked the growth of Toxoplasma gondii in human fibroblasts. The more potent arprinocid-N-oxide inhibited growth by 50% at 20 ng/ml while arprinocid inhibited at 2 micrograms/ml. For both drugs, the host cell was less sensitive than was the parasite. Hypoxanthine did not reverse the antitoxoplasma activity of either drug. We isolated a parasite mutant, R-AnoR-1 that was 16- to 20-fold more resistant to arprinocid-N-oxide than was the wild type RH T. gondii. This mutant was not resistant to arprinocid in vitro. Arprinocid in a daily oral dose of 136 micrograms regularly protected mice against an otherwise fatal infection with RH T. gondii and 55 micrograms had some protective effect. However, all mice infected with R-AnoR-1 and treated with 360 micrograms arprinocid per day died. Since this mutant is fully sensitive to arprinocid, the form of the drug that is therapeutically active in vivo cannot be arprinocid and is likely to be arprinocid-N-oxide.


Effects of large group awareness training on participants' psychiatric status.
The impact of large group awareness training on psychiatric status was evaluated in two cohorts of participants. Clinical and Diagnostic Interview Schedule interviews were used to specify impact; a small number of stress reactions and no psychiatric casualties were identified in the more than 300 subjects studied.


A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children.
Lactobacillus GG (L-GG), an acid- and bile-resistant strain that colonizes the intestinal mucosa, has been used to manage diarrhea in children. Our objective was to evaluate the prophylactic use of L-GG to prevent diarrhea in children at high risk from a developing country in a randomized, placebo-controlled trial. Two hundred four undernourished children 6 to 24 months old from an indigent peri-urban Peruvian town received either L-GG or placebo in flavored gelatin once daily, 6 days a week, for 15 months. Episodes of diarrhea were documented by daily home visits, and diagnostic studies were done in a subset of cases. Recovery of L-GG in stool from subjects and from family contacts was examined. Subjects in the L-GG group had significantly fewer episodes of diarrhea (5.21 episodes diarrhea/child/year ['ecy'] L-GG group, 6. 02 ecy placebo group; P =.028). The decreased incidence of diarrhea in the L-GG group was greatest in the 18- to 29-month age group (P =. 004) and was largely limited to nonbreastfed children (Breastfed: 6. 59 ecy L-GG, 6.32 ecy placebo, P =.7; Nonbreastfed: 4.69 ecy L-GG, 5. 86 ecy placebo, P =.005). The duration of diarrhea episodes and the causes of diarrhea were similar in both groups, except adenovirus was more common in the placebo group. L-GG supplementation may be useful as a prophylactic measure to control diarrhea in undernourished children at increased risk, especially nonbreastfed children in the toddler age group.


HBcAg-specific IL-21-producing CD4+ T cells are associated with relative viral control in patients with chronic hepatitis B.
Function exhaustion of specific cytotoxic CD8+ T cell in chronic virus infection partly results from the low levels of CD4 help, but the mechanisms by which CD4 help T cell required to control hepatitis B virus infection are not well understood. In this study, we investigated the role of interleukin-21-producing CD4+ T cell response in viral control of hepatitis B virus infection. HBcAg-specific interleukin-21-producing CD4+ T cells in blood were detected in patients with hepatitis B virus infection. Patients with acute hepatitis B had greater HBcAg-specific interleukin-21-producing CD4+ T cells in blood compared with chronic hepatitis B patients, and there was no statistical significance between immune active chronic hepatitis B patients and inactive healthy carrier patients for these cells, whereas frequencies of these cells negatively correlated with HBV DNA levels but positively correlated with HBc18-27-specific IFN-γ-producing CD8+ T cells. Moreover, interleukin-21 sustained HBc18-27-specific CD8+ T cells in vitro, and interleukin-21 production by HBcAg-specific IL-21-producing CD4+ T cells of acute hepatitis B patients enhanced IFN-γ and perforin expression by CD8+ T cells from chronic hepatitis B patients. Our results demonstrate that HBcAg-specific interleukin-21-producing CD4+ T cell responses might contribute to viral control by sustaining CD8+ T cell antiviral function.


Modern Clinician-initiated Clinical Trials to Determine Optimal Therapy for Multidrug-resistant Gram-negative Infections.
Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial.


Changing the coronary-prone (type A) behavior pattern in a nonclinical population.
This report presents the design and initial findings of an attempt to reduce the risk of coronary heart disease in healthy men by modifying their type A behavior pattern. A group of 27 professional and executive volunteers, aged 39--59, who had been medically assessed as free from coronary heart disease, were randomly assigned to brief psychotherapy and behavior therapy groups. Each treatment group met for 14 sessions over a period of 5 months. Pre- and postmeasures of physiological (serum cholesterol, serum triglycerides, blood pressure) and psychological (anxiety, psychological symptoms, satisfaction) variables were taken. Results indicate that both treatment groups changed in the desired direction on most of the psychological and physiological variables without apparent change in habits of diet, exercise, smoking, or work load. The findings are provocative, but only tentative, leaving questions of clinical validity, durability, and generalizability unresolved. Nevertheless, they indicate that this approach to modifying type A behavior may reduce coronary risk and therefore warrants further exploration.


Mitigation of Corrosion on Magnesium Alloy by Predesigned Surface Corrosion.
Rapid corrosion of magnesium alloys is undesirable in structural and biomedical applications and a general way to control corrosion is to form a surface barrier layer isolating the bulk materials from the external environment. Herein, based on the insights gained from the anticorrosion behavior of corrosion products, a special way to mitigate aqueous corrosion is described. The concept is based on pre-corrosion by a hydrothermal treatment of Al-enriched Mg alloys in water. A uniform surface composed of an inner compact layer and top Mg-Al layered double hydroxide (LDH) microsheet is produced on a large area using a one-step process and excellent corrosion resistance is achieved in saline solutions. Moreover, inspired by the super-hydrophobic phenomenon in nature such as the lotus leaves effect, the orientation of the top microsheet layer is tailored by adjusting the hydrothermal temperature, time, and pH to produce a water-repellent surface after modification with fluorinated silane. As a result of the trapped air pockets in the microstructure, the super-hydrophobic surface with the Cassie state shows better corrosion resistance in the immersion tests. The results reveal an economical and environmentally friendly means to control and use the pre-corrosion products on magnesium alloys.


Fibroids and infertility: an updated systematic review of the evidence.
To investigate the effect of fibroids on fertility and of myomectomy in improving outcomes. Systematic literature review and meta-analysis of existing controlled studies. Private center for Reproductive endocrinology and infertility. Women with fibroids and infertility. A systematic literature review, raw data extraction and data analysis. Clinical pregnancy rate, spontaneous abortion rate, ongoing pregnancy/live birth rate, implantation rate, and preterm delivery rate in women with and without fibroids, and in women who underwent myomectomy. Women with subserosal fibroids had no differences in their fertility outcomes compared with infertile controls with no myomas, and myomectomy did not change these outcomes compared with women with fibroids in situ. Women with intramural fibroids appear to have decreased fertility and increased pregnancy loss compared with women without such tumors, but study quality is poor. Myomectomy does not significantly increase the clinical pregnancy and live birth rates, but the data are scarce. Fibroids with a submucosal component led to decreased clinical pregnancy and implantation rates compared with infertile control subjects. Removal of submucous myomas appears likely to improve fertility. Fertility outcomes are decreased in women with submucosal fibroids, and removal seems to confer benefit. Subserosal fibroids do not affect fertility outcomes, and removal does not confer benefit. Intramural fibroids appear to decrease fertility, but the results of therapy are unclear. More high-quality studies need to be directed toward the value of myomectomy for intramural fibroids, focusing on issues such as size, number, and proximity to the endometrium.


Survivor's syndrome: a comparison of the perceptions of administrators, managers, nurses and physicians during the restructuring of Ontario hospitals.
Leaders must approach organizational restructuring by addressing employees' concerns, or risk many potentially negative consequences among "survivors". This article provides important insights for administrators, managers and planners about the perceptions of people remaining on the job during the restructuring of Ontario hospitals. The findings, relevant to most organizations undergoing or considering restructuring, support the need for proactive change management, including tailored intervention strategies, to assist "survivors".


Regulation of substance P by nerve growth factor: disruption by capsaicin.
Capsaicin depleted substance P from guinea pig dorsal root ganglia and inhibited the retrograde axoplasmic transport of nerve growth factor (NGF). Doses of capsaicin which depleted substance P also inhibited the retrograde axoplasmic transport of NGF. Inhibition of the retrograde transport of NGF by capsaicin preceded substance P depletion. Supplementation of guinea pigs with mouse NGF completely prevented capsaicin-induced substance P depletion. It is concluded that capsaicin depletes substance P from primary afferent neurons of the adult guinea pig by altering the availability of NGF. The data support a role for NGF in the normal maintenance of neuropeptide levels in some sensory neurons in the adult animal.


Predictors of Access to Early Support in Families of Children with Suspected or Diagnosed Developmental Disabilities in the United Kingdom.
This study examined predictors of access to early support amongst families of 0-6-year-old children with suspected or diagnosed developmental disabilities in the United Kingdom. Using survey data from 673 families, multiple regression models were fitted for three outcomes: intervention access, access to early support sources, and unmet need for early support sources. Developmental disability diagnosis and caregiver educational level were associated with intervention access and early support access. Early support access was also associated with child physical health, adaptive skills, caregiver ethnicity, informal support, and statutory statement of special educational needs. Unmet need for early support was associated with economic deprivation, the number of household caregivers, and informal support. Multiple factors influence access to early support. Key implications include enhancing processes for formal identification of need, addressing socioeconomic disparities (e.g., reducing inequalities, increasing funding for services), and providing more accessible services (e.g., coordinating support across services, flexible service provision).


