[Lymph kinetics with technetium-99m labeled radiopharmaceuticals. Animal studies].
Aim of this study was to characterize suitable technetium-99m labeled tracers for lymphoscintigraphy by comparative animal tests. To evaluate the influence of the particle size and the organ tracer-uptake on lymphtransport animal experiments were performed on six different agents (including one control group). Activity distributions were examined in Sprague-Dawley-rats by lymphoscintigraphy; the maximum uptake (count-rate) of the whole body and in lymph nodes were analyzed by regions-of-interest-technique, respectively. Additionally, for characterization of lymphatic and extralymphatic traceruptake an intra-individual relative count-rate ratio of the liver, lung, kidneys, and spleen has been calculated following organ extraction. Organ specific differences of distribution were clearly demonstrated. Our results indicate that the kinetics of lymphoscintigraphic (99m)Tc-bound agents substantially depends on particle size. Reliable transport from the interstitium to initial lymph vessels and lymph node uptake suggested for tracers suited for lymphoscintigraphy a median size of about <100 nm. Our data could improve standardization of diagnostic methods and lead to an objective consideration of therapeutic procedures.


Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells.
The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the interconversion of pyruvate and lactate, is upregulated in human cancers, and is associated with aggressive tumor outcomes. Here we use an inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo. This was accompanied by reactivation of mitochondrial function in vitro, but not in vivo or ex vivo. Finally, using a specific small molecule LDH-A inhibitor, we demonstrated that LDH-A is essential for cancer-initiating cell survival and proliferation. Thus, LDH-A can be a viable therapeutic target for NSCLC, including cancer stem cell-dependent drug-resistant tumors.


Genome screening, reporting, and genetic counseling for healthy populations.
Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.


Association of promoter region polymorphisms of CD209 gene with clinical outcomes of dengue virus infection in Western India.
Dendritic cell specific intercellular adhesion molecule 3 grabbing non-integrin, coded by the CD209 gene, acts as an entry receptor for dengue virus. Polymorphisms in the promoter region of CD209 gene (rs735239, rs4804803, rs2287886) were investigated in 112 hospitalized cases of dengue (DEN) and 104 healthy controls to find out whether they are associated with dengue in a Western Indian population. Results revealed a significantly higher frequency of 'G' allele and 'G/G' genotype of rs2287886 and A-A-G haplotype of CD209 gene in DEN compared to healthy controls [For 'G/G' genotype, P=0.0072, Odds ratio (OR) 2.43; For A-A-G haplotype, P=0.0033, OR 2]. The frequency of A/A genotype of rs735239 was higher in DEN cases with thrombocytopenia compared to cases without thrombocytopenia (P=0.026). The results suggest that rs2287886 G/G genotype of CD209 gene is associated with development of dengue requiring hospitalization while A/A genotype of rs735239 is associated with thrombocytopenia in dengue cases.


The fatty acids of human sebaceous gland phosphatidylcholine.
The fatty acids of human sebaceous gland phosphatidylcholine were examined by gas chromatography and by analysis of the double bond positions in the C-16 and C-18 monoenes. Compared to phosphatidylcholine from other organs, sebaceous gland phosphatidylcholine was found to be deficient in essential fatty acids and poly-unsaturated fatty acids. The relatively large mono-unsaturated fatty acid fraction consisted predominantly of fatty acids with delta6- and delta8-unsaturation. Analysis indicates that the fatty acids of sebaceous gland phospholipids are predominantly of types synthesized in sebaceous glands.


Postnatal development of adrenergic and cholinergic sensitivity in the isolated rat atria.
The sensitivity to adrenergic drugs in isolated rat atria increased with the postnatal development. The cholinergic chronotropic sensitivity did not further change after birth.


Trace element concentrations of the rough limpet, Acmaea scabra, in California.
The trace element (Ag, Cd, Cu, Fe, Mn, Ni, Zn) concentrations of the rough limpet, Acmaea scabra, were determined at twelve locations along the california coastline. The mean silver concentration of the organisms was highest at Pt. La Jolla, but no elemental concentration exhibited measurable geographic differences. Simple linear correlation coefficients and multiple analysis of variance statistics indicated a general independence of the elemental concentrations from each other and from other biological and geographic variables, in the total sample.


Risk-Adapted Starting Age for Personalized Colorectal Cancer Screening: Validated Evidence From National Population-Based Studies.
A one-size-fits-all approach to colorectal cancer (CRC) screening that does not account for CRC risk factors is not conducive to personalized screening. On the basis of the principle of equal management of equal risks, we aimed to tailor and validate risk-adapted starting ages of CRC screening for individuals with different CRC risk factors. A multi-center community-based population cohort (N = 3,165,088) was used to evaluate the starting age of CRC screening with comprehensive consideration of risk factors. Age-specific 10-year cumulative risk curves were used to determine when individuals at greater risk for CRC reached the same risk level as the 50-year-old general population, which is currently the recommended starting age for CRC screening in China. During the study follow-up period (2013-2021), 4,840 incident CRCs were recorded. Family history of CRC, adverse lifestyle, and comorbidities demonstrated heterogeneous associations with CRC risk (hazard ratios, 1.05-1.55; P < .05). Men and women with CRC family history and at least 2 risk factors reached the standard benchmark risk (0.28%) for screening at the age of 40, 10 years earlier than their peers without risk factors in the general population. Proposed starting ages for CRC screening were validated in an independent community-based population cohort (N = 1,023,367). We determined a risk-adapted CRC screening starting age for individuals with various CRC risk factors. Earlier, personalized screening based on these findings could allow for scarce health resources to be dedicated to individuals who benefit most.


Effects of narcotic analgesic drugs on the cyclic adenosine 3',5'-monophosphate-adenylate cyclase system in rat brain.
1. The concentrations of cyclic adenosine 3',5'-monophosphate (cyclic AMP), measured in discrete brain areas removed from rats killed by microwave irradiation, rose transiently in most areas after the administration of morphine. The most pronounced changes, however, were found 2 h after doses of either 10 or 60 mg/kg morphine when cyclic AMP levels declined significantly in the hypothalamus, medulla and cerebellum. In morphine-tolerant rat brains there were no decreases in cyclic AMP levels. 2. Basal adenylate cyclase activity in crude nerve-ending fractions from discrete areas of rat brain was unaffected by the addition of active analgesic agonists, antagonists or inactive isomers to the assay medium in vitro, except for a nonspecific inhibition at drug concentrations of 1 mM. 3. The acute administration of morphine or levorphanol, but not dextrorphan produced transient increases in basal cyclase activity of crude nerve-ending preparations from midbrain and striatum. In morphine-tolerant rats, these changes in basal adenylate cyclase activity were no longer seen.


An adapted management of early warning signs of relapse questionnaire: Validity and reliability.
Self-management of early warning signs of relapse is critical when it comes to having an impact on the relapse rate and developing methods to successfully handle and manage those signs of relapse. The purpose of this study was to test the validity and reliability of the adapted management of early warning signs of relapse questionnaire. Consisted of two main steps: first, adapting and validating, which involved a literature review, a panel of experts, the calculation of the CVI, the Kaiser-Meyer-Olkin (KMO) test, Bartlett's test of sphericity, and exploratory factor analysis (EFA); and secondly, reliability analysis, using the test-retest method, to assess the questionnaire's internal consistency (Cronbach's alpha) and reproducibility (intraclass correlation coefficient-ICC). The results showed that the questionnaire adapted was valid and reliable and can represent each item of the questionnaire for assessing the self-management of early warning signs of relapse. This proves that all 20 items used to assess it are appropriate for assessing the effectiveness of the patients' and their primary caregivers' abilities to self-manage early warning signs of relapse.


Trichomonas vaginalis degrades nitric oxide and expresses a flavorubredoxin-like protein: a new pathogenic mechanism?
Besides possessing many physiological roles, nitric oxide (NO) produced by the immune system in infectious diseases has antimicrobial effects. Trichomoniasis, the most widespread non-viral sexually transmitted disease caused by the microaerophilic protist Trichomonas vaginalis, often evolves into a chronic infection, with the parasite able to survive in the microaerobic, NO-enriched vaginal environment. We relate this property to the finding that T. vaginalis degrades NO under anaerobic conditions, as assessed amperometrically. This activity, which is maximal (133 +/- 41 nmol NO/10(8) cells per minute at 20 degrees C) at low NO concentrations (< or = 1.2 microM), was found to be: (i) NADH dependent, (ii) cyanide insensitive and (iii) inhibited by O(2). These features are consistent with those of the Escherichia coli A-type flavoprotein (ATF), recently discovered to be endowed with NO reductase activity. Using antibodies against the ATF from E. coli, a protein band was immunodetected in the parasite grown in a standard medium. If confirmed, the expression of an ATF in eukaryotes suggests that the genes coding for ATFs were transferred during evolution from anaerobic Prokarya to pathogenic protists, to increase their fitness for the microaerobic, parasitic life style. Thus the demonstration of an ATF in T. vaginalis would appear relevant to both pathology and evolutionary biology. Interestingly, genomic analysis has recently demonstrated that Giardia intestinalis and other pathogenic protists have genes coding for ATFs.


A case report of thoracic endometriosis - A rare cause of haemothorax.
The presence of endometrial tissue in airways, pleura and lung parenchyma is called thoracic endometriosis syndrome (TES). It is a rare pathology, and typically consists of catamenial pneumothorax, haemothorax, haemoptysis, and pulmonary nodules. We report a case of a 36-year-old woman with thoracic endometriosis causing catamenial haemothorax. The diagnosis of thoracic endometriosis is complicated and often delayed. TES should be suspected in a reproductive age woman with exacerbating symptoms during the menstruation. Treatment may be medical and surgical.


