Comparison of conventional autoradiography with a new DNA enzyme immunoassay for the detection of hepatitis C virus-polymerase chain reaction amplification products.
The detection of HCV-PCR amplification products by DNA enzyme immunoassay (DEIA) was compared with conventional hybridization carried out with a 32P-labelled oligonucleotide probe. The detection limit of both methods was shown to be between 100 pg and 1 ng of amplicon. All serum samples of 40 HCV-seropositive patients were positive after PCR in autoradiography, but only 38 with the DEIA technique (sensitivity 95%). There were no false-positive reactions by either method. The advantage of the DEIA method was the fast and non-radioactive detection of HCV amplicons. DEIA combines the specificity of the hybridization event with the speed of an ELISA procedure and is suitable for HCV-PCR.


Alcoholic hepatitis: granulocyte chemotactic factor from Mallory body-stimulated human peripheral blood mononuclear cells.
The characteristic histopathological features of acute alcoholic hepatitis include hyaline degeneration of hepatic parenchymal cells (Mallory bodies), hepatocellular necrosis, and granulocyte infiltration of the liver. The chemotactic response of neutrophils to highly purified Mallory bodies was studied. Mallory bodies, per se, were not chemotactic for granulocytes, nor did they generate chemotactic factors when incubated with serum. However, a factor(s) chemotactic for both granulocytes and mononuclear cells was generated when Mallory bodies were incubated with mononuclear cells, both from patients with alcoholic hepatitis or from normal controls. It was concluded that Mallory bodies stimulate peripheral blood mononuclear cells to release a factor chemotactic for granulocytes and mononuclear cells. This factor may be important in the etiology of the cellular infiltration in the livers of patients with alcoholic hepatitis.


Metals and methylotrophy: Via global gene expression studies.
A number of minerals, such as copper, cobalt, and rare earth elements (REE), are essential modulators of microbial one-carbon metabolism. This chapter provides an overview of the gene expression study design and analysis protocols for uncovering REE-induced changes in methylotrophic bacteria. By interrogating relationships and differences in total gene expression induced by mineral micronutrients, a deeper understanding of gene regulation at a systems scale can be gained. With careful design and execution of RNA-sequencing experiments, thorough processing and assessment of read quality can be utilized to assess and adjust for possible biases. By ensuring only quality data are utilized in downstream processes, differential gene expression, overrepresented analyses, and gene-set enrichment analyses provide reliable and reproducible representation of pathways and functions which are being affected by changes in environmental conditions.


Anomalous blueshift of aperture resonance enabled by the loss of a thin film.
The substrate effects on aperture resonance have been widely studied because the resonance peak position is key for sensing, communications, and field enhancement applications. So far, the theoretical works have focused on the lossless infinite substrate case, which only explains the resonance peak redshift by the substrate index. The loss effect has not been investigated yet because lossy infinite substrate significantly reduces the aperture transmission. Therefore, this work studied the loss effect on aperture resonance via an analytic model of the transmission though slot antennas on a finite substrate. When the substrate thickness was very thin compared to the wavelength, the transmittance remained high even for a large imaginary part of the refractive index; furthermore, the developed model predicted a strong blueshift when this imaginary part exceeds the real part. Besides, the zero of the imaginary part of the coupling strength was crucial in determining the resonance frequency for both infinite and finite substrates. Thus, this study can contribute to the material characterization, label-free detection, and efficient design of active metamaterials.


Thymol regulates the functions of immune cells in the rat peritoneal cavity after l-arginine-induced pancreatitis.
The present study aimed to evaluate the protective action of thymol towards l-arginine-induced acute pancreatitis (AP) by studying the function of rat peritoneal immune cells. Rat peritoneal exudate cells (PECs), obtained 24 h after the injection of l-arginine (350 mg/100 g of b.w.), were evaluated for mitochondrial activity (MTT assay), adherence capacity (methylene-blue assay), and phagocyte enzyme activity (myeloperoxidase, MPO, assay). The activity of α-amylase and free MPO, as well as the concentration of reactive oxygen species (ROS, i.e. O2-), were determined in the peritoneal exudate fluid. Also, serum α-amylase activity determination and pancreatic tissue pathohistological analysis were performed. The administered thymol (50 and 100 mg/kg, per os) caused a significant decrease in the PEC mitochondrial activity and adherence capacity when compared with these functions of PECs isolated from rats with AP. A decrease in cellular MPO activity, as well as in the levels of ROS, α-amylase, and free MPO in peritoneal exudates was found in animals treated with thymol compared to the control animals with AP. Additionally, thymol administration prevented an increase in serum α-amylase activity, accompanied by the decrease in pancreatic tissue damage that follows l-arginine application. The present results showed that thymol exerts significant immunomodulatory properties and a potential to silence PEC functions in inflammatory conditions such as the AP induced by l-arginine.


Polysaccharides produced by Enterobacter cloacae induce apoptosis in cervical cancer cells.
The effects and possible mechanism of polysaccharides produced by Enterobacter cloacae (EPS) on cervical cancer cells (Hela and SiHa) were investigated in vitro in the current study. The results showed that supplementation of EPS inhibited the proliferation of HeLa and SiHa cells in a concentration- and time-dependent manner. In addition, the EPS also induced the apoptosis of the cervical cancer cells by changing the nuclear morphology and decreasing the mitochondrial membrane potential. Furthermore, the EPS-induced apoptosis was associated with the regulation of Bcl-2 family protein expression. In particular, the pro-apoptotic protein Bak-1 was increased and anti-apoptotic protein Bcl-2 was decreased with the increasing concentration at certain range of EPS. These results indicated that EPS might induce the apoptosis of cervical cancer cells through an intrinsic apoptotic pathway, and EPS may act as potent antitumor agents.


An unusual nucleolar ring-like structure in axotomized hamster facial motoneurons.
Structures consisting of connecting rings surrounding a fibrillar core were observed within nucleoli of developing normal and axotomized hamster facial motoneurons. A few appeared in the nucleoplasm, attached to coiled bodies. Their peculiar structure and temporal association with neuronal maturation may reflect a transient state of ribosomal RNA transcription.


[German Terminology of the Revised Atlanta Classification of Acute Pancreatitis: Glossary Based on the New German S3 Guideline on Acute, Chronic, and Autoimmune Pancreatitis].
The Atlanta classification published in 1992 was supposed to classify the severity and complications in acute pancreatitis with the goal of providing uniform terminology for clinicians and researchers. After continuous evolution, the revised Atlanta classification was published in 2012. In this updated classification, imaging aspects were better integrated and unclear terms were better defined. To date, this terminology for disease grading, severity, and local complications has been solely available in English. This prevented wide acceptance of the classification by the German-speaking medical community. Therefore, an expert team of the German Radiological Society translated the terms based on German medical literature. This translation was approved by consensus in the new S3 guideline meeting in February 2020 with an approval rate of 97.3 %. This manuscript explains the translated and approved German terminology of the revised Atlanta classification and offers additional imaging examples. KEY POINTS:: · The revised Atlanta classification allows correct definition of the grading and complication assessment of acute pancreatitis.. · An expert group translated the terms into the German language. The translation was approved by the S3 guideline committee for pancreatitis.. · Based on the new German S3 guideline for pancreatitis, the translated terms should be employed consistently.. CITATION FORMAT: · Schreyer AG, Seidensticker M, Mayerle J et al. German Terminology of the Revised Atlanta Classification of Acute Pancreatitis: Glossary Based on the New German S3 Guideline on Acute, Chronic, and Autoimmune Pancreatitis. Fortschr Röntgenstr 2021; 193: 909 - 918.


46,XX male syndrome with mullerianosis of the urinary bladder: A new clinical entity.
Müllerianosis of the urinary bladder is a rare entity characterized by the presence of an admixture of at least two types of müllerian tissue in the muscularis propria of the bladder. We report the case of a 43-year-old male patient presented for urological evaluation due to episodes of total gross hematuria. Physical examination revealed ambiguous external genitalia. Abdomiopelvic CT scan revealed a tumor at the level of the bladder floor. Transurethral resection of the bladder lesions was done and histopathological studie confirmed the diagnosis of müllerianosis. Karyotype analysis showed a 46 XX male syndrome.


ECG-derived cardiopulmonary analysis of pediatric sleep-disordered breathing.
The diagnosis of sleep-disordered breathing (SDB) and evaluation of sleep quality in the pediatric population is dependent on resource intensive attended polysomnography. An ECG-derived cardiopulmonary coupling sleep spectrogram (CPC) analysis previously described in adults can provide information about the severity of SDB and coupled interactions of sleep modulated autonomic drive and respiration. We hypothesized that CPC algorithm-derived metrics will correlate with nasal pressure-based apnea-hypopnea scoring in pediatric population. A total of 63 subjects (mean 6.2 years; range 2-12 years) were analyzed by both CPC and conventional nasal flow and desaturation scoring obtained during cardiorespiratory recordings. The characteristics of CPC indices and correlation with conventional SDB scoring were computed. High-frequency coupling (HFC), the CPC marker of stable sleep state, is reduced in proportion to SDB. The HFC durations are negatively correlated with the nasal flow-derived respiratory disturbance index (RDI), a CPC-derived RDI (CPC-RDI), and the 3% oxygen desaturation index (correlation coefficient -0.60, -0.78 and -0.54, respectively). CPC-RDI has a strong positive correlation with the conventional nasal-flow RDI (correlation coefficient 0.70). In this group with a mean nasal-flow RDI 36.1/h, the percentage of correct CPC diagnosis was 85.7% in total, 40% in the non-severe group (10 subjects, RDI <20/h) and 94.3% in the severe group (53 subjects, RDI >20/h). ECG-derived sleep spectrogram metrics are correlated with nasal flow-derived respiratory abnormality in pediatric SDB. In suitable clinical contexts, this method may have screening utility and possibly allow tracking of treatment effects, specifically in the children with severe SDB.


A model to study cell injury: morphological changes of the proximal tubule of the rat kidney during ischemia and during recovery from ischemic injury in vivo.
Studies on structural cell changes as a function of ischemia time and studies on the recovery process of ischemically injured cells have implications for our general understanding of the features of cellular reaction to injury. For this reason a model was worked out to follow the morphological changes taking place in the proximal tubule of the rat kidney during ischemia and during recovery from an ischemic episode. The pars convoluta and the pars recta of the proximal tubule were examined separately and compared with one another.