Schistosoma mansoni, S. haematobium, and S. japonicum: identification of genus- and species-specific antigenic egg glycoproteins.
Immunoreactive egg glycoproteins of Schistosoma mansoni, S. haematobium, and S. japonicum which are genus- and species-specific, or react with sera of patients infected with other parasites, have been identified. Egg proteins were labeled with Iodine-125, and the concanavalin A-binding glycoproteins were immunoprecipitated with sera of patients infected with one of four species of Schistosoma or Trichinella spiralis, Taenia solium, Echinococcus granulosus, Entamoeba histolytica, or Wuchereria bancrofti. These immunoprecipitates were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Despite the strikingly different patterns of glycoproteins of the African species, the antibody immune responses of patients infected with S. mansoni and S. haematobium were found to be so similar that differentiation could not be established. In contrast, sera of patients infected with S. japonicum, S. mekongi, or parasites not of the genus Schistosoma, immunoprecipitated fewer of the major S. mansoni or S. haematobium glycoproteins. Likewise, antibody immune responses of patients infected with the Oriental schistosomes (S. japonicum and S. mekongi) could not be differentiated. Only a few quantitative differences were noted between our S. mansoni egg glycoprotein extract and a standardized soluble egg antigen extract. This study provides an explanation for the extensive cross-reactivity observed in diagnostic assays which utilize various fractions of schistosomal egg extracts as the antigen.


In vitro inhibition of expression of virulence genes responsible for colonization and systemic spread of enteric pathogens using Bifidobacterium bifidum secreted molecules.
Enteric pathogens such as Salmonella enterica serovar Typhimurium and Enterohaemorrhagic Escherichia coli require an initial indispensable step of attachment or invasion of enterocytes before they can produce systemic disease and translocate to their target organs. Prevention of either of these steps will result in an avirulent state and limit their pathogenicity. In vitro tests demonstrated that molecules secreted by Bifidobacterium bifidum interfere with both attachment and invasion. The main regulatory genes controlling the virulence factors essential for these pathogenicity steps were efficiently down-regulated when treated with chromatographically separated B. bifidum cell free fractions as measured by reporter constructs and confirmed by RT-PCR. Moreover, the ability of both pathogens to colonize eukaryotic cells was significantly reduced, and the capacity of Salmonella to survive and multiply within macrophages was also diminished upon treatment with these bioactive molecules. These results indicate that probiotic Bifidobacteria strains may represent an effective alternative approach to control food-borne enteric pathogens.


Trends in mosquito species distribution modeling: insights for vector surveillance and disease control.
Species distribution modeling (SDM) has become an increasingly common approach to explore questions about ecology, geography, outbreak risk, and global change as they relate to infectious disease vectors. Here, we conducted a systematic review of the scientific literature, screening 563 abstracts and identifying 204 studies that used SDMs to produce distribution estimates for mosquito species. While the number of studies employing SDM methods has increased markedly over the past decade, the overwhelming majority used a single method (maximum entropy modeling; MaxEnt) and focused on human infectious disease vectors or their close relatives. The majority of regional models were developed for areas in Africa and Asia, while more localized modeling efforts were most common for North America and Europe. Findings from this study highlight gaps in taxonomic, geographic, and methodological foci of current SDM literature for mosquitoes that can guide future efforts to study the geography of mosquito-borne disease risk.


Temporal order of cognitive and functional loss in a nursing home population.
The order in which cognition and the ability to perform activities of daily living (ADLs) are lost in an institutionalized aged population was examined. Understanding the order of loss of function is important for preparing caregivers and planning of care. The conditional probabilities of the inability to perform activity A when there exists the inability to perform activity B were explored in secondary analyses of cross-sectional data describing 408 nursing home residents. Residents' abilities to perform ADLs were rated by nursing staff using Linn and Linn's Rapid Disability Rating Scale (RDRS-2); cognitive functioning was rated by social workers and nursing staff using a modified version of Reisberg et al.'s Brief Cognitive Rating Scale (BCRS, with 4 axes: orientation, concentration, recent memory, and past memory). The results regarding ADLs confirm previous findings of a natural order of loss of ability (from the one lost first to last): bathing, dressing, grooming, toileting, walking, and eating. The examination of order in the loss of concentration, recent memory, past memory, and orientation revealed that these seem to be lost concurrently when the cutpoint was 3 (i.e., relatively normal functioning vs. moderate and severe dementia). When the cutpoint was 6 (i.e., severe dementia vs. higher levels of functioning), the order that emerged was: recent memory, past memory, concentration, and orientation. Although there is a significant relationship between loss of ability to perform ADLs and stage of cognitive impairment, the loss of any specific ADL is not uniquely related to any one stage of cognitive deterioration in this diverse population. This may be explained by the high prevalence of disease in this institutionalized population, as exemplified by the 60% suffering from arthritis and the 17% suffering from neurological disorders other than dementia.


Influence of cadmium on the morphology and functionality of haemocytes in the compound ascidian Botryllus schlosseri.
In order to get insights into the effects of cadmium (Cd) on cell morphology and functions, we exposed haemocytes of the colonial ascidian Botryllus schlosseri to sub-lethal concentrations of CdCl(2). Results indicate that Cd hampers haemocyte spreading and phagocytosis in a dose-dependent way, through the alteration of the actin cytoskeleton. In addition, the metal decreases the stability of the internal membranes, as revealed by the Neutral Red assay. The fraction of cells showing positivity for the lysosomal enzyme acid phosphatase is also reduced in the presence of Cd, whereas the number of cells responsive to the Annexin-V assay and showing chromatin condensation increases, suggesting a metal-dependent induction of apoptosis in exposed cells. As Cd is a known cause of oxidative stress, the decrease in the percentage of cells positive to the assay for superoxide anion, observed at low Cd concentrations, is indicative of the synthesis of metal-chelating molecules, such as metallothioneins, whereas, the increase at high Cd concentrations suggests a depletion of the cell reducing redox potential.


[Issues and difficulties in the relationship between patients and caregivers in painful sickle cell vaso-occlusive crisis].
Sickle cell patients in acute pain situation experiment cognitive, behavioral and emotional changes that can accentuate their pain and disrupt communication with caregivers. On the other hand, caregivers have to face pain assessment difficulties and their own psychological reactions to their patient's pain. The gap between the patient's experience and caregiver's evaluation can lead to conflict and non-adherence treatment, and have a direct impact on the sickle cell disease prognosis. There is nothing inevitable about these phenomena, whose knowledge allows the action and opens up prospects for improving the management of sickle cell disease pain. This article is a narrative review updating the interactions between acute pain and some configurations, such as the inability to discern emotions, catastrophizing, post-traumatic stress or feeling ostracized. The overestimation of patient's addiction by caregivers also influences the pain itself. Open communication, as well as some treatments, medicated or not, a consistent institutional organization and a multidisciplinary approach altogether have an analgesic role by acting on pain cognitive and emotional components.


Depressive Symptoms and the Effectiveness of a Urate-Lowering Therapy in a Clinical Trial.
This ancillary study examined the impact of depressive symptoms on the effectiveness of a urate-lowering therapy in the context of a clinical trial. Participants included 67 adults (ages 18-40) with elevated blood pressure who were enrolled in a double-blind, randomized, crossover clinical trial evaluating the effectiveness of allopurinol (300 mg/d) versus placebo to decrease blood pressure. Depressive symptoms were measured at the beginning of each 4-week phase with the Center for Epidemiological Studies Depression scale (CESD-10). Serum urate (sUA) was assessed at the beginning and end of each treatment phase. Compliance to treatment was measured by having detectable oxypurinol levels. Linear regressions tested associations between depressive symptoms and change in sUA in each phase, adjusting for sex and race. Logistic regression predicted compliance from depressive symptoms. Participants had a mean age of 27 years and were 64% male and 39% African American. sUA levels decreased during the allopurinol treatment period but did not change during the placebo period. Higher depressive symptoms at pretreatment were associated with an attenuated urate-lowering response during the allopurinol phase (β = 0.24, p < 0.05), but had no effect on sUA changes during the placebo phase. Depressive symptoms were not associated with treatment compliance assessed by oxypurinol levels. Depressive symptoms were associated with reduced efficacy of allopurinol treatment for hyperuricemia in a clinical trial targeting hypertension. Studies evaluating the efficacy of urate-lowering therapies may benefit from screening for depressive symptoms.


Crystal structure of IRF-3 in complex with CBP.
Transcriptional activation of interferon beta (IFN-beta), an antiviral cytokine, requires the assembly of IRF-3 and CBP/p300 at the promoter region of the IFN-beta gene. The crystal structure of IRF-3 in complex with CBP reveals that CBP interacts with a hydrophobic surface on IRF-3, which in latent IRF-3 is covered by its autoinhibitory elements. This structural organization suggests that virus-induced phosphoactivation of IRF-3 triggers unfolding of the autoinhibitory elements and exposes the same hydrophobic surface for CBP interaction. The structure also reveals that the interacting CBP segment can exist in drastically different conformations, depending on the identity of the associating transcription cofactor. The finding suggests a possible regulatory mechanism in CBP/p300, by which the interacting transcription factor can specify the coactivator's conformation and influence the transcriptional outcome.


