Diagnostic Yield of Electroencephalography When Seizure Is Suspected in Acute Ischemic Stroke.
Seizures are a common complication after an ischemic stroke. Electroencephalography can assist with the diagnosis of seizures however, the diagnostic yield of its use when seizure is suspected in the setting of acute ischemic stroke is unknown. We aim to evaluate the yield and cost of EEG in the acute ischemic stroke setting. We conducted a retrospective chart review of patients admitted to a single academic tertiary care center in the United States between September 1, 2015 to November 30, 2019 with a primary diagnosis of acute ischemic stroke and who were monitored on electroencephalography (EEG) for suspected seizures (total number of 70 patients). The primary outcome was how often EEG monitoring changed clinical management defined as starting, stopping, or changing the dose of an anti-epileptic drug. Secondary analysis was estimating the cost of EEG monitoring per change in management. We identified 126 patients admitted with acute ischemic stroke who underwent EEG of which 70 met all inclusion and exclusion criteria. EEG monitoring resulted in a change in management in 22 patients (31%). Predictors associated with EEG monitoring resulting in a change in management were admission to the ICU, pre-existing atrial fibrillation, and symptomatic hemorrhagic transformation. Estimated cost of EEG per change in management was $1374.96 USD. EEG monitoring resulted in a changed management in nearly one-third of patients admitted with acute ischemic stroke suspected of having seizures.


Apathy syndrome in cocaine dependence.
The cocaine abstinence syndrome has been associated with a range of symptoms, including apathy and depression. Although initial studies reported high prevalence rates of 'apathy/amotivation' and depression, validated rating scales of apathy were not then available. Using a validated measure of apathy, we hypothesized that newly abstinent cocaine-dependent subjects would report increased apathy compared with non-cocaine-using control subjects. Furthermore, because apathy and depression are dissociable in other neuropsychiatric syndromes, we examined whether they were dissociable in recently abstinent cocaine-dependent subjects. Following 4 days of monitored abstinence, cocaine-dependent subjects (n=11) and non-drug-using control subjects (n=19) were administered standardized tests of apathy and depression. Cocaine-dependent subjects had elevated scores on the apathy rating scale compared with the control group, but the groups did not differ in ratings of depression. These data suggest that apathy is present during the initial phases of abstinence for a subset of cocaine-dependent individuals. This group may benefit from targeted pharmacological intervention.


Thermodynamic properties of the effector domains of MARTX toxins suggest their unfolding for translocation across the host membrane.
MARTX (multifunctional autoprocessing repeats-in-toxin) family toxins are produced by Vibrio cholerae, Vibrio vulnificus, Aeromonas hydrophila and other Gram-negative bacteria. Effector domains of MARTX toxins cross the cytoplasmic membrane of a host cell through a putative pore formed by the toxin's glycine-rich repeats. The structure of the pore is unknown and the translocation mechanism of the effector domains is poorly understood. We examined the thermodynamic stability of the effector domains of V. cholerae and A. hydrophila MARTX toxins to elucidate the mechanism of their translocation. We found that all but one domain in each toxin are thermodynamically unstable and several acquire a molten globule state near human physiological temperatures. Fusion of the most stable cysteine protease domain to the adjacent effector domain reduces its thermodynamic stability ∼ 1.4-fold (from D G H 2 O 21.8 to 16.1 kJ mol(-1) ). Precipitation of several individual domains due to thermal denaturation is reduced upon their fusion into multi-domain constructs. We speculate that low thermostability of the MARTX effector domains correlates with that of many other membrane-penetrating toxins and implies their unfolding for cell entry. This study extends the list of thermolabile bacterial toxins, suggesting that this quality is essential and could be susceptible for selective targeting of pathogenic toxins.


High-intensity interval training effects in cardiorespiratory fitness of lung cancer survivors: a systematic review and meta-analysis.
To assess the exercise intervention focused on high-intensity interval training (HIIT) in lung cancer survivors. We performed a literature search using PubMed, Web of Science, and Science Direct (last search March 2021). Quality assessment and risk of bias were assessed using the Downs and Black scale and the Cochrane tool. A total of 305 patients of 8 studies were assessed, with their mean age ranging from 61 ± 6.3 to 66 ± 10 years in the exercise group and from 58.5 ± 8.2 to 68 ± 9 years in the control group. A systematic review and meta-analysis of randomized controlled trials and pilot randomized controlled trials was performed. We included controlled trials testing the effect of HIIT in lung cancer survivors versus the usual care provided to these patients. The data were pooled and a meta-analysis was completed for cardiorespiratory fitness (VO2peak). We selected 8 studies, which included 305 patients with lung cancer: 6 studies were performed around surgical moment, one study during radiotherapy's treatment, and other during target therapy. After pooling the data, exercise capacity was included in the analysis. Results showed significant differences in favour to HIIT when compared to usual care in cardiorespiratory fitness (standard mean difference = 2.62; 95% confidence interval = 1.55, 3.68; p < 0.00001). The findings indicated a beneficial effect of HIIT for improving cardiorespiratory fitness in lung cancer patients in early stages around oncological treatment moment. Nevertheless, this review has several limitations, the total number of studies was low, and the stage and subtype of lung cancer patients were heterogeneous that means that the conclusions of this review should be taken with caution. Review registration: PROSPERO Identifier: CRD42021231229.


HLA antigens and myasthenia gravis in Japan.
Recent studies have noted an increased association of the histocompatibility antigen HLA-B8 with myasthenia gravis in Caucasian patients. The HLA types of 63 Japanese patients with myasthenia were compared to those of 271 controls. The present study was designed to assess correlations between HLA antigens, sex, age at onset, the presence of autoantibodies and thymic morphology. HLA-B12 was increased Japanese patients, especially females with early age at onset, and in addition it was significantly correlated with thymic hyperplasia. HLA-B5 was frequently found in the patients with thymoma. Statistically the most frequent haplotype found in this disease was HLA-A10-HLA-B12.


Long-term leisure-time physical activity and risk of all-cause and cardiovascular mortality: dose-response associations in a prospective cohort study of 210 327 Taiwanese adults.
We aimed to investigate the dose-response associations of long-term leisure-time physical activity (LTPA) obtained from repeated measures with all-cause and cardiovascular disease (CVD) mortality outcomes in Taiwanese adults. We included 210 327 participants with self-reported LTPA at least in two medical examinations (867 968 data points) for up to 20 years (median, IQR: 4.8 years, 2.3-9.0). Dose-response relationships were modelled with restricted cubic spline functions and Cox regressions HRs (95% CIs) adjusted for main covariates. During up to 23 years of follow-up (3 655 734 person-years), 10 539 participants died, of which 1919 of CVD. We observed an inverse, non-linear dose-response association between long-term LTPA and all-cause and CVD mortality. Compared with the referent (0 metabolic equivalent of task (MET) hours/week), insufficient (0.01-7.49 MET hours/week), recommended (7.50-15.00 MET hours/week) and additional (>15 MET hours/week) amounts of LTPA had a lower mortality risk of 0.74 (0.69-0.80), 0.64 (0.60-0.70) and 0.59 (0.54-0.64) for all-cause mortality and 0.68 (0.60-0.84), 0.56 (0.47-0.67) and 0.56 (0.47-0.68) for CVD mortality. When using only baseline measures of LTPA, the corresponding mortality risk was 0.88 (0.84-0.93), 0.83 (0.78-0.88) and 0.78 (0.73-0.83) for all-cause and 0.91 (0.81-1.02), 0.78 (0.68-0.89) and 0.80 (0.70-0.92) for CVD mortality. Long-term LTPA was associated with lower risks of all-cause and CVD mortality. The magnitude of risk reductions was larger when modelling repeated measures of LTPA compared with one measure of LTPA at baseline.