Complete genome sequence of Peptoniphilus sp. strain ING2-D1G isolated from a mesophilic lab-scale completely stirred tank reactor utilizing maize silage in co-digestion with pig and cattle manure for biomethanation.
The bacterium Peptoniphilus sp. strain ING2-D1G (DSM 28672), a mesophilic and obligate anaerobic bacterium belonging to the order Clostridiales was isolated from a biogas-producing lab-scale completely stirred tank reactor (CSTR) optimized for anaerobic digestion of maize silage in co-fermentation with pig and cattle manure. In this study, the whole genome sequence of Peptoniphilus sp. strain ING2-D1G, a new isolate potentially involved in protein breakdown and acidogenesis during biomass degradation, is reported. The chromosome of this strain is 1.6Mb in size and encodes genes predicted to be involved in the production of acetate, lactate and butyrate specifying the acidogenic metabolism of the isolate.


Metastability, instability, and state transition in neocortex.
Mesoscopic patterns of neural activity were sought in multichannel EEGs of rabbits that were trained to respond to conditioned stimuli (CSs) in visual, auditory and somatic modalities. Spatiotemporal patterns were sought of oscillations in the beta and gamma ranges. The techniques required for preprocessing EEGs in search of global patterns were diametrically opposed to those needed for localization of modular EEG signals. Frames were found in the form of intermittent spatial patterns of phase and amplitude modulation (AM and PM) of carrier waves in beta and gamma ranges that served to classify EEG frames with respect to CSs. A model based on the intentional action-perception cycle is proposed to complement the information processing model.


Costimulatory signals potently modulate the T cell inhibitory capacity of the therapeutic CD11a antibody Efalizumab.
The therapeutic CD11a antibody Efalizumab interferes with psoriasis pathogenesis by blocking T cell activation and migration. We have performed a detailed analysis on its effects during the activation of human T cells and found that the capability of Efalizumab to inhibit proliferation and cytokine production of T cells critically depends on the quality and quantity of costimulatory signals. Efalizumab potently inhibited the proliferation and cytokine production of human T cells costimulated via ICOS, OX40, CD27 or 4-1BB, but did not significantly inhibit T cells that received stimuli via CD2 or CD28. The capacity of CD2 and CD28 signals to interfere with the T cell inhibitory effects of Efalizumab was also observed upon stimulation of T cells with allogeneic DC. Furthermore, studies with T cells from psoriasis patients indicated that Efalizumab therapy induces inhibition of T cell responses that can be reverted by CD2 or CD28 signals.


Agreement between cardiac output measurements by pulse wave analysis using the Pressure Recording Analytical Method and transthoracic echocardiography in patients with veno-venous extracorporeal membrane oxygenation therapy: An observational method comparison.
Measuring cardiac output (CO) is important in patients treated with veno-venous extracorporeal membrane oxygenation (vvECMO) because vvECMO flow and CO need to be balanced. Uncalibrated pulse wave analysis with the Pressure Recording Analytical Method (PRAM) may be suitable to measure CO in patients with vvECMO therapy. To assess the agreement between CO measured by PRAM (PRAM-CO; test method) and CO measured by transthoracic echocardiography (TTE-CO; reference method). A prospective observational method comparison study. The ICU of a German university hospital between March and December 2021. Thirty one adult patients with respiratory failure requiring vvECMO therapy: 29 of the 31 patients (94%) were treated for COVID-19 related respiratory failure. PRAM-CO and TTE-CO were measured simultaneously at two time points in each patient with at least 20 min between measurements. A radial or femoral arterial catheter-derived blood pressure waveform was used for PRAM-CO measurements. TTE-CO measurements were conducted using the pulsed wave Doppler-derived velocity time integral of the left ventricular outflow tract (LVOT) and the corresponding LVOT diameter. PRAM-CO and TTE-CO were compared using Bland-Altman analysis and the percentage error (PE). We defined a PE of <30% as clinically acceptable. Mean ± SD PRAM-CO was 6.86 ± 1.49 l min -1 and mean TTE-CO was 6.94 ± 1.58 l min -1 . The mean of the differences between PRAM-CO and TTE-CO was 0.09 ± 0.73 l min -1 with a lower 95% limit of agreement of -1.34 l min -1 and an upper 95% limit of agreement of 1.51 l min -1 . The PE was 21%. The agreement between PRAM-CO and TTE-CO is clinically acceptable in adult patients with vvECMO therapy.


Identification of a variant HLA-A*3401 allele, A*340102, in an educational DNA typing sample.
A*340102 was first identified in an ASEATTA Educational DNA typing sample, which typed as A*3401, 3401variant. The variant differs from A*3401 by a single silent substitution in exon 2 at nucleotide 309, codon 79 (GGG-->GGT).


Long-term outcome of Lyme disease in children given early treatment.
Sixty-three patients treated with appropriate antimicrobial therapy between 1985 and 1990 for physician-documented erythema migrans were identified. A telephone interview program 1 to 6 years after the initial episode of Lyme disease revealed that none of the patients had evidence of carditis, arthritis, or neurologic complications attributable to Lyme disease. A new episode of erythema migrans was reported in 7 (11%) of the patients 1 to 4 years after the initial episode.


[Injuries of the cervical spine and spinal cord in patients with ankylosing spondylitis--diagnosis using magnetic resonance imaging].
Magnetic resonance (MR) imaging results in 8 from 14 ankylosing spondylitis patients treated of traumatic cervical spine and spinal cord injuries are presented. Focal changes within spinal cord were most common among complications (62%), epidural hematoma was found in 50% of cases. Neurological status has worsened in patients with post-traumatic spinal cord pathology.


[Promotion of next generation primary care physicians: initiatives in the university training of medical students].
There is, and will be a serious shortage of young primary care physicians in Germany. Initiatives at medical faculties focusing on primary care may increase the recruitment of young primary care physicians. The present report describes national and international university initiatives, as well as programs for the recruitment of primary care physicians, and reports on their evaluation. We searched medical data bases, journals and the internet using corresponding key words in the sense of a pragmatic review article. We also contacted experts who were questioned on this topic. Initiatives for increasing the recruitment of young general practitioners were identified at nine medical faculties in Germany. The underlying hypothesis of the existing programs is that the decision to become a primary care physician depends on the time point, extent and quality of the training at medical school. The decisive limitation of existing programs is that they have been sparsely evaluated. The available results from evaluations consistently indicate quite large positive effects on the recruitment rates; however, the underlying study designs are highly prone to bias. The identified initiatives can be grouped into three different models: (1) postgraduate studies, (2) specialized curricula for selected students with high interest in primary care and (3) longitudinal integration of primary care teaching in the obligatory curriculum. Different aspects, such as selection of the curricular model, definition of content, reimbursement of personnel and material expenses as well as evaluation are relevant to the planning and implementation of such initiatives.


Rewiring of chromatin state and gene expression by transposable elements.
Transposable elements form a major fraction of the genome in various eukaryotic species. Although deleterious effects of transpositions within the genome have been reported, recent findings suggest that transposable elements can function as novel regulatory elements to fine-tune gene expression. Transposable elements can impact the chromatin state through processes such as heterochromatin formation, enhancer-promoter interactions, and chromatin boundary formation, mainly because of the functions of chromatin-based pathways that regulate the expression of transposable elements via DNA methylation and repressive histone modification. Therefore, transposable elements can rewire the chromatin state and gene expression depending on their insertions. Here, we review the findings that reveal the role of transposable elements as modifiers of the chromatin state and gene expression as well as the molecular mechanisms capable of inducing these changes.


Simulating the changes in carbon structure during the burn-off process.
Using a simple energetic criterion, we modelled the process of activation of 'soft' activated carbons. Eighteen carbon samples, differing in degree of graphitisation, and obtained using Molecular Dynamics annealing of an amorphous carbon precursor were studied. For all samples, the geometric pore size distribution was calculated using the method proposed by Bhattacharya and Gubbins. Adsorption isotherms for Ar at 87 K were simulated and analysed using different approaches widely applied in adsorption science (α(s), DA, APD, ND, BET). It is shown that our approach leads to similar changes in microporosity (with the rise in carbon burn-off) to those observed in real experiments. Moreover, the conclusions about the reality of popular methods of carbon porosity characterisation are given.


Patient-Reported Experience and Outcome Measures in People Living with Diabetes: A Scoping Review of Instruments.
Diabetes mellitus is a global public health concern, with over 463 million people living with this chronic disease. Pathology complexity, management difficulty, and limited participation in care has resulted in healthcare systems seeking new strategies to engage people living with diabetes. Patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) were developed to address the gap between the healthcare system expectation and patient preference. This study aimed to review the existing literature on PREMs and PROMs specific to type 1 and 2 diabetes, and report the dimensions report the dimensions they have measured. A scoping review was conducted from January 1985 to March 2020 of six databases, MEDLINE, EMBASE, PsycINFO, CINHAL, Scopus, and BiblioPro, to identify PREM and PROM instruments specific for type 1 and 2 diabetes. Overall, 34 instruments were identified, 32 PROMs and two PREMs. The most common instrument included outcomes related to quality of life at 44% (n = 15), followed by satisfaction (whether with treatment, device, and healthy habits) at 26% (n = 9). Furthermore, instruments regarding personal well-being accounted for 15% (n = 5). For instruments that measure experiences of persons with diabetes, there were two scales of symptoms, and one related to the attitude patients have toward the disease. Diabetes-specific validated instruments mainly focus on quality of life, education, and treatment, and sometimes overlap each other, in their subscales and assessment dimensions. Constructs such as cultural and religious beliefs, leisure, and work life may need more attention. There appears to be a gap in instruments to measure experiences of individuals who "live with diabetes" and seek to lead a "normal life."