Resting-state oscillations reveal disturbed excitation-inhibition ratio in Alzheimer's disease patients.
An early disruption of neuronal excitation-inhibition (E-I) balance in preclinical animal models of Alzheimer's disease (AD) has been frequently reported, but is difficult to measure directly and non-invasively in humans. Here, we examined known and novel neurophysiological measures sensitive to E-I in patients across the AD continuum. Resting-state magnetoencephalography (MEG) data of 86 amyloid-biomarker-confirmed subjects across the AD continuum (17 patients diagnosed with subjective cognitive decline, 18 with mild cognitive impairment (MCI) and 51 with dementia due to probable AD (AD dementia)), 46 healthy elderly and 20 young control subjects were reconstructed to source-space. E-I balance was investigated by detrended fluctuation analysis (DFA), a functional E/I (fE/I) algorithm, and the aperiodic exponent of the power spectrum. We found a disrupted E-I ratio in AD dementia patients specifically, by a lower DFA, and a shift towards higher excitation, by a higher fE/I and a lower aperiodic exponent. Healthy subjects showed lower fE/I ratios (< 1.0) than reported in previous literature, not explained by age or choice of an arbitrary threshold parameter, which warrants caution in interpretation of fE/I results. Correlation analyses showed that a lower DFA (E-I imbalance) and a lower aperiodic exponent (more excitation) was associated with a worse cognitive score in AD dementia patients. In contrast, a higher DFA in the hippocampi of MCI patients was associated with a worse cognitive score. This MEG-study showed E-I imbalance, likely due to increased excitation, in AD dementia, but not in early stage AD patients. To accurately determine the direction of shift in E-I balance, validations of the currently used markers and additional in vivo markers of E-I are required.


A multi-modal diagnostic model improves detection of cardiac amyloidosis among patients with diagnostic confirmation by cardiac biopsy.
Timely recognition of cardiac amyloidosis is clinically important, but the diagnosis is frequently delayed. We sought to identify a multi-modality approach with the highest diagnostic accuracy in patients evaluated by cardiac biopsy, the diagnostic gold standard. Consecutive patients (N = 242) who underwent cardiac biopsy for suspected amyloidosis within an 18-year period were retrospectively identified. Cardiac biomarker, ECG, and echocardiography results were examined for correlation with biopsy-proven disease. A prediction model for cardiac amyloidosis was derived using multivariable logistic regression. The overall cohort was characterized by elevated BNP (median 727 ng/mL), increased left ventricular wall thickness (IWT; median 1.7 cm), and reduced voltage-to-mass ratio (median 0.06 mm/[g/m2]). One hundred and thirteen patients (46%) had either light chain (n = 53) or transthyretin (n = 60) amyloidosis by cardiac biopsy. A prediction model including age, relative wall thickness, left atrial pressure by E/e', and low limb lead voltage (<0.5 mV) showed good discrimination for cardiac amyloidosis with an optimism-corrected c-index of 0.87 (95% CI 0.83-0.92). The diagnostic accuracy of this model (79% sensitivity, 84% specificity) surpassed that of traditional screening parameters, such as IWT in the absence of left ventricular hypertrophy on ECG (98% sensitivity, 20% specificity) and IWT with low limb lead voltage (49% sensitivity, 91% specificity). Among patients with an advanced infiltrative cardiomyopathy phenotype, traditional biomarker, ECG, and echocardiography-based screening tests have limited individual diagnostic utility for cardiac amyloidosis. A prediction algorithm including age, relative wall thickness, E/e', and low limb lead voltage improves the detection of cardiac biopsy-proven disease.


Effect of manual soft tissue therapy on the pain in patients with chronic neck pain: A systematic review and meta-analysis.
To systematically evaluate the impact of manual soft tissue therapy (MSTT) on the degree of pain in patients with chronic neck pain (CNP). Trials included in the meta-analysis were identified by searching 5 English databases, including the PubMed, Embase, Cochrane Library, Web of Science and U.S. Clinical Trial Registry databases. The search was conducted with the subject terms neck pain, soft tissue treatment, massage, and myofascial release. We assessed the included trials using the Cochrane risk-of-bias tool. STATA statistical software version 16.0 was used for statistical analysis. Additionally, subgroup analysis and sensitivity analysis were performed to analyze the sources of heterogeneity and assess the stability of the research results. Begg's funnel plot and Egger's publication bias plot were used to assess potential publication bias. This systematic review included a total of 12 randomized controlled trials (566 patients in total). The participants were between 18 and 85 years old. Most of the included studies were of medium quality. This meta-analysis validated the effectiveness of MSTT in alleviating pain symptoms in patients with CNP (ES: 0.83; 95% CI: 1.15 to -0.51; P = 0.001). Egger's publication bias plot and Begg's funnel plot indicated that there may be potential publication bias. This meta-analysis found that MSTT has a significant effect on alleviating the pain of patients with CNP. In addition, the use of different pain measurement tools may influence effect of the intervention, but more clinical studies are needed in the future to determine the specific effect.


The relationship between rabbit semen characteristics and reproductive performance after artificial insemination.
The relationships between several rabbit buck semen traits, concerning either the ejaculate or the dose inseminated (volume, mass motility, pH, percentage of motile sperm (PMS), concentration, number of total and motile sperm per ejaculate and per insemination dose) and the reproductive performance of does was investigated in 839 inseminations involving 54 bucks and 111 does. Four genetic types were involved: INRA1601 strain (A), INRA2066 strain (B) and the two reciprocal crossbreds (AB and BA). The mating design was A x A, B x B, (AB or BA) x (AB or BA). Semen was diluted (1:9) and a constant volume of 0.5 ml was inseminated 2-4h after collection. Therefore, the total number of spermatozoa per dose was variable and proportional to the initial concentration. Mass motility significantly influenced the kindling rate. Taken separately, volume, PMS and concentration did not influence the kindling rate but their product, the number of motile sperm per ejaculate, did. Litter size (total born) was significantly influenced by concentration and all variables depending on it, particularly the number of total and motile sperm per dose. However, reproductive performances were predominantly influenced by the physiological status of the does at insemination (lactation stage and receptivity).


[The study of malocclusion of treatment priority index in Xi'an adolescent].
To evaluate the prevalence of malocclusion and orthodontic treatment priority in adolescent. 591 boys and 567 girls (aged 12 years old) were studied with their study models and the treatment priority index (TPI) were obtained. 7.03% adolescent had orthodontic treatments (TPI 1:21.33%, TPI 2:47.06%, TPI 3-TPI 5:31.61%). TPI is a valid tool to evaluate malocclusion and orthodontic treatment priority. It's very important to establish a regular examination system need for orthodontic treatment in school.


Decrease of miR-622 expression promoted the proliferation, migration and invasion of cholangiocarcinoma cells by targeting regulation of c-Myc.
To explore the mechanism of miR-622 in regulating the proliferation, migration and invasion of cholangiocarcinoma (CCA) cells. Quantitative real-time PCR was conducted to measure the expression of miR-622 and c-Myc in CCA tissues and cell lines. Protein level of c-Myc was measured by Western blot. The effect of miR-622 on cell proliferation, migration and invasion was analyzed by MTT assay and Transwell chamber migration assay. Luciferase reporter assay was performed to measure the effect of miR-622 on c-Myc. miR-622 expression was downregulated in both CCA tissues and cell lines, while c-Myc expression was uregulated. Overexpression of miR-622 in CCA cells was statistically correlated with a decrease of cell proliferation, migration and invasion, while inhibition of miR-622 made an inverse result. We also proved c-Myc was identified as a target gene of miR-622 in CCA. Moreover, we found overexpression of c-Myc can strengthen the effects of miR-622 on the proliferation, migration and invasion of CCA cells. Decrease of miR-622 promotes the proliferation, migration and invasion of CCA cells by directly targeting c-Myc.


Pelvic bone marrow sparing radiotherapy for cervical cancer: A systematic review and meta-analysis.
Concurrent chemo-radiotherapy in patients with locally advanced cervical cancer has significant hematologic toxicities (HT), leading to treatment disruption and affecting patient prognosis. We performed the meta-analysis to assess the clinical benefit of pelvic (active) bone marrow (BM) sparing radiotherapy. A systematic methodological search of six primary electronic databases was performed. This systematic review mainly assessed the differences in pelvic (active) BM dose-volume parameters (DVP), hematologic toxicity of pelvic (active) BM sparing versus non-sparing radiotherapy plans. The secondary objective was to explore optimal dose limitation regimens and evaluate other radiation-induced toxicities (gastrointestinal and urological toxicity (GT/UT)). Random-effects models were used for meta-analysis. Final 65 publications that met inclusion criteria were included in the meta-analysis and descriptive tables. Meta-analysis of mean pelvic BM-DVP differences showed that pelvic BM-V10,20,40,50 (Vx: volume of BM receiving ≥ X Gy) were reduced by -4.6% [95% CI: -6.6, -2.6], -10.9% [-13.2, -8.6], -7.3% [-9.5, -5.2] and -3.4% [-4.3, -2.4] in pelvic BM-sparing plans. Pelvic BM sparing radiotherapy decreased G2/3+ HT [odds ratio (OR) 0.31, (0.23, 0.41)/0.42, (0.28, 0.63)], without increasing GT [G2/3+: OR 0.76, (0.51, 1.14)/0.90, (0.47, 1.74)] and UT [G2/3+: OR 0.91, (0.57, 1.46)/0.54, (0.25, 1.17)]. Pelvic active BM sparing radiotherapy also reduced HT [G2/3+ HT: OR 0.42, (0.23, 0.77)/0.34, (0.16, 0.72)]. There were significant variations between publications in dose restriction regimens. The pelvic BM protection radiotherapy can decrease BM dose and HT. Moreover, it does not increase GT and UT. The clinical benefit of pelvic active BM protection needs to be further validated in randomized controlled trials.


[Personality tests done by the "Freiburg Personality Inventory" on patients after leg amputation (author's transl)].
47 patients after leg amputation were investigated by the "Freiburg Personality Inventory" (FPI). Results showed that the personality structure of these patients corresponds to that of the normal population.


