Internalizing and externalizing subtypes in female patients with co-occurring post-traumatic stress disorder and substance use disorders.
Research has described subtypes with more internalizing and more externalizing symptoms in samples of patients with post-traumatic stress disorder (PTSD) and samples of patients with substance use disorders (SUD). This study sought to examine the respective subtypes in female PTSD-SUD patients and potential relationships with substance use characteristics. We performed a latent class analysis (LCA) in 343 adult female participants of a multisite therapy trial on PTSD and SUD. We derived externalizing symptoms from the Assessment of DSM-IV Personality Disorders (ADP-IV) questionnaire. We assessed internalization using the Symptom Checklist-27 (SCL-27) and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). We collected substance use-related information using the Addiction Severity Index-Lite (ASI-lite). LCA suggested four latent classes including an externalizing (10.8%), a moderately internalizing class (31.0%), and a highly internalizing class (22.0%), as well as a class with a low severity of psychological symptoms (36.3%). Externalizing participants used more substances than any other class, while the duration of substance use did not differ between groups. Regular use started at a significantly younger age among the members of the highly internalizing subgroup compared to the moderately internalizing and low severity participants, but at an older age compared to the externalizing group members. The finding of two internalizing subgroups along with an externalizing and a low severity class emphasizes the heterogeneity and complexity of populations with PTSD and SUD. This heterogeneity bears implications for research among this group of patients, but also for their treatment, especially considering our results on differences in substance use.


Ichthyosiform dermatosis, keratitis, and deafness.
Two patients had an unusual ichthyosiform dermatosis, neurosensory deafness, and vascularizing keratitis. There was no family history of the disorder and no consanguinity. A squamous cell carcinoma of the tongue developed in one child. The association of such an eruption and deafness in previously reported cases is reviewed.


Hemagglutinating activity in extracts of mycelia from submerged mushroom cultures.
Extracts from mycelia of seven different mushrooms agglutinated erythrocytes of several species. More than one agglutinating factor was identified in the extracts of three different mycelia. Agglutination was partially inhibited nonspecifically by high concentrations of glucose, galactose, mannose, fucose, and rhamnose.


Three cases of rigid bronchoscopic removal of carinal masses: Case report.
Tracheal tumors are rare diseases. They can cause narrowing of a central airway, a severe respiratory distress, and death. The objective of this case series is to highlight the role of rigid bronchoscopy in diagnosing and treating carina masses which are difficult to remove surgically. Tumor excision was performed by the rigid bronchoscopic intervention. Additional treatment was administered according to the diagnosis of each individual patient. After the procedure, patients' symptoms were improved and stenotic central airways were reopened. Rigid bronchoscopy can be a good therapeutic option to reestablish airway patency and a bridge treatment for further definitive treatment.


Development of the General surgery prioritisation tool implemented in New Zealand in 2018.
Patients waitlisted for elective general surgery in New Zealand used to be prioritised by multiple tools that were inconsistent, did not reflect clinical judgement and were not validated. We describe the development and implementation of a national prioritisation tool for elective general surgery in New Zealand, which could be applicable to other OECD countries. The tool aims to achieve equity of access, transparency, reliability and should be aligned with clinical judgement. The General Surgery Prioritisation Tool Working Group commenced development of a prioritisation tool in 2014 which showed strong correlation with clinical judgement (r = 0.89), excellent test-retest reliability (r = 0.98) and significantly lower variability (p < 0.001). Preliminary findings showed no significant difference in scores attributable to age, gender or ethnicity. General Surgeons were in favour of the tool criteria and agreed on the importance of prioritisation; however a minority opposed its introduction. Health organisations and general practitioner groups were in favour, however, along with many surgeons, expressed apprehensions regarding subjectivity, manipulation, equity of access and degree of benefit. Despite reservations, the majority of stakeholders were supportive and through collaboration between clinicians and the government, the tool was implemented in 2018 in New Zealand. Overall, the prioritisation tool is a reliable method of assessing priority, demonstrating transparency and reflecting clinical judgement, with equity of access to be further assessed by evaluation in clinical practice.


Evidence for the existence of a common ancestor of scorpion toxins affecting ion channels.
All scorpion toxins from different 30 species are simply reviewed. A new classification system of scorpion toxins is first proposed: scorpion toxins are classified into three families (long-chain scorpion toxins with 4 disulfide bridges, short-chain scorpion toxins with 3 disulfide bridges, and intermediate-type scorpion toxins with 3 or 4 disulfide bridges). Intermediate-type scorpion toxins provide a strong proof for the conclusion that channel toxins from scorpion venoms evolve from a common ancestor. Common organization of precursor nucleotides and genomic sequence, similar 3-dimensional structure, and the existence of intermediate type scorpion toxins and functionally intercrossing scorpion toxins show that all scorpion toxins affecting ion channels evolve from the common ancestor, which produce millions of scorpion toxins with function-diversity.


Cellular distribution of a human I-A-like (DS/DC) antigen on normal and neoplastic lymphoid cells.
Previous biochemical studies have shown that B cell specific, monoclonal antibody, McAb 33.1, reacts with a class II antigen that represents a human analogue of murine I-A (DS/DC) antigens (J. Exp. Med. 158:1924, 1983). McAb 33.1 recognizes a polymorphic human B lymphocyte specific antigen present on mu+, B1+ peripheral B cells, B lymphoid cell lines, activated B cells, and neoplastic B lymphoid cells. Of 100 HLA-D/DR typed EBV-transformed lymphoblastoid cell lines tested, only those from DR3,3 and DR7,7 individuals failed to react with McAb 33.1. The 33.1 antigen is present at lower concentrations on B cells from blood, tonsil, spleen, and lymph node when compared to B cell lines. By contrast, the antigen is not detectable on blood T lymphocytes, T cell lines, or mitogen activated T cells and it is absent on monocytes of some individuals or is present only on a minor subpopulation (approximately 20%). McAb 33.1 should facilitate the functional, structure, and molecular dissection of the human Ia system.


Ethnic minority GP trainees at risk for underperformance assessments: a quantitative cohort study.
Recent studies suggest that ethnic minority students underperform in standardised assessments commonly used to evaluate their progress. This disparity seems to also hold for postgraduate medical students and GP trainees, and may affect the quality of primary health care, which requires an optimally diverse workforce. To address the following: 1) to determine to what extent ethnic minority GP trainees are more at risk of being assessed as underperforming than their majority peers; 2) to investigate whether established underperformance appears in specific competence areas; and 3) to explore first- and second-generation ethnic minority trainees' deviations. Quantitative retrospective cohort design in Dutch GP specialty training (start years: 2015-2017). In 2020-2021, the authors evaluated files on assessed underperformance of 1700 GP trainees at seven Dutch GP specialty training institutes after excluding five opt-outs and 165 incomplete datasets (17.4% ethnic minority trainees). Underperformance was defined as the occurrence of the following, which was prompted by the training institute: 1) preliminary dropout; 2) extension of the educational pathway; and/or 3) mandatory coaching pathways. Statistics Netherlands (CBS) anonymised the files and added data about ethnic group. Thereafter, the authors performed logistic regression for potential underperformance analysis and χ2 tests for competence area analysis. Ethnic minority GP trainees were more likely to face underperformance assessments than the majority group (odds ratio [OR] 2.41, 95% confidence interval [CI] = 1.67 to 3.49). Underperformance was not significantly nested in particular competence areas. First-generation ethnic minority trainees seemed more at risk than their second-generation peers. Ethnic minority GP trainees seem more at risk of facing educational barriers than the majority group. Additional qualitative research on underlying factors is essential.


Impact of omalizumab on quality-of-life outcomes in patients with moderate-to-severe allergic asthma.
Moderate-to-severe allergic asthma has a substantial impact on patients' quality of life (QOL). Despite care consistent with treatment guidelines, many patients with moderate-to-severe asthma still experience variability in asthma control, signaling an unmet need within this population. Omalizumab has recently demonstrated clinical efficacy and safety in treating IgE-mediated asthma. To summarize asthma-related QOL outcomes associated with omalizumab therapy in moderate-to-severe allergic asthma. A systematic review and meta-analysis of asthma-related QOL on data from published clinical trials and unpublished clinical study reports were conducted on omalizumab. The Juniper Asthma Quality of Life Questionnaire (AQLQ) measured asthma-related QOL. Statistically significant results for asthma-related QOL end points consistently favored omalizumab over placebo. Moderate to large effect sizes in the omalizumab groups were observed across the clinical trials and during study extension phases. A meta-analysis indicated a 1.6- to 2-fold increase in moderate (> or = 1 point) and a 1.8- to 2.1-fold increase in large (> or = 1.5 point) improvements in AQLQ overall scores in the omalizumab-treated group compared with placebo during the steroid-stabilization and steroid-reduction phases of the trials. Significant differences and large effect sizes favoring omalizumab were observed despite the control group receiving active, guideline-consistent treatment. The meta-analysis findings demonstrate that omalizumab treatment provides QOL benefits in patients with moderate-to-severe allergic asthma.


The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response.
Mycotoxins are structurally diverse fungal metabolites that can contaminate a variety of dietary components consumed by animals and humans. It is considered that 25% of the world crop production is contaminated by mycotoxins. The clinical toxicological syndromes caused by ingestion of moderate to high amounts of mycotoxins and their effect on the immune system have been well characterized. However, no particular attention has been focused on the effects of mycotoxins on the local intestinal immune response. Because of their location, intestinal epithelial cells (IECs) could be exposed to high doses of mycotoxins. As a component of the innate local immune response, intestinal epithelial cells have developed a variety of mechanisms which act to reduce the risk of infection by microorganisms or intoxication by toxic compounds. This review summarises the innate immune response developed by intestinal epithelial cells and reports the literature concerning the effects of mycotoxins on them. Particularly, the effects of mycotoxins on the maintenance of a physical barrier by epithelial cells will be discussed together with their effect on extrinsic protective components of the innate intestinal immunity: mucus secretion, antimicrobial peptide generation, IgA and pro-inflammatory cytokine release.


The effect of heparin on the interaction of factor VIII and human platelets in vitro.
Heparin was found to inhibit the interaction between human factor VIII and platelets. This was noted in two different systems, namely, platelet aggregation induced by neuraminidase-treated human cryoprecipitate and platelet aggregation induced by ristocetin-human factor VIII complex. Heparin appeared to have an inhibitory effect on the above systems similar to that reported on bovine factor VIII-induced platelet aggregation.