Adsorptive removal of organic pollutants from milk-processing industry effluents through chitosan-titanium dioxide nanoadsorbent-coated sand.
Milk-processing industry effluent (MPIE) poses severe problems for aquatic and environmental systems, especially in the South Asian region. Therefore, its treatment is of great interest. This study deals with the investigation of chitosan titanium dioxide nanoadsorbent (CTiO2) coated onto sand particles via calcination that are used to remove the emerging pollutants. The adsorptive properties of these developed adsorbents are compared with those of the nascent sand without coating as well as with the chitosan titanium dioxide nanoadsorbent coated sand (CTiO2-CS). Batch adsorption experiments were performed to investigate the percent reduction efficiency (%RE) of organic pollutants in terms of biological oxygen demand (BOD) and chemical oxygen demand (COD) from synthetic and real effluents. The maximum %RE of BOD (96.76) and COD (98.91) was achieved at 1.5 M dose of CTiO2-CS, 120 min of contact time, pH 6.5, an initial BOD concentration of 900 mg/L, and an agitation speed of 400 rpm. Similarly, the %RE of COD was found to be 86.75 for synthetic effluent and 90.97 for real effluent at initial COD concentrations of 8000 mg/L. Pseudo-second-order and Langmuir models are found to be the best fits for BOD and COD adsorption. The diffusion model suggests that surface adsorption as well as intraparticle diffusion contribute to the actual adsorption process. Regeneration experiments were performed for four cycles, and CTiO2-CS was found to be the most regenerable adsorbent material. The performance of the adsorbent was compared with previous studies, and it was found to have excellent adsorption capacity. As a result, the developed filter bed could be used as a promising superadsorbent for the removal of organic load in MPIE.


Molecular insights into peptide agonist engagement with the PTH receptor.
The parathyroid hormone (PTH) 1 receptor (PTH1R) is a G protein-coupled receptor (GPCR) that regulates skeletal development and calcium homeostasis. Here, we describe cryo-EM structures of the PTH1R in complex with fragments of the two hormones, PTH and PTH-related protein, the drug abaloparatide, as well as the engineered tool compounds, long-acting PTH (LA-PTH) and the truncated peptide, M-PTH(1-14). We found that the critical N terminus of each agonist engages the transmembrane bundle in a topologically similar fashion, reflecting similarities in measures of Gαs activation. The full-length peptides induce subtly different extracellular domain (ECD) orientations relative to the transmembrane domain. In the structure bound to M-PTH, the ECD is unresolved, demonstrating that the ECD is highly dynamic when unconstrained by a peptide. High resolutions enabled identification of water molecules near peptide and G protein binding sites. Our results illuminate the action of orthosteric agonists of the PTH1R.


A linkage map for the hybridising toads Bombina bombina and B. variegata (Anura: Discoglossidae).
Stable hybrid zones in which ecologically divergent taxa give rise to a range of recombinants are natural laboratories in which the genetic basis of adaptation and reproductive isolation can be unraveled. One such hybrid zone is formed by the fire-bellied toads Bombina bombina and B. variegata (Anura: Discoglossidae). Adaptations to permanent and ephemeral breeding habitats, respectively, have shaped numerous phenotypic differences between the taxa. All of these are, in principle, candidates for a genetic dissection via QTL mapping. We present here a linkage map of 28 codominant and 10 dominant markers in the Bombina genome. In an F2 cross, markers that were mainly microsatellites, SSCPs or allozymes were mapped to 20 linkage groups. Among the 40 isolated CA microsatellites, we noted a preponderance of compound and frequently interleaved CA-TA repeats as well as a striking polarity at the 5' end of the repeats.


Population Dynamics of Heliothrips haemorrhoidalis (Thysanoptera: Thripidae) in Strawberry Cultivars in Southern Brazil.
Heliothrips haemorrhoidalis is a polyphagous thrips species that has been reported as a potential pest in strawberry cultivation in Brazil. Since it has only recently emerged as a pest species in production areas, understanding seasonal trends in the species' activity is particularly important for designing management strategies. Therefore, this study aims to investigate the influence of climate factors (temperature and relative humidity) and six strawberry cultivars ('Albion', 'Aromas', 'Camino Real', 'Monterey', 'Portola', and 'San Andreas') on the population dynamics of H. haemorrhoidalis during the 2018-2019 and 2019-2020 growing seasons in southern Brazil. The greatest peak in thrips populations in the cultivars assessed occurred between January and March (summer) in both growing seasons. The relationship between the incidence of H. haemorrhoidalis and temperature was observed to be negative during the autumn, spring, and summer months but positive during winter. Relative humidity levels above 70% had a negative influence on the abundance of insects. Populations of H. haemorrhoidalis varied between the cultivars as follows: 'Aromas' > 'Monterey' > 'San Andreas' > 'Albion' > 'Camino Real' > 'Portola'. Cross-sections of strawberry leaves showed that 'Monterey' had the highest density of nonglandular trichomes/mm2 (7.26), while 'Portola' cultivar, the greatest predominance of glandular trichomes/mm2 (12.67), which may have contributed to the incidence of H. haemorrhoidalis. The demographic information presented on H. haemorrhoidalis in strawberry cultivars provides a starting point to better understand the insect's population dynamics. These results also indicate that climatic conditions are a limiting factor for the development of H. haemorrhoidalis.


Nutrition, the gastrointestinal tract and the acquired immune deficiency syndrome. Facts and perspectives.
Diarrhoea and malnutrition are common findings in patients with the Acquired Immune Deficiency Syndrome (AIDS). In this disease, enteropathy leads to fat and D-xylose malabsorption and chronic non-specific inflammation of the small bowel. Moreover, gastrointestinal infection can induce severe diarrhoea. Depletion in real body cell mass, body fat content, and weight loss have been observed. Nutritional therapy is mandatory when weight loss is 10% or greater. Enteral feeding is not easily achieved. Parenteral feeding including fat as a nonprotein calorie source improves general condition. The use of intravenous fat emulsions has been hypothesized to have several beneficial effects. Fluidisation of human immunodeficiency virus membranes by lipid emulsions through cholesterol extraction could decrease the infectivity of the virus. Long term intravenous nutrition may be more than a treatment for malabsorption and depletion; it may possibly have direct pharmacological effects.


An expanded look at evaluating clinical performance: faculty use of anecdotal notes in the U.S. and Canada.
The evaluation of students in a clinical setting is often subjective and completed differently among faculty. To describe and compare evaluation practices, faculty were asked to rank order student clinical activities important enough to write an anecdotal note regarding. A total of 15 behaviors were presented and faculty were asked to prioritize their importance. Faculty were also asked demographic information regarding clinical teaching status. The frequency of writing an anecdotal note was requested, and if student notes were documented routinely or only at the end of the semester. After securing Institutional Review Board (IRB) review, ten percent of nursing programs were selected randomly using online data websites for listings of all public and private U.S. and Canadian nursing programs. A 23% response rate was obtained from the electronic survey (n = 849). A small percent of faculty reported the use of anecdotal notes only when they felt disciplinary action against a student was required, and eleven percent reported they were able to complete clinical evaluations without supplemental records. Describing faculty record-keeping practices provides greater understanding of nursing student evaluation. Nursing is the largest health profession in the world, and faculty accuracy in identifying clinical proficiency is vital to patient outcomes.