Effect of PEA-OXA on neuropathic pain and functional recovery after sciatic nerve crush.
Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, the damage to peripheral nerve can cause a loss of sensory function and produces a persistent neuropathic pain. N-Acylethanolamines (NAEs) involve a family of lipid molecules existent in animal and plant, of which is N-palmitoylethanolamide (PEA) that arouses great attention owing to its anti-inflammatory, analgesic, and neuroprotective activities. The modulation of specific amidases for NAEs (and in particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA) could be a condition to preserve its levels. Here, we investigated, in a mice model of sciatic nerve crush, the effect of 2-pentadecyl-2-oxazoline (PEA-OXA) the oxazoline of PEA that reportedly modulates activity of NAAA. In this experimental model, the mice, following the sciatic nerve crush, were treated daily with PEA-OXA at a dose of 10 mg\kg for 14 days. Therefore, we evaluated the effects of PEA-OXA on the degree of injury, on the inhibition of neuropathic pain, and on the inflammatory process, as in the improvement of reparative processes and therefore in the restoration of locomotor function. Our results showed that PEA-OXA (10 mg/kg) treatment, daily, for 14 days after sciatic nerve crush, have an anti-inflammatory and neuroprotective effect and moreover have an analgesic protective effect on hypersensitivity, and improve the functional recovery after nerve crush. Therefore, treatment with PEA-OXA as a whole has shown a protective effect, which makes it a powerful candidate for the treatment of peripheral nerve injury and neuropathic pain.


The Use of Tn-Seq and the FiTnEss Analysis to Define the Core Essential Genome of Pseudomonas aeruginosa.
Transposon-insertion sequencing (Tn-Seq) allows for identification of bacterial genes and pathways essential for growth under a given condition. A transposon mutant is created by the stable and random integration of a transposable element into a genome of interest, followed by a period of outgrowth and selection for relative fitness on one or more growth media. By pooling hundreds of thousands of mutants, sequencing the transposon-genomic DNA junctions, and mapping sequencing reads to the genome, one can identify an abundance of reads in nonessential insertion regions and the absence of reads in essential regions and thus identify which genes are essential for a given growth condition. By performing this method iteratively across multiple strains and growth conditions, one can define a core essential genome for a species. Here, we describe this methodology in detail and its application for the species Pseudomonas aeruginosa, from generating mutants to the analysis of nonessential versus essential genes using the freely available software "FiTnEss".


Immediate post-operative pain in anterior cruciate ligament reconstruction surgery with bone patellar tendon bone graft versus hamstring graft.
Pain in the immediate post-operative period after anterior cruciate ligament (ACL) surgery, apart from an unpleasant experience for the patient, can act as a barrier for static quadriceps contractions and optimum execution of the initial rehabilitation protocol resulting in slow recovery and a later return to full function for a sportsperson. There is no report in the literature comparing pain in the immediate post-operative period after using the two most widely used autografts, bone patellar tendon bone (BPTB) graft and hamstring graft. The present study compared the visual analogue scale (VAS) pain score in the immediate post-operative period after arthroscopic ACL reconstruction with the BPTB and hamstring autografts. Both groups consisted of 50 patients each. The mean age of the BPTB and hamstring cohorts was 26.9 ± 7.3 years (age range 18-59 years) and 26.7 ± 9.0 years (age range 17-52 years), respectively. Unpaired t test was applied to compare pain scores between the BPTB and hamstring cohorts. In the present study, patients in the BPTB cohort showed higher mean pain scores across all the post-operative time intervals except at 6 h. However, the difference in the mean VAS pain score at post-operative 6, 12,18, 24, 36 and 48 h in the two groups was statistically not significant (p value of 1, 0.665, 0.798, 0.377, 0.651 and 0.215 at 6, 12, 18, 24, 36 and 48 h, respectively). Our study concludes that the arthroscopic ACL reconstruction with BPTB autograft and hamstring autograft is associated with similar pain in the immediate post-operative period. As a result, aggressive physiotherapy regime is not affected by the type of graft being used for ACL reconstruction, as the pain scores in the immediate post-operative period are similar for both techniques. Clinical Trials Registry-India, CTRI/2016/01/006502.


A simple colorimetric method for determination of serum triglycerides with lipoprotein lipase and glycerol dehydrogenase.
A simplified enzymic procedure to determine accurately serum triglycerides is described. Serum triglycerides are hydrolyzed completely to free fatty acids and glycerol by lipoprotein lipase from Pseudomonas fluorescens. The released glycerol is oxidized with glycerol dehydrogenase from Erwinia aroideae in the presence of NAD+, were the reduction of the enzyme-linked NAD+ is coupled to the reduction of nitro blue tetrazolium as a chromogenic indicator with phenazine methosulfate serving as an intermediate electron carrier of NADH. The absorbance at 570 nm is measured. The method requies only 20 microliter of serum and a 10-min incubation and is rapid and simple. The present method offers the measurement of a high concentration of triglyceride up to 1000 mg/dl serum. The results obtained by the present method show good correlation with those obtained by the glycerol kinase method (correlation coefficient, 0.989) or the acetylacetone method (correlation coefficient, 0.979). These results suggest that the proposed method will be utilized as a method or routine clinical test.


Non-steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease.
Pharmaceutical antagonism of the mineralocorticoid receptor (MR) can protect against organ damage caused by elevated aldosterone levels in patients experiencing heart failure (HF), chronic kidney disease (CKD), primary aldosteronism, and hypertension. While traditional steroid-based MR antagonists effectively reduce mortality rates and extend patient survival, their broad application has been limited by significant side effects, most notably hyperkalaemia. Recently, finerenone (BAY 94-8862) has emerged as a next-generation non-steroidal dihydropyridine-based MR antagonist designed to minimize off-target effects while maintaining potent efficacy. In this review, the outcomes of finerenone therapy in several diseases associated with MR activity are explored. The (pre-) clinical efficacy of finerenone is compared with that of traditional steroid-based MR antagonists. Finally, recent and ongoing clinical trials using finerenone to treat chronic HF, CKD, and diabetic nephropathy are discussed. Taken together, pre-clinical and clinical evidence suggests that finerenone may achieve equivalent organ-protective effects with reduced levels of electrolyte disturbance compared with traditional steroid-based MR antagonists. This supports further clinical development of finerenone for the treatment of cardiovascular and renal disease.


Comparison of three different phosphorescent methodologies in solution for the analysis of naphazoline in pharmaceutical preparations.
We present results from a comparative study of three proposed phosphorimetric methods for determination of naphazoline (NPZ) in solution. The first method is based on use of micelles to stabilize phosphorescence signals in solutions at room temperature (MS-RTP). The second is based on the use of a heavy atom salt and sodium sulfite as an oxygen scavenger to obtain room-temperature phosphorescence (HAI-RTP) in solution. The last method employs an optical sensor for NPZ based on the phosphorescent properties of the analyte on a solid sensor phase. The aim of this work was to compare time consumption, simplicity, sensitivity, selectivity, detection, and quantification limits for use of these three phosphorimetric methods to determine naphazoline in pharmaceutical preparations. The most simple, sensitive, and reproducible of the three methods for naphazoline analysis is the HAI-RTP method. Detection limits are 4.9, 1.7, and 9.4 ng mL(-1), respectively, for the MS-RTP, HAI-RTP, and optosensor methods.


Abdominal obesity and hydration status as protective factors against mortality in older adults: A prospective study.
The aim of this study was to assess the association between different anthropometric and body composition techniques for defining obesity status and to investigate their clinical implications in older hospitalized patients, both during their hospitalization and after discharge. This prospective study included patients ≥60 y of age. They were followed for 18 mo to assess mortality and hospital length of stay. Anthropometric measurements and body composition were evaluated, including body mass index (BMI), waist circumference, waist-to-height ratio, body fat percentage, total body water percentage, and muscle mass. These measurements are associated with prognosis and survival. A higher BMI, excessive body fat, higher total body water percentage, and abdominal obesity were associated with a lower risk for death (P < 0.05). Higher hydration levels were identified as an independent protective factor against mortality. Obesity, defined by body fat percentage, was associated with a shorter hospital stay (P < 0.05). The present study adds to the growing body of evidence supporting the existence of the obesity paradox in hospitalized older patients. Additionally, our novel finding reveals that higher levels of total body water percentage are associated with decreased odds of mortality. The study emphasizes the importance of considering other anthropometric measurements and body composition in addition to BMI, considering its limitations. These findings have important implications for health care providers when recommending changes in nutritional status for the older adult population.


Conducting and Lithiophilic MXene/Graphene Framework for High-Capacity, Dendrite-Free Lithium-Metal Anodes.
Li-metal anode is widely acknowledged as the ideal anode for high-energy-density batteries, but seriously hindered by the uncontrollable dendrite growth and infinite volume change. Toward this goal, suitable stable scaffolds for dendrite-free Li anodes with large current density (>5 mA cm-2) and high Li loading (>90%) are highly in demand. Herein, a conductive and lithiophilic three-dimensional (3D) MXene/graphene (MG) framework is demonstrated for a dendrite-free Li-metal anode. Benefiting from its high surface area (259 m2 g-1) and lightweight nature with uniformly dispersed lithiophilic MXene nanosheets as Li nucleation sites, the as-formed 3D MG scaffold showcases an ultrahigh Li content (∼92% of the theoretical capacity), as well as strong capabilities in suppressing the Li-dendrite formation and accommodating the volume changes. Consequently, the MG-based electrode exhibits high Coulombic efficiencies (∼99%) with a record lifespan up to 2700 h and is stable for 230 cycles at an ultrahigh current density of 20 mA cm-2. When coupled with Li4Ti5O12 or sulfur, the MG-Li/Li4Ti5O12 full-cell offers an enhanced capacity of 142 mAh g-1 after 450 cycles, while the MG-Li/sulfur cell delivers an improved rate performance, implying the great potential of this 3D MG framework for building long-lifetime, high-energy-density batteries.