Relationship between plasma and cerebrospinal fluid norepinephrine and dopamine metabolites in a nonhuman primate.
Major and minor pathways of metabolism in the mammalian CNS result in the formation of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NMN) from norepinephrine (NE), and homovanillic acid (HVA) and 3-methoxytyramine (3-MT) from dopamine (DA), respectively. The correlational relationships between HVA and 3-MT and between MHPG and NMN in primate CSF and plasma have not been described. These relationships may help to elucidate the usefulness of CSF and plasma metabolites as indices of CNS NE and DA activity. In addition, because NMN is unlikely to cross the blood-brain barrier. CSF NMN concentrations would not be confounded by contributions from plasma, which is a major issue with CSF MHPG. We have obtained repeated samples of plasma and CSF from drug-naive male squirrel monkeys and have measured the concentrations of MHPG, HVA, NMN, and 3-MT to define their correlational relationships. For the NE metabolites, significant correlations were obtained for CSF MHPG and NMN (r = 0.806, p less than 0.001), plasma MHPG and CSF NMN (r = 0.753, p less than 0.001), and plasma and CSF MHPG (r = 0.776, p less than 0.001). These results suggest that CSF and plasma MHPG and CSF NMN may reflect gross changes in whole brain steady-state noradrenergic metabolism. Only a single significant relationship was demonstrated for the DA metabolites, with CSF 3-MT correlating with plasma HVA (r = 0.301, p less than 0.025). The results for the DA metabolites probably reflect regional differences in steady-state brain dopaminergic metabolism.


The effects of safety climate on vessel accidents in the container shipping context.
This study empirically evaluates the influence of safety climate on vessel accidents from a seafarer's perspective, specifically in the container shipping context. Factor analysis revealed six safety climate dimensions: management safety practices, supervisor safety practices, safety attitude, safety training, job safety, and co-workers' safety practices. Logistic regression analysis was used to evaluate the effects of safety climate dimensions on vessel accidents in respect of crew fatality and vessel failure. Study findings indicated that management safety practices, safety training, and job safety dimensions significantly affect crew fatality incidence, and the job safety dimension has a significant influence on vessel failure. Overall, results suggest the job safety dimension has the most important effect on vessel accidents, followed by management safety practices and safety training dimensions. Theoretical and practical implications of the findings for vessel accident prevention in the container shipping context are discussed.


Development of a surrogate model based on patient weight, bone mass and geometry to predict femoral neck strains and fracture loads.
Osteoporosis and related bone fractures are an increasing global burden in our ageing society. Areal bone mineral density assessed through dual energy X-ray absorptiometry (DEXA), the clinically accepted and most used method, is not sufficient to assess fracture risk individually. Finite element (FE) modelling has shown improvements in prediction of fracture risk, better than aBMD from DEXA, but is not practical for widespread clinical use. The aim of this study was to develop an adaptive neural network (ANN)-based surrogate model to predict femoral neck strains and fracture loads obtained from a previously developed population-based FE model. The surrogate model performance was assessed in simulating two loading conditions: the stance phase of gait and a fall. The surrogate model successfully predicted strains estimated by FE (r2=0.90-0.98 for level gait load case, r2=0.92-0.96 for the fall load case). Moreover, an ANN model based on three measurements obtainable in clinics (femoral neck length (level gait) or maximum femoral neck diameter (fall), femoral neck bone mass, body weight) was able to give reasonable predictions (r2=0.84-0.94) for all of the strain metrics and the estimated femoral neck fracture load. Overall, the surrogate model has potential for clinical applications as they are based on simple measures of geometry and bone mass which can be derived from DEXA images, accurately predicting FE model outcomes, with advantages over FE models as they are quicker and easier to perform.


Potential of beta-galactosidase-expressing Toxoplasma gondii for in situ localization and observation of rare stages of the parasite life cycle.
A cyst-forming strain of Toxoplasma gondii was transfected with the Escherichia coli LacZ gene and expressed beta-galactosidase constitutively. This strain has been used to localize and analyze the early stages of development and reactivation of T. gondii in mice. The chromogenic detection of the enzyme allows an easy detection of the parasites after light fixation and therefore allows a submacroscopic analysis of tissue distribution within the organism. Also, it allows further embedding and retrieval of rare stages for electron microscopic observation. that detect the presence of the parasite and initiate the response, and (2) the early stages of reactivation, when the cysts are supposed to break open and release the infectious bradyzoïtes. We have taken advantage of the possibility of detecting the enzymatic activity of beta-galactosidase (beta-gal) in transfected parasites to show that one could perform a semi-macroscopic detection and that this was compatible with further analysis by histological or electron microscopic techniques, being therefore able to detect the rare events and then to analyze them further with more refined morphological techniques.


A homeostatic mechanism counteracting K(+) -evoked choline release in adult brain.
Choline (Ch) is an essential nutrient as the biosynthetic precursor of acetylcholine (ACh) and phospholipids. Under resting conditions, the intracellular accumulation of Ch (above 10-fold), which is positively charged, is governed by the membrane potential and follows the Nernst equation. Accordingly, in synaptosomes from adult rats during depolarization, we observed a linear relationship between release of free cytoplasmic Ch and KCl concentration (2.7-120 mm). The K(+) -evoked Ch release was Ca(2+) -independent and did not originate from ACh or phospholipid hydrolysis. In superfused brain slices of adult rats, however, a K(+) -induced Ch efflux was absent. Also, under in vivo conditions, 30-60 mm KCl failed to increase the extracellular Ch level as shown by microdialysis in adult rat hippocampus. On the contrary, in brain slices from 1-week-old rats, high K(+) as well as 4-aminopyridine evoked a marked Ch efflux in a concentration-dependent fashion. This phenomenon faded within 1 week. Hemicholinium-3 (HC-3, 1 and 10 microm), a blocker of cellular choline uptake, caused a marked efflux of choline from adult rat slices but no or significantly less release from immature slices. We conclude that depolarization of synaptic endings causes a Ca(2+) -independent release of free cytoplasmic Ch into the extracellular space. In adult rat brain, this elevation of Ch is counteracted by a homeostatic mechanism such as uptake into brain cells.


HOPX is a tumor-suppressive biomarker that corresponds to T cell infiltration in skin cutaneous melanoma.
Skin cutaneous melanoma (SKCM) is the most threatening type of skin cancer. Approximately 55,000 people lose their lives every year due to SKCM, illustrating that it seriously threatens human life and health. Homeodomain-only protein homeobox (HOPX) is the smallest member of the homeodomain family and is widely expressed in a variety of tissues. HOPX is involved in regulating the homeostasis of hematopoietic stem cells and is closely related to the development of tumors such as breast cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. However, its function in SKCM is unclear, and further studies are needed. We used the R language to construct ROC (Receiver-Operating Characteristic) curves, KM (Kaplan‒Meier) curves and nomograms based on databases such as the TCGA and GEO to analyze the diagnostic and prognostic value of HOPX in SKCM patients. Enrichment analysis, immune scoring, GSVA (Gene Set Variation Analysis), and single-cell sequencing were used to verify the association between HOPX expression and immune infiltration. In vitro experiments were performed using A375 cells for phenotypic validation. Transcriptome sequencing was performed to further analyze HOPX gene-related genes and their signaling pathways. Compared to normal cells, SKCM cells had low HOPX expression (p < 0.001). Patients with high HOPX expression had a better prognosis (p < 0.01), and the marker had good diagnostic efficacy (AUC = 0.744). GO/KEGG (Gene Ontology/ Kyoto Encyclopedia of Genes and Genomes) analysis, GSVA and single-cell sequencing analysis showed that HOPX expression is associated with immune processes and high enrichment of T cells and could serve as an immune checkpoint in SKCM. Furthermore, cellular assays verified that HOPX inhibits the proliferation, migration and invasion of A375 cells and promotes apoptosis and S-phase arrest. Interestingly, tumor drug sensitivity analysis revealed that HOPX also plays an important role in reducing clinical drug resistance. These findings suggest that HOPX is a blocker of SKCM progression that inhibits the proliferation of SKCM cells and promotes apoptosis. Furthermore, it may be a new diagnostic and prognostic indicator and a novel target for immunotherapy in SKCM patients.


Functional analysis of abscisic acid 8'-hydroxylase.
Abscisic acid (ABA) plays an important role in the control of seed dormancy and germination. Identification of hormone metabolism genes from a particular plant species of interest is an essential step in hormone research. The function of these gene products is validated by biochemical analysis using heterologous expression systems, such as E. coli and yeast. ABA 8'-hydroxylase is a subfamily of P450 monooxygenases and is encoded by CYP707A genes. CYP707A catalyzes the committed step in the major ABA catabolic pathway. In this chapter, we describe the methods for RNA extraction from seeds, cloning the CYP707A cDNAs, protein expression in yeast, and biochemical analysis of their gene products.


Health-related quality of life and coping strategies adopted by COVID-19 survivors: A nationwide cross-sectional study in Bangladesh.
This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh. This is a cross-sectional study of 2198 adult, COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali-translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QoLBREF) questionnaires were used. The data collection period was from October 2020 to March 2021. Males 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations (p<0.005) with physical, psychological and social relationships, whereas gender showed only a significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed a significant correlation with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategies (p<0.001); whereas gender and co-morbidities showed a significant correlation with problem-focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies(p<0.001). Survivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem-focused coping, with emotion-focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants. This study represents the real scenario of nationwide health-associated quality of life and coping strategies during and beyond the Delta pandemic.