Medicinal plants used to treat the most frequent diseases encountered in Ambalabe rural community, Eastern Madagascar.
Traditional medicine remains the only health care available in many rural areas in Madagascar like the rural community of Ambalabe, located in a very remote area in the eastern part of the country. With limited access to modern medicine, the local population uses medicinal plants to treat most diseases. In this study, we aimed to inventory medicinal plants used by local people and how those relate to the treatment of the most frequent diseases encountered in Ambalabe. We interviewed participants in order to identify the most frequent diseases in the region and the medicinal plants used to treat them. The local physician was asked about the most frequent diseases, and ethnobotanical surveys to record medicinal plants and their uses, using semi-structured interviews and free listing, were conducted among 193 informants in local villages, of which 54 % were men and 46 % were women, ageing from 16 to 86 years. The local names, the uses of each plant species and the way they are prepared and administered were recorded and accompanied by herbarium specimens for identification. We also interviewed four traditional healers to elicit more details on the preparation and the use of plants. Our research allowed us to identify six most frequent diseases, namely diarrhea, malaria, stomach-ache, cough, bilharzia and dysentery. Among 209 plant species identified as having medicinal use, 83 species belonging to 49 families and 77 genera were used to treat these diseases. Our analyses highlighted the 11 commonly used species for their treatment, and also 16 species with a high fidelity level (FL ≥ 75 %) for each ailment. Diarrhea is one of the diseases with high number of species recorded. This study highlighted the closed relationship between people in Ambalabe and plant species, especially when faced with frequent diseases. However, most of the species used were collected in the surroundings of the villages. Few species were from Vohibe forest in which a management system on the use of plant species was already established. Therefore, a sustainable use management should be considered for wild species from which medicinal plants are highly abundant.


An investigation of the expression mechanism of LTP of AMPA receptor-mediated synaptic transmission at hippocampal CA1 synapses using failures analysis and dendritic recordings.
There is considerable controversy surrounding the mechanism of expression of long-term potentiation of AMPA receptor-mediated synaptic transmission in the CA1 region of the hippocampus, a process thought to be important for learning and memory in the mammalian CNS. We have re-examined the expression mechanism of this form of synaptic plasticity using whole-cell dendritic recordings, minimal stimulation to activate one or a few synapses, and failures analysis. Dendritic recordings provide improved resolution of small synaptic events, as compared to previous studies using somatic recordings, because there is less dendritic filtering of signals. We find that long-term potentiation (LTP) is associated with changes in the size of synaptic responses when they occur (potency) in all cells and this is accompanied by significant decreases in failure rate in approximately 60% of the experiments. This suggests that in some cells an increase in quantal amplitude is the sole expression mechanism for LTP and, in the cells where failure rate decreased, there is an additional mechanism causing a change in quantal content.


[A successful repair of traumatic thoracic aortic injury and descending colon perforation at acute phase].
A 41-year-old man suffered from traffic accident was referred to us because of chest and back pain. The CT examination showed periaortic hematoma and aortography revealed aneurysmal formation at the distal site to the left subclavian artery. We repaired the aortic injury with prosthetic graft at the acute phase successfully. As the results of the conservative treatment of the traumatic aortic injury are poor, we recommend operation at the acute phase.


Prepubertal gonorrhea.
Two cases of gonococcal urethritis in male children are presented and the records of 45 other children with gonorrhea are reviewed. The presentation, diagnosis and treatment are discussed. Data on the mode of transmission are presented with emphasis on the high incidence of gonorrhea in family members or close contacts of infected children, or a history of sexual abuse.


Extracting Atomic Contributions to Binding Free Energy Using Molecular Dynamics Simulations with Mixed Solvents (MDmix).
Mixed solvents MD (MDmix) simulations have proved to be a useful and increasingly accepted technique with several applications in structure-based drug discovery. One of the assumptions behind the methodology is the transferability of free energy values from the simulated cosolvent molecules to larger drug-like molecules. However, the binding free energy maps (ΔGbind) calculated for the different moieties of the cosolvent molecules (e.g. a hydroxyl map for the ethanol) are largely influenced by the rest of the solvent molecule and do not reflect the intrinsic affinity of the moiety in question. As such, they are hardly transferable to different molecules. To achieve transferable energies, we present here a method for decomposing the molecular binding free energy into accurate atomic contributions. We demonstrate with two qualitative visual examples how the corrected energy maps better match known binding hotspots and how they can reveal hidden hotspots with actual drug design potential. Atomic decomposition of binding free energies derived from MDmix simulations provides transferable and quantitative binding free energy maps.


Solitary fibrous tumor of the lung.
Solitary fibrous tumors are mesenchymal entities integrated in a mixed group of hemangiopericytoma-like neoplasms. Although classically presented as a pleura-based mass, there are extrapleural sites including the lung. We present the clinical, imaging, and histological features of a solitary fibrous tumor of the lung.


A simulation support system for solving large physiological models on microcomputers.
Although physiological modeling and computer simulation have become useful research tools to test new scientific theories and to design and analyze laboratory experiments, developing a new model can be a tedious process because the investigator must often write very complex and specific routines for data input and output. To facilitate the design of new models (as well as the use of existing models), we have developed MODSIM, a FORTRAN-based simulation support system for the IBM PC computer than can accommodate very large dynamic models having up to several thousand equations. It provides the investigator with utilities for continuous on-line graphical and/or tabular output, as well as facilities for dynamic interaction with the model. The user must only supply a model as a list of mathematical equations written in FORTRAN, along with the initial values of the model variables and parameters. The model is precompiled, compiled, and then linked to the MODSIM utilities. Without further programming, the user can then solve the model, select variables for graphical output, and stop the model at any time to analyze the data or to change a parameter before resuming the simulation. This simulation system makes it very easy to develop new models that actively interact with the experimental research of the investigator.


Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton's Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis.
Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of multiple diseases, such as B-cell malignances, asthma, and rheumatoid arthritis. A series of novel aminotriazines were identified as highly selective inhibitors of BTK by a scaffold-hopping approach. Subsequent SAR studies of this series using two conformationally different BTK proteins, an activated form of BTK and an unactivated form of BTK, led to the discovery of a highly selective BTK inhibitor, 4b. With significant efficacy in models in vivo and good ADME and safety profiles, 4b was advanced into preclinical studies.


Depressive symptoms, physical activity, and weight gain in premenopausal Latina and White women.
Describe changes and examine the association between depressive symptoms, physical activity, body mass index (BMI), and perceived health among Latina (n=81) and White (n=151) women in the first year of the late-premenopausal stage. Longitudinal study focused on the biopsychosocial health of midlife women (ages 40-50 years) with regular menstrual cycles and not taking hormones. Frequency of depressive symptoms, BMI, waist to hip ratios, and self-reported physical activity levels were obtained at 6-month intervals and perceived health at 12 months. Results are reported here for 232 women who remained premenopausal (low FSH/regular cycles) for the first 12 months. Depressive symptoms were similar for Latinas (11.1+/-9.8) and Whites (11.1+/-8.2) and increased by 2.3 points over time for all women. Latinas had higher BMI (28+/-5.7, p<0.01) than Whites (26+/-5.7). Body weight increased an average of 1.2 lbs over 12 months for both groups. Both groups reported sub-optimal levels of physical activity that did not change over time, but Latinas reported higher levels at all 3 time points. Controlling for age and ethnicity, women in service or agricultural occupations reported higher activity levels than women in other roles. Better perceived health at 12 months was predicted by lower baseline BMI (r=0.43, p<0.01) and fewer depressive symptoms (r=0.38, p<0.01). Depressive symptoms, weight gain and physical inactivity among women in the late-premenopausal stage point to the need for interventions focused on causal factors other than hormonal changes and menopause.