Loss of natural dentition: multi-level effects among a geriatric population.
To quantify the impact of edentulousness on residual ridge volume, denture stomatitis (DS), as well as oral health behaviours among geriatric denture-wearers. Residual ridge resorption (RRR) is the primary intraoral complication of complete edentulism, but individual variation among geriatric patients has been observed. Data collection relied upon a 10-year retrospective chart review of all complete denture-wearing geriatric patients presenting at the Removable Prosthodontics Clinic, Dental School of Athens, between 1993 and 2002. Analyses relied on descriptive, bivariate, and multivariate methods based on ordinal logistic regression. A total of 873 records of geriatric patients (age mean = 72; median = 70; range = 65-95) comprised our analytical sample. Subjects' mean (SD) time since edentulation was 7.7 (10.2) years. Eleven percent were diagnosed with temporomandibular disorder (TMD). While 28% of patients reported cleaning their dentures at least daily, 6% presented with denture stomatitis (DS). Each added year of edentulism increased the odds of mandibular RRR: OR (95% CI) = 1.05 (1.03, 1.07). Nightly denture wear was the strongest risk factor for DS. Finally, independent of age and sex, each year of being edentulous increased the odds of presenting with TMD: OR (95% CI) = 1.03 (1.01, 1.05). Time since edentulation was strongly associated with mandibular but not maxillary RRR, as well as TMD development.


Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon.
Genetic mutations involving oncogenes and tumor-suppressor genes occur in carcinogenesis, and may affect biologic behavior of neoplasms. In this study, we analyzed the prognostic value of mutational analysis in colon carcinoma. Archival pathology specimens from 70 consecutive patients, resected for stage III colon carcinoma, were analyzed for point mutations by amplification and direct sequencing of exons from the K-ras-2 and the TP53 genes (topographic genotyping). Mutations were compared with adverse histopathologic features (poor differentiation, vascular and lymphatic invasion, mucin production) as prognostic markers. Five-year survival was 75% in patients with nonmutated lesions, significantly lower (21%) with TP53 mutations (P = 0.01), and intermediate with K-ras-2 only (45%) or both K-ras-2 and TP53 mutations (36%). A TP53 mutation carried the highest relative risk of death (2.39; 95% confidence interval, 1.29 to 4.42; P = 0.006). There was an additive effect on the risk of death between TP53 mutations and adverse histopathologic features. The information derived from mutational analysis is creating new prognostic variables that may play a role in the choice of therapy for colorectal carcinoma.


GRP78(BiP) facilitates the cytosolic delivery of anthrax lethal factor (LF) in vivo and functions as an unfoldase in vitro.
Anthrax toxin is an A/B bacterial protein toxin which is composed of the enzymatically active Lethal Factor (LF) and/or Oedema Factor (EF) bound to Protective Antigen 63 (PA63) which functions as both the receptor binding and transmembrane domains. Once the toxin binds to its cell surface receptors it is internalized into the cell and traffics through Rab5- and Rab7-associated endosomal vesicles. Following acidification of the vesicle lumen, PA63 undergoes a dynamic change forming a beta-barrel that inserts into and forms a pore through the endosomal membrane. It is widely recognized that LF, and the related fusion protein LFnDTA, must be completely denatured in order to transit through the PA63 formed pore and enter the eukaryotic cell cytosol. We demonstrate by protease protection assays that the molecular chaperone GRP78 mediates the unfolding of LFnDTA and LF at neutral pH and thereby converts these proteins from a trypsin resistant to sensitive conformation. We have used immunoelectron microscopy and gold-labelled antibodies to demonstrate that both GRP78 and GRP94 chaperones are present in the lumen of endosomal vesicles. Finally, we have used siRNA to demonstrate that knock-down of GRP78 results in the emergence of resistance to anthrax lethal toxin and oedema toxin action.


Effect of geometrical optimization on the treatment volumes and the dose homogeneity of biplane interstitial brachytherapy implants.
The isodose distributions of HDR stepping source brachytherapy implants can be modified by changing dwell times and this procedure is called optimization. The purpose of this study is to evaluate the effect of geometrical optimization on the brachytherapy volumes and the dose homogeneity inside the implant and to compare them with non-optimized counterparts. A set of biplane breast implants consisting of 84 different configurations have been digitized by the planning computer and volumetric analysis was performed for both non-optimized and geometrically optimized implants. Treated length (TL), treated volume (V100), irradiated volume (V50), overdose volume (V200) and quality index (QI) have been calculated for every non-optimized implant and compared to its corresponding geometrically optimized implant having a similar configuration and covering the same target length. The mean TL was 74.48% of the active length (AL) for non-optimized implants and was 91.87% for optimized implants (P < 0.001). The mean QI was 1.83 for non-optimized implants and 2.17 for optimized implants (P < 0.001). The mean V50/V100 value was 2.71 for non-optimized implants and 2.65 for optimized implants (P < 0.001) and the mean V200/V100 value was 0.09 for non-optimized implants and 0.10 for optimized implants (P < 0.001). By performing geometrical optimization it is possible to implant shorter needles for a given tumour to adequately cover the target volume with the reference isodose and thus surgical damage is reduced. The amount of healthy tissues outside the target receiving considerable radiation is significantly reduced due to the decrease in irradiated volume. Dose homogeneity inside the implant is significantly improved. Although there is a slight increase of overdose volume inside the implant, this increase is considered to be negligible in clinical applications.


Intrinsic variability of latency to first-spike.
The assessment of the variability of neuronal spike timing is fundamental to gain understanding of latency coding. Based on recent mathematical results, we investigate theoretically the impact of channel noise on latency variability. For large numbers of ion channels, we derive the asymptotic distribution of latency, together with an explicit expression for its variance. Consequences in terms of information processing are studied with Fisher information in the Morris-Lecar model. A competition between sensitivity to input and precision is responsible for favoring two distinct regimes of latencies.


Antimicrobial susceptibilities of Staphylococcus aureus isolated from animal and human sources in Brazil.
The susceptibilities of 760 Staphylococcus aureus strains isolated from animal infections (400), human infections (300) and healthy human carriers (60) to seven antibiotics were determined by an agar dilution technique. The isolates from human infections were more resistant to a wider spectrum of antibiotics than were the strains from animal infections and healthy human carriers. Amikacin and gentamicin were the most active drugs against all groups of strains.


Branching Out: Finding Success in New Areas of Practice.
In recent years, researchers and practitioners in behavior analysis have called for expanding the application of the science to new, socially relevant areas. The authors of this article work in the areas of applied animal behavior and organizational behavior management, and we are often asked for guidance and mentoring to help behavior analysts transition into our domains. Here, we offer actionable guidance for bridging the gap between behavior analysis graduate training and career paths that are not yet common for behavior analysts. Working in new practice areas involves a great deal of problem solving without much support. Thus, obtaining high-quality, in-depth training in behavior analysis is essential. We recommend building competence in a new area of practice by finding a mentor or community of practice and then seeking paid employment in that area as soon as possible. Finally, when one begins to work in a new area, it is essential to be realistic and humble. We offer practical advice for implementing each of these suggestions.


In vivo Leukemogenesis Model Using Retrovirus Transduction.
Various genetic alterations such as chromosomal translocation cause leukemia. For examples, gene rearrangements of the mixed-lineage leukemia (MLL) gene generate MLL fusion genes, whose products are potent oncogenic drivers in acute leukemia. To better understand the mechanism of disease onset, several murine leukemia models using retroviral gene transduction, xenograft, or Cre-mediated chromosomal translocation have been developed over the past twenty years. Particularly, a retroviral gene transduction-mediated murine leukemia model has been frequently used in the leukemia research field. Here, we describe the detailed protocol for this model.


Translation and Validation of the Thai Version of the Nasal Obstruction Symptom Evaluation (NOSE) Scale.
The Nasal Obstruction Symptom Evaluation (NOSE) was developed to evaluate subjective outcomes of patients with deviated nasal septum and symptomatic nasal obstruction. Considering the differences in individuals' cultural, cross-cultural translation, adaptation, and validation of the instrument are necessary. The current study aimed to translate and validate the Thai version of the NOSE Questionnaire for patients with nasal septum deviation. A single-center prospective instrument validation study. Thai tertiary referral center. The study was conducted to translate and adapt the original English version of the NOSE to Thai. After translating, psychometric testing was conducted. The primary outcomes were validity (content, construct, and discriminant), reproducibility (test-retest procedure), and internal consistency (reliability). A total of 105 participants, of which 46 were patients with nasal airway obstruction and 59 were healthy asymptomatic volunteers, were enrolled in this study. The Thai-NOSE was found to be adequate for all tested psychometric properties with high internal consistency (Cronbach's α = .942), and to discriminate accurately between patients and healthy controls. The interitem and item-total correlations indicated a related construct among all items. A high level of reproducibility of the questionnaire was obtained in the test-retest procedure for each item (γ = 0.898). The initial test and retest scores indicated adequate reproducibility. The Thai-NOSE questionnaire is a reliable instrument with appropriate psychometric properties for assessing the severity and impact of nasal airway obstruction in patients with nasal septum deviation.


Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians.
Genome-wide association studies in Europeans and Asians have identified numerous variants in the transmembrane protease serine 6 (TMPRSS6) and transferrin (TF) genes that are associated with changes in iron status. We sought to investigate the effects of common TMPRSS6 and TF gene SNPs on iron status indicators in a cohort of healthy Africans from rural Gambia. We measured iron biomarkers and haematology traits on individuals participating in the Keneba Biobank with genotype data on TMPRSS6 (rs2235321, rs855791, rs4820268, rs2235324, rs2413450 and rs5756506) and TF (rs3811647 and rs1799852), n = 1316. After controlling for inflammation, age and sex, we analysed the effects of carrying either single or multiple iron-lowering alleles on iron status. TMPRSS6 rs2235321 significantly affected plasma hepcidin concentrations (AA genotypes having lower hepcidin levels; F ratio 3.7, P = 0.014) with greater impact in individuals with low haemoglobin or ferritin. No other TMPRSS6 variant affected hepcidin. None of the TMPRSS6 variants nor a TMPRSS6 allele risk score affected other iron biomarkers or haematological traits. TF rs3811647 AA carriers had 21% higher transferrin (F ratio 16.0, P < 0.0001), 24% higher unsaturated iron-binding capacity (F ratio 12.8, P < 0.0001) and 25% lower transferrin saturation (F ratio 4.3, P < 0.0001) compared to GG carriers. TF rs3811647 was strongly associated with transferrin, unsaturated iron-binding capacity (UIBC) and transferrin saturation (TSAT) with a single allele effect of 8-12%. There was no association between either TF SNP and any haematological traits or iron biomarkers. We identified meaningful associations between TMPRSS6 rs2235321 and hepcidin and replicated the previous findings on the effects of TF rs3811647 on transferrin and iron binding capacity. However, the effects are subtle and contribute little to population variance. Further genetic and functional studies, including polymorphisms frequent in Africa populations, are needed to identify markers for genetically stratified approaches to prevention or treatment of iron deficiency anaemia.