Semiparametric inference on the penetrances of rare genetic mutations based on a case-family design.
A formal semiparametric statistical inference framework is proposed for the evaluation of the age-dependent penetrance of a rare genetic mutation, using family data generated under a case-family design, where phenotype and genotype information are collected from first-degree relatives of case probands carrying the targeted mutation. The proposed approach allows for unobserved risk factors that are correlated among family members. Some rigorous large sample properties are established, which show that the proposed estimators were asymptotically semi-parametric efficient. A simulation study is conducted to evaluate the performance of the new approach, which shows the robustness of the proposed semiparamteric approach and its advantage over the corresponding parametric approach. As an illustration, the proposed approach is applied to estimating the age-dependent cancer risk among carriers of the MSH2 or MLH1 mutation.


Moxifloxacin Concentrations in the Knee Joint, Tibial Bone, and Soft Tissue When Combined with Rifampicin: A Randomized Porcine Microdialysis Study.
Peri and postoperative antibiotics are key adjuvant treatment tools in the management of periprosthetic joint infection (PJI). The aim of this study was to evaluate the effect of rifampicin on the area under the moxifloxacin concentration-time curve from 0 to 24 hours (AUC0-24) in the synovial fluid of the knee joint, tibial bone, and adjacent subcutaneous tissue under steady-state conditions using microdialysis in a porcine model. Twenty female pigs were randomized to receive oral treatment with moxifloxacin monotherapy (Group A, n = 10) of 400 mg once daily for 3 days or a combination therapy (Group B, n = 10) of 400 mg of moxifloxacin once daily for 3 days and 450 mg of rifampicin twice daily for 7 days. Microdialysis was used for sampling the synovial fluid of the knee joint, tibial cancellous and cortical bone, and adjacent subcutaneous tissues. Plasma samples were taken as a reference. Measurements were obtained for 24 hours. Coadministration of moxifloxacin and rifampicin resulted in reductions of the moxifloxacin AUC0-24 in all targeted tissue compartments by 67% to 85% (p < 0.05). The corresponding change in plasma was 20% (p = 0.49). For both groups, the tissue penetration (the ratio of tissue free fraction AUC0-24 to plasma free fraction AUC0-24 [fAUCtissue/fAUCplasma]) was incomplete in all investigated compartments. The highest moxifloxacin tissue penetration was in the knee joint synovial fluid: 0.59 (Group A) and 0.24 (Group B). The lowest tissue penetration was in the cortical bone: 0.17 (Group A) and 0.03 (Group B). We found a significant reduction of the moxifloxacin concentration, expressed as the AUC0-24, in tissues relevant to acute PJI treatment when coadministered with rifampicin. The concentrations within the targeted tissue compartments were reduced significantly more than the concentrations in plasma, which may be particularly important as plasma concentrations are used in clinical practice to assess moxifloxacin treatment sufficiency.


Relevant increase of CTX-M-producing Escherichia coli carriage in school-aged children from rural areas of the Bolivian Chaco in a three-year period.
The aim of this study was to perform two cross-sectional surveys on the fecal carriage of CTX-M-producing Enterobacterales in school-aged children from rural areas of the Bolivian Chaco (2016 vs 2019). A total of 757 fecal samples were collected from school-aged children living in nine indigenous communities (n=337, 2016; n=420, 2019). After a first passage onto MacConkey agar (MCA), samples were plated onto MCA plus cefotaxime 2 µg/mL (MCA-CTX), and a loopful of the bacterial growth was used as a template for the detection of group 1, 2, 8/25, and 9 blaCTX-M variants by multiplex reverse transcriptase polymerase chain reaction . Positive samples were tested again for detecting, identifying, and characterizing CTX-M-positive isolates. Growth onto MCA-CTX was obtained with 208 samples (27.5%; 62/337, 2016; 146/420, 2019), of which 201 (96.6%) were positive for blaCTX-M genes. Overall, a relevant increase of fecal carriage of CTX-M-producing Enterobacterales was observed in the study period: 17,5% (59/337) in 2016 compared with 33,8% (142/420) in 2019, p<0.01. Nonetheless, the relative group distribution of CTX-M groups remained stable, with group 1 being the prevalent, followed by group 9 and group 8/25. Group 2 was not detected. The present study demonstrated an alarming spread of CTX-M enzymes in rural areas of the Bolivian Chaco, where antibiotics consumption is limited. Further studies are encouraged to better understand the dissemination dynamics of such relevant resistance determinants.


Osteoarticular Infections Caused by Erysipelothrix rhusiopathiae: Case Report and Literature Review.
We present a case of Erysipelothrix rhusiopathiae spondylodiscitis in an otherwise healthy man, occurring 1 year after exposure. The patient was cured after 6 weeks of treatment with amoxicillin followed by ciprofloxacin without surgery. Erysipelothrix rhusiopathiae can cause severe osteoarticular infections with a delayed presentation following exposure to the pathogen.


Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants.
To analyze different methods to assess postnatal growth in a cohort of very premature infants (VPI) in a clinical setting and identify potential early markers of growth failure. Study of growth determinants in VPI (≤32 weeks) during hospital stay. Nutritional intakes and clinical evolution were recorded. Growth velocity (GV: g/kg/day), extrauterine growth restriction (%) (EUGR: weight < 10th centile, z-score < -1.28) and postnatal growth failure (PGF: fall in z-score > 1.34) at 36 weeks postmenstrual age (PMA) were calculated. Associations between growth and clinical or nutritional variables were explored (linear and logistic regression). Sample: 197 VPI. GV in IUGR patients was higher than in non-IUGRs (28 days of life and discharge). At 36 weeks PMA 66.0% of VPIs, including all but one of the IUGR patients, were EUGR. Prevalence of PGF at the same time was 67.4% (IUGR patients: 48.1%; non-IUGRs: 70.5% (p = 0.022)). Variables related to PGF at 36 weeks PMA were initial weight loss (%), need for oxygen and lower parenteral lipids in the first week. The analysis of z-scores was better suited to identify postnatal growth faltering. PGF could be reduced by minimising initial weight loss and assuring adequate nutrition in patients at risk.


Reconstitution of a phospholipid flippase from rat liver microsomes.
The endoplasmic reticulum is the principal site of synthesis and initial incorporation of membrane lipids in eukaryotic cells; the enzymes of glycerolipid biosynthesis are exclusively located on its cytoplasmic surface. To maintain a phospholipid bilayer in this organelle, newly synthesized phospholipids must be translocated to the lumenal surface. Consistent with this are measurements indicating that movement of phospholipids across microsomal membranes is rapid, with a half-time less than 5 min (refs 3 and 4). Rapid movement of phospholipids has also been detected across the plasma membrane of Bacillus megaterium, another site of de novo lipid biosynthesis. The rapid transmembrane movement of phosphatidylcholine has not been detected, however, in vesicles prepared from microsomal lipids. These latter data suggest involvement in the endoplasmic reticulum of a phospholipid-translocating protein, as was first proposed by Bretscher who called it 'flippase'. Here we report reconstitution of a phospholipid flippase from rat liver microsomes into lipid vesicles.


Congenital diaphragmatic hernia: hypoplastic lung and pulmonary vasoconstriction.
The abnormal pulmonary vasculature of the infant with congenital diaphragmatic hernia combined with a single expanded lung creates persistent pulmonary hypertension. Survival depends on the ability of the myocardium to withstand this increased work load until the second lung expands and pulmonary hypertension ceases.


Gynecomastia: Simultaneous Subcutaneous Mastectomy and Areolar Reduction with Minimal Inconspicuous Scarring.
Acceptable scar positioning on the anterior male chest is very limited. In Gynecomastia surgery, an obvious areolar incision is the most sensitive indicator of a previous operation; a less apparent scar is indispensable for the patient's psychological satisfaction. Whenever only areolar diameter reduction is required, the circumareolar incision must be performed in a position leaving the least conspicuous scar. Standard excision of an outer doughnut of areolar skin results in a visible and unnatural peri-areolar scar. The peri-nipple excision of areolar skin leaves the skin-areola junction undisturbed. When combined with a transverse areolar infra-nipple incision, access for subcutaneous mastectomy is facilitated. With this approach, risk of nipple vascular compromise is thought to be reduced, and necrosis of areolar pigmented skin virtually impossible. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord.
In vertebrates, central nervous system (CNS) protection is dependent on many immune cells including microglial cells. Indeed, activated microglial cells are involved in neuroinflammation mechanisms by interacting with numerous immune factors. Unlike vertebrates, some lophotrochozoan invertebrates can fully repair their CNS following injury. In the medicinal leech Hirudo medicinalis, the recruitment of microglial cells at the lesion site is essential for sprouting of injured axons. Interestingly, a new molecule homologous to vertebrate C1q was characterized in leech, named HmC1q (for H. medicinalis) and detected in neurons and glial cells. In chemotaxis assays, leech microglial cells were demonstrated to respond to human C1q. The chemotactic activity was reduced when microglia was preincubated with signaling pathway inhibitors (Pertussis Toxin or wortmannin) or anti-human gC1qR antibody suggesting the involvement of gC1qR in C1q-mediated migration in leech. Assays using cells preincubated with NO chelator (cPTIO) showed that C1q-mediated migration was associated to NO production. Of interest, by using anti-HmC1q antibodies, HmC1q released in the culture medium was shown to exhibit a similar chemotactic effect on microglial cells as human C1q. In summary, we have identified, for the first time, a molecule homologous to mammalian C1q in leech CNS. Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms.


Current trends in heparin use during arterial vascular interventional radiology.
This study was designed to assess the current use of heparinized saline and bolus doses of heparin in non-neurological interventional radiology and to determine whether consensus could be reached to produce guidance for heparin use during arterial vascular intervention. An interactive electronic questionnaire was distributed to members of the British Society of Interventional Radiology regarding their current practice in the use, dosage, and timing of heparin boluses and heparinized flushing solutions. A total of 108 completed questionnaires were received. More than 80% of respondents used heparinized saline with varying concentrations; the most prevalent was 1,000 IU/l (international units of heparin per liter) and 5,000 IU/l. Fifty-one percent of interventionalists use 3,000 IU as their standard bolus dose; however, the respondents were split regarding the timing of bolus dose with ~60% administering it after arterial access is obtained and 40% after crossing the lesion. There was no consensus on altering dose according to body weight, and only 4% monitored clotting parameters. There seems to be some coherence among practicing interventionalists regarding heparin administration. We hypothesize that heparinized saline should be used at a recognized standard concentration of 1,000 IU/l as a flushing concentration in all arterial vascular interventions and that 3,000 IU bolus is considered the standard dose for straightforward therapeutic procedures and 5000 IU for complex, crural, and endovascular aneurysm repair work. The bolus should be given after arterial access is obtained to allow time for optimal anticoagulation to be achieved by the time of active intervention and stenting. Further research into clotting abnormalities following such interventional procedures would be an interesting quantifiable follow-up to this initial survey of opinions and practice.