Outreach services to brothels facilitate sexually transmissible infection testing for Asian sex workers in regional Australia.
Outreach services providing sexually transmissible infection (STI) testing on-site in brothels were introduced in 2012 by Pacific Clinic Newcastle, Australia. Asian female sex workers (FSW) were more likely than non-culturally and linguistically diverse (CALD) FSW to access testing via outreach services than in clinics (OR 2.38, 95% CI 1.82-3.11, P < 0.0001) and to test positive for chlamydia or gonorrhoea (OR 2.58, 95% CI 1.58-4.20, P = 0.0001). Outreach services offering testing on-site in brothels are recommended to facilitate access for Asian FSW in similar settings.


Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike-ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics*.
Gold complexes have a long tradition in medicine and for many examples antirheumatic, anticancer or anti-infective effects have been confirmed. Herein, we evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targets of severe acute respiratory syndrome coronaviruses (SARS-CoV). The gold metallodrugs were effective inhibitors of the interaction of the SARS-CoV-2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process. The gold metallodrugs were also efficient inhibitors of the papain-like protease (PLpro) of SARS-CoV-1 and SARS-CoV-2, which is a key enzyme in the viral replication. Regarding PLpro from SARS-CoV-2, the here reported inhibitors are among the very first experimentally confirmed examples with activity against this target enzyme. Importantly, the activity of the complexes against both PLpro enzymes correlated with the ability of the inhibitors to remove zinc ions from the labile zinc center of the enzyme. Taken together, the results of this pilot study suggest further evaluation of gold complexes as SARS-CoV antiviral drugs.


What Hong-Ou-Mandel interference says on two-photon frequency entanglement.
Not much, in the end. Here we put forward some considerations on how Hong-Ou-Mandel interferometry provides signatures of frequency entanglement in the two-photon state produced by parametric down-conversion. We find that some quantitative information can be inferred in the limit of long-pulse pumping, while the short-pulse limit remains elusive.


Nonylphenol enhances apoptosis induced by serum deprivation in PC12 cells.
Although nonylphenol is well known as an endocrine disrupting chemical, there is little information concerning biological effect of nonylphenol. In this study, we investigated effect of nonylphenol on apoptosis induced by serum deprivation in PC12 cells using TUNEL and DNA fragmentation assays. In addition, changes in contents of proapoptotic factors, Bad and Bax, and antiapoptotic factor, Bcl-2, and enzyme activity of caspase-3 were studied. Below 100 ng/ml of nonylphenol increased TUNEL signals, DNA fragmentation and content of proapoptotic factor, Bad as compared to those by serum deprivation without nonylphenol. Furthermore, addition of nonylphenol enhanced caspase-3 activity and Z-VAD, caspase-3 inhibitor, diminished such effect. These results indicated that below 100 ng/ml of nonylphenol enhanced apoptosis induced by serum deprivation via caspase-3 activation in PC12 cell.


Protocol for a pilot randomised controlled trial evaluating feasibility and acceptability of cognitive remediation group therapy compared with mutual aid group therapy for people ageing with HIV-associated neurocognitive disorder (HAND) in Toronto, Canada.
HIV-associated neurocognitive disorder (HAND) may affect 30%-50% of people ageing with HIV. HAND may increase stress and anxiety, and impede coping. Psychosocial group therapy may ameliorate HAND's symptoms, yet the ideal intervention is unclear. This protocol outlines a pilot randomised controlled trial (RCT)-designed using community-based participatory research-to pilot cognitive remediation group therapy (CRGT) against an active comparator. This is a pilot, parallel design, two-arm RCT that will recruit participants diagnosed with the mild neurocognitive disorder form of HAND from a neurobehavioural research unit at a tertiary care hospital in Toronto, Canada. Eligibility criteria include age ≥40 years, known HIV status for 5+ years, English fluency, able to consent and able to attend 8 weeks of group therapy. Eligible participants will be randomised to one of two treatment arms, each consisting of eight-session group interventions delivered once weekly at 3 hours per session. Arm 1 (novel) is CRGT, combining mindfulness-based stress reduction with brain training activities. Arm 2 (active control) is mutual aid group therapy. The primary outcomes are feasibility, measured by proportions of recruitment and completion, and acceptability, determined by a satisfaction questionnaire. The secondary outcome is intervention fidelity, where content analysis will be used to assess facilitator session reports. A between-group analysis will be conducted on exploratory outcomes of stress, anxiety, coping and use of intervention activities that will be collected at three time points. Ethical approval was obtained from the Research Ethics Boards of St. Michael's Hospital and the University of Toronto. Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. This study could provide insight into design (eg, recruitment, measures) and intervention considerations (eg, structure, content) for a larger trial to lessen the burden of cognitive decline among people ageing with HIV. NCT03483740; Pre-results.


Regulatory network reconstruction reveals genes with prognostic value for chronic lymphocytic leukemia.
The clinical course of chronic lymphocytic leukemia (CLL) is highly variable; some patients follow an indolent course, but others progress to a more advanced stage. The mutational status of rearranged immunoglobulin heavy chain variable (IGVH) genes in CLL is a feature that is widely recognized for dividing patients into groups that are related to their prognoses. However, the regulatory programs associated with the IGVH statuses are poorly understood, and markers that can precisely predict survival outcomes have yet to be identified. In this study, (i) we reconstructed gene regulatory networks in CLL by applying an information-theoretic approach to the expression profiles of 5 cohorts. (ii) We applied master regulator analysis (MRA) to these networks to identify transcription factors (TFs) that regulate an IGVH mutational status signature. The IGVH mutational status signature was developed by searching for differentially expressed genes between the IGVH mutational statuses in numerous CLL cohorts. (iii) To evaluate the biological implication of the inferred regulators, prognostic values were determined using time to treatment (TTT) and overall survival (OS) in two different cohorts. A robust IGVH expression signature was obtained, and various TFs emerged as regulators of the signature in most of the reconstructed networks. The TF targets expression profiles exhibited significant differences with respect to survival, which allowed the definition of a reduced profile with a high value for OS. TCF7 and its targets stood out for their roles in progression. TFs and their targets, which were obtained merely from inferred regulatory associations, have prognostic implications and reflect a regulatory context for prognosis.


Biaxial Mechanical Evaluation of Absorbable and Nonabsorbable Synthetic Surgical Meshes Used for Hernia Repair: Physiological Loads Modify Anisotropy Response.
The aim of this study was to obtain information about the mechanical properties of six meshes commonly used for hernia repair (Surgipro(®), Optilene(®), Infinit(®), DynaMesh(®), Ultrapro™ and TIGR(®)) by planar biaxial tests. Stress-stretch behavior and equibiaxial stiffness were evaluated, and the anisotropy was determined by testing. In particular, equibiaxial test (equal simultaneous loading in both directions) and biaxial test (half of the load in one direction following the Laplace law) were selected as a representation of physiologically relevant loads. The majority of the meshes displayed values in the range of 8 and 18 (N/mm) in each direction for equibiaxial stiffness (tangent modulus under equibiaxial load state in both directions), while a few achieved 28 and 50 (N/mm) (Infinit (®) and TIGR (®)). Only the Surgipro (®) mesh exhibited planar isotropy, with similar mechanical properties regardless of the direction of loading, and an anisotropy ratio of 1.18. Optilene (®), DynaMesh (®), Ultrapro (®) and TIGR (®) exhibited moderate anisotropy with ratios of 1.82, 1.84, 2.17 and 1.47, respectively. The Infinit (®) scaffold exhibited very high anisotropy with a ratio of 3.37. These trends in material anisotropic response changed during the physiological state in the human abdominal wall, i.e. T:0.5T test, which the meshes were loaded in one direction with half the load used in the other direction. The Surgipro (®) mesh increased its anisotropic response (Anis[Formula: see text] = 0.478) and the materials that demonstrated moderate and high anisotropic responses during multiaxial testing presented a quasi-isotropic response, especially the Infinit(®) mesh that decreased its anisotropic response from 3.369 to 1.292.