Active commuting reduces the risk of wrist fractures in middle-aged women-the UFO study.
Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus. Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture. The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years. Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk. This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.


Wheat germ agglutinin inhibits nerve fiber growth and concanavalin A stimulates nerve fiber initiation in cultures of dorsal root ganglia neurons.
Treatment of dorsal root ganglion (DRG) neurons with the lectin wheat germ agglutinin (WGA; 25 micrograms/ml), which binds to N-acetylglucosamine containing glycoconjugates, inhibits nerve fiber growth in culture. DRG neurons treated with WGA have significantly reduced total output in nerve fiber length per neuron as well as reductions in the average length of the individual nerve fibers extended. The inhibition of nerve fiber growth by WGA is concentration-dependent, specific, reversible and not mimicked by treatment with several metabolic poisons. In contrast, treatment with the lectin concanavalin A (25 micrograms/ml), which binds to mannose-containing glycoconjugates, increases the number of nerve fibers produced per neuron. These results suggest that lectins which bind to distinct carbohydrate moieties can differentially regulate nerve fiber growth.


A simple model explains the cell cycle-dependent assembly of centromeric nucleosomes in holocentric species.
Centromeres are essential for chromosome movement. In independent taxa, species with holocentric chromosomes exist. In contrast to monocentric species, where no obvious dispersion of centromeres occurs during interphase, the organization of holocentromeres differs between condensed and decondensed chromosomes. During interphase, centromeres are dispersed into a large number of CENH3-positive nucleosome clusters in a number of holocentric species. With the onset of chromosome condensation, the centromeric nucleosomes join and form line-like holocentromeres. Using polymer simulations, we propose a mechanism relying on the interaction between centromeric nucleosomes and structural maintenance of chromosomes (SMC) proteins. Different sets of molecular dynamic simulations were evaluated by testing four parameters: (i) the concentration of Loop Extruders (LEs) corresponding to SMCs, (ii) the distribution and number of centromeric nucleosomes, (iii) the effect of centromeric nucleosomes on interacting LEs and (iv) the assembly of kinetochores bound to centromeric nucleosomes. We observed the formation of a line-like holocentromere, due to the aggregation of the centromeric nucleosomes when the chromosome was compacted into loops. A groove-like holocentromere structure formed after a kinetochore complex was simulated along the centromeric line. Similar mechanisms may also organize a monocentric chromosome constriction, and its regulation may cause different centromere types during evolution.


Seasonal occurrence and distribution of microbial indicators and pathogens in the Rhode River of Chesapeake Bay.
The seasonal incidence and occurrence of indicator organisms and pathogens were studied at four sites in the Rhode River, a subestuary of Chesapeake Bay. The highest frequency of occurrence of total and fecal coliforms and fecal streptococci was in Muddy Creek, a marsh area receiving pasture land runoff. Second highest frequency of occurrence of these bacteria was in Cadle Creek, a populated area. Lowest measurements of these parameters were obtained at stations in the central portion of the Rhode River. No Salmonella spp. were detected by the methods employed in this study. However, it is concluded that if these organisms are present, the concentrations are less than or equal to 1 organism per liter. The presence of Clostridium botulinum was detected in 12% of the samples tested.


Small lesion classification on abbreviated breast MRI: training can improve diagnostic performance and inter-reader agreement.
To determine whether the diagnostic performance and inter-reader agreement for small lesion classification on abbreviated breast MRI (AB-MRI) can be improved by training, and can achieve the level of full diagnostic protocol MRI (FDP-MRI). This retrospective study enrolled 1165 breast lesions (≤ 2 cm; 409 malignant and 756 benign) from 1165 MRI examinations for reading test. Twelve radiologists were assigned into a trained group and a non-trained group. They interpreted each AB-MRI twice, which was extracted from FDP-MRI. After the first read, the trained group received a structured training for AB-MRI interpretation while the non-trained group did not. FDP-MRIs were interpreted by the trained group after the second read. BI-RADS category for each lesion was compared to the standard of reference (histopathological examination or follow-up) to calculate diagnostic accuracy. Inter-reader agreement was assessed using multirater k analysis. Diagnostic accuracy and inter-reader agreement were compared between the trained and non-trained groups, between the first and second reads, and between AB-MRI and FDP-MRI. After training, the diagnostic accuracy of AB-MRI increased from 77.6 to 84.4%, and inter-reader agreement improved from 0.410 to 0.579 (both p < 0.001), which were higher than those of the non-trained group (accuracy, 84.4% vs 78.0%; weighted k, 0.579 vs 0.461; both p < 0.001). The post-training accuracy and inter-reader agreement of AB-MRI were lower than those of FDP-MRI (accuracy, 84.4% vs 92.8%; weighted k, 0.579 vs 0.602; both p < 0.001). Training can improve the diagnostic performance and inter-reader agreement for small lesion classification on AB-MRI; however, it remains inferior to those of FDP-MRI. • Training can improve the diagnostic performance for small breast lesions on AB-MRI. • Training can reduce inter-observer variation for breast lesion classification on AB-MRI, especially among junior radiologists. • The post-training diagnostic performance and inter-reader agreement of AB-MRI remained inferior to those of FDP-MRI.


Body composition assessment in children with inflammatory bowel disease: A comparison of different methods.
To assess different techniques to measure body composition in paediatric patients with inflammatory bowel disease using dual energy X-ray absorptiometry as a reference method. We hypothesised that a three-compartment model may demonstrate superiority over other methods as skinfold thickness equations and bioelectrical impedance analysis. Body composition was assessed using skinfold thickness equations, bioelectrical impedance analysis and the three-compartment model. Data obtained with these methods were compared to the results obtained by dual energy X-ray absorptiometry. Statistical analysis was performed using Spearman's correlation and Bland-Altman's limits of agreement method. Twenty-one paediatric patients with inflammatory bowel disease were included: 11 females and 10 males; mean age for the entire group: 14.3 years, range 12-16 years. In children with inflammatory bowel disease, skinfold thickness equations, bioelectrical impedance analysis and the three-compartment model showed reliable measurements with small differences in the percentage of total body fat and good limits of agreements. The assessment of body composition using bioelectrical impedance analysis provides a valid and accurate method in children with inflammatory bowel disease as compared to dual energy X-ray absorptiometry. In the future, superiority of 3-compartment model in research and clinical settings of nutritional intervention and disease status in children with inflammatory bowel disease remains to be demonstrated.


Manifestation of the Wolff-Parkinson-White syndrome during isoprenaline infusion and carotid sinus massage.
In a patient with transient WPW syndrome the electrocardiographic pattern of preexcitation could repeatedly be induced by carotid sinus massage during isoprenaline infusion. Adrenergic and cholinergic discharge may favor the conduction of the impulse over an accessory nonfunctional A-V bundle.


Relative Effects of Various Factors on Ice Ball Formation and Ablation Zone Size During Ultrasound-Guided Percutaneous Cryoneurolysis: A Laboratory Investigation to Inform Clinical Practice and Future Research.
Ultrasound-guided percutaneous cryoneurolysis provides analgesia using cold temperatures to reversibly ablate peripheral nerves. Cryoneurolysis probes pass a gas through a small internal annulus, rapidly lowering the pressure and temperature, forming an ice ball to envelope the target nerve. Analgesia is compromised if a nerve is inadequately frozen, and laboratory studies suggest that pain may be paradoxically induced with a magnitude and duration in proportion with the incomplete ablation. We therefore investigated the relative effects of various factors that may contribute to the size of the ice ball and the effective cryoneurolysis zone. A cryoprobe was inserted into a piece of meat, a gas was passed through for 2 min, and the resulting ice ball width (cross-section) and length (axis parallel to the probe) were measured using ultrasound, with the temperature evaluated in nine concentric locations concurrently. The factor with the greatest influence on ice ball size was probe gauge: in all probe types, a change from 18 to 14 increased ice ball width, length, and volume by up to 70%, 113%, and 512% respectively, with minimum internal temperature decreasing as much as from -5 to -32 °C. In contrast, alternating the type of meat (chicken, beef, pork) and the shape of the probe tip (straight, coudé) affected ice ball dimensions to a negligible degree. The ice ball dimensions and the zone of adequate temperature drop were not always correlated, and, even within a visualized ice ball, the temperature was often inadequate to induce Wallerian degeneration. Percutaneous probe design can significantly influence the effective cryoneurolysis zone; visualizing a nerve fully encompassed in an ice ball does not guarantee adequate treatment to induce the desired Wallerian degeneration because ice forms at temperatures between 0 and -20 °C, whereas only temperatures below -20 °C induce Wallerian degeneration. The correlation between temperatures in isolated pieces of meat and perfused human tissue remains unknown, and further research to evaluate these findings in situ appears highly warranted.


Transchelation of 99mTc from low affinity sites to high affinity sites of antibody.
An exclusive labeling of high affinity sites of IgG and its F(ab')2 fragments with 99mTc was accomplished. Antibody was first labeled in 0.1 M acetate buffer at pH 4.5, using stannous chloride as a reducing agent. Thus, high capacity, low affinity sites and low capacity, high affinity sites were both labeled. These 99mTc complexes were stable at pH 4.5 and 7.0; however, they became destabilized at pH 8.2 and 9.0. Transchelation of 99mTc to DTPA took place at the higher pH values and leveled off at 54% 99mTc-F(ab')2 and 73% 99mTc-IgG. These results indicate that the majority of 99mTc bound to the low affinity sites was transchelated to the high affinity sites rather than to DTPA since low affinity sites account for 84% of total F(ab')2 sites and 76% of IgG sites. Biodistribution data in mice at 2.5 h postinjection were consistent with this hypothesis in that tissue concentrations of 111In-DTPA-F(ab')2 were similar to the reequilibrated 99mTc-F(ab')2 but were much higher than that of the unequilibrated 99mTc-F(ab')2.