A vision for incorporating human mobility in the study of human-wildlife interactions.
As human activities increasingly shape land- and seascapes, understanding human-wildlife interactions is imperative for preserving biodiversity. Habitats are impacted not only by static modifications, such as roads, buildings and other infrastructure, but also by the dynamic movement of people and their vehicles occurring over shorter time scales. Although there is increasing realization that both components of human activity substantially affect wildlife, capturing more dynamic processes in ecological studies has proved challenging. Here we propose a conceptual framework for developing a 'dynamic human footprint' that explicitly incorporates human mobility, providing a key link between anthropogenic stressors and ecological impacts across spatiotemporal scales. Specifically, the dynamic human footprint integrates a range of metrics to fully acknowledge the time-varying nature of human activities and to enable scale-appropriate assessments of their impacts on wildlife behaviour, demography and distributions. We review existing terrestrial and marine human-mobility data products and provide a roadmap for how these could be integrated and extended to enable more comprehensive analyses of human impacts on biodiversity in the Anthropocene.


Patient-reported experiences and views on the Cytosponge test: a mixed-methods analysis from the BEST3 trial.
The BEST3 trial demonstrated the efficacy and safety of the Cytosponge-trefoil factor 3, a cell collection device coupled with the biomarker trefoil factor 3, as a tool for detecting Barrett's oesophagus, a precursor of oesophageal adenocarcinoma (OAC), in primary care. In this nested study, our aim was to understand patient experiences. Mixed-methods using questionnaires (including Inventory to Assess Patient Satisfaction, Spielberger State-Trait Anxiety Inventory-6 and two-item perceived risk) and interviews. Participant satisfaction, anxiety and perceived risk of developing OAC. General practices in England. Patients with acid reflux enrolled in the intervention arm of the BEST3 trial and attending the Cytosponge appointment (N=1750). 1488 patients successfully swallowing the Cytosponge completed the follow-up questionnaires, while 30 were interviewed, including some with an unsuccessful swallow.Overall, participants were satisfied with the Cytosponge test. Several items showed positive ratings, in particular convenience and accessibility, staff's interpersonal skills and perceived technical competence. The most discomfort was reported during the Cytosponge removal, with more than 60% of participants experiencing gagging. Nevertheless, about 80% were willing to have the procedure again or to recommend it to friends; this was true even for participants experiencing discomfort, as confirmed in the interviews.Median anxiety scores were below the predefined level of clinically significant anxiety and slightly decreased between baseline and follow-up (p < 0.001). Interviews revealed concerns around the ability to swallow, participating in a clinical trial, and waiting for test results.The perceived risk of OAC increased following the Cytosponge appointment (p<0.001). Moreover, interviews suggested that some participants had trouble conceptualising risk and did not understand the relationships between test results, gastro-oesophageal reflux and risk of Barrett's oesophagus and OAC. When delivered during a trial in primary care, the Cytosponge is well accepted and causes little anxiety. ISRCTN68382401.


Recombination in human coxsackievirus B5 strains that caused an outbreak of viral encephalitis in Henan, China.
In 2011, human coxsackievirus B5 (CVB5) caused an outbreak of viral encephalitis in Henan, China. Complete genome sequence analysis based on two isolates showed that the 5' half of the genome (nt 1-4540) had high similarity (>97 %) to that of CVB5 strain GU376747, and the 3' half (nt 4700-7402) showed high similarity (>96 %) to that of human coxsackievirus B3 (CVB3) strain GQ141875. These isolates had the highest similarity (97.7 %) to the Changchun strain, based on the complete genome, rather than to other CVB5 strains isolated from Henan in recent years. There were therefore at least two groups of CVB5 circulating in Henan Province, which evolved at different rates.


Immune response of a marsupial (Monodelphis domestica) to sheep red blood cells.
A study of the humoral immune response of a marsupial, Monodelphis domestica, was performed using sheep red blood cells as the immunogen and a hemolytic titration as the assay. The primary response to a single intramuscular injection was similar to that observed in other mammalian species, except that the titers remained high for as long as 37 weeks after the initial injection. The secondary response was weaker than the primary response and diminished as early as 15 weeks after the initial injection (and only 11 weeks after the single booster injection). The hyperimmune response was similar to the secondary response, except that the titers remained consistent for up to 10 weeks and then fell to very low levels at 35 weeks. The data support the view that the primary humoral response of this marsupial is similar to that of eutherian mammals. However, the secondary and hyperimmune responses appear to be very weak, if present at all.


Structural characterization of a galacturonic acid-rich polysaccharide from Ziziphus Jujuba cv. Muzao.
Jujube (Zizyphus jujuba Mill.) have been widely used as a health food and medicinal herb in oriental medicine. In the present study, a novel galacturonic acid-rich polysaccharide (PZMP3-2) was isolated from Zizyphus Jujuba cv. Muzao through hot water extraction, ethanol precipitation, and purification with DEAE-Sepharose Fast Flow and Sephacryl S-300 column chromatography. The chemical structures of PZMP3-2 were elucidated by methylation analysis, along with HPGPC, FT-IR spectroscopy, GC-MS, 1D NMR spectroscopy, and 2D NMR spectroscopy. Its morphological properties were further characterized by SEM, AFM, and XRD. Monosaccharide compositional analysis of PZMP3-2 revealed the presence of rhamnose, arabinose, galactose, and galacturonic acid at a molar ratio of 1.74:2.00: 1.00:18.69, and the HPGPC data demonstrated an average molecular weight of 58.21 kDa. Structural and linkage analysis by GC-MS and NMR spectroscopy suggested that PZMP3-2 was a homogalacturonan (HG)-like pectic polysaccharide branched at C-2 with some Araf and Rhap residues. Such unique structure of PZMP3-2 may indicate distinct bioactivities and further application in food and even clinic.


Recent advances in avian virology.
Selected, recent research on the following avian diseases, and their causative viruses, has been reviewed: chicken anaemia, infectious bursal disease, turkey rhinotracheitis, avian nephritis, fowlpox, influenza, infectious bronchitis and turkey enteritis.


Patient-specific learning in real time for adaptive monitoring in critical care.
Intensive care monitoring systems are typically developed from population data, but do not take into account the variability among individual patients' characteristics. This study develops patient-specific alarm algorithms in real time. Classification tree and neural network learning were carried out in batch mode on individual patients' vital sign numerics in successive intervals of incremental duration to generate binary classifiers of patient state and thus to determine when to issue an alarm. Results suggest that the performance of these classifiers follows the course of a learning curve. After 8h of patient-specific training during each of 10 monitoring sessions, our neural networks reached average sensitivity, specificity, positive predictive value, and accuracy of 0.96, 0.99, 0.79, and 0.99, respectively. The classification trees achieved 0.84, 0.98, 0.72, and 0.98, respectively. Thus, patient-specific modeling in real time is not only feasible but also effective in generating alerts at the bedside.


The DC-module of doublecortin: dynamics, domain boundaries, and functional implications.
The doublecortin-like (DC) domains, which usually occur in tandem, constitute novel microtubule-binding modules. They were first identified in doublecortin (DCX), a protein expressed in migrating neurons, and in the doublecortin-like kinase (DCLK). They are also found in other proteins, including the RP1 gene product which-when mutated-causes a form of inherited blindness. We previously reported an X-ray structure of the N-terminal DC domain of DCLK (N-DCLK), and a solution structure of an analogous module of human doublecortin (N-DCX). These studies showed that the DC domain has a tertiary fold closely reminiscent of ubiquitin and similar to several GTPase-binding domains. We now report an X-ray structure of a mutant of N-DCX, in which the C-terminal fragment (residues 139-147) unexpectedly shows an altered, "open" conformation. However, heteronuclear NMR data show that this C-terminal fragment is only transiently open in solution, and assumes a predominantly "closed" conformation. While the "open" conformation may be artificially stabilized by crystal packing interactions, the observed switching between the "open" and "closed" conformations, which shortens the linker between the two DC-domains by approximately 20 A, is likely to be of functional importance in the control of tubulin polymerization and microtubule bundling by doublecortin.


Diagnostic pitfalls of less well recognized HbH disease.
HbH disease had been introduced as a mild anemia disease. It recently has become the most challenging hemoglobinopathy due to the increasingly described genotype patterns and very variable phenotypic presentations in different ethnics. Phenotypic severity of HbH syndrome is not simply related to the degree of α-globin deficiency and being influenced by several environmental and/or genetic factors. Hence, more investigation needs to identify factors like other genetic loci linked and/or unlinked to the α-globin genes affecting molecular mechanisms that influence clinical expression of HbH disease. Altogether, the complicated pathophysiology of HbH disease makes it to be known as a poorly understood syndrome. It may offer the hypothesis that it is a multifactorial disease, which needs to be investigated by more comprehensive genetic approach like genome wide association studies (GWAS) looking for genetic variants. Moreover, extended haplotype analysis to find out probable specific association between haplotypes of modifier genes and disease severity in patients with a specific HbH genotype may be a key point. In this review, we aim to provide important information regarding phenotypic presentation of different genotypes that have been described worldwide. It may help geneticists regarding challenging health care aspects of HbH disease in a specific ethnic.