Influence of Selective Laser Trabeculoplasty (SLT) on the iStent inject® outcomes.
To evaluate the influence of Selective Laser Trabeculoplasty (SLT) on iStent inject® outcomes in open-angle glaucoma (OAG). In this retrospective comparative cohort outcome study, 66 patients who were treated with two iStent inject® devices were included. Patients were divided into two subgroups consisting of patients without SLT treatment prior to surgery and patients who had been treated previously with 360° SLT but without sufficient response. Outcome measures included intraocular pressure (IOP) and number of antiglaucoma medications after 6 weeks with three, six, 12, and 24 month follow-ups. Mean preoperative IOP decreased from 20.4 ± 5.3 mmHg to 14.8 ± 3.0 mmHg for patients without SLT treatment prior to surgery (p = 0.001) and from 19.2 ± 4.5 mmHg to 14.0 ± 1.6 mmHg for patients with insufficient response to 360° SLT treatment (p = 0.027) at 12 months after iStent inject® implantation. No significant difference was found between the two groups (p > 0.05). The number of antiglaucoma medications did not change in both groups (p > 0.05) and showed no significant difference between the two groups (p > 0.05). Prior SLT treatment seems to have no negative influence on the IOP lowering-effect of iStent inject® implantation in patients with OAG. It is therefore an appropriate incremental procedure with no exclusion criterion for an iStent inject® implantation.


Systematic review: Impact of meningococcal vaccination on pharyngeal carriage of meningococci.
To investigate the effect of meningococcal vaccines on pharyngeal carriage of meningococci. Systematic review. MEDLINE and EMBASE were searched for relevant studies. Controlled trials and observational studies which used comparison groups or compared carriage rates before and after vaccination were included in the review. Twenty-nine studies satisfied the inclusion criteria. Twenty-five studies reported the effect of a polysaccharide vaccine, one the effect of a serogroup C conjugate vaccine and three the impact of serogroup B outer-membrane vaccines on overall and/or serogroup-specific meningococcal carriage rates. Ten studies of meningococcal polysaccharide vaccines found reduced serogroup-specific carriage; seven of these focussed on high-risk groups and had a short follow-up period. Only one of five studies of civilian populations in Africa showed a significantly reduced carriage. Many studies had methodological shortcomings. The one study which assessed the effect of a meningococcal conjugate vaccine on carriage showed a significant impact. Three studies of serogroup B outer-membrane protein vaccines showed no effect on carriage. A few well-designed trials of the impact of meningococcal vaccines on carriage have been undertaken. Such studies should be an essential component of the evaluation of new meningococcal vaccines, particularly those introduced to control epidemic meningococcal disease in Africa.


Present-self, past-self and the close-other: neural correlates of assigning trait adjectives to oneself and others.
Information regarding the past-self may be viewed as information referring to other people. However, evidence supporting this notion at the neural level is rather sparse and it remains unclear whether the past-self is processed like any 'other' or like the close-other only. The aim of this event-related potential study was to investigate this issue. A reflection task requiring evaluation of positive and negative trait adjectives with respect to present- and past-self, a close-other and a famous person was applied. We hypothesized that the past-self and close-other conditions would share their neural underpinnings. The process of reflection on the past-self and close-other was indeed associated with similar mean amplitudes of the late positive component (LPC), whereas in the case of the past-self vs. famous person comparison LPC was significantly enhanced for the past-self. Analogous effects were observed when LPC was calculated for trials with traits judged as either suitable or unsuitable to describe a person who was the target of reflection. Thus, these findings suggest that the processing of information related to the past-self resembles processing of information related to a personally relevant other. Moreover, sex-differences were observed in reaction times and LPC amplitudes for responses reflecting the positivity bias.


Integrated leachate management approach incorporating nutrient recovery and removal.
This manuscript presents an integrated management scheme for leachate which employed struvite precipitation to recover ammonia nitrogen and phosphorus, aerobic granular sludge process for carbon oxidation (in the form of BOD and sCOD) and single stage anaerobic ammonia oxidation (ANAMMOX) for nitrogen management. The influent fed to the integrated treatment scheme was a mixture of anaerobic digester centrate and real leachate in 4:1 ratio. Almost 77% recovery of phosphorus and 25% removal of NH4+-N were accomplished through struvite precipitation at an optimum pH of 9. High pH contributed to free ammonia loss during struvite precipitation experiments. In the aerobic granular sludge reactor overall, BOD5, COD and NH4+-N removal percentages were 74%, 45% and 35% and in the PN/A reactor, overall 35% removal of total inorganic nitrogen (TIN) was observed. More than 80% BOD removal was recorded in the granular reactor with soluble COD (sCOD) removal fluctuating between 28 and 57% depending on the operational phase. High-throughput amplicon sequencing of 16S rRNA gene targeting V4 region revealed a dominance of phylum Planctomycetes, in the PN/A reactor system. Presence of Rhodobacteraceae, Xanthomonadaceae, Flavobacteriaceae in the granular biomass confirmed the defined redox zones inside mature granules indicating simultaneous removal of nitrogen (N) and organics in aerobic granular sludge technology. Exposing the synthetically cultured aerobic granules directly to the mixture of leachate and centrate unveiled an alteration in physical characteristics of granules; however, reactor operational data and microbial community analysis ascertain the effectiveness of the treatment scheme treating two urban waste-streams.


Design and evaluation of a dashboard to support the comprehension of the progression of patients with dementia in day centers.
In day centers, people with dementia are assigned to specific groups to receive care according to the progression of the disease. This article presents the design and evaluation of a dashboard aimed at facilitating the comprehension of the progression of people with dementia to support decision-making of healthcare professionals (HCPs) when determining patient-group assignment. A participatory design methodology was followed to build the dashboard. The grounded theory methodology was utilized to identify requirements. A total of 8 HCPs participated in the design and evaluation of a low-fidelity prototype. The perceived usefulness and perceived ease of use of the high-fidelity prototype was evaluated by 15 HCPs (from several day centers) and 38 psychology students utilizing a questionnaire based on the technology acceptance model. HCPs perceived the dashboard as extremely likely to be useful (Mdn=6.5 out of 7) and quite likely to be usable (Mdn=6 out of 7). Psychology students perceived the dashboard as quite likely to be useful and usable (both with Mdn=6). Making use of a participatory design helped foster in HCPs a sense of ownership of the dashboard, thus facilitating its acceptance. The creation of low-fidelity and high-fidelity prototypes led to identifying valuable, timely, and specific feedback at different stages of the development process as well as to establishing a set of lessons learned for the development of dashboards in the healthcare domain.


Five-weekend care of the elderly certificate course: continuing professional development activity for family physicians.
Primary care practitioners have unique clinical challenges in caring for elderly patients and require educational courses that are specifically designed for their needs in caring for this patient population. To improve family physicians' knowledge of and confidence in managing common geriatric problems. The accredited course curriculum is delivered on 5 weekends over approximately 6 months.Each weekend focuses on a different theme including cognitive impairment, gait disorders, mental health and pain management, geriatric medical problems, and failure to thrive. Participants complete written assignments between weekend sessions, which involve self-reflection on how the new knowledge and skills gained through the course will be incorporated in the management of elderly patients in their practices. The 5-Weekend Care of the Elderly Certificate Course is an accredited continuing professional development program for primary care practitioners. Preliminary evaluation suggests improvement in participants' self-rated knowledge of and confidence in managing geriatric problems. Qualitative data show positive changes in clinical practice.


Illness Beliefs in Chronic Fatigue Syndrome: A Study Involving Affected Adolescents and their Parents.
The aim of the study was too investigate the beliefs of young people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and their parents, about illness causes and management. Twenty-one young people with CFS/ME and their parents participated in an open-ended interview. Infective causes were identified by the majority of respondents, and psychological ones by a minority. Many highlighted reducing activity and resting in symptom management. Positive and negative experiences of psychiatric and psychological treatments were recorded. Professionals should carefully explore the illness related beliefs of young people with CFS/ME and parental beliefs in order to agree treatment plans.


Comparison of PCR, electrochemical enzyme-linked immunosorbent assays, and the standard culture method for detecting salmonella in meat products.
An electrochemical enzyme-linked immunosorbent assay (ELISA) coupled with flow injection analysis (ELISA-FIA) and a PCR-based method using ST11 and ST15 primers for detecting salmonellae in meat were evaluated in comparison with the International Organization for Standardization (ISO) culture method. The methods were applied to experimentally contaminated and naturally contaminated meat samples. The results showed that both ELISA-FIA and PCR allowed detection of salmonella in a product contaminated with a low number of the microorganisms (1 to 10 salmonellae/25 g) after only 5 h of incubation of preenrichment broth, and they were just as effective as the ISO method.


Is it Useful to Repeat Magnetic Resonance Imaging of the Sacroiliac Joints After Three Months or One Year in the Diagnosis of Patients With Chronic Back Pain and Suspected Axial Spondyloarthritis?
To investigate the value of repeated magnetic resonance imaging (MRI) of the sacroiliac (SI) joints in diagnosing chronic back pain patients in whom axial spondyloarthritis (SpA) is suspected and to examine determinants of positive MRI findings in SI joints. Patients with chronic back pain (duration 3 months-2 years, age ≥16 years, age at onset <45 years) with ≥1 SpA feature who were included in the Spondyloarthritis Caught Early cohort underwent visits at baseline, at 3 months, and at 1 year. Visits included an evaluation of all SpA features and repeated MRI of SI joints. MRI-detected axial SpA positivity (according to the definition from the Assessment of SpondyloArthritis international Society) was evaluated by 2 or 3 well-trained readers who were blinded with regard to clinical information. The likelihood of a positive MRI finding at follow-up visits (taking into consideration contributing factors) was calculated by generalized estimating equation analysis. Of the 188 patients, 38.3% were male, the mean ± SD age was 31.0 ± 8.2 years, and the mean ± SD symptom duration was 13.2 ± 7.1 months. Thirty-one patients (16.5%) had positive MRI findings in the SI joints at baseline. After 3 months and after 1 year, the MRI results had changed from positive to negative in 3 of 27 patients (11.1%) and 11 of 29 patients (37.9%), respectively, which was attributable in part to the initiation of anti-tumor necrosis factor therapy. Status changes from negative to positive were seen in 5 of 116 patients (4.3%) after 3 months and in 10 of 138 patients (7.2%) after 1 year. HLA-B27 positivity and male sex were independent determinants of the likelihood of a positive MRI scan at any time point (42% in HLA-B27+ men and 6% in HLA-B27- women). If the baseline results were negative, the likelihood of a positive scan at follow-up was very low (≤7%). MRI-detected status changes in the SI joints were seen in a minority of the patients, and both male sex and HLA-B27 positivity were important predictors of MRI positivity. Our findings indicate that conducting MRI scans after 3 months or after 1 year in patients with suspected early axial SpA is not diagnostically useful.