American gastroenterological association institute technical review on the use of gastrointestinal medications in pregnancy.
This literature review and the recommendations therein were prepared for the American Gastroenterological Association Institute Clinical Practice and Economics Committee. The paper was approved by the Committee on February 22, 2006 and by the AGA Institute Governing Board on April 20, 2006.


Fatal diving accidents in Genoa (North-West Italy) from 1968 to 2021: Forensic approach and literature review.
Scuba diving is one of the most common and practised water sport activities in Genoa, especially in the more recent years. Although scuba diving is generally considered a safe activity, this does not exclude the possibility of serious or fatal accidents from happening. This retrospective study investigates the case history of deaths resulting from diving accidents recorded by the Municipal Morgue of Genoa over a period of 53 years, specifically from 1968 to 2021. Of the total 52 deaths covered by the study, 48 were male with an age range of 16-71 years. In 25 of these subjects, pre-existing pathological conditions of a cardiovascular nature, not recognised at the time of death, were reported. Out of the total deaths studied, 9 subjects died following a diving accident related to free diving, while 43 subjects died from scuba or rebreather diving. Among the latter subjects, the cause of death was attributed to drowning in 17 cases, arterial gas embolism (AGE) from pulmonary over-distension in 11 cases, cardio-circulatory arrest (CA) favoured by pre-existing and non-existing heart disease known prior to the death in 10 cases, decompression sickness (DCS) in 2 cases, a combination of DCS and AGE in 2 cases and oxygen intoxication in 1 case. Twelve of the fatal accidents occurred in the marine area near the village of Arenzano, where the shipwreck of the oil tanker, the "Haven", sank in 1991 and is today the largest shipwreck explored by divers in the Mediterranean Sea. In all cases of diving deaths, a multi-disciplinary approach is important: in particular, the role of the forensic pathologist is essential in order to accurately reconstruct the dynamics of the accident, thus identifying the predisposing or triggering factors that led to death, and defining the cause of it.


Bladder drainage during labor: a randomized controlled trial.
To compare two bladder draining methods during labor on time to delivery, cost and nursing preference. This trial randomized 139 women with singleton pregnancies in active labor or undergoing induction of labor. Eligibility required an anticipated vaginal delivery with a clinical indication for bladder catheterization (epidural). Participants were randomly assigned to either indwelling or intermittent catheterization. The primary outcome was time to delivery; secondary outcomes were nurse preference, cost and route of delivery. A sample size of 138 women would be needed for 80% power to detect a 30 min difference in the time to delivery interval with a 0.05 alpha error. Outcome data was available for 138 patients (72 indwelling and 66 intermittent). The time to delivery was similar among the two groups (13.8 h for indwelling and 14.4 h for intermittent). Route of delivery and cost estimate was similar in both groups; however, nurses preferred the indwelling method. Indwelling catheterization is recommended as the standard method for bladder drainage in laboring women with epidural.


Conversion of left ventricular endocardial positions from patient-independent co-ordinates into biplane fluoroscopic projections.
Electrocardiographic body surface mapping is used clinically to guide catheter ablation of cardiac arrhythmias by providing an estimate of the site of origin of an arrhythmia. The localisation methods used in our group produce results in left-ventricular cylinder co-ordinates (LVCCs), which are patient-independent but hard to interpret during catheterisation in the electrophysiology laboratory. It is preferable to provide these results as three-dimensional (3D) co-ordinates which can be presented as projections in the biplane fluoroscopic views that are used routinely to monitor the catheter position. Investigations were carried out into how well LVCCs can be converted into fluoroscopic projections with the limited anatomical data available in contemporary clinical practice. Endocardial surfaces from magnetic resonance imaging (MRI) scans of 24 healthy volunteers were used to create an appropriate model of the left-ventricular endocardial wall. Methods for estimation of model parameters from biplane fluoroscopic images were evaluated using simulated biplane data created from these surfaces. In addition, the conversion method was evaluated, using 107 catheter positions obtained from eight patients, by computing LVCCs from biplane fluoroscopic images and reconstructing the 3D positions using the model. The median 3D distance between reconstructed positions and measured positions was 4.3mm.


Clinical observations on 600 cases of recurrent laryngeal nerve paralysis.
A statistical review was made on 600 cases of recurrent laryngeal nerve paralysis who visited the author's clinic during the last 16 years. The yearly incidence, the age and sex distributions and the classifications of the causes of paralysis were presented and discussed. A special attention was given to the topics of associated laryngeal paralysis, bilateral recurrent laryngeal nerve paralysis and the so-called epidemic paralysis. A brief comment was also made on diagnosis and treatment of recurrent laryngeal nerve paralysis in general.


Should We Move Up the Clock on Preventive Intervention in Marfan's Disease?
Gradual dilatation of the ascending aorta is a common phenomenon in patients with Marfan's disease, which often leads to dissection and rupture. It is estimated that around two-thirds of the patients either die or require major surgery before the age of 42 years. In the mirror of the experience of 40 years with aortic wall reinforcement, the author forward the postulate that whenever the ascending aorta of an individual with proven Marfan's disease reaches adult size, that is, approximately 3.5 cm in diameter, the wall of his/her ascending aorta should be reinforced to prevent further expansion.


Dual mechanisms of a Sri Lankan traditional polyherbal mixture in the improvement of pancreatic beta cell functions and restoration of lipoprotein alterations in streptozotocin induced diabetic rats.
Traditional polyherbal preparations have been utilized in Sri Lanka since ancient times and have gained a wide acceptance throughout the country. Although an extensive body of evidence supports the use of traditional herbal mixtures in the treatment of diabetes mellitus, only a few polyherbal mixtures have been subjected to systematic scientific investigations and their mechanisms for long-term glucose control remain unclear. In general, scientific evaluations of the effectiveness of antidiabetic formulations which are prescribed by traditional practitioners have received great attention, and therefore uncovering their mechanism of action would be beneficial. The aim of the present study was to investigate the therapeutic efficacy, in terms of antidiabetic and antihyperlipidaemic activities, of a well-known traditional polyherbal mixture composed of leaves of Murraya koenigii L., -cloves of Allium sativum L., - fruits of Garcinia quaesita Pierre and seeds of Piper nigrum L. in streptozotocin induced diabetic rats. Equal amounts from each of the above plant parts (100 g) were mixed together and extracted into cold water, hot water (3 h, refluxed) and water-acetone (1:1) separately. Dose response study of cold water, hot water, and water-acetone extracts of the polyherbal mixture at three selected doses of 0.5 g/kg, 1.0 g/kg and 1.5 g/kg was conducted in streptozotocin (STZ) induced diabetic rats. Based on the dose response data, hot water and water-acetone extracts at the therapeutic dose of 1.0 g/kg were administered to STZ induced diabetic rats (n = 6/group) daily for 30 days in the long-term study. Glibenclamide (0.5 mg/kg) was used as the positive control. Glycaemic parameters, pancreatic β cell restoration, and lipid profile were evaluated in diabetic rats treated with the plant extract mixture. HPLC fingerprints of hot water and water-acetone extracts of the polyherbal mixture were compared with those of extracts of individual plants with the respective solvents, in the standardisation protocol. The hot water and water-acetone extracts were shown to be active in the dose response study and 1.0 g/kg was selected for the long term study. Treatment with the hot water and water-acetone extracts of the polyherbal mixture and glibenclamide significantly lowered the glycated haemoglobin by 19%, 26%, and 43%, respectively, at the end of the intervention (p < 0.05). The serum insulin concentration was significantly increased (p < 0.05) upon the plant treatment, corroborating the evidence of β-cell restoration in the pancreas of H and E stained sections. Moreover, the above extracts reported an impressive restoration of lipoproteins in diabetic rats compared to the diabetic control rats. The homeostatic assessment of β-cell functions (HOMA-β) was also improved in rats treated with the hot water and water-acetone extracts of the polyherbal mixture. The HPLC fingerprints of the polyherbal mixture and the individual plants showed shifts in some peaks and formation of new peaks. The results revealed that the aforementioned polyherbal mixture possesses potent antihyperglycaemic and antihyperlipidaemic effects with considerable restoration of pancreatic β-cells, justifying the traditional use of the mixture in diabetes associated dyslipidaemia.


Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers.
This review summarizes recent evidence on how mid-life hypertension, hyperhomocysteinemia (HHcy) and blood pressure variability, as well as late-life hypotension, exacerbate Alzheimer's disease (AD) and dementia risk. Intriguingly, HHcy also increases the risk for hypertension, revealing the importance of understanding the relationship between comorbid cardiovascular risk factors. Hypertension-induced dementia presents more evidently in women, highlighting the relevance of sex differences in the impact of cardiovascular risk. We summarize each major antihypertensive drug class's effects on cognitive impairment and AD pathology, revealing how carbonic anhydrase inhibitors, diuretics modulating cerebral blood flow, have recently gained preclinical evidence as promising treatment against AD. We also report novel vascular biomarkers for AD and dementia risk, highlighting those associated with hypertension and HHcy. Importantly, we propose that future studies should consider hypertension and HHcy as potential contributors to cognitive impairment, and that uncovering the underlying molecular mechanisms and biomarkers would aid in the identification of preventive strategies.


Survivorship After Periprosthetic Femur Fracture: Factors Affecting Outcome.
Data addressing risk factors predictive of mortality and reoperation after periprosthetic femur fractures (PPFxs) are lacking. This study examined survivorship and risk ratios for mortality and reoperation after surgical treatment for PPFx and associated clinical risk factors. A retrospective review was performed for 291 patients treated surgically for PPFx between 2004 and 2013. Primary outcomes were death and reoperation. Mortality at 1 year was 13%, whereas the rate of reoperation was 12%. Greater span of fixation and revision arthroplasty (vs open reduction internal fixation) trended toward a lower likelihood of reoperation. After PPFx, patients have a 24% risk of either death or reoperation at 1 year. Factors contributing to increased mortality are nonmodifiable. Risk of reoperation is minimized with greater span of fixation and performance of revision arthroplasty.


Randomised controlled trial of bariatric surgery versus a community weight loss programme for the sustained treatment of idiopathic intracranial hypertension: the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) protocol.
Effective treatments are lacking for idiopathic intracranial hypertension (IIH), a condition characterised by raised intracranial pressure (ICP) and papilloedema, and found primarily in obese women. Weight loss and lowering body mass index (BMI) have been shown to lower ICP and improve symptoms in IIH; however, weight loss is typically not maintained, meaning IIH symptoms return. The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) will assess whether bariatric surgery is an effective long-term treatment for patients with IIH with a BMI over 35 kg/m2. The National Institute for Health and Care Excellence recommends bariatric surgery in people with a BMI over 35 kg/m2 and a qualifying comorbidity; currently IIH does not qualify as a comorbidity. IIH:WT is a multicentre, open-label, randomised controlled clinical trial of 64 participants with active IIH and a BMI over 35 kg/m2. Participants will be randomised in a 1:1 ratio to bariatric surgery or a dietary weight loss programme and followed up for 5 years. The primary outcome measure is ICP at 12 months. Secondary outcome measures include ICP at 24 and 60 months, and IIH symptoms, visual function, papilloedema, headache, quality of life and cost-effectiveness at 12, 24 and 60 months. IIH:WT is registered as ISRCTN40152829 and on ClinicalTrials.gov as NCT02124486 and is in the pre-results stage.


Bat and rat neurons differ in theta-frequency resonance despite similar coding of space.
Both bats and rats exhibit grid cells in medial entorhinal cortex that fire as they visit a regular array of spatial locations. In rats, grid-cell firing field properties correlate with theta-frequency rhythmicity of spiking and membrane-potential resonance; however, bat grid cells do not exhibit theta rhythmic spiking, generating controversy over the role of theta rhythm. To test whether this discrepancy reflects differences in rhythmicity at a cellular level, we performed whole-cell patch recordings from entorhinal neurons in both species to record theta-frequency resonance. Bat neurons showed no theta-frequency resonance, suggesting grid-cell coding via different mechanisms in bats and rats or lack of theta rhythmic contributions to grid-cell firing in either species.


Analysis of experimental spectra of phosphine in the Tetradecad range near 2.3 μm using ab initio calculations.
Due to its major interest for the chemistry of planetary atmospheres and exobiology, accurate spectroscopy data of phosphine are required for the search of signatures of this molecule in astronomical observations. In this work, high resolution infrared laboratory spectra of phosphine were analyzed for the first time in the full Tetradecad region (3769-4763 cm-1) involving 26 rotationally resolved bands. Overall, 3242 lines were assigned in spectra previously recorded by Fourier transform spectroscopy at temperatures 200 K and 296 K, using a combined theoretical model based on ab initio calculations. The total nuclear motion Hamiltonian of PH3 including ab initio potential energy surface, was reduced to an effective Hamiltonian using the high-order contact transformation method adapted to vibrational polyads of the AB3 symmetric top molecules, followed by empirical optimization of the parameters. At this step, the experimental line positions were reproduced with a standard deviation of 0.0026 cm-1 that provided unambiguous identification of observed transitions. The effective dipole transition moments of the bands were obtained by fitting to the intensities obtained from variational calculations using the ab initio dipole moment surface. The assigned lines were used to newly determine 1609 experimental vibration-rotational levels up to Jmax = 18 with energy in the range 3896-6037 cm-1 that represents significant extension towards higher energies compared to previous works. Transitions for all 26 sublevels of the Tetradecad were identified but with noticeably fewer transitions for fourfold excited bands because of their weaker intensity. At the final step, pressure-broadened half widths were attached to each transition and a composite line list adopting ab initio intensities and empirical line positions corrected to the accuracy of about 0.001 cm-1 for strong and medium transitions was validated against experimental spectra available in the literature.


A transcriptome-wide association study implicates specific pre- and post-synaptic abnormalities in schizophrenia.
Schizophrenia is a complex highly heritable disorder. Genome-wide association studies (GWAS) have identified multiple loci that influence the risk of developing schizophrenia, although the causal variants driving these associations and their impacts on specific genes are largely unknown. We identify a significant correlation between schizophrenia risk and expression at 89 genes in the dorsolateral prefrontal cortex (P ≤ 9.43 × 10-6), including 20 novel genes. Genes whose expression correlate with schizophrenia were enriched for those involved in abnormal CNS synaptic transmission (PFDR = 0.02) and antigen processing and presentation of peptide antigen via MHC class I (PFDR = 0.02). Within the CNS synaptic transmission set, we identify individual significant candidate genes to which we assign direction of expression changes in schizophrenia. The findings provide strong candidates for experimentally probing the molecular basis of synaptic pathology in schizophrenia.