The cytochrome P450 2B4-NADPH cytochrome P450 reductase electron transfer complex is not formed by charge-pairing.
Attempts to covalently link NADPH-cytochrome P450 reductase to cytochrome P450 2B4 using a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylisopropyl)carbodiimide, were unsuccessful, despite the fact that under the same conditions about 30% of P450 2B4 could be covalently linked with cytochrome b5 in a functionally active complex (Tamburini, P. P., and Schenkman, J. B. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 11-15). This suggested that the functional electron transfer complex between P450 2B4 and reductase is not stabilized by electrostatic forces. Raising the ionic strength of the medium is disruptive to salt bridges and was used to further test whether P450 2B4 and the reductase form charge-pairing complexes. Instead of inhibiting electron transfer, high ionic strength increased the apparent fast phase rate constant and the fraction of P450 2B4 reduced in the fast phase. The possibility that electron transfer between NADPH-cytochrome P450 reductase and P450 2B4 is diminished by charge repulsion was examined. Consistent with this hypothesis, the Km of P450 2B4 for reductase was decreased 26-fold by increasing the ionic strength from 10 to 100 mM sodium phosphate without affecting the Vmax. The rate of benzphetamine N-demethylation also was increased by elevation of the ionic strength. Electron transfer from the reductase to other charged redox acceptors, e.g. cytochrome c and ferricyanide, was also stimulated by increased ionic strength. However, no similar stimulation was observed with the uncharged acceptor 1,4-benzoquinone. Polylysine, a polypeptide that binds to anionic sites, enhanced electron transfer from NADPH to ferricyanide and the apparent fast phase of reduction of cytochrome P450. The results are consistent with the hypothesis that charges on NADPH-cytochrome P450 reductase and cytochrome P450 decrease the stability of the electron transfer complex.


ERCC1 gene +262A/C polymorphism associated with risk of gastric cardiac adenocarcinoma in nonsmokers.
Polymorphisms in DNA repair gene may alter an individual's DNA repair capacity and be associated with the risk of various cancers. This study was designed to investigate whether ERCC1 +262A/C and XPF -357A/C polymorphisms affect individual susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). In 389 ESCC patients vs. 778 healthy controls and 262 GCA patients vs. 524 healthy controls in a high incidence region of northern China, ERCC1 +262A/C polymorphism and XPF -357A/C polymorphism were genotyped by the method of polymerase chain reaction ligase detection reaction (PCR-LDR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. Family history of upper gastrointestinal cancers (UGIC) may increase the risk of ESCC and GCA. Allelotype and genotype distributions of ERCC1 +262A/C and XPF -357A/C polymorphisms in ESCC and GCA patients were not significantly different from that in their respective controls (p >0.05). Compared with ERCC1 +262C/C genotype, A/A genotype decreased the risk of GCA in nonsmokers (age, gender and family history of UGIC adjusted odds ratio [OR] = 0.30, 95% confidence interval [CI] = 0.13-0.70). Neither the A/C nor the C/C genotype was associated with the overall risk of ESCC and GCA when compared with the XPF -357A/A genotype. ERCC1 +262A/A genotype may reduce the risk of GCA for nonsmokers. XPF -357A/C polymorphism was not associated with the risk of ESCC and GCA in a population of a high-incidence region in northern China.


Effect of N-Acetylcystein on butyrate-treated Chinese hamster ovary cells to improve the production of recombinant human interferon-beta-1a.
Sodium butyrate (NaBu) is used as a productivity enhancer for the production of therapeutic recombinant proteins in Chinese hamster ovary (CHO) cells. However, NaBu is well-known for having a cytotoxic effect, thereby inducing apoptosis. As an endeavor to reduce this defect, we studied 11 antioxidants known for inhibiting apoptosis, according to a Plackett-Burman statistical design on CHO cells producing recombinant interferon-beta-1a (IFN-beta). None of the antioxidants that we tested were as effective as N-acetylcystein (NAC) from the point of view of maintaining long-term survival of CHO cells and increasing the production of IFN-beta. In 7.5-L perfusion bioreactor cultures, the addition of NaBu and NAC elongated the culture period to almost 200 h throughout production phase and increased the production yield by 2-fold compared to control cultures containing only NaBu. Glycosylation patterns of produced IFN-beta at each run were also compared in IEF analysis. IEF profiles of where NaBu and NAC were added showed to be more isoforms with a lower pI than those of the control run. The sialic acid content was also increased by 17.7% according to HPLC analysis. Taken together, the data obtained demonstrate that the addition of NAC has positive effects on the elongation of the culture period, improving the production and increasing the sialylation of IFN-beta in NaBu-treated CHO cells.


Uncommon anomalies of the left pulmonary artery during VATS lobectomy for lung cancer.
The key to avoid intraoperative complications due to failure in the preoperative detection of pulmonary vascular anomalies is to perform a careful hilar dissection.


GIS-augmented survey of poultry farms with respiratory problems in Haryana.
Among various infectious diseases of poultry, diseases of the respiratory tract are responsible for considerable economic losses. The present study was conducted to evaluate some of the risk factors, which included locations of farm, ventilation facilities, number of farms in 1 km2 area, agro-climatic zone, and age of flock in relation to respiratory problem in Haryana, India. One hundred poultry flocks with respiratory problems were identified and selected for conducting the survey. The "ODK Collect" app installed on a smartphone was used to capture coordinates of the farms. The collected data was accessed through http://odkproject-iirs.appspot.com/ . The location of farms was mapped with the help of QGIS. All the three parameters, viz., morbidity, mortality (p < 0.001), and case fatality rate (CFR) (p = 0.045), were significantly higher in birds of age 0-2 weeks. Natural ventilation was the most common facility observed in the present study (51/100). Maximum morbidity and mortality were observed in small flocks (< 10,000), whereas maximum CFR was observed in medium-sized flocks (> 10,000-30,000), and there was a significant difference in morbidity, mortality, and CFR. Further, there was a significant difference between agro-climatic zones with respect to morbidity and mortality (p < 0.001). It can be concluded that age, flock size, and agro-climatic conditions have an impact on intensity of diseases especially respiratory diseases. Therefore, special precautions should be taken for young flock. Flock size should be adequate, and such management practices should be adopted that are suitable for particular climatic conditions.


A general method for the detection and mapping of submicrogram quantities of glycosaminoglycan oligosaccharides on polyacrylamide gels by sequential staining with azure A and ammoniacal silver.
A sensitive method has been developed for the visualization of nonradiolabeled glycosaminoglycan oligosaccharides resolved by polyacrylamide gel electrophoresis using fixation with azure A followed by staining with ammoniacal silver. This method, which can detect as little as 1-2 ng of a single oligosaccharide species, can be used to stain a few micrograms of a complex oligosaccharide mixture. The combination of gradient polyacrylamide gel electrophoresis and sequential azure A/silver staining can be applied to the analysis of all the complex glycosaminoglycans (i.e., heparin, heparan sulfate, chondroitin/dermatan sulfate, keratan sulfate) and hyaluronate, as well as to comparisons of specificities of the glycosaminoglycan-degrading enzymes. This procedure may be particularly valuable in situations where the availability of glycosaminoglycan is very limited and/or where radiolabeling is impractical or undesirable.


Screening and Evaluation of Excellent Blackberry Cultivars and Strains Based on Nutritional Quality, Antioxidant Properties, and Genetic Diversity.
To screen and evaluate excellent blackberry cultivars and strains, 17 indexes of plant growth and fruit horticultural and nutritional characteristics were measured, 20 simple sequence repeat (SSR) markers were analyzed, the fingerprints of 23 blackberry cultivars and strains were constructed, and the processing characteristics of 10 excellent cultivars and strains were evaluated. The results showed that 'Chester' and 'Shuofeng' had the highest plant yield (6.5 kg per plant), of which the 'Chester' fruit also had the highest hardness (2.78 kg/cm2). 'Kiowa' had the highest single fruit weight (10.43 g). '10-5n-2' had the highest total anthocyanin content (225.4 mg/100 g FW) and total polyphenol content (3.24 mg/g FW), but a low plant yield. These results suggest that 'Shuofeng' and 'Chester' are the top two blackberry cultivars planted in Nanjing, with the best growth and comprehensive quality. Moreover, a total of 119 alleles were detected with an average number of 6 alleles per locus. The polymorphism information content (PIC) was 0.374~0.844, with an average of 0.739, indicating a high genetic diversity among the 23 blackberry cultivars and strains. This study provides insight into the plant growth, fruit characteristics and genetic diversity of the 23 blackberry cultivars and strains, and is thus conducive to the protection and utilization of blackberry cultivars and strains.


Pediatric body composition based on automatic segmentation of computed tomography scans: a pilot study.
Body composition during childhood may predispose to negative health outcomes later in life. Automatic segmentation may assist in quantifying pediatric body composition in children. To evaluate automatic segmentation for body composition on pediatric computed tomography (CT) scans and to provide normative data on muscle and fat areas throughout childhood using automatic segmentation. In this pilot study, 537 children (ages 1-17 years) who underwent abdominal CT after high-energy trauma at a Dutch tertiary center (2002-2019) were retrospectively identified. Of these, the CT images of 493 children (66% boys) were used to establish normative data. Muscle (psoas, paraspinal and abdominal wall) and fat (subcutaneous and visceral) areas were measured at the third lumbar vertebral (L3) level by automatic segmentation. A representative subset of 52 scans was also manually segmented to evaluate the performance of automatic segmentation. For manually-segmented versus automatically-segmented areas (52 scans), mean Dice coefficients were high for muscle (0.87-0.90) and subcutaneous fat (0.88), but lower for visceral fat (0.60). In the control group, muscle area was comparable for both sexes until the age of 13 years, whereafter, boys developed relatively more muscle. From a young age, boys were more prone to visceral fat storage than girls. Overall, boys had significantly higher visceral-to-subcutaneous fat ratios (median 1.1 vs. 0.6, P<0.01) and girls higher fat-to-muscle ratios (median 1.0 vs. 0.7, P<0.01). Automatic segmentation of L3-level muscle and fat areas allows for accurate quantification of pediatric body composition. Using automatic segmentation, the development in muscle and fat distribution during childhood (in otherwise healthy) Dutch children was demonstrated.


Comparison of New Ballards score and Parkins score for gestational age estimation.
This prospective analytical study was done to compare the accuracy of New Ballards score (NBS) and Parkins score (PS) in assessing the gestational age (GA) in newborns. The GA of 284 babies was assessed by the NBS and PS within 24 hours of birth. The two methods of assessment were compared using the Bland Altmann Plot. The mean difference between the two measurements was 1.530576. 95% of the values lay within the limits of agreement which are -1.82982 and 4.890974. The two methods are found to be in acceptable agreement. Parkins score enables us to easily assess the gestational age of babies within ±12 days, especially in sick and preterm babies.


Why frightening imaginary worlds? Morbid curiosity and the learning potential of horror.
In addition to satisfying a predisposition for exploration, fiction with imaginary worlds may also appeal to morbid curiosity, an adaptive motivation to seek out information about dangerous situations. Most imaginary worlds contain narrative elements of danger, and immersion in such worlds may provide people with information that would be costly to acquire in the real world.