Life's Mechanism.
The multifarious internal workings of organisms are difficult to reconcile with a single feature defining a state of 'being alive'. Indeed, definitions of life rely on emergent properties (growth, capacity to evolve, agency) only symptomatic of intrinsic functioning. Empirical studies demonstrate that biomolecules including ratcheting or rotating enzymes and ribozymes undergo repetitive conformation state changes driven either directly or indirectly by thermodynamic gradients. They exhibit disparate structures, but govern processes relying on directional physical motion (DNA transcription, translation, cytoskeleton transport) and share the principle of repetitive uniplanar conformation changes driven by thermodynamic gradients, producing dependable unidirectional motion: 'heat engines' exploiting thermodynamic disequilibria to perform work. Recognition that disparate biological molecules demonstrate conformation state changes involving directional motion, working in self-regulating networks, allows a mechanistic definition: life is a self-regulating process whereby matter undergoes cyclic, uniplanar conformation state changes that convert thermodynamic disequilibria into directed motion, performing work that locally reduces entropy. 'Living things' are structures including an autonomous network of units exploiting thermodynamic gradients to drive uniplanar conformation state changes that perform work. These principles are independent of any specific chemical environment, and can be applied to other biospheres.


Correction: Improvement in cardiac dysfunction with a novel circuit training method combining simultaneous aerobic-resistance exercises. A randomized trial.
[This corrects the article DOI: 10.1371/journal.pone.0188551.].


Acceptability ratings of tracheoesophageal speech.
Thirty-one naive listeners rated the intelligibility and acceptability of tracheoesophageal, esophageal, and normal laryngeal speech of 15 adult speakers. Intelligibility was measured using a multiple-choice word test while acceptability was rated on a seven-point equal-appearing interval scale. Judgments were made on the features of fluency, pitch/quality, speech rate, inflection, and overall acceptability. Tracheoesophageal speech was found not to differ significantly from normal speech in intelligibility, rate, and inflection, but was less acceptable for fluency, pitch/quality and overall acceptability. Tracheoesophageal speech was more acceptable than esophageal speech for all features measured.


Qualitative comparison of dietary choices and dietary supplement use among older adults with and without a history of colorectal cancer.
To explore colorectal cancer survivors' beliefs about diet, dietary supplements, health, and cancer in relation to beliefs of a similar group without colorectal cancer. In-depth, semistructured, open-ended interviews were used to examine perceptions. Twenty-two participants (10 colorectal cancer survivors and 12 from a comparison group) from the North Carolina Strategies for Improving Diet, Exercise, and Screening Study. Verbatim interview transcripts were coded and analyzed. Comparisons were made between colorectal cancer survivors and the comparison group. Three main themes emerged: the influence of significant life events on dietary change, concerns about contaminants in the food supply, and a lack of physician guidance in dietary supplement selection. The experience of colorectal cancer is significant and may lead to dietary change among some survivors, but these findings do not suggest that it is necessarily more influential than other life events. Participants sought to control diet (for coping or survival) and also felt that diet cannot be controlled (due to the contamination of the food supply). Although many lacked guidance from physicians about dietary supplements, they were comfortable making their own decisions to self-treat. Enhanced understanding of the themes that guide selection of diet and dietary supplements can provide a context for dietitians in practice and researchers conducting behavioral interventions.


Natural killer cells have an activated profile in early Parkinson's disease.
Immune dysregulation is heavily implicated in Parkinson's disease (PD) but the role of Natural Killer (NK) cells has not been well characterised. Accumulating evidence indicates the immune response peaks early in the disease, hence this study focused on characterising NK cells in recently diagnosed PD. PBMCs were obtained from PD cases (< 2 years duration) and age-matched controls and immunophenotyped using flow cytometry. We found an increased proportion and number of NK cells (CD3-CD56+), mature cytotoxic NK cells (CD3-CD16 + CD56dim), and NK cells expressing the activation marker, NKG2D. This implies NK cells are activated in the earliest stages of PD.


Investigation of micelles and anionic cyclodextrins as pseudostationary phases for the capillary electrophoresis separation of oligosaccharides derivatized with 2-amino-benzamide.
Oligomers of glucose and oligosaccharides released from glycoproteins were derivatized with 2-aminobenzamide. As this fluorophore imparts no charge to the oligosaccharides, several strategies were investigated to achieve capillary electrophoresis (CE) separation of both neutral and charged derivatized glycans. Micellar electrokinetic capillary chromatography (MEKC) with the addition of anionic surfactants was evaluated as a first approach: sodium dodecyl sulfate (SDS) produced the best separation of the oligoglucose fragments, where the migration was inversely related to their degree of polymerization. To demonstrate the applicability of this method for complex carbohydrate analysis, oligosaccharide mixtures derived from ribonuclease B (RNase B) and alpha-acid glycoprotein (alpha-AGP) were analyzed. A satisfactory separation for the high-mannose structures found in RNase B could be obtained, whereas charged oligosaccharides from alpha-AGP were poorly resolved. Cyclodextrin-modified CE was chosen as the second approach: the effect of the addition of sulfobutylether-beta-cyclodextrin (SBE-beta-CD) or sulfobutylether-gamma-cyclodextrin (SBE-gamma-CD) on the electrophoretic mobilities and resolution of neutral and charged oligosaccharides was then studied. Selectivity of sialylated structures could be further improved by using anionic cyclodextrins (CDs) instead of micelles. However, this latter approach failed to baseline-resolve the different high-mannose structures of RNase B. A successful separation of the complex mixture of oligosaccharides from alphaalpha-AGP was obtained with the addition of 4% of SBE-gamma-CD and triethylamine (TEA) in a phosphate buffer, pH 6.7.


Surfactant proteins in the diagnosis of fetal lung maturity. I. Predictive accuracy of the 35 kD protein, the lecithin/sphingomyelin ratio, and phosphatidylglycerol.
The concentration of the major surfactant protein with a molecular weight of 35 kD was determined in 469 amniotic fluid specimens from 284 pregnancies by the two-site simultaneous immunoassay with monoclonal antibodies. The predictive accuracy of the 35 kD protein was compared with that of the lecithin/sphingomyelin ratio and phosphatidylglycerol (the lung profile). Immature levels of 35 kD protein (less than 0.6 micrograms/ml) predicted 59% of all cases of respiratory distress syndrome (RDS) with an accuracy of 91%, and mature levels of 35 kD protein (greater than 3.0 micrograms/ml) predicted 68% of all infants who did not have RDS with an accuracy of 100%. The overall accuracy of the 35 kD protein in predicting the risk of developing respiratory distress syndrome was similar to that of the lung profile. In addition, testing with 35 kD protein improved the predictive value of an indeterminate lung profile (lecithin/sphingomyelin ratio of 1:1.9 and no phosphatidylglycerol) from 52% to 74%. The present results show that the lecithin/sphingomyelin ratio, phosphatidylglycerol, and 35 kD apoprotein have additive effects in improving the accuracy of the diagnosis of lung maturity.


Relationship between antitumor efficiency of photodynamic therapy with photoditasine and photoenergy density.
We studied the effect of photodynamic therapy with photoditasine at different protocols of photoenergy exposure on morphofunctional parameters of M-1 sarcoma. It was found that proliferative activity of tumor cells (evaluated by immunostaining for PCNA) nonlinearly decreases after exposure to 150, 300, and 600 J/cm2. The main form of cell death during the early period after photodynamic therapy was direct photocoagulation necrosis caused by destruction of sensitized cell structures and ischemic necrosis developing as a result of alteration of vascular network in the tumors. Photoenergy density was not essential for the intensity of induced apoptosis.


Non-viral gene delivery systems.
Non-viral gene delivery systems have the potential to create viable pharmaceuticals from nucleic acids. These DNA delivery systems contain lipids and/or cationic polymers. In order for these systems to be developed into commercial products, several barriers must be overcome. These include obstacles in manufacturing, formulation and stability. In vivo, problems of extracellular non-specific interactions and intracellular trafficking to the nucleus are also encountered. Recent progress has been made in overcoming these issues.


Meckel diverticulum in the pediatric population: Patient presentation and performance of imaging in prospective diagnosis.
To determine the most common presentations of Meckel diverticulum (MD) in children and the performance of imaging modalities in prospective diagnosis. A 28-year retrospective review was performed of children under 18 years of age with MD listed as a diagnosis on pathology and/or surgical reports. The medical record was reviewed to determine presenting clinical scenarios. All imaging performed for each case was reviewed. Seventy-six patients met inclusion criteria. Of the surgically removed MD, most presented with abdominal symptoms (n = 31, 41%); gastrointestinal (GI) bleeding (n = 15, 20%), or both abdominal symptoms and GI bleeding (n = 7, 9%). Twenty-nine percent of MD were discovered incidentally at surgery performed for other reasons. Of the symptomatic MD, only 31% were prospectively diagnosed. For patients with abdominal symptoms, CT had a sensitivity of 13% (3/24) while nuclear medicine (NM) scan had a sensitivity of 0% (0/2). For patients with GI bleed, CT had a sensitivity of 29% (2/7) and NM scan had a sensitivity of 71% (10/14). For patients with both abdominal symptoms and GI bleed, CT was 0% (0/2) and NM scan 75% (3/4) sensitive. MD as a cause of abdominal symptoms and gastrointestinal bleeding may be difficult to diagnose due to nonspecific presentations and nonspecific findings. Most prospectively diagnosed MD are on NM scan in patients with GI bleed with abdominal pain (sensitivity of >70%). CT is relatively insensitive for MD in all symptomatology groups (0 to 29%).