Urea-stimulated K-Cl cotransport in equine red blood cells.
The effect of urea and its interactions with oxygen tension (PO2), cell volume and inhibitors of protein phosphatases/kinases (PP/PK) on the K influx into equine red blood cells were studied. K influx was measured using 86Rb as a radioactive tracer for K. As in other species, Cl-dependent K influxes were stimulated by urea, with peak fluxes occurring at about 750 mM. This effect was not mediated via changes in cell volume or following formation of cyanate, the hydrolysis product of urea. Stimulation by urea was prevented by pre-treatment with calyculin A (100 nM) at all urea concentrations tested. At low concentrations, urea-stimulated influx was O2 dependent, and sensitive to changes in cell volume and subsequent treatment with calyculin A. By contrast, at high concentrations, urea-stimulated influxes were largely unaffected by these manipulations. Like pharmacological manipulations, e.g. by N-ethylmaleimide, staurosporine and depletion of intracellular Mg by A23187, but unlike cell swelling per se, urea was able to affect transport regardless of PO2. K-Cl cotransport in cells treated with N-ethylmaleimide (1 mM) alone, or with combinations of N-ethymaleimide and calyculin A, was no longer stimulated by addition of urea, rather it was inhibited. Results are consistent with urea acting predominantly as a direct inhibitor of the regulatory PK, with a smaller inhibitory effect downstream of this phosphorylation step possibly on the transporter itself.


Lifelong n-3 Polyunsaturated Fatty Acid Exposure Modulates Size of Mammary Epithelial Cell Populations and Expression of Caveolae Resident Proteins in Fat-1 Mice.
Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been associated with reduced breast cancer risk; however, the exact mechanism remains elusive. Female wildtype (WT) and fat-1 mice were fed a 10% safflower diet until 6 weeks of age. Mammary gland epithelial cells (EC) were isolated and EC populations were determined by CD24 surface expression. Fat-1 mice expressed 65%, 20%, and 15% while WT mice expressed 65%, 26% and 9% for non-, myo- and luminal ECs, respectively. The luminal EC population was significantly greater in fat-1 mice (p ≤ 0.05), while the total number of mammary ECs were similar between groups (p = 0.79). Caveolae was isolated from ECs and Her-2/neu, ER-α and cav-1 protein expression was determined by Western blotting. Fat-1 mice had a two-fold greater ER-α (p ≤ 0.05) and a 1.5-fold greater cav-1 (p ≤ 0.05) expression than WT with a similar amount of Her-2/neu protein (p = 0.990) between groups. Overall, this study provides novel mechanistic evidence by which n-3 PUFA modifies early mammary gland development that may potentially reduce breast cancer risk later in life.


Acid challenge to the human esophageal mucosa: effects on epithelial architecture in health and disease.
The histological changes that occur in the squamous epithelium in response to acute acid challenge was examined in healthy controls and proton pump inhibitor-treated gastroesophageal reflux disease (GERD) patients and related to the state of untreated erosive GERD in a saline-controlled, randomized perfusion study. In the basal state a stepwise significant increase in the thickness of the basal cell layer, papillary length, and dilatation of intercellular spaces (DIS) was seen when the three groups were compared. Acid perfusion induced a slight increase in the height of the basal cell layer mainly in healthy volunteers; this layer appears to be reactive to acute acid challenge as well as to acid suppressive therapy. DIS increases promptly in response to acute acid exposure in the healthy epithelium but no changes were seen in the lengths of the papillae or regarding DIS in the GERD patients. A protective effect of luminal nitric oxide on DIS development is suggested.


Milk consumption and cancer incidence: a Norwegian prospective study.
Relationships between milk intake and cancer incidence were investigated after 11 1/2 years of follow-up of 15,914 individuals. A diagnosis of cancer was made in a total of 1,422 individuals. No association was established with total cancer incidence, in analyses adjusted for sex, age and residential characteristics. However, a strong positive association with milk consumption was observed for cancers of the lymphatic organs (odds ratio 3.4 for greater than or equal to 2 glasses per day vs less than 1; 95% confidence interval 1.4-8.2). An inverse association was found for cancer of the bladder. Kidney cancer and cancers of the female reproductive organs (except the uterine cervix) showed weak positive associations with milk intake.


Properties and connections of cat fastigiospinal neurons.
1. Neurons in the cat fastigial nucleus that project to the upper cervical spinal segments (fastigiospinal neurons) were fired by antidromic stimulation of the contralateral spinal cord. Dye ejection from the recording electrode was used to show that most neurons were in the rostral half of the fastigial nucleus. 2. Fastigiospinal neurons can be excited and/or inhibited by stimulation of forelimb and hindlimb nerves and by stimulation of the vestibular nerve. These inputs converge on many neurons. 3. Antidromic microstimulation was used to trace fastigiospinal axons to the vicinity of motor nuclei in in C2-C3. 4. The rostral fastigial nucleus was stimulated in preparations with the medial longitudinal fasciculus transected by a wide lesion that impinged on the medial reticular formation in the caudal medulla, to eliminate some potential axon reflexes. Short-latency EPSPs were recorded in some trapezius and biventer-cervicis motoneurons. In many cases there was little or no occlusion between these EPSPs and others evoked by stimulation of the vestibular nerve ipsilateral to the motoneurons. 5. Movement of the stimulating electrode and placement of this electrode lateral to the fastigial nucleus show that the zone from which low threshold EPSPs can be evoked is localized. 6. Latency measurements and lack of temporal facilitation with double shocks suggest that the EPSPs are monosynaptic. The evidence suggests that they are caused by fastigiospinal fibers terminating on motoneurons.


Increasing prevalence and influencing factors of childhood asthma: a cross-sectional study in Shanghai, China.
Asthma has been a global problem, especially in children. We aim to evaluate the contemporary prevalence and influencing factors of asthma among children aged 3-7 years in Shanghai, China. A random sample of preschool children was included in this study. The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma. Multivariable logistic regression models were used to evaluate the associations between independent variables and childhood asthma. Of 6389 preschool children who were invited to take part in this study, 6163 (response rate: 96.5%) completed the questionnaire and were included in the analysis. The overall prevalence of asthma was 14.6% which increased more than six folds from 2.1% in 1990. Being male, younger age, preterm delivery, being born in spring or autumn, being delivered by elective cesarean section without indication, miscarriage, high socioeconomic status, having allergy history, and exposure to passive smoking, latex paint, and dust were potential risk factors for childhood asthma. Spending more time outdoors (> 30 min/day), having indoor plants, and cleaning rooms more frequently were potential protective factors. The prevalence of childhood asthma in Shanghai has increased dramatically during the past three decades. The findings about risk and protective factors of childhood asthma could be used to develop appropriate strategies to prevent and control childhood asthma in Shanghai and in other similar metropolitan cities.


Evaluation of NICU Nurses' Competence in Pain Assessment 5 Years After Implementation of the COMFORTneo Scale.
Adequate pain management of preterm and sick newborn infants is a critical issue in the neonatal intensive care unit, as the infants are small and vulnerable with limited resources to deal with pain and stressful experiences. The use of pain assessment instruments, however, must be applied correctly to achieve consistency and improve continuity in care and treatment among clinicians. To assess the development of neonatal intensive care unit nurses' interrater agreement in using the COMFORTneo pain assessment tool 5 years after initial implementation, and to identify items needing further development through analysis of discrepancies among nurses' COMFORTneo scores. An evaluation study with a pre- and postdesign comparing nurses' interrater reliability in assessing infant pain using the COMFORTneo pain assessment tool at baseline and 5-year follow-up. Eighty-five percent of the nurses in the follow-up group (n = 26) had improved their skills 5 years after the implementation, and the improvement was significant (P < .000). We also found that interrater reliability was satisfactory (κ scores ≥0.65) for all the items of the COMFORTneo tool. However, to obtain "very good" interrater reliability (κ scores ≥0.80) 3 items were identified needing increased focus. A thorough implementation of a national clinical guideline has been partially effective in ensuring that nurses used the COMFORTneo in their daily practice, which increased their competence in pain assessment. Further research into the education of nurses on the efficacy of pain scales, nonpharmacologic and pharmacologic therapies, and individualized pain assessment is needed to better address pain management.


Peritonealization of lymphoceles complicating renal transplantation: dangers of percutaneous aspiration.
Lymphocele is a known complication of renal transplantation. The diagnosis is easily made by sonographic technics. Although one may perform percutaneous aspiration or drainage or both, we found that peritonealization of the lymphocele may be more advantageous.


Medium-term outcomes of the S-ROM modular femoral stem in revision hip replacement.
The objective of this study was to analyse results achieved with the S-ROM modular stem in revision surgery. A retrospective observational study was conducted from 2007 to 2015 including 51 patients who had a follow-up of ≥ 2 years and complete medical history. The mean age was 66.5 years old (34-87). The main reason for revision was aseptic loosening (38 cases, 74.5%), followed by infection (10, 19.6%), instability (2, 3.9%) and an adverse reaction associated with a metal-on-metal hip implant (1, 2%). Using the Paprosky classification, there were 22 cases of type I (43.1%), 27 of type II (52.9%) and 2 of type IIIA (4%). At the end of the follow-up, radiological parameters were assessed using Engh's criteria. Pre- and postoperative clinical status was assessed using the Harris Hip Score, a visual analogue scale and the Merle D'Aubigné score. The mean follow-up period was 5.7 years (2-10). The mean Harris Hip Score improved from 45.5 points (22-65) to 85.8 (55-100) (p < 0.001), and the final mean Merle D'Aubigné scores were 5.2, 4.6 and 5.6 for pain, ability to walk and mobility, respectively. Osseointegration was confirmed in all except one patient with fibrous non-union. No aseptic loosening has been recorded. Postoperative complications were deep infection in four cases (7.8%) and dislocation in three (5.9%). This study indicates good medium-term outcomes using a modular hip replacement system with porous-coated proximal sleeves in revision surgery in patients with Paprosky type I and II defects.