Intracellular K+, Na+ and Cl- concentrations and membrane potential in human monocytes.
The relationship between the resting membrane potential and the intracellular ionic concentrations in human monocytes was investigated. Cell volume, cell water content, and amount of intracellular K+, Na+, and Cl- were measured to determine the intracellular concentrations of K+ (Ki), Na+ (Nai) and Cl- (Cli) of monocytes, and of lymphocytes and neutrophils. Values found for monocytes were similar to those for neutrophils, i.e., cell volumes were 346 and 345 micron3, respectively, cell water content 78%, and Ki, 128 and 125, Nai, 24 and 26, and Cli, 102 and 103 mmol/l cell water, respectively. Lymphocytes, however, had different values: 181 micron3 cell volume, 77% cell water content, and for Ki, Nai, and Cli, 165, 37, and 91 mmol/l cell water, respectively. The resting membrane potential of cultured human monocytes (range -30 to -40 mV), determined by measurement of the peak potential occurring within the first milliseconds after microelectrode entry, was most dependent on extracellular K+, followed by Cl-, and Na+. The membrane permeability ratio of Cl- to K+ was estimated by use of the constant field equation to be 0.23 (range 0.22 to 0.30).


Nitrodopamine vs dopamine as an intermediate layer for bone regeneration applications.
The aim of this paper was to present a parallel investigation of the poly(dopamine) (DP) and nitrodopamine (NDP) structures deposited on titanium surface (Ti) and titanium oxide nanotubes (NT-TiO2/Ti) and to highlight their advantages and drawbacks to serve as an intermediary layer for bone regeneration applications. This study outlines some hypotheses regarding the manner in which these compounds are able to form a stable film that could serve as bioadhesive. The paper is also a study of structuring and evolution of film architecture for two coatings, polydopamine and nitrodopamine in terms of surface structure, stability, wettability, morphology, adhesion and ability to protect the titanium surface. All investigations are based on the data provided by surface characterization techniques: SEM, RAMAN, XRD, XPS, wettability and flexural strength. The impact of polydopamine and nitrodopamine coatings on the biocompatibility of titanium nanotubes was investigated in vitro. Cell morphology, viability, proliferation and pre-osteoblast differentiation were examined in detail. It was highlighted that both DP and NDP functionalized TiO2 nanotubes display good cell response in terms of cell spreading, formation of focal adhesions, cell viability and proliferation, suggesting their suitability for applications in bone regeneration field. However, NDP coated TiO2 nanotubes demonstrated an enhanced osteogenic potential compared to DP coated substrates.


Valve-in-valve transcatheter aortic valve implantation overcoming hostile anatomy: Evolut R for the treatment of Mitroflow bioprosthesis dysfunction.
Redo surgery is regarded as the first-line treatment option for patients presenting with prosthetic valve degeneration. However, many patients have concomitant co-morbidities and this option is associated with significant risk. Transcatheter valve-in-valve implantation is an alternative strategy depending on the bioprosthetic valve that is being treated. The Sorin Mitroflow bioprosthetic aortic valve has been regarded as a contraindication to valve-in-valve treatment due to the high risk of coronary obstruction. We here present the case of a patient with small peripheral vasculature who underwent successful transfemoral valve-in-valve implantation and subsequently discuss the challenges and technical aspects that require consideration.


Porous nanoparticles with engineered shells release their drug cargo in cancer cells.
Highly porous nanoscale metal-organic frameworks (nanoMOFs) attract growing interest as drug nanocarriers. However, engineering "stealth" nanoMOFs with poly(ethylene glycol) (PEG) coatings remains a main challenge. Here we address the goal of coating nanoMOFs with biodegradable shells using novel cyclodextrin (CD)-based oligomers with a bulky structure to avoid their penetration inside the open nanoMOF porosity. The PEG chains were grafted by click chemistry onto the CDs which were further crosslinked by citric acid. Advantageously, the oligomers' free citrate units allowed their spontaneous anchoring onto the nanoMOFs by complexation with the iron sites in the top layers. Up to 31 wt% oligomers could be firmly attached by simple incubation with the nanoMOFs in an aqueous medium. Moreover, the anticancer drug doxorubicin (DOX) was successfully entrapped in the core-shell nanoMOFs with loadings up to 41 wt%. High resolution STEM (HR-STEM) showed that the organized crystalline structures were preserved. Remarkably, at the highest loadings, DOX was poorly released out of the nanoMOFs at pH 7.4 (<2% in 2 days). In contrast, around 80% of DOX was released out at pH 4.5 of artificial lysosomal fluid in 24 h. Confocal microscopy investigations showed that the DOX-loaded nanoMOFs penetrated inside Hela cancer cell together with their PEG shells. There, they released the DOX cargo which further diffused inside the nucleus to eradicate the cancer cells.


Role acquisition, socialization, and retention: unique aspects of a mentoring program.
Banner Good Samaritan Medical Center, a level-one tertiary care teaching facility in the southwest United States, developed an 18-month RN mentoring program in response to the national nursing shortage and a desire to promote nursing retention at the institution.


Limiting homologous recombination at stalled replication forks is essential for cell viability: DNA2 to the rescue.
The disease-associated nuclease-helicase DNA2 has been implicated in DNA end-resection during DNA double-strand break repair, Okazaki fragment processing, and the recovery of stalled DNA replication forks (RFs). Its role in Okazaki fragment processing has been proposed to explain why DNA2 is indispensable for cell survival across organisms. Unexpectedly, we found that DNA2 has an essential role in suppressing homologous recombination (HR)-dependent replication restart at stalled RFs. In the absence of DNA2-mediated RF recovery, excessive HR-restart of stalled RFs results in toxic levels of abortive recombination intermediates that lead to DNA damage-checkpoint activation and terminal cell-cycle arrest. While HR proteins protect and restart stalled RFs to promote faithful genome replication, these findings show how HR-dependent replication restart is actively constrained by DNA2 to ensure cell survival. These new insights disambiguate the effects of DNA2 dysfunction on cell survival, and provide a framework to rationalize the association of DNA2 with cancer and the primordial dwarfism disorder Seckel syndrome based on its role in RF recovery.


CYP2C9, but not CYP2C19, polymorphisms affect the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects.
Although cytochrome P450 (CYP) 2C9 was thought to be the main pathway for glyburide (INN, glibenclamide) metabolism in vivo, studies in vitro indicated that CYP2C19 had a more dominant effect. This study investigated the relative influence of CYP2C9 and CYP2C19 genotypes on the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects. Three groups of healthy male Chinese subjects (n=6 per group) were enrolled, as follows: group I, CYP2C9*1/*1 and CYP2C19 extensive metabolizers (EMs); group II, CYP2C9*1/*1 and CYP2C19 poor metabolizers (PMs); and group III, CYP2C9*1/*3 and CYP2C19 EMs. Subjects received single oral doses of 5 mg glyburide. Multiple blood samples were collected, and the plasma glyburide concentrations were determined by an HPLC method. The plasma glucose and insulin concentrations were also measured up to 2 hours after dosing. No significant differences in glyburide pharmacokinetics were observed between CYP2C19 EM and PM subjects who had the CYP2C9*1/*1 genotype (group I versus group II). Their respective values for area under the plasma concentration-time curve from time 0 to infinity (AUC0-infinity) and elimination half-life (t1/2) were 0.46+/-0.13 microg.h/mL versus 0.57+/- 0.11 microg.h/mL (P=.569) and 2.09+/-0.22 hours versus 2.24+/- 0.27 hours (P=.721). However, significant increases in AUC(0-infinity) (125% and 82%; P=.008 and .024, respectively) and t1/2 (71% and 60%; P=.003 and .007, respectively) were observed when CYP2C9*1/*3 subjects (group III) were compared with CYP2C9*1/*1 subjects in group I or II. Blood glucose reductions at 2 hours after dosing were 41.8%, 23.9%, and 27.7% in groups I, II, and III, respectively (P=.029), and hypoglycemia developed in 3 of 6 CYP2C9*1/*3 carriers and 2 of 12 CYP2C9*1/*1 carriers. CYP2C9, but not CYP2C19, polymorphism appears to exert a dominant influence on glyburide pharmacokinetics and pharmacodynamics in vivo. Further studies in diabetic patients with long-term dosing are warranted to confirm these findings.


Evaluation of patients undergoing senning repair with two-dimensional contrast echocardiography.
The postoperative anatomy of the Senning interatrial diversion was defined by two-dimensional contrast echocardiography in ten patients. A modified apical four-chamber view proved most valuable, allowing for simultaneous visualization of both the systemic venous atrium and the pulmonary venous atrium. The anatomy was confirmed with two-dimensional contrast echocardiography utilizing catheters placed in the systemic venous atrium and pulmonary venous atrium at the time of surgery. In addition, in several of the patients, we were able to detect atrial or ventricular level shunts which were not clinically apparent. One patient who was judged to have a significant shunt by two-dimensional contrast echocardiography had no anatomic site found at autopsy to explain the shunting. We conclude that two-dimensional contrast echocardiography can define the postoperative anatomy following Senning repair allowing for immediate and future evaluation. Shunting at the atrial and ventricular levels can also be detected, but the method is very sensitive and difficult to quantitate or correlate clinically.


Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.
Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the activated, open-channel state of a pLGIC by specific, state-dependent binding to this site.


Exploring Definition of Cyberbullying and its Forms From the Perspective of Adolescents Living in Pakistan.
There exists a great disparity in the literature on the definition of cyberbullying. This research aimed to explore the definition and forms of cyberbullying from adolescents' perspectives. Six focus groups (N = 36) were conducted with participants aged 16-21 years (M = 17.6, SD = 1.8). The focus group guide was used to gain an understanding of adolescents' perceptions and experiences of cyberbullying. The thematic analysis revealed that, contrary to the literature, participants do not apply traditional bullying definition (intention, repetition, and power imbalance) to cyberbullying. They argue about the relevance of traditional bullying criteria in certain contexts. For example, they stressed upon the perception of the victim, if the victim perceives something emotionally damaging, then intention, repetition and power imbalance become completely irrelevant. Memes and cybermobs were also found to be novel forms of cyberbullying. The current research extends the literature by adding adolescents' perceived definitions and novel forms of cyberbullying.


Anthraquinone acted as a catalyst for the removal of triphenylmethane dye containing tertiary amino group: Characteristics and mechanism.
Herein, we found that anthraquinone (AQ) acted as a catalyst for the rapid and effective removal of triphenylmethane dye containing tertiary amino group (TDAG). Results showed that AQ had an enhanced catalytic reactivity towards the removal of TDAG compared to hydro-quinone, which was further proved and explained using density functional theory (DFT) calculations. AQs could achieve a TDAG removal efficiency and rate of approximately 100% and 0.3583 min-1, respectively, within 20 min. Quenching experiments and electron paramagnetic resonance (EPR) tests indicated that the superoxide radical (O2•-) generated through the catalytic reduction of an oxygen molecule (O2) by AQ contributed to the effective removal of the TDAG. In addition, it was found that the electrophilic attack of the O2•- radical on the TDAG was the driving force for the dye degradation process. Decreasing the pH led to protonation of the substituted group of AG, which resulted in formation of an electron deficient center in the TDAG molecule (TDAG-EDC+) through delocalization of the π electron. Therefore, the possibility of the electrophilic attack for the dye by the negative O2•- radical was significantly enhanced. This study revealed that the H+ and the O2•- generated by the catalytic reduction of O2 have synergistic effects that led to a significant increase in the dye removal rate and efficiency, which were higher than those obtained through persulfate oxidation.


Advances in probes and methods for clinical EPR oximetry.
EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings.


Antihypertensive effects of the hydro-ethanol extract of Senecio serratuloides DC in rats.
Senecio serratuloides DC is used in folk medicine for treating hypertension, skin disorders, internal and external sores, rashes, burns and wounds. This study aimed at investigating the antihypertensive effects of the hydroethanol extract of S. serratuloides (HESS) in N-Nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats. Acute toxicity of HESS was first determined to provide guidance on doses to be used in this study. Lorke's method was used to determine safety of the extract in mice. Female Wistar rats were treated orally once daily with L-NAME (40 mg/kg) for 4 weeks and then concomitantly with L-NAME (20 mg/kg) and plant extract (150 and 300 mg/kg), captopril (20 mg/kg) or saline as per assigned group for 2 weeks followed by a 2-week period of assigned treatments only. Blood pressure was monitored weekly. Lipid profile, nitric oxide, renin and angiotensin II concentrations were determined in serum while mineralocorticoid receptor concentration was quantified in the kidney homogenate. Nitric oxide (NO) concentration was determined in serum and cardiac histology performed. HESS was found to be non-toxic, having a LD50 greater than 5000 mg/kg. Blood pressure increased progressively in all animals from the second week of L-NAME treatment. HESS treatment significantly and dose-dependently lowered systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.01), low density lipoprotein cholesterol (p < 0.01) and triglycerides (p < 0.01). It significantly prevented L-NAME induced decrease in serum angiotensin II (p < 0.01), high density lipoprotein cholesterol (p < 0.001) and serum nitric oxide concentrations (p < 0.001). HESS also significantly (p < 0.01) prevented collagen deposition in cardiac tissue. The hydro-ethanol extract of Senecio serratuloides showed antihypertensive, antihyperlipidemic and cardioprotective effects in rats thus confirming its usefulness in traditional antihypertensive therapy and potential for antihypertensive drug development.


MRI receiver frequency response as a contributor to Nyquist ghosting in echo planar imaging.
To study the frequency response characteristic of the MRI signal receiver system as a contributing factor to the formation of Nyquist ghosting in echo-planar imaging (EPI). Experimental work was undertaken on a 1.5 T system. A cylindrical test object filled with water was imaged axially with EPI in the center of the quadrature, transmit-receive head coil. In the first set of experiments, the water conductivity was increased progressively with the addition of salt between EPI acquisitions. In the second set of experiments, the conductivity of the water in the test object was kept constant and EPI images were acquired at several different bandwidths. A computer simulation was also implemented to demonstrate the impact of changes in the frequency response characteristic of the signal receiver system on EPI Nyquist ghosting. Experimental and simulation results showed that Nyquist ghosting increased with the variation of the frequency response characteristic within the effective frequency range determined by the image bandwidth. One can increase the variation in the frequency response characteristic by increasing its steepness over the image's bandwidth window when coil loading is decreased, or by increasing the effective frequency range when image bandwidth is increased. The results of this research may help reduce Nyquist ghosting in EPI studies when the imaging coil is not sufficiently loaded, such as in pediatric and phantom studies.


Bromocriptine inhibits 2-deoxy-D-glucose-stimulated gastric acid secretion in the rat.
The influence of bromocriptine on the secretagogue-induced gastric acid secretion was examined in rats. The drug inhibited the gastric acid secretion centrally stimulated by 2-deoxy-D-glucose (2DG) in anesthetized or conscious rats. Apomorphine also prevented 2DG-induced acid secretion in anesthetized rats but not in conscious rats. Neither bromocriptine nor apomorphine significantly influenced the acid secretion induced peripherally by electrical vagus stimulation or gastrin. The antisecretory effect of bromocriptine was reversed by dopamine antagonists in anesthetized or conscious rats, but not by apomorphine in anesthetized rats. The results suggest that in rats, the antisecretory effect of bromocriptine on 2DG-stimulated acid secretion is partly due to its central dopamine agonistic action, but that of apomorphine may be due to dopaminergic plus other mechanisms.


Cognitive, social, and behavioral manifestations of the co-occurrence of autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review.
This work aimed to review recent research on the characteristics of individuals who have both autism spectrum disorder and attention-deficit/hyperactivity disorder due to their high co-occurrence. Thirty-four studies were analyzed and main findings summarized in two content domains focusing on areas that could enhance our understanding of the cognitive and behavioral characteristics of individuals with autism spectrum disorder + attention-deficit/hyperactivity disorder (ASD+). Most of the results suggested that ASD+ is a co-occurring condition associated with more severe impairments in cognitive functioning, adaptive behavior, and increased likelihood to present more emotional/behavioral problems. These results will be helpful to provide improved care plans for individuals with both attention-deficit/hyperactivity disorder and autism spectrum disorder.


Vascular access in previously catheterised children and adolescents: a prospective study of 131 consecutive cases.
Vascular access for cardiac catheterisation of children and young adults who have had previous catheter procedures is often difficult. To assess the influence of age at and type and technique of previous cardiac catheterisation on the ease of vascular access for subsequent study of paediatric and adolescent patients. Tertiary referral centre for paediatric cardiology. 478 Consecutive patients aged 1 day to 19 years undergoing cardiac catheterisation over a 12 month period, including 131 patients who had had previous catheterisation(s). Prospective study, recording for each patient the age, weight, diagnosis, vascular access (artery, vein, or both), vessels eventually catheterised, access time, total duration of the procedure, and details of any previous catheter studies. Of 131 patients who had had previous catheterisations, 80 (61%) had been studied once previously, 38 (29%) twice, and 13 (10%) on three or more occasions. The right femoral vessels were cannulated without difficulty in 72 cases (55%). Elective cannulation of left femoral vessels (because of scar tissue on the right side) or upper body vessels was undertaken in 18 cases (14%). Problems cannulating the right femoral vessels were encountered in 41 cases (31%); the vein was blocked in 29, the artery in six and the femoral veins were blocked bilaterally in six cases. The mean (SD) access time was significantly prolonged in these 41 children (41(18) v 21(13) minutes, p < 0.001) as was total duration of the procedure (116(31) v 94(34) minutes, p < 0.001). Children who had had a saphenous vein cut down as neonates subsequently had a blocked ipsilateral femoral vein in 10/15 cases (67%). Risk factors for problematic cannulation also included a higher number of previous catheterisation procedures. Difficulties with vascular access are common in children and adolescents who have had previous cardiac catheterisations. In those who have had cut down or multiple previous studies, elective entry to the left femoral vessels should be undertaken and procedure time may be prolonged. Such cases should therefore be performed under general anaesthesia.


A dual role for an aspartic acid in glycosylasparaginase autoproteolysis.
Glycosylasparaginase uses an autoproteolytic processing mechanism, through an N-O acyl shift, to generate a mature/active enzyme from a single-chain precursor. Structures of glycosylasparaginase precursors in complex with a glycine inhibitor have revealed the backbone in the immediate vicinity of the scissile peptide bond to be in a distorted trans conformation, which is believed to be the driving force for the N-O acyl shift to break the peptide bond. Here we report the effects of point mutation D151N. In addition to the loss of the base essential in autoproteolysis, this mutation also eradicates the backbone distortion near the scissile peptide bond. Binding of the glycine inhibitor to the autoproteolytic site of the D151N mutant does not restore the backbone distortion. Therefore, Asp151 plays a dual role, acting as the general base to activate the nucleophile and holding the distorted trans conformation that is critical for initiating an N-O acyl shift.