Control of central metabolism's architecture in Escherichia coli: An overview.
Understanding metabolic networks' architecture is central to successfully manipulating metabolic fluxes in microbial cell factories. The transition of central metabolism's architecture from acetogenic to gluconeogenic and from the canonical monocyclic architecture of the Krebs tricarboxylic acids (TCA) cycle to a bicyclic architecture in which the TCA and the dicarboxylic acids (DCA) cycles work in unison, with the glyoxylate bypass fulfilling the anaplerotic function, has been the subject of much debate and remains elusive. In this article, the author sheds light on the intricacies surrounding the transition of central metabolism from one architecture to another and shows that the transition from the monocyclic architecture to the bicyclic architecture is triggered in response to a minimum threshold signal of growth rate (≲0.40h-1) and is a consequence of competitions, on the one hand. between phosphotransacetylase (PTA) and α-ketoglutarate dehydrogenase (α-KGDH) for their common co-factor, free HS-CoA, and, on the other hand, between catabolic and anaplerotic routs for acetyl phosphate. Further restriction of carbon supply in the bioreactor to the point of starvation forces E. coli to further modify its central metabolism to the PEP-glyoxylate architecture to maintain the redox balance. Interestingly the sudden change from hunger ('famine') to carbon excess ('feast') leads to yet another architecture in which the methylglyoxal pathway figure prominently to maintain the adenylate energy charge. Moreover, the author sheds light on the biochemical implications of each architecture.


COVID-19-related acute kidney injury; incidence, risk factors and outcomes in a large UK cohort.
Acute kidney injury (AKI) is common among patients hospitalised with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in patients with COVID-19 in a large UK tertiary centre. We analysed data of consecutive adults admitted with a laboratory-confirmed diagnosis of COVID-19 across two sites of a hospital in London, UK, from 1st January to 13th May 2020. Of the 1248 inpatients included, 487 (39%) experienced AKI (51% stage 1, 13% stage 2, and 36% stage 3). The weekly AKI incidence rate gradually increased to peak at week 5 (3.12 cases/100 patient-days), before reducing to its nadir (0.83 cases/100 patient-days) at the end the study period (week 10). Among AKI survivors, 84.0% had recovered renal function to pre-admission levels before discharge and none required on-going renal replacement therapy (RRT). Pre-existing renal impairment [odds ratio (OR) 3.05, 95%CI 2.24-4,18; p < 0.0001], and inpatient diuretic use (OR 1.79, 95%CI 1.27-2.53; p < 0.005) were independently associated with a higher risk for AKI. AKI was a strong predictor of 30-day mortality with an increasing risk across AKI stages [adjusted hazard ratio (HR) 1.59 (95%CI 1.19-2.13) for stage 1; p < 0.005, 2.71(95%CI 1.82-4.05); p < 0.001for stage 2 and 2.99 (95%CI 2.17-4.11); p < 0.001for stage 3]. One third of AKI3 survivors (30.7%), had newly established renal impairment at 3 to 6 months. This large UK cohort demonstrated a high AKI incidence and was associated with increased mortality even at stage 1. Inpatient diuretic use was linked to a higher AKI risk. One third of survivors with AKI3 exhibited newly established renal impairment already at 3-6 months.


Diagnostic accuracy of T and N stages with endoscopy, stomach protocol CT, and endoscopic ultrasonography in early gastric cancer.
Preoperative accurate diagnosis of the T and N stages in early gastric cancer (EGC) is important in determining the application of various limited treatments. The aim of this study is to analyze the accuracy of T and N staging of EGC with esophagogastroduodenoscopy (EGD), Stomach protocol CT (S-CT), and endoscopic ultrasonography (EUS), and the factors influencing the accuracy. Four hundred and thirty-four patients preoperatively diagnosed as EGC using EGD or S-CT and undergoing curative gastrectomy at Seoul National University Hospital in 2005 were included. The T and N stage reviewed by experienced personnel were compared with the surgical pathology. The predictive values for EGC of EGD, S-CT, and EUS were 87.4%, 92.2%, and 94.1%, respectively. The predictive values for node negativity of S-CT, and EUS were 90.1% and 92.6%, respectively. The factors leading to underestimation of T stage with EGD were the upper third location, the size greater than 2 cm, and diffuse type of tumor. Those with S-CT were female sex, the upper third location and lesion size greater than 2 cm. Before applying limited treatment for EGC, a surgeon should consider the risk factors of underestimation of T stage with EGD or S-CT.


Acute effect of leptin on hepatic glycogenolysis and gluconeogenesis in perfused rat liver.
Leptin circulates in blood and is involved in body weight control primarily via hypothalamic receptors. To examine its direct metabolic action, effects of short-term portal leptin infusion: 1) on postprandial basal and epinephrine-stimulated glycogenolysis; and 2) on postabsorptive lactate-stimulated gluconeogenesis were studied in isolated perfused rat livers. Incremental epinephrine (150 pmol x min-1 x g-1 liver)-stimulated glucose release (in micromol/g liver within 30 minutes; control: 28.3 +/- 2.8) was suppressed (P <.05) by 44% (15.8 +/- 1.6), by 48% (14.6 +/- 4.1), and by 53% (13.3 +/- 2.1) during insulin (3 pmol x min-1 x g-1 liver), leptin (30 pmol x min-1 x g-1 liver), and simultaneous leptin + insulin infusion. Perfusate cyclic adenosine monophosphate increased approximately twofold during epinephrine stimulation in all groups. Neither leptin nor insulin affected hepatic lactate production, bile flow, or portal pressure in the fed state. In the postabsorptive state (20-hour fasting), rates of lactate (10 mmol/L)-dependent hepatic glucose release (in micromol. min-1 x g-1 liver; control: 0.12 +/- 0.01) were increased (P <.01) to 0.35 +/- 0.02 and to 0.24 +/- 0.01 by glucagon (3 pmol x min-1 x g-1 liver) and by leptin (15 pmol x min-1 x g-1 liver), respectively. In parallel, lactate uptake rates (in micromol x min-1 x g-1 liver) were higher in the presence of both glucagon (0.90 +/- 0. 03) and leptin (0.84 +/- 0.02) compared with control (0.68 +/- 0.04). In conclusion, leptin modulates hepatic glucose fluxes and may contribute to direct humoral regulation of liver glycogen stores in the fasted as well as in the fed state.


[Disaster Literacy Status and the Influencing Factors: A National Survey of 107997 Chinese Nurses].
To study the level of disaster literacy among nurses in China and the influcing factors and to provide scientific basis for developing effective interventions to improve the disaster literacy among Chinese nurses. Between September 2021 and October 2021, an online survey was conducted among nurses from health care institutions in eastern, central, western, and northeastern China by using a cross-sectional survey design and convenience sampling. The content of the survey included the surveyed nurses' sociodemographic characteristics, occupational characteristics, disaster relief characteristics, self-efficacy, and disaster literacy level. A disaster literacy model developed previously was used to assess the nurses' disaster literacy. A total of 107997 nurses were covered in the survey and their disaster literacy score was found to be 255.62±53.92. According to the findings of multiple linear regression, the protective factors for disaster literacy among Chinese nurses included the following, being based in Eastern region (non-standardized regression coefficient [ B]=2.365, 95% confidence interval [ CI]: 1.647-3.082), male sex ( B=9.418, 95% CI: 7.892-10.944), bachelor's degree or higher level of education ( B=3.822, 95% CI: 3.195-4.450), tertiary-level hospitals ( B=3.569, 95% CI: 3.000-4.138), military/local public hospitals ( B=2.606, 95% CI: 1.750-3.463), emergency department ( B=2.921, 95% CI: 2.149-3.694), intermediate professional title ( B=2.918, 95% CI: 2.209-3.627), senior professional title ( B=5.801, 95% CI: 4.448-7.155), participation in disaster rescue ( B=5.566, 95% CI: 5.020-6.112), the institution being previously involved in disaster emergency rescue ( B=3.257, 95% CI: 2.429-4.084), the institution having set up disaster rescue team ( B=5.967, 95% CI: 5.103-6.831), having received nursing education in disaster preparedness in school ( B=6.205, 95% CI: 5.621-6.790), having received on-the-job disaster preparedness education and training ( B=8.776, 95% CI: 8.027-9.525), and self-efficacy ( B=5.117, 95% CI: 5.069-5.165). In China, disaster literacy among nurses is at a medium to low level and needs to be improved. For the next step, efforts should be focused on nurses with the following features, being based in the central and western regions, female sex, having completed junior college education or less, no nursing education in disaster preparedness in school, having junior professional titles, being from gynecology, pediatrics, and auxiliary departments, working in grassroots medical and health institutions and primary and secondary-level hospitals, neither the individual respondent nor her institution having any experience in disaster rescue, the institution having no disaster rescue team, not having any on-the-job nursing education and training in disaster preparedness, and having low self-efficacy. Measures should be taken to improve their disaster literacy level.


[Experimental and numerical investigation of fluid-particle-interactions in water].
For the development of improved sediment transport models, the basic understanding of the interaction between the solid particle and the moving fluid (water) is important. In this article, current developments in the field of fluid-particle interaction are presented based on two research articles by Gold et al. (2023) and Worf et al. (2022). One presented in this article uses state of the art measurement methods to investigate the flow around spheres of different densities that oscillate in initially resting body of water. For the spherical pendulum a similar vortex shedding characteristic was observed for all investigated fluid density ratios (m*=ρS/ρF=1.14,14.95, density ratio between solid and fluid). A new object tracking method (DOT) is also presented, which enables temporally and spatially resolved analysis of flow structures in the fluid field. The experimental results of Gold et al. (2023) show, that vortex shedding occurs during the first period. This vortex propagates downward and eventually dissipates. Furthermore, a damping optimum of the spherical pendulum in the range of m*=2.50 was observed. Additionally, an experiment with a cylindrical pendulum with m∗=4.98 was investigated numerically utilizing an immersed boundary method. The process of creation and separation up to the dissipation of a vortex ring was described. Furthermore, this investigation by Worf et al. (2022) described the creation of tip vortices. These were connected with the development of the three-dimensional flow and added mass coefficient.