The collaborative roles of stakeholders in supporting the adoption of sustainability in SMEs.
There is growing concern among governments around the world about the need to enhance the social and environmental performance of small and medium enterprises (SMEs), seen as key actors in efforts to achieve national sustainability goals. However, despite efforts made to promote their role in this area, SMEs still struggle to integrate social and environmental concerns into their business practices. Barriers that impede the integration of sustainable development in SMEs include a limited awareness of the impacts and benefits associated with sustainability, a lack of time and resources, and a lack of skills and expertise. The aims of this study are to examine the key collaborative roles that a range of stakeholders can play to support sustainability adoption in SMEs and to understand how these roles contribute to overcoming barriers to adoption. Building on thirteen case studies, this study found that stakeholders play five different and complementary collaborative roles in supporting sustainability practices within SMEs, namely that of trainer, analyst, coordinator, specialist, and financial provider. The study shows that these five roles can be performed by a wide range of local stakeholders and can contribute to overcoming different barriers to the integration of sustainability practices within SMEs. These findings demonstrate that one key way for governments to improve the sustainability performance of SMEs may be to facilitate and shape the development of stakeholder networks capable of performing these five critical roles as part of efforts to promote sustainability adoption within firms.


The Use of Information Communication Technologies in a South African Deaf Older Adult Population Living in a Residential Care Home to Communicate with Emigrant Family Members.
South Africa has experienced considerable international outward migration in the last half century, which has had a severe psychological impact on members of families affected by this phenomenon. Older parents who remain behind may experience feelings of loss and isolation. Information Communication Technologies (ICTs) are useful in maintaining relationships between family members separated by migration and increasingly allow migrant families to experience a virtual co-presence despite geographical separation. However, the process may be challenging, especially for older people with hearing difficulties. This article reports on a qualitative study exploring the perceptions of a group of older adults who have difficulty hearing and who live in a residential care home about using ICTs to communicate with family abroad. Interview data were analysed using thematic analysis. Most of the participants used either a fixed line telephone or a mobile phone. They reported challenges in communicating with family members abroad arising from their deafness, as well as difficulties using technological devices together with their hearing aids. These challenges resulted in feelings of helplessness and frustration. Although the data collection took place prior to the COVID-19 pandemic, these findings may be of particular relevance to situations such as those during the pandemic when many older adults became more reliant on technology to communicate with family members because of restrictions on direct contact. Accordingly, suggestions are made to address challenges in communication between older adults and loved ones who are geographically separated.


The Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE): Construct and Content Validation Using a Modified Delphi Method.
In order to scale-up successful innovations, more evidence is needed to evaluate programs that attempt to address the rising prevalence of diabetes and the associated burdens on patients and the healthcare system. This study aimed to assess the construct and content validity of the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE), a tool developed to guide the evaluation, design and implementation with built-in knowledge translation principles. A modified Delphi method, including 3 individual rounds (questionnaire with 7-point agreement/importance Likert scales and/or open-ended questions) and 1 group round (open discussion) were conducted. Twelve experts in diabetes, research, knowledge translation, evaluation and policy from Canada (Ontario, Quebec and British Columbia) and Australia participated. Quantitative consensus criteria were an interquartile range of ≤1. Qualitative data were analyzed thematically and confirmed by participants. An importance scale was used to determine a priority multi-level indicator set. Items rated very or extremely important by 80% or more of the experts were reviewed in the final group round to build the final set. Participants reached consensus on the content and construct validity of DEFINE, including its title, overall goal, 5-step evaluation approach, medical and nonmedical determinants of health schematics, full list of indicators and associated measurement tools, priority multi-level indicator set and next steps in DEFINE's development. Validated by experts, DEFINE has the right theoretic components to evaluate comprehensively diabetes prevention and management programs and to support acquisition of evidence that could influence the knowledge translation of innovations to reduce the burden of diabetes.


The complementary role of computerized axial transmission tomography and radionuclide imaging of the brain.
Computerized axial transmission tomography and radionuclide imaging are complementary procedures, and the following recommendations are made as to their use. Where there is no real clinical suspicion of intracranial disease, either modality can be used for "rule out" screening; the choice can frequently be made on the basis of which modality is cheaper or more quickly available. It should be remembered that "quicker" is often "cheaper". Total cost is determined, not only by the cost of the procedure, but also the per diem costs incurred in waiting for that procedure. Thus the more expensive modality may, in effect, be cheaper if delays are shorter. Screening of the elderly patient, particularly when atrophy or communicating hydrocephalus is of clinical concern, should be by the CT method because of its ability to visualize cerebrospinal fluid spaces. When clinical signs and symptoms point to intracranial abnormality, both modalities should be utilized. If either study done first is normal, use of the other modality is mandatory. When the first study is positive with pathognomonic findings for a specific disease, which totally explains the patient's neurologic problems, the second study need not be employed. Such examples might include the fresh cerebral hemorrhage demonstrated by CT imaging, the AV malformation defined by dynamic-static radionuclide imaging, or multifocal metastatic lesions defined by either. However, when the clinical picture is not totally and satisfactorily explained by the demonstrated disease, the other modality should also be employed. Under many circumstances, neither study will be so reliable, specific, and free of false-negative or false-positive findings as to warrant ignoring the additional information potentially available from the other study.


Is mitral annuloplasty an effective treatment for severe atrial functional mitral regurgitation?
Unlike secondary mitral regurgitation (MR) in the setting of left ventricular disease, results of surgical treatment of severe atrial functional MR has remained largely unspoken. The aim of this study is to analyze short to midterm results of isolated ring annuloplasty in patients with severe atrial functional MR, in comparison with a matched cohort of patients with secondary MR. A retrospective review of our Institutional database was carried out to find all patients fulfilling strict echocardiographic criteria to define atrial functional MR. A control group of patients with MR secondary to ventricular disease was selected. All patients underwent mitral repair by means of isolated ring annuloplasty. Mortality, reoperation for severe MR, and recurrence of MR were assessed by clinical and echocardiographic follow-up. Cumulative incidence function (CIF) of recurrence of MR using death and reoperation as the competitive risk was used. Twenty patients were selected for the study group and 25 for the control group. There were no differences between the two groups in terms of mortality and reoperation rate. At 2 years, the CIF of recurrence of MR ≥ 3+ and ≥ 2+ was significantly higher in patients with secondary MR compared to patients with atrial functional MR (20.8 ± 8.29% vs 5.9 ± 5.71% and 45.8 ± 10.17% vs 5.9 ± 5.71%) CONCLUSION: In patients with severe atrial functional MR, mitral valve repair by means of isolated ring annuloplasty seems a more effective and durable treatment as compared to patients with MR secondary to ventricular disease. Larger cohorts with longer follow up are needed to confirm these results.


Regular at-home abdominal paracentesis via Tenckhoff catheter in patients with refractory congestive heart failure.
Peritoneal dialysis (PD) is increasingly used for the long-term management of refractory congestive heart failure (CHF). Patients with severe CHF and ascites were treated with regular at-home abdominal paracentesis via Tenckhoff catheter. We investigated the outcome of those patients, aiming to identify potential prognostic factors for longer survival. Patients with refractory CHF referred by cardiologists to the PD unit from years 2009 to 2019 and treated with regular at-home abdominal paracentesis via Tenckhoff catheter without peritoneal exchanges, were enrolled into this prospective observational study. From the total of 69 refractory CHF patients treated with PD, 18 (26%) were managed with regular at-home abdominal paracentesis via Tenckhoff catheter and improved without the need for peritoneal exchanges for fluid removal (no peripheral oedema or pulmonary congestion) or for solutes removal. Median survival of severe CHF patients treated with abdominal paracentesis was 13.5 months (0-34 months). Long-term survivors demonstrated significant improvement in the New York Heart Association (NYHA) functional class, improvement in kidney function and decrease in serum C-reactive protein (CRP) and Brain natriuretic peptide (BNP) compared with their baseline status. A subgroup of patients with shorter survival were more likely to have evidence of liver cirrhosis and significantly lower serum sodium compared with patients with longer survival. Refractory CHF patients with massive ascites could be successfully treated with regular at-home abdominal paracentesis via Tenckhoff catheter. This treatment provides a useful alternative to periodical percutaneous paracentesis on as-needed basis.


Exosomes derived from hypoxic bone marrow mesenchymal stem cells rescue OGD-induced injury in neural cells by suppressing NLRP3 inflammasome-mediated pyroptosis.
Exosomes have been shown to have therapeutic potential for cerebral ischemic diseases. In this study, we investigated the neuroprotective effects of normoxic and hypoxic bone marrow mesenchymal stromal cells-derived exosomes (N-BM-MSCs-Exo and H-BM-MSCs-Exo, respectively) on oxygen-glucose deprivation (OGD) injury in mouse neuroblastoma N2a cells and rat primary cortical neurons. The proportions of dead cells in N2a and primary cortical neurons after OGD injury were significantly increased, and N-BM-MSCs-Exo (40 μg/ml) could reduce the ratios, noteworthily, the protective effects of H-BM-MSCs-Exo (40 μg/ml) were more potent. Western blotting analysis indicated that N-BM-MSCs-Exo decreased the expression of NLRP3, ASC, Caspase-1, GSDMD-N, cleaved IL-1β and IL-18 in N2a cells. However, H-BM-MSCs-Exo (40 μg/ml) was more powerful in inhibiting the expression of these proteins in comparison with N-BM-MSCs-Exo. Similar results were obtained in primary cortical neurons. Immunofluorescence assays showed that after N-BM-MSCs-Exo and H-BM-MSCs-Exo treatment, the co-localization of NLRP3, ASC, Caspase-1 and the GSDMD translocation from the nucleus to the cytoplasm and membrane after OGD injury were reduced in N2a cells and primary cortical neurons, and H-BM-MSCs-Exo had a more obvious effect. In addition, N-BM-MSCs-Exo and H-BM-MSCs-Exo significantly reduced lactate dehydrogenase (LDH) release and the IL-18 levels in cell culture medium in N2a cells and primary cortical neurons. Once again H-BM-MSCs-Exo induced these effects more potently than N-BM-MSCs-Exo. All of these results demonstrated that N-BM-MSCs-Exo and H-BM-MSCs-Exo have significant neuroprotective effects against NLRP3 inflammasome-mediated pyroptosis. H-BM-MSCs-Exo has a more pronounced protective effect than N-BM-MSCs-Exo and may be used to ameliorate the progression of cerebral ischemia and hypoxia injury in patients.