Ratio developmental quotients from the Bayley are comparable to later IQs from the Stanford-Binet.
Ratio developmental quotients (DQs) from Bayley Scales administered after age 30 months were compared to Stanford-Binet IQs secured later. Means from two testings of 42 mentally retarded children were almost identical. The DQs and IQs correlated .81, p less than .001. These findings justify the use of Bayley ratio quotients to determine intellectual level of children who are too old for the Bayley norms but too retarded to earn a basal level on the Stanford-Binet.


Decrease in natural killer cell activity in kidney allograft recipients.
The natural killer cell activity (NKCA) of a population of 66 functioning kidney allograft recipients (followed up for over 9 years) was assessed on K562 and DORA cell line targets. The 51Cr specific release test showed a rapid, sharp decrease in NKCA as early as 3 months after grafting, reaching a minimal level between 7 and 60 months (5 +/- 5 vs. 45 +/- 19% 51Cr release; P less than 0.001). Patients showing an almost total lack of NKCA were roughly the same whether assessed on K562 or DORA targets. NKCA tended to be restored in long-term transplanted patients (greater than 61 months). Control populations, aside from 32 healthy individuals, consisted of 11 haemodialysed patients as well as patients submitted to corticosteroid therapy for more than one year (8 cases of giant cell arteritis and 4 chronic asthmas). Haemodialysed patients exhibited normal NKCA (whether previously grafted or not). Corticosteroid-treated patients showed either no significant modification (K562 target) or a borderline decrease (DORA target) in NKCA. Azathioprine or corticosteroid dosage intake on the day of the test did not influence the level of graft recipient NKCA. The natural cytotoxicity of peripheral blood lymphocytes (PBL) from recipients lacking in activity (less than 5% 51Cr release) was not restored by exogenous (type alpha) interferon. and PBL of recipients with low NKCA scores produced normal levels of purified interferon after 24-h Sendai virus exposure. No inhibitory effects of sera obtained from recipients lacking NKCA nor any active suppressor cells from their PBL could be evidenced, thus suggesting an actual loss of natural killer progenitors (or an "insensitivity" to interferon) in those patients. Corticosteroids, as opposed to azathioprine, were able to decrease the in vitro NKCA of healthy donor PBL at pharmacological concentrations.


Outcome analysis of laparoscopic incisional hernia repair and risk factors for hernia recurrence in liver transplant patients.
Incisional hernia is a common complication after liver transplantation (LT). Immunosuppression, obesity, and use of steroids are known risk factors. The purpose of the retrospective study was to summarize and evaluate experiences and results of laparoscopic intraperitoneal onlay mesh (IPOM) hernia repair. We reviewed our liver transplant patients over a seven-yr period with laparoscopic incisional hernia repair (LIHR) to direct our attention on risk factors for hernia recurrence after hernia repair. Fifty-four patients after LT with incisional hernia were treated with laparoscopic repair, 42 male and 12 female patients of overall mean age of 58 ± 9 yr and body mass index (BMI) of 25 ± 4 kg/m(2) . A total of 755 LTs were performed at our institution in this time period, resulting in 7.15% of patients undergoing laparoscopic hernia repair. The mean postoperative hospital stay after was nine d. During the follow-up, nine recurrent hernias were noted (17%). BMI (p = 0.001) and sirolimus as immunosuppressive therapy were significantly associated with hernia recurrence (p = 0.014). LIHR is a safe and feasible method to treat hernias after LT. BMI and sirolimus as immunosuppressive therapy are risk factors for recurrence of hernia after laparoscopic hernia repair.


Culture-bound syndromes: the story of dhat syndrome.
Culture-bound syndrome is a term used to describe the uniqueness of some syndromes in specific cultures. Dhat (semen-loss anxiety) has been considered to be an exotic 'neurosis of the Orient'. To ascertain the presence of similar symptoms and syndromes in different cultures and historical settings. Electronic and manual literature searches were used to gather information on the existence and description of semen-loss anxiety in different cultures and settings. Most of the empirical studies on dhat syndrome have emerged from Asia, whereas its concepts have been described historically in other cultures, including Britain, the USA and Australia. The different sources indicate the universality of symptoms and global prevalence of this condition, despite its image as a 'neurosis of the Orient'. It appears that dhat (semen-loss anxiety) is not as culture-bound as previously thought. We propose that the concept of culture-bound syndromes should be modified in line with DSM-IV recommendations.


Premature aging syndromes: From patients to mechanism.
Aging is an inevitable consequence of human life resulting in a gradual deterioration of cell, tissue and organismal function and an increased risk to develop chronic ailments. Premature aging syndromes, also known as progeroid syndromes, recapitulate many clinical features of normal aging and offer a unique opportunity to elucidate fundamental mechanisms that contribute to human aging. Progeroid syndromes can be broadly classified into those caused by perturbations of the nuclear lamina, a meshwork of proteins located underneath the inner nuclear membrane (laminopathies); and a second group that is caused by mutations that directly impair DNA replication and repair. We will focus mainly on laminopathies caused by incorrect processing of lamin A, an intermediate filament protein that resides at the nuclear periphery. Hutchinson-Gilford Progeria (HGPS) is an accelerated aging syndrome caused by a mutation in lamin A and one of the best studied laminopathies. HGPS patients exhibit clinical characteristics of premature aging, including alopecia, aberrant pigmentation, loss of subcutaneous fat and die in their teens as a result of atherosclerosis and cardiovascular complications. Here we summarize how cell- and mouse-based disease models provided mechanistic insights into human aging and discuss experimental strategies under consideration for the treatment of these rare genetic disorders.


Molecular differentiation of sibling species in the Galactomyces geotrichum complex.
PCR-analysis, multilocus enzyme electrophoresis and molecular karyotyping were used to characterize 52 strains belonging to the genus Galactomyces. The resultant data revealed that a PCR method employing the universal primer N21 and microsatellite primer (CAC)5 is appropriate for the distinction of four Ga. geotrichum sibling species, Ga. citri-aurantii and Ga. reessii. Better separation was achieved with the UP primer N21; each species displayed a specific pattern with very low intraspecific variation. We propose to use the primer N21 for the differentiation of the six taxa composing the genus Galactomyces. Multilocus enzyme electrophoresis revealed genetic homogeneity of each sibling species within the Ga. geotrichum complex. On the other hand, the four sibling species, having from 41 to 59% of nDNA homology and similar phenotypic characteristics, are clearly distinguished based on their electrophoretic profiles using two enzymes: mannose-6-phosphate isomerase (MPI) and phosphoglucomutase (PGM). Despite the same number of chromosomal bands, different karyotype patterns were found in Ga. geotrichum sensu stricto and its two sibling species A and B. Within each sibling species, chromosome length polymorphism was observed, in particular for small bands, allowing discrimination to the strain level.


Determination of trace amounts of gold in acid-attacked environmental samples by atomic absorption spectrometry with electrothermal atomization after preconcentration.
A method for determination of trace amounts of gold in environmental samples (rocks, soils, sediments, and waters) by atomic absorption spectrometry with electrothermal atomization (ETAAS) after preconcentration using a chelating sorbent Spheron Thiol 1000 is described. The method accurately determines gold between 0.001 and several tens of grams per ton in samples having complex variations in mineralogy. Pulverized samples are roasted at 650 degrees C to oxidize any sulfide and/or carbonaceous material. Samples are then subjected to a series of acid treatments to eliminate any silica matrix and to dissolve the sample. The Spheron Thiol 1000 is added to the sample solution, and then with sorbed gold is filtered out, washed, and ignited at 550 degrees C. The residue is dissolved in aqua regia, evaporated, dissolved in distilled water, transferred to a volumetric flask, and analyzed by ETAAS. The limits of detection of gold, based on the 3 sigma definition, were 0.5 ng g(-1) for 10-g samples (rocks, sediments, soils) and 0.05 ng mL(-1) for 1-L water samples. Precision of determination expressed by the relative standard deviation varied from 2.9% to 16.4%. The accuracy of the method is verified by analysis of certified reference materials. The obtained analytical results are in good agreement with attested values. The developed method was applied for gold determination in environmental samples affected by the acidification (acid mine drainage which is mainly a product of pyrite oxidation) from an open quartzite mine in the Sobov region situated NE of the city of Banská Stiavnica (Slovakia).


Biologically active components in Madia sativa seed oil.
Biologically active components in lipids (fatty acids, phospholipids, sterols and tocopherols) from three varieties of Madia sativa seeds introduced in Bulgaria (BGR 457 and BGR 458 with German origin, and BGR 459 with US origin) were investigated. Glyceride oil in the seeds was found to be 36.6, 34.2 and 35.4%, respectively. Total phospholipid content was 2.4, 1.7 and 2.6% and the main classes were phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine. The amount of sterols in the oil was 0.3% for all samples and the major component was β-sitosterol, followed by campesterol and stigmasterol. Total tocopherols in the oils were 768, 795 and 856 mg kg-1, respectively and α-tocopherol predominated (more than 70.0%). Fatty acid composition of triacylglycerols and sterol esters was also established. Main fatty acids in triacylglycerols were linoleic (47.5-50.5%), oleic (30.2-32.4%) and palmitic acids (13.0-13.5%). The content of saturated fatty acids (palmitic and stearic) in sterol esters (40.1-50.9%) was significantly higher than in triacylglycerols (18.3-19.4%).


Failure of radiation therapy in stage I and II glottic squamous cell carcinoma.
Radiation therapy is frequently employed for Stage I and II lesions of the glottis. This study of the clinical course of patients with such cancers of the glottis was undertaken in an attempt to determine the period of greatest risk for recurrence and the most common location of recurrence, which can have treatment implications.