Identification of particular epithelial areas and cells that transport polypeptide-coated nanoparticles in the nasal respiratory mucosa of the rabbit.
The active transcytosis of many different polypeptides (either presented free or adsorbed on latex nanoparticles), found in the respiratory mucosa of the upper nasal concha, has previously been shown to be proportional to the total volume of the lymphoid aggregates present in the tissue. By combining the use of fluorescent nanoparticles, flux measurements, confocal and scanning electron microscopy and conventional histology, it is shown in this paper that: (i) the areas of epithelium overlying lymphoid aggregates are the only transporting polypeptides; (ii) the respiratory epithelium in these areas consists mainly of non-ciliated microvillar cells, with numerous ciliated cells and rare mucous goblet cells at the periphery of the area only; (iii) non-ciliated microvillar cells are distinguishable in cells with well developed finger-like microvilli and cells with an irregularly pleated apical membrane, similar to that of intestinal and bronchial antigen-sampling M-cells; (iv) groups of polypeptide-coated nanospheres are found bound to this latter type of cells, demonstrating that these are the transporting cells, detected at the first stage of the transcytotic cycle.


Changes in hemopoiesis of mice of the C3H strain following transplantation of Gardner lymphosarcoma and infection with LDH-virus. I. Circulating blood.
The values of red and white blood count, of spleen and liver weight were determined in mice of the C3H strain after transplantation of Gardner solid lymphosarcoma contaminated with LDH-virus and after infection of LDH-virus, and compared with those found in normal intact mice. Special attention was devoted to early post-transplantation period and the final stage of tumor growth. The second day after infection of mice with LDH-virus, leukopenia with marked lymphopenia was observed, together with a reduced number of reticulocytes and spleen enlargement. The same changes became more pronounced in tumorous mice on the second posttransplantation day. The changes--with the exception of spleen enlargement--following LDH-virus infection became normalized within the period of the final stage of tumor growth. Contrarily, in mice with tumors in the final stage of the disease besides spleen enlargement also the reduced erythrocyte counts, leukopenia with pronounced lymphopenia and thrombocytopenia were found.


Power of the 2-locus TDT for testing the interaction of two susceptibility genes.
We recently proposed a new strategy: 2-locus TDT for detecting two susceptibility genes through their interaction in trio families. We apply our method to two candidate genes, A and C, on the Genetic Analysis Workshop 15 (GAW15) simulated rheumatoid arthritis data and study the power to identify an interactive effect of these genes.This study was performed with full knowledge of the answers.


Sensitivity and representativeness of one-health surveillance for diseases of zoonotic potential at health facilities relative to household visits in rural Guatemala.
Most human and animal disease notification systems are unintegrated and passive, resulting in underreporting. Active surveillance can complement passive efforts, but because they are resource-intensive, their attributes must be evaluated. We assessed the sensitivity and representativeness of One-Health surveillance conducted at health facilities compared to health facilities plus monthly household visits in three rural communities of Guatemala. From September 2017 to November 2018, we screened humans for acute diarrheal, febrile and respiratory infectious syndromes and canines, swine, equines and bovines for syndromic events or deaths. We estimated the relative sensitivity as the incidence rate ratio of detecting an event in health facility surveillance compared to household surveillance from Poisson models. We used interaction terms between the surveillance method and sociodemographic factors or time trends to assess effect modification as a measure of relative representativeness. We used generalized additive models with smoothing splines to model incidence over time by surveillance method. We randomized 216 households to health facility surveillance and 198 to health facility surveillance plus monthly household visits. Health facility surveillance alone was less sensitive than when combined with household surveillance by 0.42 (95% CI: 0.34, 0.53), 0.56 (95% CI: 0.39, 0.79), 0.02 (95% CI: 0.00, 0.10), 0.28 (95% CI: 0.15, 0.50) and 0.22 (95% CI: 0.03, 0.92) times for human acute infections, human severe acute infections, and deaths in canines, swine and equines, respectively. Health facility surveillance alone underrepresented Spanish speakers (interaction p-value = 0.0003) and persons in higher economic assets (interaction p-values = 0.0008). The trend in incidence over time was different between the two study groups, with a larger decrease in the group with household surveillance (all interaction p-values <0.10). Surveillance at health facilities under ascertains syndromes in humans and animals which leads to underestimation of the burden of zoonotic disease. The magnitude of under ascertainment was differentially by sociodemographic factors, yielding an unrepresentative sample of health events. However, it is less time-intensive, thus might be sustained over time longer than household surveillance. The choice between methodologies should be evaluated against surveillance goals and available resources.


Comparing ozone metrics on associations with outpatient visits for respiratory diseases in Taipei Metropolitan area.
This study reported cumulative 6-day (lag 0-5 days) relative risks (RR) and confidence intervals (CI) of daily outpatient visits for total respiratory disease (RD), asthma, and chronic airway obstruction not otherwise classified (CAO) associated with three ozone metrics (daily 1-h maximum (O3, 1 h max), 8-h average maximum (O3, 8 h max), 24-h average (O3, 24 h avg)), and an alternative oxidant indicator (Ox) in Taipei Metropolitan, using distributed lag non-linear models after controlling for potential confounders. The Ox showed the strongest association with outpatient visits for total RD (RR = 1.10, 95% CI: 1.10, 1.11) and asthma (RR = 1.18, 95% CI: 1.00, 1.39) in the cold season. The O3, 24 h avg appeared to be the optimal ozone metric associating with total RD than O3, 1 h max and O3, 8 h max based on model selection. In conclusion, outpatient visits for total RD associated with ozone vary with ozone metrics, disease and season.


Emergency embolization in posttraumatic hemobilia in a child.
The authors report a case of hemobilia in a ten-year-old boy after abdominal trauma. An intrahepatic false aneurysm was successfully embolized during the diagnostic angiogram. This is, to their knowledge, the first pediatric case successfully embolized with posttraumatic hemobilia.


Exposure to PM2.5 induces neurotoxicity, mitochondrial dysfunction, oxidative stress and inflammation in human SH-SY5Y neuronal cells.
Ambient air pollution is a global public health issue. Recent evidence suggests that exposure to fine aerosolized particulate matter (PM) as small as ≤2.5 microns (PM2.5) is neurotoxic to brain structures. Many studies also suggest exposure to PM2.5 may cause neurotoxicity and affect brain function. However, the molecular mechanisms by which PM2.5 exerts these effects are not fully understood. Thus, we evaluated the hypothesis that PM2.5 exposure exerts its neurotoxic effects via increased oxidative and inflammatory cellular damage and mitochondrial dysfunction using human SH-SY5Y neuronal cells. Here, we show PM2.5 exposure significantly decreases viability, and increases caspase 3 and 9 protein expression and activity in SH-SY5Y cells. In addition, PM2.5 exposure decreases SH-SY5Y survival, disrupts cell and mitochondrial morphology, and significantly decreases ATP levels, D-loop levels, and mitochondrial mass and function (maximal respiratory function, COX activity, and mitochondrial membrane potential) in SH-SY5Y cells. Moreover, SH-SY5Y cells exposed to PM2.5 have significantly decreased mRNA and protein expression levels of survival genes (CREB and Bcl-2) and neuroprotective genes (PPARγ and AMPK). We further show SH-SY5Y cells exposure to PM2.5 induces significant increases in the levels of oxidative stress, and expression levels of the inflammatory mediator's TNF-α, IL-1β, and NF-κB. Taken together, these results provide the first evidence of the biochemical, molecular and morphological effects of PM2.5 on human neuronal SH-SY5Y cells, and support our hypothesis that increased mitochondrial disruption, oxidative stress and inflammation are critical mediators of its neurotoxic effects. These findings further improve our understanding of the neuronal cell impact of PM2.5 exposure, and may be useful in the design of strategies for the treatment and prevention of human neurodegenerative disorders.


Subsistence strategy changes during the Middle to Upper Paleolithic transition reveals specific adaptations of Human Populations to their environment.
The transition from Middle to Upper Paleolithic is a major biological and cultural threshold in the construction of our common humanity. Technological and behavioral changes happened simultaneously to a major climatic cooling, which reached its acme with the Heinrich 4 event, forcing the human populations to develop new strategies for the exploitation of their environment. The recent fieldwork at Les Cottés (France) transitional site offers a good opportunity to document subsistence strategies for this period and to provide for the first time high-resolution insights on its evolution. We present the results of the complete zooarchaeological and taphonomic analysis of the transitional sequence, associated with a large regional synthesis of the subsistence strategy evolution during the Middle to Upper Paleolithic. We conclude that, while there is no major change in the hunting strategies, the butchery activities evolved in strict correlation with the development of range weapons. In addition, the demise of carnivore seems to be a consequence of the human pressure on the environment. Our study demonstrates how the faunal component of the environment became a structuring element of the human social organization, being at the base of future cultural evolutions.


Evaluating "startup readiness" for researchers: case studies of research-based startups with biopharmaceutical research topics.
For research domains such as life sciences, which pursue fundamental scientific understanding and applications intended for immediate use, academic entrepreneurship has played a pivotal role in commercialization. This paper presents an evaluation method of researchers related to user-inspired fundamental research, using global databases of startup finances and academic research papers of "startup readiness." Case studies of startups related to biopharmaceutical research topics suggest that the biopharmaceutical field has rich opportunities stemming from scientific research, commercialization, and entrepreneurship. This evaluation method sorts specific industry segments by which financing activities are active, and by which related growing research topics attract increased academic attention. We constructed networks of author citation and co-authorship from paper citation networks related to research topics in industry segments in the biopharmaceutical domain. Results obtained across all research topics we surveyed demonstrated that authors in the top 10% of degree centrality ranking in both networks are far more likely to be startup participants than other authors. Our computational approach might provide convenient, dynamic, global, and real-time understanding of the "startup readiness" of researchers working with research topics for which academic attention is emerging in actively financed biopharmaceutical fields.


Screening of Adverse Prognostic Factors and Construction of Prognostic Index in Previously Untreated Concurrent Follicular Lymphoma and Diffuse Large B-Cell Lymphoma.
Concurrent follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) (defined as FL/DLBCL) have been considered an important pathological feature in cell lymphoma. However, clinicopathological information and prognostic factors in these cases are scarce. The aim of this study was to construct a prediction index to compare with traditional prognostic models. Retrospectively enrolled, previously untreated FL/DLBCL (n = 121) patients, as well as those with pure FL 1-3a (n = 471), were assessed. De novo DLBCL (n = 529) were used as controls. Kaplan-Meier curves were plotted to compare the outcomes among the three groups. Multivariate analysis identified risk factors associated with overall survival (OS) in FL/DLBCL patients. A clinicopathological prognosis index (CPPI) was developed to predict OS based on the Cox proportional hazards model. The outcomes of FL/DLBCL patients were intermediate between pure FL 1-3a and de novo DLBCL patients, with a 5-year PFS of 70%, 59%, and 48% (P < 0.05) and 5-year OS of 80%, 70% and 60% (P < 0.05), respectively. Cox regression analysis showed that the prognostic factors of OS for FL/DLBCL patients included FL grade, cell of origin, and Ann Arbor stage. A nomogram and clinicopathological prognostic index (CPPI) were developed to predict the OS for FL/DLBCL patients based on these factors. The area under the curve (AUC) of the CPPI for 3- and 5-year OS prediction was 0.782 and 0.860, respectively. This was superior to that of the International Prognostic Index (IPI), Follicular Lymphoma International Prognostic Index (FLIPI), and FLIPI2 in the 0.540-0.819 (P < 0.01) range. A valid OS estimation in FL/DLBCL patients, using the recommended CPPI, may be useful in routine clinical practice.