Regulation of osteoclast apoptosis and motility by small GTPase binding protein Rac1.
The role of Rac1 in osteoclast survival and bone-resorbing activity was examined using adenovirus vector expression systems. Rac1 is critically involved in M-CSF receptor signaling and mediates survival signaling primarily through PI3K/Akt pathways. Rac1 also plays a significant role in bone resorptive activity, probably by regulating the motility of osteoclasts. Rac1 is a member of Rho family small G-proteins, and recent studies have revealed that it mediates anti-apoptotic signals in some types of cells. Rac1 is reported to be required for the cytoskeletal organization and bone-resorbing activity of osteoclasts, but their roles in osteoclast survival and function are not fully elucidated. We constructed the adenovirus vector carrying cDNA of either the dominant negative Rac1 (Rac1(DN)) or constitutively active Rac1 (Rac1(CA)) gene, and osteoclast-like cells (OCLs) generated in mouse co-culture system were infected with these viruses. To examine the role of Rac1 in osteoclast survival and function, we performed pit formation assays, survival assays, and Western blotting, including an activated-Rac1 pull-down assay using adenovirus-infected OCLs. To further clarify the mechanism of Rac1 regulation in osteoclast survival, some specific inhibitors and adenovirus vectors of signal transduction molecules were used. To quantify membrane movement before and after macrophage colony-stimulating factor (M-CSF) treatment, OCLs expressing either enhanced green fluorescent protein (EGFP) or Rac1(DN) were recorded with a time-lapse video microscope. Adenovirus vector-mediated dominant negative Rac1 (Rac1(DN)) expression significantly reduced pit formation, and promoted their apoptosis. M-CSF rapidly activated Rac1, and the prosurvival effect of M-CSF for OCLs was abrogated by Rac1(DN) overexpression. Constitutively active Rac1 enhanced OCL survival, which was completely suppressed by phosphatidylinositol 3'-kinase (PI3K) inhibitors, whereas a Mek inhibitor had only partial effect. Rac1(DN) also partially blocked the activation of Akt induced by the overexpressing catalytic subunit of PI3K. Using time-lapse video microscopy, we found that Rac1(DN) expression reduced membrane ruffling and the spreading of OCLs in response to M-CSF. Small guanosine triphosphatase (GTPase) Rac1 is critically involved in M-CSF receptor signaling and mediates survival signaling of osteoclasts primarily by modulating PI3K/Akt pathways. Rac1 also plays a significant role in the bone resorptive activity of cells, probably by regulating the motility of osteoclasts.


Screening and Identification of Prognostic Tumor-Infiltrating Immune Cells and Genes of Endometrioid Endometrial Adenocarcinoma: Based on The Cancer Genome Atlas Database and Bioinformatics.
Endometrioid endometrial adenocarcinoma (EEA) is one of the most common tumors in the female reproductive system. With the further understanding of immune regulation mechanism in tumor microenvironment, immunotherapy is emerging in tumor treatment. However, there are few systematic studies on EEA immune infiltration. In this study, prognostic tumor-infiltrating immune cells (TIICs) and related genes of EEA were comprehensively analyzed for the first time through the bioinformatics method with CIBERSORT algorithm as the core. Gene expression profile data were downloaded from the TCGA database, and the abundance ratio of TIICs was obtained. Kaplan-Meier analysis and Cox regression analysis were used to identify prognostic TIICs. EEA samples were grouped according to the risk score in Cox regression model. Differential analysis and functional enrichment analyses were performed on high- and low-risk groups to find survival-related hub genes, which were verified by Tumor Immune Estimation Resource (TIMER). Four TIICs including memory CD4+ T cells, regulatory T cells, natural killer cells and dendritic cells were identified. And two hub gene modules were found, in which six hub genes including APOL1, CCL17, RBP4, KRT15, KRT71, and KRT79 were significantly related to overall survival and were closely correlated with some certain TIICs in the validation of TIMER. In this study, four prognostic TIICs and six hub genes were found to be closely related to EEA. These findings provided new potential targets for EEA immunotherapy.


Modified technique for coarctation of aorta with hypoplastic distal aortic arch.
A combination of coarctation of aorta with various severity of distal arch hypoplasia frequently occurs in newborns. Traditional techniques in the neonatal period such as extended end-to-end anastomosis or inner curve patch are controversial. Arch geometry has a marked role in long-term outcomes. We introduce a modified Amato technique of distal aortic arch enlargement with native tissue-to-tissue reconstruction. Neonatal patients with coarctation of aorta and distal aortic arch hypoplasia who underwent surgical reconstruction using this technique between January 2016 and December 2019 in our center were included. Patients with concomitant complex heart defects were excluded. Data were obtained from echo protocols, CT scans before and after repair. The dimensions of the arch were assessed using Z-score, arch geometry was evaluated with height/width ratio. Thirty-two patients (22 males, 10 females) were included. Median age and weight were 7 days (5; 18) and 3.5 kg (3.1; 4.0), respectively. The Z-score of distal part of the arch before and after procedure was significantly different (<0.01). No mortality, recoarctation, or bronchial compression was found during 18 (6-38) months of follow-up. Modified technique for coarctation of aorta with hypoplastic distal aortic arch provides favorable geometry of the aorta with a low risk of morbidity. The proper selection and accurate technique could minimize potential risks. This method is relatively safe and might improve long-term outcomes associated with the geometry of aorta.


Clinical and demographic factors associated with delayed diagnosis of bipolar disorder: Data from Health Outcomes and Patient Evaluations in Bipolar Disorder (HOPE-BD) study.
The diagnosis of Bipolar Disorder (BD) is frequently delayed. In this study, we aimed to examine the clinical and demographic factors associated with delayed diagnosis of BD, defined as the difference between the age at first mood episode (depressive, manic, or hypomanic) and the age at the correct diagnosis of BD, using data from a Canadian multicentre naturalistic study. The sample included 192 patients with Bipolar I Disorder (BD-I) and 127 with Bipolar II Disorder (BP-II) who participated in the Health Outcomes and Patient Evaluations in Bipolar Disorder (HOPE-BD) study. Sociodemographic characteristics and clinical features that had been previously associated with delayed diagnosis of BD were included in the analysis. The median delay in diagnosis was 5.0 years in BD-I and 11.0 years in BD-II. Clinical factors such as earlier age of onset, lifetime suicide attempts and comorbid anxiety disorders were associated with a longer delay, whereas the presence of lifetime psychotic symptoms and psychiatric hospitalizations were associated with a shorter delay. Quantile regression analysis showed older age at which professional help was first sought and younger age of onset as predictors of increased delay in diagnosis of BD-I and BD-II. Depression as first episode predicted longer delay in diagnosis of BD-I but not BD-II. Our findings identified the ongoing lag in identification of a BD diagnosis and the clinical markers most associated with this delay, highlighting the need for implementation of strategies for early identification and interventions in BD.


Comparison of dose-response curves for alpha factor-induced cell division arrest, agglutination, and projection formation of yeast cells. Implication for the mechanism of alpha factor action.
MAT alpha cells of the yeast Saccharomyces cerevisiae produce a polypeptide mating pheromone, alpha factor. MATa cells respond to the pheromone by undergoing several inducible responses: the arrest of cell division, the production of a cell surface agglutinin, and the formation of one or more projections on the cell surface commonly termed the "shmoo" morphology. Dose-response curves were determined for each of these inducible responses as a function of alpha factor concentration. It is shown that under conditions commonly employed in previous studies, the dose-response for cell division arrest is determined by the rate at which cells inactivate the alpha factor. In order to achieve conditions where inactivation would not be the dominant parameter, the cell division response to alpha factor was monitored at low cell densities. Under conditions of essentially no alpha factor destruction, the dose of alpha factor at which cells exhibit a half-maximal response for cell division arrest (2.5 X 10(-10) M) is nearly the same as that at which cells exhibit a half-maximal response for agglutination induction (1.0 X 10(-10) M). On the contrary, the half-maximal response for projection formation was obtained at doses of alpha factor 2 orders of magnitude higher (1.4 X 10(-8) M). These results are consistent with the same high affinity alpha factor receptor mediating both cell division arrest and agglutination induction. A different system of lower affinity must mediate projection formation. Alternatively, if the same system and receptor are used, then a much higher occupancy is required for the induction of projections compared to division arrest and agglutination induction.


Markers of sedentarism: the joint Canada/U.S. Survey of health.
The Joint Canada/United States Survey of Health (JCUSH) was a one-time collaborative survey undertaken by Statistics Canada and the National Center for Health Statistics. This analysis provides country-, sex-, and age-specific comparative markers of adult obesity and sedentarism, defined as independent and collective groupings of self-reported leisure-time inactivity (<1.5 MET-hours/day), usual occupational sitting, and no/low active transportation (<1 hour/week). Logistic regression assessed the likelihood of sedentarism in U.S. vs. Canada, with and without adjusting for BMI-defined obesity categories: healthy weight (18.5 ≤ BMI <25 kg/m2; n = 3542), overweight (25 ≤ BMI < 30 kg/m2; n = 2,651), and obesity (BMI ≥ 30 kg/m2; n = 1470). Compared with Canadians, U.S. adults are 24% more likely to be overweight/ obese, 59% more likely to be inactive in leisure-time, 19% more likely to report no/low active transportation, and 39% more likely to collectively report all sedentarism markers, adjusting for sex and age. Focusing on obese individuals in both countries, obese U.S. residents were 90% more likely to be inactive during leisure-time, 41% more likely to report no/low active transportation, and 73% more likely to report all sedentarism markers. This ecological analysis sheds light on differential risks of obesity and sedentarism in these neighboring countries.