BET inhibitors impair leukemic stem cell function only in defined oncogenic subgroups of acute myeloid leukaemias.
Bromodomain and Extra-Terminal inhibitors (BETi) such as OTX015 are active in Acute Myeloid Leukaemias (AML). Their activity on Leukemic Stem Cells (LSCs) is less documented. We interrogated the anti-LSC activity of OTX015 in a niche-like long-term culture in 26 primary AML samples and validated our findings in vivo. OTX015 impaired LSCs in AMLs harbouring Core Binding Factor or KMT2A gene fusions, NPM1 or chromatin/spliceosome genes mutations, but not in those with aneuploidy/TP53 mutations. In four patients, we dissected the transcriptomic footprint of Bet inhibition on LSCs versus blasts. Our results can instruct future clinical trials of BETi in AML.


Comparative study on two kidney graft rinsing and preservation solutions in terms of the post-transplantation risk of delayed graft function and cost.
To determine whether Belzer solution (Viaspan, Bristol-Myers Squibb, Brussels, Belgium), which is more expensive than Eurocollins solution, was better at preventing delayed graft function (DGF) and whether it was cost-effective as it could potentially reduce post-transplantation complications. The risk of occurrence of complications associated with the use of these two rinsing and preserving solutions was estimated from a survey of 106 patients undergoing renal transplantation between 1 January 1993 and 31 March 1998. Both efficacy and adverse outcomes were recorded along with the costs directly associated with the transplantation procedure in the hospital setting: hospitalization, rinsing and preserving solutions, medical and technical interventions and diagnostic tests. For the 45 kidney grafts rinsed and preserved with Eurocollins (strategy S1: n1 = 45) the cost/graft was estimated at 40 euros. With Viaspan (strategy S2: n2 = 61) the corresponding cost/graft was 424 euros. Logistic regression analysis showed that Viaspan was better than Eurocollins solution (ebeta = 0.437; P = 0.05) in preventing DGF. Overall, S2 was less expensive than S1, from the hospital's perspective. The mean difference per patient was 278 euros, which amounts to a saving of 2% of the total cost per renal transplantation. For rinsing and preserving kidney grafts Belzer solution is therefore preferable to Eurocollins solution.


Squamous cell carcinoma antigen-IgM is associated with hepatocellular carcinoma in patients with cirrhosis: A prospective study.
Squamous cell carcinoma antigen (SCCA)-IgM complex has been described as a promising tool to identify patients with progressive liver disease at higher risk of hepatocellular carcinoma (HCC) development in retrospective studies. To assess the clinical value of this biomarker in patients with cirrhosis in a prospective study. Patients with overt cirrhosis were prospectively evaluated at 6-month intervals for HCC development and decompensation with clinical examination, liver ultrasound, α-fetoprotein measurement. SCCA-IgM was measured in serum by immunoenzymatic assay. Median follow-up duration was 52 months (range 12-68 months). 70 patients (26% male; mean age 56±10 years) were enrolled. The main aetiological factors were alcohol (44%) and hepatitis C (34%). Baseline values of SCCA-IgM were significantly higher in patients who developed HCC. Positivity of the biomarker at baseline was associated with a significantly shorter HCC-free survival, while α-fetoprotein (cut off >20 ng/ml) was not significant. SCCA-IgM positivity and hepatitis C were significant prognostic factors for HCC development. The biomarker was not associated with the development of clinical complications of cirrhosis. This prospective study demonstrates that in patients with cirrhosis SCCA-IgM is associated with HCC development and may be useful for clinical management of cirrhotic patients at higher risk of HCC development.


Safety and feasibility of same-day discharge laparoscopic radical prostatectomy: a systematic review.
Day case or same-day discharge (SDD) pure laparoscopic or robot-assisted radical prostatectomy (RP) has risen over the last few years with the aim of discharging patients within 24 h, reducing costs and length of stay, and facilitating return to active life. We perform a systematic review of literature to evaluate the feasibility of SDD RP. A systematic review search was performed and the following bibliographic databases were accessed: PubMed, Science Direct, Scopus, and Embase. This was carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. Based on the literature search of 509 articles, 12 (1378 patients) met the inclusion criteria (mean age: 63 years). All studies were unicentric except one. The mean SDD surgeries experience per centre was 66 cases .The means operative time and blood loss were 154 min and 126.5 ml, respectively. Mean SDD failure was 7.4%. Concomitant lymph node dissection was performed in 56.2%. The overall complication rate was 10.2% of cases; with a majority of Clavien grade I or II. Mean readmission rate after discharge was 5%. SDD generated cost reductions compared to inpatient surgery with variable differences according to the considered healthcare system. Day-case RP is a safe and feasible strategy in selected cases with multicentre proofs of concept. Its widespread use in routine practice needs further research due to biases in patient selection. Implementation of peri-operative pathways such as ERAS and prehabilitation improves patient adherence to SDD.


Translation initiation and its deregulation during tumorigenesis.
Regulation of protein synthesis at the level of translation initiation is fundamentally important for the control of cell proliferation under normal physiological conditions. Conversely, misregulation of protein synthesis is emerging as a major contributory factor in cancer development. Most bulk protein synthesis is initiated via recognition of the mRNA 5' cap and subsequent recognition of the initiator AUG codon by a directional scanning mechanism. However, several key regulators of tumour development are translated by a cap-independent pathway. Here we review eukaryotic translation initiation, its regulation and the ways in which this regulation can break down during tumorigenesis.


WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.
The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.


Rare earth filters for intraoral radiography: exposure reduction as a function of kV(p) with comparisons of image quality.
Radiographs of phantoms were produced using E-speed film and various rare earth X-ray beam filters. The rare earth filters considerably reduced the amount of radiation needed to produce diagnostic quality images and, in many cases, improved image quality. These filters can be implemented easily and inexpensively in a clinical setting, resulting in radiation exposure reductions of up to 71%.


Herbicide promotes the conjugative transfer of multi-resistance genes by facilitating cellular contact and plasmid transfer.
The global dissemination of antibiotic resistance genes (ARGs), especially via plasmid-mediated horizontal transfer, is becoming a pervasive health threat. While our previous study found that herbicides can accelerate the horizontal gene transfer (HGT) of ARGs in soil bacteria, the underlying mechanisms by which herbicides promote the HGT of ARGs across and within bacterial genera are still unclear. Here, the underlying mechanism associated with herbicide-promoted HGT was analyzed by detecting intracellular reactive oxygen species (ROS) production, extracellular polymeric substance composition, cell membrane integrity and proton motive force combined with genome-wide RNA sequencing. Exposure to herbicides induced a series of the above bacterial responses to promote HGT except for the ROS response, including compact cell-to-cell contact by enhancing pilus-encoded gene expression and decreasing cell surface charge, increasing cell membrane permeability, and enhancing the proton motive force, providing additional power for DNA uptake. This study provides a mechanistic understanding of the risk of bacterial resistance spread promoted by herbicides, which elucidates a new perspective on nonantibiotic agrochemical acceleration of the HGT of ARGs.


Influence of histamine H1- and H2-receptor blockers on sympathetic vasodilator and vasoconstrictor responses in canine paw.
1 Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15-20 mg/kg) and atropine. The H2-receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra-arterially did not depress significantly these vasodilator responses. The subsequent administration of tripelennamine in the dose of 2.5-5 mg/kg intravenously and 4 mg intra-arterially produced a significant blockade of the response to histamine and reduced the sustained vasodilator response to nerve stimulation. 2 In guanethidine-treated dogs, tripelennamine administered in the same dose following burimamide produced a blockade of the response to histamine comparable to that in the bretylium experiments, but decreased only the sustained vasodilator response to stimulation at 1 Hz. When the order of administration of the antihistamines was reversed in another group of guanethidine-treated dogs, tripelennamine had only a slight blocking effect on the response to histamine and did not affect the responses to nerve stimulation. Burimamide exerted a significant blocking effect on the response to histamine, but not to nerve stimulation. Another H2-receptor blocking agent, metiamide, when given after tripelennamine, also had a marked blocking effect on the response to histamine and almost abolished the vasodilator response to 4-methylhistamine, an H2-agonist. Nevertheless, even in the presence of this profound histamine blockade, the sustained vasodilator response to nerve stimulation remained unchanged. 3 In another group of experiments vasoconstrictor responses to exogenous noradrenaline and sympathetic stimulation were initially depressed by burimamide and later returned to control values. Tripelennamine increased these responses by its uptake blocking action. 4 It is concluded that the sustained vasodilator response is not antagonized by a specific antihistaminic action. The decrease in the sustained vasodilator response produced by antihistamines is produced attributable to potentiation of a residual adrenergic vasoconstricotr effect not completely blocked by bretylium.


Movement and self-control in protein assemblies. Quasi-equivalence revisited.
Purposeful switching among different conformational states exerts self-control in the construction and action of protein assemblies. Quasi-equivalence, conceived to explain icosahedral virus structure, arises by differentiation of identical protein subunits into different conformations that conserve essential bonding specificity. Mechanical models designed to represent the energy distribution in the structure, rather than just the arrangement of matter, are used to explore flexibility and self-controlled movements in virus particles. Information about the assembly of bacterial flagella, actin, tobacco mosaic virus and the T4 bacteriophage tail structure show that assembly can be controlled by switching the subunits from an inactive, unsociable form to an active, associable form. Energy to drive this change is provided by the intersubunit bonding in the growing structure; this self-control of assembly by conformational switching is called "autostery", by homology with allostery. A mechanical model of the contractile T4 tail sheath has been constructed to demonstrate how self-controlled activation of a latent bonding potential can drive a purposeful movement. The gradient of quasi-equivalent conformations modelled in the contracting tail sheath has suggested a workable mechanism for self-determination of tail tube length. Concerted action by assemblies of identical proteins may often depend on individually differentiated movements.