Stimulation of non-neuronal cell proliferation in vitro by mitogenic factors present in highly purified sympathetic neurons.
Sympathetic neurons have been demonstrated to contain one or more mitogens which are active on highly purified non-neuronal cells cultured in medium containing an optimal concentration of fetal calf serum. Neurons and homologous non-neuronal cells were separated by a method recently developed in this laboratory. The highly purified neurons were either sonicated or homogenized prior to addition to nonneuronal cultures. The presence of neuronal sonicate (1) greatly stimulated [3H]thymidine incorporation into acid-precipitable macromolecules without altering the soluble [3H]thymidine pool, (2) increased both the fraction of non-neuronal cells which took up [3H]thymidine and the density of labeling as observed by autoradiography, and (3) increased the number of cells present in treated cultures after 40 h. The enhancement of [3H]thymidine incorporation was dose-dependent and did not involve cyclic AMP. Addition of neuronal sonicate also caused marked non-neuronal cell elongation which resulted in the elaboration of very long cell processes. The active factor(s) in the neuronal sonicate were partially heat-labile. Norepinephrine was ruled out as a possible mitogenic factor.


The prevalence of refractive errors in college students in Israel.
To determine the prevalence of refractive errors in Jewish and Arab college students in Israel and associations with ethnicity and sex. In this retrospective cross-sectional study, first-year college students underwent non-cycloplegic autorefraction and answered a questionnaire to assess age, sex, and self-identified ethnicity. Spherical equivalent refractive error (SER) was calculated, and the prevalence of hyperopia (>+0.50 Diopter, D), emmetropia (>-0.50 to +0.50 D), myopia (≤-0.50D, low ≤-0.50 to >-3.0D, moderate <-3.0 to >-6.0D, high ≤-6.0D), and astigmatism (>0.50D) were determined. Groups were compared using Chi-square or Fisher test. Univariate and multivariate analyses were conducted to identify factors associated with refractive errors. Participants (n = 807) had a mean age of 22.1 ± 2.6 years (range: 17-30 years) and SER of -1.7 ± 2.2D (range: -13.3 to +5.7D). The prevalence and 95% confidence internal of myopia was 66.3% (63.0-69.6). Jewish students had a higher prevalence than Arab students for myopia (69.2% vs 60.3%), moderate (18.5% vs 12.2%) and high myopia (5.9% vs 1.9%) and astigmatism (51.4% vs 43.9%, p<0.05 for all), but not low myopia or hyperopia. Females had a higher prevalence of myopia than males (68.1% vs 58.7%, p<0.03). Jewish ethnicity was associated with myopia (OR=1.48, p = 0.01) and moderate myopia (OR=1.72, p = 0.01), and studying optometry was associated with moderate myopia (OR=1.63, p = 0.02). Sex and age were not associated with myopia. Myopia prevalence in Israeli college students is high, showing associations with Jewish, but not Arab, ethnicity, suggesting that ethnic factors may play a role in the refractive differences between Arabs and Jews.


Is human papilloma virus associated with salivary gland neoplasms? An in situ-hybridization study.
HPV can infect cells of epithelial origin and is closely associated with carcinomas. Studies investigating its presence in salivary gland neoplasms are few and conflicting. Detection of HPV types 16 & 18 was done on 34 formalin-fixed, paraffin-embedded archival material of different salivary gland neoplasms using Digene HPV types 16 & 18 probe using in situ hybridization technique. Eight of neoplastic salivary gland specimens were positively infected by HPV types 16 & 18. Seven of them were benign (4 Warthin's tumour, 2 pleomorphic adenoma and one myoepithelioma), in addition to one malignant specimen (lymphoma). Correlation was found between the incidence of HPV infection and histological differentiation of salivary gland neoplasms. An association exists between HPV infections and salivary gland neoplasms. However, given the sparse pattern of reactive cells, it cannot be confirmed that this virus is implicated in the aetiology of this group of tumours.


RstA, a two-component response regulator, plays important roles in multiple virulence-associated processes in enterohemorrhagic Escherichia coli O157:H7.
Enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) causes bloody diarrhea and hemolytic-uremic syndrome. EHEC O157 encounters varied microenvironments during infection, and can efficiently adapt to these using the two-component system (TCS). Recently, a functional TCS, RstAB, has been implicated in the regulation of virulence of several bacterial pathogens. However, the regulatory function of RstAB in EHEC O157 is poorly understood. This study aimed at providing insights into the global effects of RstA on gene expression in EHEC O157. In the present study, we analyzed gene expression differences between the EHEC O157 wild-type strain and a ΔrstA mutant using RNA-seq technology. Genes with differential expression in the ΔrstA mutant compared to that in the wild-type strain were identified and grouped into clusters of orthologous categories. RstA promoted EHEC O157 LEE gene expression, adhesion in vitro, and colonization in vivo by indirect regulation. We also found that RstA could bind directly to the promoter region of hdeA and yeaI to enhance acid tolerance and decrease biofilm formation by modulating the concentration of c-di-GMP. In summary, the RstAB TCS in EHEC O157 plays a major role in the regulation of virulence, acid tolerance, and biofilm formation. We clarified the regulatory function of RstA, providing an insight into mechanisms that may be potential drug targets for treatment of EHEC O157-related infections.


A proposal for a new classification of soleus muscle morphology.
The soleus muscle (SM) is located in the superficial posterior compartment of the leg, together with the gastrocnemius muscle (GM) and plantaris muscle. There is little information on the morphological variability (pennation) of the SM. The aim of the study is to characterize the variations in the morphology of the pennation of the SM and to create the first accurate classification. Eighty lower limbs (40 left, and 40 right) fixed in 10% formalin solution were examined. The morphology of the central tendon, medial and lateral aponeuroses was evaluated, together with the pennation angle. In all cases, the soleus muscle was present. Four types could be distinguished based on muscle fibre morphology. In order of frequency: Type 1 - bipennate (43.75%); Type 4 - non-pennate (36.25%); Type 2 - unipennate (15%); Type 3 - multipennate (5%). No significant difference in type distribution was observed with regard to body side (p=0.9018) or gender (p=0.0844). The soleus muscle is characterized by high morphological variability. Based on the pennation angle, four types (1-4) of soleus muscle are distinguishable.


Response of selenoproteins gene expression profile to mercuric chloride exposure in chicken kidney.
Kidney is a primary target organ for mercuric chloride (HgCl2) toxicity. Selenium (Se) can exert antagonistic effect on heavy metals-induced organ toxicity by regulating the expression of selenoproteins. The objective of this study was to investigate the effect of HgCl2 on the gene expression of selenoproteins in chicken kidney. Sixty male Hyline brown chickens were randomly and evenly divided into two groups. After acclimatization for one week, chickens were provided with the standard diet as well as non-treated water (CON group), and standard diet as well as HgCl2-treated water (250 ppm, HgCl2 group). After seven weeks, kidney tissues were collected to examine the mRNA expression levels of 25 selenoproteins genes and protein expression levels of 4 selenoproteins. Moreover, correlation analysis and principal component analysis (PCA) were used to analyze the expression patterns of 25 selenoproteins. The results showed that HgCl2 exposure significantly decreased the mRNA expression of Glutathione peroxidase 1 (GPX1), GPX4, Thioredoxin reductase 2 (TXNRD2), Iodothyronine deiodinase 1 (DIO1), Methionine-Rsulfoxide reductase 1 (SELR), 15-kDa selenoprotein (SEP15), selenoprotein I (SELI), SELK, SELM, SELN, SELP, SELS, SELT, SELW, and SEPHS2. Meanwhile, HgCl2 exposure significantly increased the mRNA expression of GPX3, TXNRD1, and SELU. Western blot analysis showed that the expression levels of GPX3, TXNRD1, SELK, and SELN were concordant with these mRNA expression levels. Analysis results of selenoproteins expression patterns showed that HgCl2-induced the main disorder expression of selenoproteins with antioxidant activity and endoplasmic reticulum resident selenoproteins. In conclusion, selenoproteins respond to HgCl2 exposure in a characteristic manner in chicken kidney.