Long-Term Outcomes after Pediatric Injury: Results of the Assessment of Functional Outcomes and Health-Related Quality of Life after Pediatric Trauma Study.
Disability and impaired health-related quality of life can persist for months among injured children. Previous studies of long-term outcomes have focused mainly on children with specific injury types rather than those with multiple injured body regions. This study's objective was to determine the long-term functional status and health-related quality of life after serious pediatric injury, and to evaluate the associations of these outcomes with features available at hospital discharge. We conducted a prospective observational study at 7 Level I pediatric trauma centers of children treated for at least 1 serious (Abbreviated Injury Scale severity 3 or higher) injury. Patients were sampled to increase the representation of less frequently injured body regions and multiple injured body regions. Six-month functional status was measured using the Functional Status Scale (FSS) and health-related quality of life using the Pediatric Quality of Life Inventory. Among 323 injured children with complete discharge and follow-up assessments, 6-month FSS score was abnormal in 33 patients (10.2%)-16 with persistent impairments and 17 previously normal at discharge. Increasing levels of impaired discharge FSS score were associated with impaired FSS and lower Pediatric Quality of Life Inventory scores at 6-month follow-up. Additional factors on multivariable analysis associated with 6-month FSS impairment included older age, penetrating injury type, severe head injuries, and spine injuries, and included older age for lower 6-month Pediatric Quality of Life Inventory scores. Older age and discharge functional status are associated with long-term impairment of functional status and health-related quality of life. Although most seriously injured children return to normal, ongoing disability and reduced health-related quality of life remained 6 months after injury. Our findings support long-term assessments as standard practice for evaluating the health impacts of serious pediatric injury.


Prenatal diagnosis of chromosomal abnormalities in women with high risk pregnancies.
Prenatal diagnosis helps in averting the birth of infants with chromosomal abnormalities. Fluorescence in situ hybridization (FISH) has been introduced as a potentially powerful tool in clinical cytogenetics. Several studies have reported successful prenatal diagnosis of chromosomal abnormalities in high risk pregnancies using FISH, however there are no reported studies from an Indian set up. Prenatal diagnosis for the detection of chromosomal abnormalities was carried out by conventional cytogenetics in the present study in the foetuses of high risk pregnancies in women attending a tertiary care facility in north India. These cases were further analyzed using FISH, to test the efficiency and utility of this technique for prenatal detection of common aneuploidies. A total of 82 women with high risk pregnancies (81 singleton, 1 twin) were included in the study. Prenatal diagnosis was performed in these women using conventional chromosomal analysis (CCA) and interphase or metaphase FISH on chorionic villus or amniotic fluid or cord blood samples. Chromosomal analysis was successful in 80 instances and uninformative in 2. Abnormal karyotypes were detected in five (6.09%) of these women. FISH was successful in all the subjects and the results were in conformity to the cytogenetic results. In the 2 women where cytogenetic analysis was uninformative, results were given on the basis of interphase FISH. The study clearly demonstrates that prenatal diagnosis is useful in the detection of chromosomal abnormalities in foetuses of women with high risk pregnancies. FISH is a powerful sensitive molecular cytogenetic technique, through which specific chromosomal abnormalities can be diagnosed/identified rapidly and accurately and may be used as an adjunct to conventional cytogenetic analysis.


Characterisation of c-Fos expression in the central nervous system of mice following right atrial injections of the 5-HT3 receptor agonist phenylbiguanide.
Cardiopulmonary receptors relay signals to the central nervous system via vagal and spinal visceral afferents. To date there are no detailed topographical studies in mice indicating the distribution of central neurones activated following stimulation of cardiopulmonary afferents. In anaesthetised mice, we injected the 5-HT(3) receptor agonist phenylbiguanide (PBG), a drug that is known to stimulate cardiopulmonary afferent C-fibres, into the right atrium of the heart and mapped c-Fos expression within specific regions of the central nervous system. Intra-atrial injection of PBG produced a reflex cardiorespiratory response including a pronounced bradycardia and a respiratory depression. Using immunohistochemical detection of the protein product of the immediate-early gene c-fos, we mapped the brain regions affected by cardiopulmonary 5-HT(3) receptor stimulation. Within the nucleus of the solitary tract (nTS) of PBG-injected mice, we detected an increased number of c-Fos-positive nuclei in the dorsolateral and gelatinous parts at the level of the area postrema (-7.48 mm bregma) but not at more rostral or caudal levels (-7.76, -7.20, -6.84 and -6.36 mm bregma) relative to vehicle-injected control mice. In addition, c-Fos expression in the crescent part of the lateral parabrachial nucleus was decreased in PBG-injected mice whereas no significant differences were detected between PBG-injected and control mice in the number of c-Fos-positive nuclei in the dorsal part of the lateral parabrachial nucleus. PBG injections had no significant effects on the number of c-Fos-positive catecholaminergic neurones within the C1/A1, C2/A2, A5, A6 and A7 cell groups. Likewise, PBG injections had no significant effects on c-Fos expression in other central regions involved in cardiorespiratory control or cardiorespiratory reflexes (selected non-catecholaminergic nuclei in the medulla and midbrain periaqueductal gray, the paraventricular nucleus of the hypothalamus and the central nucleus of the amygdala). Identification of specific regions of the nTS complex involved in relaying signals from afferent cardiopulmonary C-fibres to the central nervous system will be useful for future studies aimed at understanding neural mechanisms underlying cardiopulmonary reflexes and physiological responses to cardiopulmonary disease.


Maternal salinity influences anatomical parameters, pectin content, biochemical and genetic modifications of two Salicornia europaea populations under salt stress.
Salicornia europaea is among the most salt-tolerant of plants, and is widely distributed in non-tropical regions. Here, we investigated whether maternal habitats can influence different responses in physiology and anatomy depending on environmental conditions. We studied the influence of maternal habitat on S. europaea cell anatomy, pectin content, biochemical and enzymatic modifications under six different salinity treatments of a natural-high-saline habitat (~ 1000 mM) (Ciechocinek [Cie]) and an anthropogenic-lower-saline habitat (~ 550 mM) (Inowrocław [Inw]). The Inw population showed the highest cell area and roundness of stem water storing cells at high salinity and had the maximum proline, carotenoid, protein, catalase activity within salt treatments, and a maximum high and low methyl esterified homogalacturonan content. The Cie population had the highest hydrogen peroxide and peroxidase activity along with the salinity gradient. Gene expression analysis of SeSOS1 and SeNHX1 evidenced the differences between the studied populations and suggested the important role of Na+ sequestration into the vacuoles. Our results suggest that the higher salt tolerance of Inw may be derived from a less stressed maternal salinity that provides a better adaptive plasticity of S. europaea. Thus, the influence of the maternal environment may provide physiological and anatomical modifications of local populations.


International quantification of microplastics in indoor dust: prevalence, exposure and risk assessment.
This international scale study measured the prevalence of indoor microplastics (MPs) in deposited dust in 108 homes from 29 countries over a 1-month period. Dust borne MPs shape, colour, and length were determined using microscopy and the composition measured using μFTIR. Human health exposure and risk was assessed along with residential factors associated with MPs via a participant questionnaire. Samples were categorised according to each country's gross national income (GNI). Synthetic polymers dominated in low income (LI) (39%) and high income (HI) (46%) while natural fibres were the most prevalent in medium income (MI) (43%) countries. Composition and statistical analysis showed that the main sources of MPs and dust were predominantly from indoor sources. Across all GNI countries, greater vacuuming frequency was associated with lower MPs loading. High income country samples returned higher proportions of polyamides and polyester fibres, whereas in LI countries polyurethane was the most prominent MPs fibre. Exposure modelling showed infants (0-2 years) were exposed to the highest MPs dose through inhalation (4.5 × 10-5 ± 3 × 10-5) and ingestion (3.24 × 10-2 ± 3.14 × 10-2) mg/kg-Bw/day. Health risk analysis of constituent monomers of polymers indicates cancer incidence was estimated at 4.1-8.7 per million persons across age groups. This study's analysis showed socio-economic factors and age were dominant variables in determining dose and associated health outcomes of MPs in household dust.


Predictors of loneliness in caregivers of persons with Parkinson's disease.
This study examined loneliness among caregivers of individuals with Parkinson's disease (PD). The sample included 70 caregivers (74% female; 96% spouses) who were currently living with the patient. A postal survey was sent to caregivers of persons with PD on the mailing list of a regional Parkinson association; response rate was 39%. Assessment instruments included the UCLA Loneliness Scale, Social Provisions Scale, Hoehn and Yahr (caregiver version), a perceived Self-Efficacy Scale developed previously for use with PD caregivers, and questions related to both patient and caregiver characteristics. Caregivers reported more loneliness than all similar normative groups except Alzheimer caregivers (P<0.001 to P=0.011). Hierarchical regression analyses were used to determine whether patient or caregiver characteristics were more predictive of loneliness. Results indicated that patient variables accounted for only 12% of the variance in loneliness, whereas caregiver variables accounted for an additional 46% of the variance (P<0.01). Among the significant individual caregiver predictors of greater loneliness were less education, lower perceived self-efficacy (both P<0.05) and poorer physical health (P<0.01). It was also found that persons attending caregiver support groups reported less loneliness (P<0.05) and more perceived support (P<0.05) than those not attending support groups. Because loneliness was significantly predicted by caregiver rather than patient variables, it is possible that strategic interventions for caregivers could ameliorate loneliness.


Athletic Trainers' Use of Support Systems for Balancing Roles as an Athletic Trainer and Parent.
Work-life balance is a topic of interest in the athletic training profession. Particularly for parents, managing work and home roles can be challenging. Social support has been identified as a resource for improving athletic trainers' balance and quality of life and warrants further investigation. To explore the sources and perceptions of social support among athletic trainers with children. Qualitative study. Collegiate and secondary school settings. Thirty-two athletic trainers who worked in the collegiate (12) or secondary school (20) setting participated. All individuals (19 females, 13 males) were parents, and they ranged in age from 25 to 72 years, with 2 to 52 years of experience as athletic trainers. Participants were recruited from a larger cross-sectional survey. A semistructured interview was developed by the research team and reviewed by a peer expert in the field. Respondents completed the interview protocol, which contained questions in numerous areas related to work-life balance. Data analyses were guided by the research questions related to social support and used a phenomenologic approach. We researchers immersed ourselves in the data and engaged in a coding process. Researcher triangulation and peer review were used to establish credibility. Our participants found social support in their work and home lives. Support was described by source (eg, supervisors, coworkers, spouses, family, friends) and type (eg, emotional, tangible, network). Respondents perceived that support stemmed from understanding, flexibility, sharing responsibilities, and shared life experiences, which aided them in balancing their roles. Athletic trainers valued social support and used different types of support to help create work-life balance. Support in the workplace, at home, and from the profession is necessary for athletic trainers who are parents, as it provides a means to help balance roles and responsibilities.