Regeneration and development. An amphibian call to arms.
Unlike axolotls, the urodele Notophthalmus viridescens completes two metamorphoses and emerges from its aquatic environment to mate as a fully terrestrial adult. Larval and adult limb regeneration are commonly treated as roughly equivalent processes and, at least in part, as a recapitulation of embryonic development. We compared larval limb development to regeneration of both larval and adult forelimbs and found that there are substantial differences in developmental pattern among larvae and adults. The larval pattern of preaxial dominance is absent in adult regenerates: adult regenerates instead develop digits synchronously, and they do so before proximal autopodial elements have formed discrete aggregation zones. By contrast, larval regenerates follow a pattern of sequential digit formation from anterior to posterior, like their embryonic limb buds. Based upon these morphological clues, we conclude that larval regenerates are unlikely to exhibit features of epimorphic regeneration seen in adults, but are more likely to represent a form of developmental regulation. Furthermore, we confirm that post-metamorphic limb regeneration is not a simple recapitulation of ontology at the morphological level. These distinctions may help to explain and interpret some experiments and observations of regeneration in neotenic or paedomorphic urodeles.


How undergraduates historically underrepresented in biomedical sciences value multiple components of a research training program.
To promote diversity in the STEM workforce, undergraduate research training programs incorporating a variety of intervention strategies have been developed to support students from historically underrepresented backgrounds in overcoming numerous systemic barriers to pursuing careers in science. However, relatively little research has focused on how students experience and value these interventions and the ways in which the interventions support student success. The current study analyzed qualitative interviews from participants (n=15) in a comprehensive research training program for undergraduates historically underrepresented in biomedical research to investigate the student perspective on how specific program components address barriers and support their research training, academic progress, and career preparation. Findings indicated that students benefit from authentic research experiences, mentoring, supplemental curriculum, financial assistance, and a supportive program environment. Participants described how the program helped them address financial concerns, navigate academic and career choices, build science identity and efficacy, and feel a sense of belonging within a caring community. The study highlights how multi-faceted research training programs offering a variety of supports can contribute to student retention and development according to the needs and circumstances of individual students.


Sodium houttuynia alleviates airway inflammation in asthmatic mice by regulating FoxP3/RORγT expression and reversing Treg/Th17 cell imbalance.
Synthetized from a natural oil of Houttuynia cordata, sodium houttuynia was reported to have anti-inflammatory effects. The present study aimed to investigate whether sodium houttuynia could alleviate the characteristic airway inflammation and Treg/Th17 cell imbalance of asthma in vivo. Experimental mice with neutrophilic asthma were injected with sodium houttuynia or dexamethasone (alone or in combination) intraperitoneally. The airway reactivity was measured, and bronchoalveolar lavage fluid was collected for cell count. Hematoxylin/eosin and periodic acid-Schiff staining were performed to assess pulmonary inflammation and mucus hypersecretion. Immunohistochemical analysis was conducted to determine the expression of IL-10, IL-17A, FoxP3, and RORγT in the lung tissue, and the serum levels of IL-10 and IL-17A were analyzed by ELISA. The proportion of CD4+CD25+FoxP3+ Treg and Th17 cells within the CD4+ T cell subset of splenocytes was analyzed by flow cytometry. FoxP3 and RORγT mRNA and protein expressions in the lung were analyzed by real-time PCR and western blot, respectively. Overall, sodium houttuynia was found to ameliorate the Treg/Th17 cell imbalance and reduce the airway inflammation, hyperresponsiveness, and mucus hypersecretion by increasing the frequency of CD4+CD25+FoxP3+ Treg cells and the secretion of IL-10, while decreasing the proportion of Th17 cells and IL-17A production. Although the regulatory effect of sodium houttuynia was not as good as that achieved with dexamethasone, combination of the two compounds showed improved inhibitory effects on airway hyperresponsiveness, inflammation, and mucus hypersecretion. Hence, sodium houttuynia may be beneficial for the treatment of asthma.


[Alpha-mannosidase activity of different human biological fluids].
Two distinct alpha-mannosidases have been found in biological fluids by investigating the effect of pH on activity, the effect of Co2+ and Zn2+ and by determining the Michaelis constant. The two enzymes are designated as S, predominating in serum (optimum pH about 5.6) and U, predominating in urine (optimum pH about 4.2). In cerebro-spinal fluid, the amount of alpha-mannosidase S is almost the same as that of alpha-mannosidase U. Alpha-mannosidase S activity in sera is significantly higher in children than in adults.


Herbimycin-A attenuates ischaemia-reperfusion induced pulmonary neutrophil infiltration.
To determine whether pharmacological induction of heat shock proteins (HSPs) by herbimycin-A (a tyrosine-kinase inhibitor) would protect against neutrophil-mediated lung injury in an animal model of lower torso ischaemia-reperfusion. Sprague-Dawley rats were randomised into three groups: the control group underwent midline laparotomy only; the ischaemia-reperfusion (IR) group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; the third group (HerbIR) was pretreated with herbimycin-A 18 h prior to IR insult. Wet to dry lung weight ratio (W:D), bronchoalveolar lavage protein concentration (BALprot), tissue myeloperoxidase activity (MPO) and bronchoalveolar lavage neutrophil count (BALPMN) were measured. Heat shock protein 72 (HSP72) expression in lung, intestine, mesentery and liver was measured using Western immunoblotting. IR resulted in acute lung injury with tissue oedema (W:D) and neutrophil infiltration (PMO, BALPMN). Herbimycin-A, in vivo, induced HSP expression and attenuated neutrophil infiltration (MPO, BALPMN). These data indicate that herbimycin-A protects against ischaemia-reperfusion induced pulmonary neutrophil infiltration, possibly by increasing the expression of heat shock proteins.


Differences in water and vapor transport through angstrom-scale pores in atomically thin membranes.
The transport of water through nanoscale capillaries/pores plays a prominent role in biology, ionic/molecular separations, water treatment and protective applications. However, the mechanisms of water and vapor transport through nanoscale confinements remain to be fully understood. Angstrom-scale pores (~2.8-6.6 Å) introduced into the atomically thin graphene lattice represent ideal model systems to probe water transport at the molecular-length scale with short pores (aspect ratio ~1-1.9) i.e., pore diameters approach the pore length (~3.4 Å) at the theoretical limit of material thickness. Here, we report on orders of magnitude differences (~80×) between transport of water vapor (~44.2-52.4 g m-2 day-1 Pa-1) and liquid water (0.6-2 g m-2 day-1 Pa-1) through nanopores (~2.8-6.6 Å in diameter) in monolayer graphene and rationalize this difference via a flow resistance model in which liquid water permeation occurs near the continuum regime whereas water vapor transport occurs in the free molecular flow regime. We demonstrate centimeter-scale atomically thin graphene membranes with up to an order of magnitude higher water vapor transport rate (~5.4-6.1 × 104 g m-2 day-1) than most commercially available ultra-breathable protective materials while effectively blocking even sub-nanometer (>0.66 nm) model ions/molecules.


Arylene Ethynylene-Functionalized Bithiazole-Based Zinc Polymers for Ultraefficient Photocatalytic Activity.
Polymers 4 containing poly(arylene ethynylene) were synthesized and characterized systematically. Among them, 4c exhibited a remarkable H2 evolution rate (14.32 mmol h-1 g-1) with visible-light irradiation, lasting 72 h in different water qualities; the corresponding apparent quantum yield was 11.6% at 450 nm.


Performance of three generations of Xpert MRSA in routine practice: approaching the aim?
The aim of this study was to evaluate retrospectively the performance of the Xpert MRSA assay in routine practice and its current use in the intensive care unit (ICU) setting of our hospital, since a pre-emptive isolation strategy has been applied. A total of 6473 patients were routinely screened with ESwab for methicillin-resistant Staphylococcus aureus (MRSA) using three generations of rapid real-time polymerase chain reaction (PCR) (Cepheid GeneXpert) over three consecutive periods of time. Performance was evaluated using broth enrichment culture as the reference method. Our results show that the last generation of Xpert MRSA (NxG) assay is more specific (99.2% vs. 97.9%) but not more sensitive (77.8% vs. 86.9%) than the third generation. Considering the low prevalence of MRSA in our hospital, we obtained an overall low positive predictive value. In conclusion, it remains difficult to abandon the reference method in routine practice considering the possible implications of an erroneous MRSA result in the ICU.


Kinetics of the precipitation of cryoimmunoglobulins.
The kinetics of the cryoprecipitation of two monoclonal IgG and two monoclonal IgM cryoimmunoglobulins, two IgM/IgG mixed cryoglobulins and a series of cold soluble monoclonal IgG and IgM immunoglobulins in the presence of polyethylene glycol have been compared by time dependent turbidity measurements. The effects of temp and ionic strength on kinetic processes are described in detail. The monoclonal cryoimmunoglobulins display lag times which are not seen with the other proteins, suggesting a critical nucleation event. The protein concn dependence of the lag times indicate that these nucleation centers contain only a few immunoglobulin molecules. Direct evidence for the existence of precipitation nuclei was obtained from dynamic light scattering studies of two of the monoclonal proteins during their lag periods. Both proteins manifested an approx. 20% decrease in their mean diffusion coefficients (corresponding to a 25% increase in Stokes' radius) prior to detectable precipitation. This suggests the formation of nuclei between 2 and 8 times the size of the monomeric proteins. It is postulated that the increasing size of mixed cryoglobulin complexes with decreasing temp provides analogous nucleation sites. The latter stages of precipitation appear to be kinetically similar for all proteins examined, although the size and shape of the aggregates are quite variable.