Frequency of and risk factors for symptomatic bone fractures in patients with systemic lupus erythematosus.
To study risk factors for symptomatic bone fractures in patients with systemic lupus erythematosus (SLE) and to compare the frequency of fractures between SLE patients and population controls. The study included 222 SLE patients [mean age 47.0 years, disease duration 13.1 years, 204 (92%) women] and 720 population controls living in the metropolitan area of Helsinki. The history of symptomatic bone fractures in SLE patients and controls was recorded by interview, and demographic and clinical data of SLE patients were obtained by interview, clinical examination, and chart review. A history of at least one symptomatic bone fracture was recorded in 93 (42%) of all 222 patients with SLE. The risk of any fracture in 204 women with SLE compared to controls was 1.8 [95% confidence interval (CI) 1.3-2.4] and fractures in the ankle, hip, and vertebral column were more common than in female controls, with odds ratios (ORs) of 2.0 (95% CI 1.1-3.7), 5.1 (95% CI 1.2-21.5), and 4.0 (95% CI 1.8-8.6), respectively. In 18 men with SLE, compared to male controls, no difference in the frequency of fractures was observed (OR 0.7, 95% CI 0.3-2.0). Risk factors for bone fractures in women with SLE were age (p = 0.008), comorbidity (p = 0.050), and the duration of corticosteroid use (p = 0.025). Symptomatic bone fractures, especially in the ankle, hip, and vertebral column, are common in women with SLE. Special attention should be paid to preventing fractures in elderly female patients with comorbidities and a long duration of corticosteroid use.


Genetic control of NADH dehydrogenase-1 and aromatic alcohol dehydrogenase-2 in hexaploid wheat.
The genetic control of NADH dehydrogenase-1 (NDH-1) and aromatic alcohol dehydrogenase-2 (AADH-2) was investigated in Triticum aestivum cv. Chinese Spring. Evidence was obtained that NDH-1 is active as a monomer and is encoded by genes located in the p arms of the homoeologous group 4 chromosomes. The NDH-1 gene loci located in 4Ap, 4Bp, and 4Dp were designated Ndh-A1, Ndh-B1, and Ndh-D1, respectively. Aadh-A2 was previously reported to be located in 6Aq; in this study, Aadh-B2 and Aadh-D2 were localized in 6Bq and 6Dq, respectively. Alcohol dehydrogenase-1 is expressed on AADH-2 zymograms; the presence of a contaminating aliphatic alcohol in one or more reagents is suggested as the probable cause of this phenomenon.


Serum lipoprotiens in four European communities: a quantitative comparison.
Serum lipid and lipoprotein concentrations have been measured in 985 men and women sampled from communities in London, Naples, Uppsala and Geneva. This was done to define normal ranges, detect inter-population differences, and relate such differences to levels of lipids in the major lipoprotein classes of plasma. Cholesterol and triglyceride concentrations showed substantial differences between the four populations; levels of these lipids showed parallel trends, which were attributable to differences in low density lipoprotein and very low density lipoprotein concentrations. By contrast, high density lipoprotein cholesterol concentrations showed little or no interpopulation differences. Geographical differences in serum triglyceride and cholesterol levels were not correlated with variation in the prevalence of obesity.


Clinical implications of serum C-reactive protein levels in malignant fibrous histiocytoma.
Paraneoplastic syndromes (PNSs) associated with mesenchymal tumors are uncommon. Previous reports sporadically described inflammatory PNSs with elevated serum C-reactive protein (CRP) levels and leukocytosis in patients with inflammatory malignant fibrous histiocytoma (MFH) of soft tissue; however, the relationship between other subtypes of MFH and PNS has not been extensively investigated. Forty-six patients with primary MFH of soft tissues who underwent radical surgery were retrospectively analyzed. These patients were divided into 2 groups according to preoperative serum CRP level: normal (<1.0 mg/dl) and elevated (> or = 1.0 mg/dl). The correlation between serum CRP level and several clinicopathologic factors was analyzed. Correlation between preoperative serum CRP level and metastasis-free and overall survival was also investigated by univariate and multivariate analyses. Elevated preoperative serum CRP levels were found in 65% of patients with a mean of 3.7 mg/dl. There were statistically significant relationships regarding tumor size, depth, histologic subtypes, grade, stage and metastatic rate among normal and elevated CRP groups (p < 0.001, p < 0.02, p < 0.005, p < 0.001, p < 0.001 and p < 0.05, respectively). When the tumor was removed, the elevated CRP level subsided into the normal range and other abnormal laboratory findings diminished in all cases. In 11/14 relapsed cases that showed elevated CRP preoperatively, the serum CRP level re-elevated with tumor relapse. The normal CRP group showed significantly more favorable prognosis than the elevated CRP group in metastasis-free and overall survival on univariate analysis (p < 0.02, p < 0.05, respectively). Patients with MFH frequently present with an inflammatory PNS, such as elevated serum CRP level, which can be a useful marker of disease activity and a valuable prognostic indicator.


Body fat loss induced by calcium in co-supplementation with conjugated linoleic acid is associated with increased expression of bone formation genes in adult mice.
The potential of conjugated linoleic acids (CLA) and calcium in weight management in animal models and human studies has been outlined, as well as their use to prevent bone loss at critical stages. In addition, it has been suggested that bone remodeling and energy metabolism are regulated by shared pathways and involve common hormones such as leptin. We have previously shown that supplementation with CLA and calcium in adult obese mice decreases body weight and body fat. The aim of the present study was to assess the effects of these two compounds on bone and energy metabolism markers on bone. Mice (C57BL/6J) were divided into five groups according to diet and treatment (up to 56 days): control (C), high-fat diet (HF), HF+CLA (CLA), HF+calcium (Ca) and HF with both compounds (CLA+Ca). At the end of treatment, bone formation markers were determined in plasma and expression of selected bone and energy markers was determined in tibia by quantitative polymerase chain reaction. Results show that CLA was associated with decreased tibia weight and minor impact on bone markers, whereas calcium, either alone or co-supplemented with CLA, maintained bone weight and promoted the expression of bone formation genes such as bone gamma-carboxyglutamate protein 2 (Bglap2) and collagen Iα1 (Col1a1). Furthermore, it had a significant effect on key players in energy metabolism, in particular leptin and adiponectin tibia receptors. Overall, in addition to the weight loss promoting properties of calcium, on its own or co-supplemented with CLA, our results support beneficial effects on bone metabolism in mice.


A compact 0.5 T MR elastography device and its application for studying viscoelasticity changes in biological tissues during progressive formalin fixation.
To develop a method of compact tabletop magnetic resonance elastography (MRE) for rheological tests of tissue samples and to measure changes in viscoelastic powerlaw constants of liver and brain tissue during progressive fixation. A 10-mm bore, 0.5-T permanent-magnet-based MRI system was equipped with a gradient-amplifier-controlled piezo-actuator and motion-sensitive spin echo sequence for inducing and measuring harmonic shear vibrations in cylindrical samples. Shear modulus dispersion functions were acquired at 200-5700 Hz in animal tissues at different states of formalin fixation and fitted by the springpot powerlaw model to obtain shear modulus μ and powerlaw exponent α. In a frequency range of 300-1500 Hz, unfixed liver tissue was softer and less dispersive than brain tissue with μ = 1.68 ± 0.17 kPa and α = 0.51 ± 0.06 versus μ = 2.60 ± 0.68 kPa and α = 0.68 ± 0.03. Twenty-eight hours of formalin fixation yielded a 400-fold increase in liver μ, 25-fold increase in brain μ, and two-fold reduction in α of both tissues. Compact 0.5-T MRE facilitates automated measurement of shear modulus dispersion in biological tissue at low costs. Formalin fixation changes the viscoelastic properties of tissues from viscous-soft to elastic-stiff more markedly in liver than brain. Magn Reson Med 79:470-478, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Mediation analysis reveals a sex-dependent association between ABO gene variants and TG/HDL-C ratio that is suppressed by sE-selectin level.
Previous investigations have revealed an association between the ABO locus/blood group and total cholesterol and inflammatory biomarker levels. We aimed to test the statistical association of ABO locus variants with lipid profiles and levels of thirteen inflammatory markers in a Taiwanese population. A sample population of 617 Taiwanese subjects was enrolled. Five ABO gene region polymorphisms were selected and genotyped. After adjusting for clinical covariates and inflammatory marker levels, the genetic-inferred ABO blood group genotypes were associated with sE-selectin level (P = 3.5 × 10(-36)). Significantly higher total and low-density lipoprotein cholesterol (LDL-C) levels were noted in individuals with blood group A (P = 7.2 × 10(-4) and P = 7.3 × 10(-4), respectively). Interestingly, after adjusting for sE-selectin level, significantly lower high-density lipoprotein cholesterol (HDL-C) level as well as higher triglyceride (TG) level and ratio of triglyceride to HDL-C (TG/HDL-C ratio) were noted in individuals with blood group A comparing to non-A individuals (P = 0.009, P = 0.004 and P = 0.001, respectively); these associations were also observed in the group A male subjects (P = 0.027, P = 0.001, and P = 0.002, respectively). Mediation analysis further revealed a suppression effect of sE-selectin level on the association between genetic-inferred ABO blood group genotypes and TG/HDL-C ratio in total participants (P = 1.18 × 10(-6)) and in males (P = 5.99 × 10(-5)). Genetic variants at the ABO locus independently affect sE-selectin level in Taiwanese subjects, while the association of ABO locus variants with TG/HDL-C ratio is suppressed by sE-selectin level in Taiwanese males. These results provided further evidence for the mechanism in the association of ABO blood groups with atherosclerotic cardiovascular diseases.