Visual backward masking: deficits in locating targets are specific to schizophrenia and not related to intellectual decline.
Visual backward masking deficits have been postulated as potential vulnerability markers for schizophrenia. This study investigated the diagnostic specificity of a location and an identification variant of the backward masking task for schizophrenia and analyzed masking performance during the course of the tasks. The influence of schizophrenia patients' intellectual decline on masking performance was also examined. Twenty-eight schizophrenia patients were compared to 28 patients with unipolar depression and 28 healthy controls on a letter location task and a letter identification task applying a low spatial frequency mask. Schizophrenia patients made significantly more detection errors on the location task than depressives at an interstimulus interval (ISI) of 50 ms and healthy controls at ISIs of 16.7, 33.3, 50, and 66.7 ms. Thus, the location masking dysfunction of schizophrenia patients was distinctive at a rather long interstimulus interval (50 ms). On the identification task the performance of schizophrenia patients did not differ from that of the two control groups. Identification but not location masking performance improved during the course of the task for all groups. Intellectual deterioration of schizophrenia patients was not correlated with location or identification masking performance. Schizophrenia patients are characterized by specific impairments in spatial visual processing which appear to be independent of intellectual decline. Potential explanations of the location masking deficit found in schizophrenia are discussed.


Optical and long wave holography: potential applications in ophthalmology.
The first part of this paper describes the process of optical holography, and discusses the possibilities and some of the merits of the application of optical holographic techniques in the field of ophthalmology, such as: 1. Holographic observation of the eye and the light-path through the cornea and the lens, leading to the evaluation of the optical constants of the eye. 2. Holographic interferometric measurements of the configuration changes which accompany accommodation or changes in the intra-ocular pressure. 3. Three-dimensional observations of the fundus. The second part of the paper is devoted to long wave holography, which has attained special attention in electromagnetic (non-optic) and ultrasonic wave propagation. Although these two forms of wave propagation differ in their physical properties, there are many similarities in their signal processing techniques, the collection of wave fronts emerging from the object, and in the visualization of images.


Evaluation of rate-dependency and internal clock effects of D-amphetamine.
The impact of two doses of d-amphetamine on rats' peak-interval performance was evaluated at two different points of training: with minimum training, 20 sessions, and with extended training, 120 sessions. At both points of training, none of the doses changed the location of the peak time; however, both doses caused a significant increase in the standard deviation of the response distribution during peak trials. Both results are incompatible with some previous empirical results, and with timing accounts that assume that dopamine modulates the pacemaker rate, but are compatible with a rate-dependent effect.


Getting a jump on recovery from sports-related concussion.
Early subthreshold aerobic exercise safely improved recovery time over a stretching regimen among adolescents in this clinical trial.


Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression.
Carcinogenesis is a complex, multistep, multipath process often described as "somatic evolution". Conventional models of cancer progression are typically based on the genetic and epigenetic changes observed in malignant and premalignant tumors. We have explored an alternative approach that emphasizes the selection forces within adaptive landscapes governing growth and evolution in in situ, microinvasive, and metastatic cancers. In each environment, specific barriers to proliferation act as strong selection forces that determine the optimal phenotypic properties that permit tumor growth and invasion. Thus, the phenotypic properties or "hallmarks" of cancer can be viewed as successful adaptations to these microenvironmental selection forces. In turn, these selection pressures are not static but will dynamically change as a result of tumor population growth and evolution. Here, we emphasize the role of hypoxia and acidosis in the progression of tumor from in situ to invasive cancer. This is a consequence of early tumor cell proliferation on epithelial surfaces, which are separated from the underlying blood supply by the intact basement membrane. As tumor cells proliferate further away from the basement membrane, the diffusion-reaction kinetics of substrate and metabolite flow to and from the blood vessels result in regional hypoxia and acidosis. Cellular adaptation to the former include upregulation of glycolysis and to the latter include upregulation of Na+/H+ exchangers (NHE1) and other acid-regulating proteins such as carbonic anhydrase. We propose this phenotype is critical for subsequent malignant growth of primary and metastatic cancers.


Identical miniature inverted repeat transposable elements flank class 1 integrons in clinical isolates of Acinetobacter spp.
Miniature inverted repeat transposable elements (MITEs) have been identified flanking class 1 integrons. We have identified and characterized a 439-bp MITE-like structure in seven Acinetobacter species isolates from Portugal and Brazil. The complete sequence similarity of the elements and flanking regions suggests that MITEs may act as mobilizable vectors for the dissemination of integrons.


Novel Radiotherapy Technologies in the Treatment of Gastrointestinal Malignancies.
Over the past 2 decades, major technical advances in radiation therapy planning and delivery have made it possible to deliver higher doses to select high-risk volumes. This has helped to expand the role of radiation therapy in the treatment of gastrointestinal malignancies. Whereas dose escalation was previously limited by the radiosensitivity of normal tissues within and adjacent to the gastrointestinal tract, advances in target delineation, patient immobilization, treatment planning, and image-guided treatment delivery have greatly improved the therapeutic ratio. More conformal radiation modalities can offer further dose optimization to target volumes while sparing normal tissue from toxicity.


Vagus nerve stimulation for intractable epilepsy in tuberous sclerosis complex.
The aim of the study described here was to characterize the efficacy and safety of vagus nerve stimulation in a population of patients with tuberous sclerosis complex (TSC) and intractable epilepsy. This retrospective study comprised 16 patients with TSC who underwent implantation of a vagus nerve stimulator for treatment of intractable epilepsy. The average age at vagus nerve stimulator implantation was 15 years (range: 2-44, SD: 12.5) and the average duration of follow-up on VNS was 4 years (range: 0.5-8.6, SD: 2.3). Outcome was rated class I (>80% seizure frequency reduction) in 3 (19%), class II (50-79% reduction) in 5 (31%), class III (<50% reduction) in 2 (13%), class IV (magnet benefit only) in 1 (6%), and class V (no improvement) in 5 (31%) patients. Intermittent magnet use was effective in aborting seizures in 8 (50%). Five (31%) patients reported an improved level of functioning. The findings suggest that the vagus nerve stimulation can be an effective and safe therapy for patients with TSC with intractable epilepsy.


Neurodevelopmental problems in children with febrile seizures followed to young school age: A prospective longitudinal community-based study in Sweden.
To estimate the accumulated prevalence of neurodevelopmental problems from preschool to school age in children with a history of febrile seizures (FS). In a community-based cohort of children with previous FS, 25/73 clinically assessed children met diagnostic criteria for neurodevelopmental disorders or had major indications of such problems at the age of 4-5 years. Parents of 54 of the 73 children accepted to take part in an interview according to the Autism-Tics, ADHD and other Comorbidities (A-TAC) inventory, when the children were 9-10 years. There was a trend for ADHD symptom scores to be higher in the FS group. Non-participants at age 9-10 years had had much higher rates of neurodevelopmental problems at 4-5 years, and the total number of such problems at either 4-5 or age 9-10 was 41% (30/73). High rates of neurodevelopmental problems (41%) were found at either age 4-5 or 9-10 years or both in this group of 73 children with FS. Non-participants at 9-10 years had had much higher rates of neurodevelopmental problems at 4-5 years. Further follow-up of this cohort is needed before definite conclusions can be drawn about whether FS should be considered a marker for more complex neurodevelopmental problems.


Monoclonal antibodies directed against human fibroblast interferon: characterization and functional studies.
Spleen cells from BALB/c mice, immunized with SDS-acrylamide gel purified human fibroblast interferon (HuIFN-beta) were fused with mouse myeloma cells. Culture fluids from the resulting hybrid cells were screened for HuIFN-beta specificity by the following tests: a solid-phase RIA using partially purified HuIFN-beta, a protein-transfer RIA using electrophoretically resolved and immobilized HuIFN-beta, and a bioassay which tests residual HuIFN-beta activity in the supernatant following immunoprecipitation. Six HuIFN-beta-specific hybridomas were identified; two were capable of partially neutralizing HuIFN-beta activity. All six antibodies bind to the beta 1-IFN polypeptide synthesized in E. coli cells containing a cloned beta 1-IFN DNA sequence. All six monoclonal antibodies were found to be IgG3/kappa.


In vitro construction of 2D and 3D simulations of the murine hematopoietic niche.
Hematopoietic stem cells (HSC) undergo multilineage differentiation or self-renewal to maintain normal hematopoiesis and to sustain the size of the HSC pool throughout life. These processes are determined by a complex interplay of molecular signals between HSC and other cellular components such as osteoblasts (OB), stromal cells, endothelial cells, and a number of extracellular matrix (ECM) proteins. Through changes in its physical properties within the bone marrow (BM) microenvironment, collagen, which is one of the most critical ECM proteins, can modulate HSC function and maintenance of the competence of the hematopoietic niche (HN). At present, there is no consensus as to how different cellular elements of the niche collaborate and interact to promote HSC self-renewal or differentiation to maintain hematopoiesis. Deciphering these interactions and the impact of mechanical properties of the collagen microstructures within the HN has critical clinical implications in the areas of stem cell homing, engraftment, and maintenance of HSC function. In this chapter, we describe several of the in vitro methodologies for establishing and maintaining HSC in vitro including the isolation of OB, stromal cells, and hematopoietic progenitor cells, as well as the establishment of both two-dimensional (2D) and three-dimensional (3D) coculture systems.