A microbiome study reveals the potential relationship between the bacterial diversity of a gymnastics hall and human health.
Currently, investigations on the microbiota of sports centers and related facilities have been carried out in some countries, which showed that Microsporum gypseum, Trichophyton mentagrophytes and T. tonsurans are important dermatoprotofungi. In China, some research on athletes and sports equipment between the fungal community and public health has made some interesting achievements. However, the bacterial group among them has not been reported. Therefore, The aim of this study was to uncover (I) gymnastic equipment is there potential pathogenic factors and (ii) is there any difference in the biomarker of bacterial in different types of gymnastic room? The samples were collected from the gymnastics halls of one university in western China and main sports equipment, including gymnastics carpets, moving barres, hoops and balls, as well as wall bars, parallel bars and horizontal bars. The 16S rDNA of all the samples was sequenced, and the analyses were performed using FaproTax, Bug base function prediction and Line Discriminant Analysis (LDA) Effect Size. A 16S rDNA sequence analysis revealed abundant bacterial species biodiversity on gymnasts and apparatuses from two gymnastics halls at a university in western China. An analysis using the FaproTax and Bugbase functional prediction platforms showed that there were some opportunistic pathogens on the athletes and equipment from the Rhythmic Gymnastics (RG) and Artistic Gymnastics (AG) halls, such as Staphylococcus and Corynebacteiaceae. Infectious agents associated with cancer induction and development, such as Ruminococcaceae, Veillonellaceae and Moraxellaceae, as well as microbial toxin producers with a potential impact on human health, were also detected. According to a line discriminant analysis (LDA effect size), the bacterial biomarker groups of the two gymnasiums were different at the phylum-genus level: for RG, Erysipelatoclostridium, Lachnospiraceae and Bacteroidales, while for AG, Rhizobiales. Based on the results of the investigation, we suggest that more comprehensive consideration should be given to indoor microbial biodiversity and related public health problems in school gymnasiums.


Deep CovDenseSNN: A hierarchical event-driven dynamic framework with spiking neurons in noisy environment.
Neurons in the brain use an event signal, termed spike, encode temporal information for neural computation. Spiking neural networks (SNNs) take this advantage to serve as biological relevant models. However, the effective encoding of sensory information and also its integration with downstream neurons of SNNs are limited by the current shallow structures and learning algorithms. To tackle this limitation, this paper proposes a novel hybrid framework combining the feature learning ability of continuous-valued convolutional neural networks (CNNs) and SNNs, named deep CovDenseSNN, such that SNNs can make use of feature extraction ability of CNNs during the encoding stage, but still process features with unsupervised learning rule of spiking neurons. We evaluate them on MNIST and its variations to show that our model can extract and transmit more important information than existing models, especially for anti-noise ability in the noisy environment. The proposed architecture provides efficient ways to perform feature representation and recognition in a consistent temporal learning framework, which is easily adapted to neuromorphic hardware implementations and bring more biological realism into modern image classification models, with the hope that the proposed framework can inform us how sensory information is transmitted and represented in the brain.


Long non-coding RNA MALAT1 modulates myocardial ischemia-reperfusion injury through the PI3K/Akt/eNOS pathway by sponging miRNA-133a-3p to target IGF1R expression.
The mechanism of myocardial ischemia-reperfusion injury (MIRI) is a complex pathophysiological process that can lead to poor patient outcomes. Although LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reported to be highly expressed in myocardial ischemia reperfusion (IR) injury, the specific mechanism remains largely unknown. This study aimed to elucidate the roles and possible mechanism of MALAT1 in myocardial IR injury. IR model was established in rats by ligation of the anterior descending artery in vivo, and H9c2 and HL-1 cells were treated by hypoxia/reoxygenation (HR) to construct the model in vitro. The small interfering RNA (siRNA) for MALAT1 and miR-133a-3p mimics, inhibitor was used to transfect the cells. The expression of MALAT1, miR-133a-3p in MIRI were evaluated using real-time quantitative polymerase chain reaction (qRT-PCR),immunohistochemistry (IHC) and western blot (WB). Relationships between MALAT1, insulin-like growth factor 1 receptor (IGF1R) with miR-133a-3p were confirmed by luciferase reporter assay. Annexin V-FITC/PI double-labeled flow cytometry, terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Cell Counting Kit-8 (CCK-8), serum creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were evaluated to examine the impact of MALAT1 on MIRI. Our results revealed that MALAT1 was highly expressed, while miR-133a-3p and IGF1R were repressed in IR and HR groups. Knockdown of MALAT1 alleviate the pro-apoptotic effect and myocardial injury in vitro and in vivo. Systematically, MALAT1 may serve as a sponge for miR-133a-3p to suppress IGF1R, which a direct target of miR-133a-3p, then inhibit the PI3K/Akt/eNOS survival pathway. Mechanistically, our study demonstrated that MALAT1 regulates PI3K/Akt/eNOS signaling via miR-133a-3p. In summary, these results suggest that MALAT1 and miR-133a-3p play important roles in MIRI. MALAT1 regulates miR-133a-3p /IGF1R axis. These results show light on the underlying mechanisms of MIRI and provide potential therapeutic targets for MIRI.


Sex Determination in Two Species of Anuran Amphibians by Magnetic Resonance Imaging and Ultrasound Techniques.
The objective of the present study was to evaluate whether gender determination in two amphibian species (Kaloula pulchra and Xenopus laevis) can be reliably carried out by means of magnetic resonance imaging (benchtop magnetic resonance imaging; BT-MRI) or ultrasound (high-resolution ultrasound; HR-US) techniques. Two species of healthy, sexually mature anurans have been used in the present study. Eight Kaloula (blind study) and six Xenopus were used as controls. Magnetic resonance imaging experiments were carried out on a low-field (1 Tesla) benchtop-MRI (BT-MRI) system. HR-US examination was performed with high-resolution equipment. Low-field BT-MRI images provided a clear and quantifiable identification of all the sexual organs present in both genders and species. The HR-US also allowed the identification of testes and ovaries in both species. Results indicate that BT-MRI allowed a very precise sex identification in both anuran species, although its use is limited by the cost of the equipment and the need for anesthesia. HR-US allowed an accurate identification of ovaries of both species whereas a precise identification of testes is limited by the ultrasonographer experience. The main advantages of this technique are the possibility of performing it without anesthesia and the higher availability of equipment in veterinary and zoo institutions.


The Design and Synthesis of Highly Branched and Spherically Symmetric Fluorinated Oils and Amphiles.
A new emulsifier design principle, based on concepts borrowed from protein science, is proposed. Using this principle, a class of highly branched and spherically symmetric fluorinated oils and amphiles has been designed and synthesized, for potential applications in the construction of fluorocarbon nanoparticles. The Mitsunobu reaction was employed as the key step for introducing three perfluoro-tert-butoxyl groups into pentaerythritol derivatives with excellent yields and extremely simple isolation procedures. Due to the symmetric arrangement of the fluorine atoms, each fluorinated oil or amphile molecule gives one sharp singlet (19)F NMR signal.


Managing plantation forests to provide short- to long-term supplies of wood to streams: a simulation study using New Zealand's pine plantations.
Riparian functions such as the recruitment of wood to streams take decades to recover after a clear-fell harvest to the stream edge. The implications of two sets of riparian management scenarios on the short- and long-term recruitment of wood to a hypothetical stream (central North Island, New Zealand) were compared through simulation modeling. In the first set (native forest buffer), a designated tree-less riparian buffer was colonized by native forest species after a pine crop (Pinus radiata) had been harvested to the stream bank. In the second set (pine to native forest buffer), native forest species were allowed to establish under the pine canopy in a designated riparian buffer. In general, the volume of wood was greater in streams with wider buffers (5-m to 50-m) and this effect increased with forest age (800 years). The pine to native forest buffer supplied more wood to the stream more quickly, and matched the long-term supply to the stream from the native forest buffer. For the native forest buffer, total wood volume was minimal for the first 70 years and then increased uniformly for the remainder of the simulation. In contrast, the pine to native forest buffer produced a bimodal response in total wood volume with the initial sharp peak at year 100 attributed to pine recruitment and a second more gradual peak lasting for the rest of the simulation, which was similar to levels in the native forest simulations. These results suggest that existing plantations could be an important source of wood to the stream during the first 100+ years of native forest development.


Neutrophil serine protease 4 is required for mast cell-dependent vascular leakage.
Vascular leakage, or edema, is a serious complication of acute allergic reactions. Vascular leakage is triggered by the release of histamine and serotonin from granules within tissue-resident mast cells. Here, we show that expression of Neutrophil Serine Protease 4 (NSP4) during the early stages of mast cell development regulates mast cell-mediated vascular leakage. In myeloid precursors, the granulocyte-macrophage progenitors (GMPs), loss of NSP4 results in the decrease of cellular levels of histamine, serotonin and heparin/heparan sulfate. Mast cells that are derived from NSP4-deficient GMPs have abnormal secretory granule morphology and a sustained reduction in histamine and serotonin levels. Consequently, in passive cutaneous anaphylaxis and acute arthritis models, mast cell-mediated vascular leakage in the skin and joints is substantially reduced in NSP4-deficient mice. Our findings reveal that NSP4 is required for the proper storage of vasoactive amines in mast cell granules, which impacts mast cell-dependent vascular leakage in mouse models of immune complex-mediated diseases.