Speciation dynamics and extent of parallel evolution along a lake-stream environmental contrast in African cichlid fishes.
Understanding the dynamics of speciation is a central topic in evolutionary biology. Here, we investigated how morphological and genomic differentiation accumulated along the speciation continuum in the African cichlid fish Astatotilapia burtoni. While morphological differentiation was continuously distributed across different lake-stream population pairs, we found that there were two categories with respect to genomic differentiation, suggesting a "gray zone" of speciation at ~0.1% net nucleotide divergence. Genomic differentiation was increased in the presence of divergent selection and drift compared to drift alone. The quantification of phenotypic and genetic parallelism in four cichlid species occurring along a lake-stream environmental contrast revealed parallel and antiparallel components in rapid adaptive divergence, and morphological convergence in species replicates inhabiting the same environments. Furthermore, we show that the extent of parallelism was higher when ancestral populations were more similar. Our study highlights the complementary roles of divergent selection and drift on speciation and parallel evolution.


Design and synthesis of analogs of vitamin E: antiproliferative activity against human breast adenocarcinoma cells.
Analogs of alpha-tocopherol (vitamin E; compounds 3-9) have been synthesized and tested for their antiproliferative activity using the human breast cancer cell line, MCF7. Compounds 6-9 were synthesized from a common symthom, rac-Trolox (14) and are soluble/miscible at physiological pH. Compounds 4, 8, and 9 were found to have antiproliferative activity at micromolar concentrations.


Postoperative large intraretinal cavity and schisis with paravascular inner break in high myopia.
To report distinct structural changes following surgery for myopic traction maculopathy (MTM). A single-center, retrospective case series. Patients with MTM who underwent vitrectomy and had persistent large intraretinal cavities and schisis were reviewed. The pre- and postoperative clinical findings and optical coherence tomography characteristics are described. Five eyes of five patients were included in the study. Three patients had prominent schisis, and four had retinal/foveal detachment before surgery. All patients underwent fovea-sparing internal limiting membrane peeling during vitrectomy and had improved vision at 3 months after surgery. Large intraretinal cavities were noted on optical coherence tomography at the first postoperative exam in three patients and 12 to 18 months postoperation in the other two. The median height of the postoperative intraretinal cavities was 704 μm (range, 445-1287 μm). Inner retinal breaks were identified in all eyes, of which four were located in the paravascular area. The intraretinal cavity and schisis remained stable during the initial follow-up for an average of 35 months; later on, at > 5 years after the initial presentation two patients developed retinal detachment and one patient underwent vitrectomy with the retina reattached postoperatively. Large intraretinal cavities and schisis can be observed after MTM surgery, associated with paravascular inner breaks. The condition can progress after a long stable period; therefore, continuous follow-up is necessary.


Impact of amyloid PET in the clinical care of veterans in a tertiary memory disorders clinic.
We aimed to characterize the clinical impact of amyloid PET (APET) in a veteran population with cognitive decline by comparing differences in management between those who did and did not have an APET. This was a retrospective observational study. Poisson regressions and logistic regression were used for comparisons. Out of 565 veterans, 197 underwent APET; positivity rate was 36.55%. Having an APET was associated with longer follow-up, and increased diagnostic variability; it was not associated with number of additional studies, cholinesterase inhibitors prescription, or referrals to research. A positive APET was associated with less diagnostic variability, fewer additional tests, greater cholinesterase inhibitor prescriptions, and more research referrals. In a medically complex, real-world population, APET yielded lower positivity rates and was not associated with classical clinical utility variables when comparing patients with and without an APET. APET may be used more to "rule out" rather than to confirm Alzheimer's disease. Amyloid PET was associated with longer follow-up, and higher diagnostic variability.No association was seen with cholinesterase inhibitors prescription, or referrals to research.In complex patients, expected amyloid PET positivity rates are lower than previously described.Amyloid PETs were used to "rule out" AD than to confirm the diagnosis of AD.


Evaluation of superficial and deep self-inflicted wrist and forearm lacerations.
Self-inflicted wrist or forearm laceration is a specific type of injury presenting to emergency departments. Many investigators have described wrist-cutting from a psychiatric viewpoint. We hypothesized that the character of patients with deep wounds is different from those with superficial wounds. We investigated patients who cut their wrist or forearms as an act of self-mutilation from the viewpoint of wound severity. We reviewed 31 patients with self-inflected wrist injuries who were treated in our medical center from 2004 through 2009. We divided them into 2 groups: deep (15 patients) and superficial (16 patients). We investigated differences in age and gender, sites of self-cutting, frequency of self-injury attempts, object used for wrist cutting, group psychiatric parameters, required wound treatments, and psychiatric history and follow-up. Younger patients were more likely to have injured themselves severely compared with older patients. Differences in clinical findings between deep and superficial injury groups included the following: (1) all male patients had deep injuries; (2) patients with superficial wounds were more likely to have cut themselves previously; (3) patients in the deep injury group tended to injure themselves at multiple sites; (4) patients in the deep injury group tended to perform self-cutting with any sharp-edged object at hand; (5) 50% of our patients had received no psychiatric care before being seen by us for their injury; and (6) one-third discontinued the psychiatric treatment prematurely. There are differences between patients who perform self-inflicted deep versus superficial wrist cutting. We also found that the ages and psychiatric diagnoses of our patients differed from previous reports. This is likely because the available literature includes only patients who received psychiatric care. We found that 50% of our patients had received no psychiatric care, which highlights the importance of hand surgeons treating these patients to initiate psychiatric consultation.


Chronic kidney disease and atrial fibrillation: A dangerous combination.
Chronic kidney disease (CKD) and atrial fibrillation (AF) are both risk factors for bleeding, stroke and mortality. The aim of our study was to investigate the interaction between CKD and atrial fibrillation and outcomes. We included 12,394 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2018 for an out-patient visit (Utrecht Cardiovascular Cohort Second Manifestation of Arterial disease cohort). Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding, ischemic stroke or mortality were calculated with Cox proportional hazard analyses. Presence of interaction between AF and CKD was examined by calculating the relative excess risk due to interaction (RERI), the attributable proportion (AP) due to interaction and the synergy index (S). Of the 12,394 patients, 699 patients had AF, 2,752 patients had CKD and 325 patients had both AF and CKD. Patients with both CKD and AF had a 3.0-fold (95% CI 2.0-4.4) increased risk for bleeding, a 4.2-fold (95% CI 3.0-6.0) increased ischemic stroke risk and a 2.2-fold (95% CI 1.9-2.6) increased mortality risk after adjustment as compared with subjects without atrial fibrillation and CKD. We did not find interaction between AF and CKD for bleeding and mortality. However, we found interaction between AF and CKD for ischemic stroke risk (RERI 1.88 (95% CI 0.31-3.46), AP 0.45 (95% CI 0.17-0.72) and S 2.40 (95% CI 1.08-5.32)). AF and CKD are both associated with bleeding, ischemic stroke and mortality. There is a positive interaction between AF and CKD for ischemic stroke risk, but not for bleeding or mortality.


Ability of 5-HT4 receptor ligands to modulate rat striatal dopamine release in vitro and in vivo.
1. The ability of 5-HT4 (5-hydroxytryptamine4) receptor ligands to modify dopamine release from rat striatal slices in vitro and in the striatum of freely moving rats was assessed by the microdialysis technique. 2. The release of dopamine from slices of rat striatum continually perfused with Krebs buffer was enhanced by 5-HT4 receptor agonists; 5-HT (10 microM), 5-methoxytryptamine (5-MeOT; 10 microM), renzapride (10 microM) and (S)-zacopride (10 microM) maximally increased dopamine release by 133 +/- 5, 214 +/- 25, 232 +/- 29 and 264 +/- 69%, respectively (mean +/- s.e.mean, n = 3-8). The drug-induced responses were maximal within the first 2 min of drug application, and subsequently declined. The non-selective 5-HT3/5-HT4 receptor antagonist, SDZ205-557 (10 microM), failed to modify basal dopamine release from striatal slices but completely antagonized the (S)-zacopride (10 microM)-induced increase in dopamine release. 3. To allow faster drug application, the modulation of dopamine release from rat striatal slices in a static release preparation was also investigated. The 5-HT4 receptor agonist, renzapride (10 microM) also enhanced dopamine release in this preparation (maximal increase = 214 +/- 35%, mean +/- s.e.mean, n = 14), whilst a lower concentration of renzapride (3 microM) was less effective. The renzapride-induced response was maximal within the first 2 min of drug application, before declining. In this preparation, the stimulation of dopamine release by renzapride (10 microM), was completely antagonized by the selective 5-HT4 receptor antagonist, GR113808 (100 nM). In addition, both the Na+ channel blocker, tetrodotoxin (100 nM) and the non-selective protein kinase A inhibitor, H7 (100 nM) completely prevented the stimulation of dopamine release induced by renzapride (10 microM). 4. In vivo microdialysis studies demonstrated that the 5-HT4 receptor agonists, 5-MeOT (10 microM), renzapride (100 microM) and (S)-zacopride (100 microM) maximally elevated extracellular levels of dopamine in the striatum by 220 +/- 20, 161 +/- 10 and 189 +/- 53%, respectively (mean +/- s.e.mean, n = 5-9). A lower concentration of renzapride (10 microM) was less effective. The elevation of extracellular striatal dopamine levels induced by either renzapride (100 microM) or (S)-zacopride (100 microM) were completely antagonized by the non-selective 5-HT4 receptor antagonist, SDZ205-557 (100 microM). In addition, the elevation of extracellular levels of dopamine induced by either 5-MeOT (10 microM) or renzapride (100 microM) was completely prevented by the selective 5-HT4 receptor antagonist, GR113808 (1 microM) and the renzapride (100 microM)-induced response was also completely prevented by the non-selective protein kinase A inhibitor, H7 (1 microM). In this in vivo preparation, both GR113808 (1 microM) and H7 (1 microM), when perfused alone, reduced extracellular levels of dopamine. 5. In conclusion, the present study provides evidence that the 5-HT4 receptor facilitates rat striatal dopamine release in vitro and in vivo.


Health and safety hazards associated with farming.
1. Farming is a dangerous occupation with many potential physical, chemical, and biological hazards. Hazards include noise, machinery, motor vehicles, electricity, temperature extremes, pressurized hydraulic fluids, grain storage facilities, hand and power tools, repetitive motion, vibration, chemicals, dusts, gases, and infectious agents. 2. Psychosocial factors related to agriculture include stress, economic considerations, poor access to health care, and injuries to minors who begin working at a young age. 3. Many who farm also work at other jobs. Farm related illnesses and injuries can be costly to non-farm employers in terms of lost work time, medical insurance, and life insurance. 4. Occupational health nurses can promote agricultural occupational health through companies that employ farmers and through community organizations, thereby contributing to a better understanding of farm related hazards and developing strategies for reducing these hazards.