Importance of emergency physicians as referral sources for academic medical centers. The Gallup Organization Healthcare Group.
To identify physician referral patterns and factors involved in the patient referral process. A telephone survey conducted on a systematic sample of physicians who referred at least one patient a month to a tertiary care center. A major southeastern tertiary care academic medical center. Self-identified emergency physicians, family physicians, general surgeons, internists, obstetrician-gynecologists, and pediatricians. None. Emergency physicians comprised 6% of the surveyed sample. Emergency physicians referred the largest number of patients each month to a tertiary care center (40 patients per month) compared with the other target specialists, who referred an average of 16 patients per month (P < .05). Specialty services most often requested by emergency physicians were internal medicine, trauma, and cardiology. Emergency physicians refer more patients to academic medical centers than any other specialty. Academic medical centers should target emergency physicians if they wish to increase their patient referral base.


The influence of secular trend for height on ascertainment and eligibility for growth hormone treatment.
Assessment of short stature in many instances is based on a comparison with the Centers for Disease Control's (CDC) growth curves. The secular trend for height may limit the utility of CDC data for contemporary populations. We investigate the effect of the secular trend on Australian and US populations. Describe CDC-defined height SDS distributions of contemporary populations for different ages and genders. Compare observed means and standard deviations (SDs) to expected values of 0 and 1. Compare frequency of individuals shorter than the CDC-1st centile to those shorter than 1st centile defined empirically from the contemporary population. Healthy Kids Queensland Survey 2006: 1686 boys, 1822 girls. Australian National Children's Nutrition and Physical Activity Survey 2007: 2415 boys, 2379 girls. US National Health and Nutrition Examination Survey 2005-2006: 2160 boys, 2118 girls. Means, SDs and normality of CDC-defined height SDS distributions. Frequency of individuals shorter than the CDC-1st centile and shorter than an empirically defined 1st centile. In Australia, means of CDC-defined height SDS distributions are always greater than 0 and the CDC-1st centile identifies only the shortest 0·5% of children. Means may vary with age and occasionally between genders in contemporary populations. Normality and SDs of 1 are retained. The secular trend has resulted in an underestimate of the number of Australian children eligible for GH treatment using the CDC-1st centile cut-off. Contemporary, local data should be used to construct standards. Using the 2nd CDC centile would approximate the 1st local centile until new standards are constructed. The secular trend does not account for the gender bias in GH therapy.


Efficacy of physiotherapy management on burnout syndrome amongst IT professionals during the COVID-19 pandemic.
Burnout is a state of emotional, physical, and mental exhaustion caused by excessive stress. Burnout weakens the energy of an individual which reduces productivity and leaves this individual helpless, hopeless, cynical, and resentful. Thus, an early diagnosis of this syndrome has to be done and ways to prevent the level of progression and complication of burnout syndrome has to be planned. To determine the efficacy of self-supervised Jacobson's relaxation technique along with Bhastrika Pranayama in reducing the level of burnout among the work-from-home IT professionals during the COVID-19 pandemic. Thirty participants with burnout syndrome were randomly divided into two groups (15 participants in each group) using random allocation. The experimental group received Jacobson's relaxation technique along with Bhastrika Pranayama, whereas the control group received diaphragmatic breathing exercises and chest expansion exercises. Pre-test and post-test values using Maslach Burnout Inventory were used to interpret the results. Data collected were analyzed statistically by the Wilcoxon Signed Rank Test. It shows that there is a significant reduction in the level of burnout in the experimental group when compared to the control group at a p-value of 0.001. From the results, it is concluded that Jacobson's relaxation technique along with diaphragmatic breathing exercises showed significant improvement in the reduction of burnout levels.


Cerebral asymmetry and behavioral lateralization in rats chronically lacking n-3 polyunsaturated fatty acids.
Anatomic and functional brain lateralization underlies hemisphere specialization for cognitive and motor control, and deviations from the normal patterns of asymmetry appear to be related to behavioral deficits. Studies on n-3 polyunsaturated fatty acid (PUFA) deficiency and behavioral impairments led us to postulate that a chronic lack of n-3 PUFA can lead to changes in lateralized behavior by affecting structural or neurochemical patterns of asymmetry in motor-related brain structures. We compared the effects of a chronic n-3 PUFA deficient diet with a balanced diet on membrane phospholipid fatty acids composition and immunolabeling of choline acetyltransferase (ChAt), as a marker of cholinergic neurons, in left and right striatum of rats. Lateral motor behavior was assessed by rotation and paw preference. Control rats had an asymmetric PUFA distribution with a right behavioral preference, whereas ChAt density was symmetrical. In deficient rats, the cholinergic neuron density was 30% lower on the right side, associated with a loss of PUFA asymmetry and behavior laterality. They present higher rotation behavior, and significantly more of them failed the handedness test. These results indicate that a lack of n-3 PUFA is linked with a lateral behavior deficit, possibly leading to cognitive disturbances.


The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men.
Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and a-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median (> or=1.301 micromol/l) was statistically significant for current smoking (OR 0.21; 95% CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06, 4.99), daily alcohol ingestion (OR 2.46; 95% CI 1.29, 4.67), each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95% CI 1.17, 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26, 1.99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0.70; 95% CI 0.53, 0.93) and each 10 micromol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12, 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and alpha-tocopherol may be strongly related.


Adsorption of basic dye from wastewater using raw and activated red mud.
Red mud, an industrial by-product generated during the processing of bauxite ore, was investigated as an inexpensive and effective adsorbent for the adsorption of methylene blue from aqueous solution. Chemical and heat treatments were applied to the raw red mud. The effects of contact time, adsorbent amount, pH, temperature and initial dye concentration were investigated. The adsorption isotherm and kinetics of the raw and activated red mud were studied. Freundlich, Temkin and Dubinin-Radushkevich isotherms were obtained using concentrations of methylene blue ranging from 10 to 70 mg/L. The results indicated that the Dubinin-Radushkevich model provides the best correlation of the experimental data. The adsorption rate data were analysed according to the pseudo-first order kinetic, pseudo-second order kinetic, intraparticle diffusion kinetic and Elovich kinetic models. The pseudo-second order kinetic was the best fit kinetic model for the experimental data.


Sample preparation for thermo-gravimetric determination and thermo-gravimetric characterization of refuse derived fuel.
Thermo-gravimetric analysis (TGA) is a useful method for characterizing fuels. In the past it has been applied to the study of refuse derived fuel (RDF) and related materials. However, the heterogeneity of RDF makes the preparation of small representative samples very difficult and this difficulty has limited the effectiveness of TGA for characterization of RDF. A TGA method was applied to a variety of materials prepared from a commercially available RDF using a variety of procedures. Applicability of TGA method to the determination of the renewable content of RDF was considered. Cryogenic ball milling was found to be an effective means of preparing RDF samples for TGA. When combined with an effective sample preparation, TGA could be used as an alternative method for assessing the renewable content of RDF.


A calcium-activated nuclease endogenous to Xenopus erythrocytes.
An endogenous nuclease is found in purified Xenopus erythrocyte nuclei. This enzyme is activated specifically by Ca2+ in the presence of which chromatin is digested into discrete fragments. Both 10 bp and 200 bp ladders are detected upon electrophoresis of DNA. This endogenous enzyme therefore resembles mammalian and chicken liver endonucleases.


Recruitment in Surgery and Interventional Radiology: Factors in Female Trainees' Specialty Decisions.
This study aims to identify factors influencing female medical students' decision-making about specialties, specifically surgery and interventional radiology (IR), in an effort to inform future recruitment and professional development strategies. An electronic survey was created to assess both qualitative and quantitative data. The survey was sent prior to a symposium for trainees interested in pursuing IR or surgery, held at University of Chicago (Chicago, IL) in February 2019. The 90 female trainees who registered were sent the survey, and 48 (53%) responded voluntarily. All respondents were female, 46% planned to pursue surgery or IR. Students pursuing surgery/IR were less concerned about being valued by their colleagues (p = 0.0073), being in charge of patients' lives (p = 0.0017), radiation exposure (p = 0.0171), chemical exposure (p = 0.0223), emotional stress (p = 0.0244), or shift work (p = 0.0045), compared to the nonsurgery/IR students. No differences were found in ranking of motivating factors, personal strengths or weaknesses, deciding factors, areas for seeking mentorship, or gender diversity. Top motivations among all respondents were intellectual rigor of medicine and becoming a mentor, while concerns were personal physical health, managing a career, pay equity, and gender-based biases. Students most often sought mentors and clerkship experience for making specialty decisions. They reported greatest strengths in empathy and resilience, and weaknesses in negotiating and public speaking. Female medical students planning to pursue surgery/IR expressed greater confidence in their contributions to patient care and lower concerns about workplace hazards. Regardless of specialty intent, female students shared scholarship motivations for a career in medicine, valued the role of mentorship, and expressed persistent concerns about gender discrimination, personal health, and skills-based weaknesses. Identifying factors influential in career decision-making is important in order to recruit and retain a more gender-diverse physician workforce.


Zirconium as a suitable reference element for estimating potentially toxic element enrichment in treated wastewater discharge vicinity.
The suitability of a reference element or normalizer used in assessing soil contamination levels using enrichment factor (EF) is important for soil quality assessment and monitoring. This study evaluated the results of using three reference elements Ti, Fe, and Zr for EF determination of Rb and Sr in soils within treated wastewater discharge vicinity, Central Botswana. The upper continental crust (UCC), world average values (WAV), and the local background values (LBV) were used in EF assessment of eight pedons. The elemental concentrations of the soils were determined with portable X-ray fluorescence (pXRF) analyzer. Relationships between the elements were strongly significant between Rb and Ti (r = 0.600, p < 0.01), Rb and Fe (r = 0.735, p < 0.01), Sr and Ti (r = 0.545, p < 0.01), and Sr and Fe (r = 0.841, p < 0.01). Second-level correlation analysis between contamination factor (CF) and EF levels showed Zr as the best reference element for Rb and Sr in the soils. Results from this study provide baseline knowledge necessary for contamination assessment and monitoring of soils with similar environmental conditions.