Alterations in regional brain neurotensin concentrations produced by atypical antipsychotic drugs.
Classical antipsychotic drugs, such as haloperidol, have been shown to increase the concentrations of neurotensin (NT) selectively in the nucleus accumbens and caudate nucleus of the rat. Several novel, putative antipsychotic drugs have also been found to produce increases in NT content in one or both of these brain regions. The present study sought to compare the effects of chronic treatment with three clinically efficacious atypical antipsychotic drugs, sulpiride, rimcazole and remoxipride, on regional brain NT concentrations to those of haloperidol. The concentrations of NT in five discrete brain regions were determined by a sensitive and specific radioimmunoassay. As previously reported, haloperidol increased NT concentrations in both the nucleus accumbens and caudate nucleus. Sulpiride and rimcazole produced significant increases in the concentration of NT in the caudate. NT concentrations were unaltered in any brain region by remoxipride at either of the doses tested. These data provide additional evidence for specific increases in regional brain NT concentrations produced by antipsychotic drugs.


Gastrointestinal perforation due to congenital absence of intestinal musculature. A case report.
A case of gastrointestinal perforation caused by congenital absence of intestinal musculature is reported. The diagnosis of this condition can be secured only by histologic examination, and removal of all diseased intestine is a prerequisite for cure.


Coactivation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells.
In primary culture of mouse cerebellar granule cells, the brain-derived neurotrophic factor (BDNF) gene is activated in an activity-dependent manner, accompanying Ca2+ influx into neurons through voltage-dependent calcium channels (VDCCs). In this study, we investigated the inducibility of secretogranin-II (Sg-II) gene in terms of Ca2+ signals evoked via VDCCs, by a comparison with BDNF and c-fos genes. Deprivation and subsequent induction of membrane depolarization by lowering and reelevating the extracellular concentration of potassium chloride (KCl), respectively, led to an decrease and then an increase in the Sg-II, BDNF and c-fos mRNA expression. The increase in Sg-II mRNA expression was detected as early as but was slower than that of BDNF one. The increase in Sg-II mRNA expression was induced depending upon the extracellular Ca2+ and inhibited by nicardipine, indicating a requirement of Ca2+ influx through VDCCs for the Sg-II as well as BDNF gene induction. Inhibition of de novo protein synthesis by cycloheximide did not affect the Sg-II induction. The response of Sg-II gene to the changes in extracellular KCl concentration was the same as that of BDNF but different from that of c-fos gene. Thus, Sg-II gene is coactivated with BDNF gene in response to the intracellular Ca2+ signals evoked via Ca2+ influx through VDCCs.


MicroRNA-183 promotes migration and invasion of CD133(+)/CD326(+) lung adenocarcinoma initiating cells via PTPN4 inhibition.
Non-small cell lung cancer (NSCLC) is the most common cancer worldwide and is a leading cause of lung cancer mortality due to early stage metastases. Cancer stem-like cells (CSLCs) or tumor-initiating cells (TICs) are rare subpopulation cells that are responsible for maintaining tumor growth and invasion leading to recurrence and metastasis. Previous studies revealed that miR-183 can mediate the invasiveness and growth of NSCLC. However, the exact role of miR-183 in regulating the biological behavior of CSLCs in NSCLC remains unclear. In the present study, we explored the regulation of protein tyrosine phosphatase non-receptor type 4 (PTPN4) by miR-183 in vitro using luciferase reporter assays, and we further analyzed the effects of miR-183 on the invasiveness of CSLCs in vitro and in vivo using transwell and bioluminescence assays. Following our finding that miR-183 binds to PTPN4 messenger RNA (mRNA) to prevent its translation through the 3'-untranslated region (UTR), we found that overexpression of miR-183 in CSLCs decreased PTPN4 protein levels while inhibition of miR-183 increased PTPN4 protein levels. The suppression of PTPN4 levels in CSLCs by miR-183 paralleled with a significant promotion in their motility in vitro and in vivo, while anti-sense miR-183 increased PTPN4 levels in CSLCs, which paralleled with a significant decrease in their invasiveness. Furthermore, correlation analysis between miR-183 and PTPN4 in clinical samples demonstrated a statistically significant inverse correlation between PTPN4 mRNA levels and miR-183. In brief, our data indicate that miR-183 plays a pro-invasive role by inverse regulation of PTPN4, and this axis may be a new therapeutic target for suppressing the metastatic capability of CSLCs in NSCLC.


Formation of Enhanced Uniform Chiral Fields in Symmetric Dimer Nanostructures.
Chiral fields with large optical chirality are very important in chiral molecules analysis, sensing and other measurements. Plasmonic nanostructures have been proposed to realize such super chiral fields for enhancing weak chiral signals. However, most of them cannot provide uniform chiral near-fields close to the structures, which makes these nanostructures not so efficient for applications. Plasmonic helical nanostructures and blocked squares have been proved to provide uniform chiral near-fields, but structure fabrication is a challenge. In this paper, we show that very simple plasmonic dimer structures can provide uniform chiral fields in the gaps with large enhancement of both near electric fields and chiral fields under linearly polarized light illumination with polarization off the dimer axis at dipole resonance. An analytical dipole model is utilized to explain this behavior theoretically. 30 times of volume averaged chiral field enhancement is gotten in the whole gap. Chiral fields with opposite handedness can be obtained simply by changing the polarization to the other side of the dimer axis. It is especially useful in Raman optical activity measurement and chiral sensing of small quantity of chiral molecule.


A hyaluronidase from Potamotrygon motoro (freshwater stingrays) venom: isolation and characterization.
Freshwater stingrays (Potamotrygon motoro) are known to cause human accidents through a sting located in its tail. In the State of Goiás, this accident happens especially during the fishing season of the Araguaia River. The P. motoro venom extracted from the sting presented hyaluronidase activity. The enzyme was purified by gel filtration on Sephacryl S-100 and ion-exchange chromatography on SP-Sepharose. A typical procedure provided 376.4-fold purification with a 2.94% yield. The molecular weight of the purified enzyme was 79 kDa as estimated by gel filtration on Sephacryl S-100. The K(m) and V(max) values for hyaluronidase, using hyaluronic acid as substrate, were 4.91 microg/ml and 2.02 U/min, respectively. The pH optimum for the enzyme was pH 4.2 and maximum activity was obtained at 40 degrees C. The hyaluronidase from P. motoro was shown to be heat instable, being stabilized by bovine albumin and DTT, and inhibited by Fe(2+), Mn(2+), Cu(2+) and heparin.


Phase 1 study of 2 high dose intensity schedules of the pan-Notch inhibitor crenigacestat (LY3039478) in combination with prednisone in patients with advanced or metastatic cancer.
Background Crenigacestat is a potent Notch inhibitor that decreases Notch signaling and its downstream biological effects. Here, we report the results from Part F of study 16F-MC-JJCA designed to evaluate the safety, pharmacokinetics (PK), and antitumor activity of crenigacestat with prednisone in advanced or metastatic cancer. The combination was planned to mitigate gastrointestinal toxicities. Methods Eligible patients (Study Part F) received crenigacestat loading dose (75 mg, escalating to 150 mg) administered thrice weekly (TIW) (F1) or twice weekly (BIW) (F2) for 2 weeks during Cycle 1, followed by 50 mg TIW from week 3 onwards. Prednisone was co-administered for 2 weeks in Cycle 1. Results Twenty-eight patients were enrolled; 11 in F1 (median age, 63 years), 17 in F2 (median age, 50 years). Dose-limiting toxicities were Grade 3 increased serum amylase and Grade 2 fatigue in F1, and Grade 4 hypophosphatemia and Grade 3 rash maculo-papular in F2. The maximum tolerated dose was 75 mg in F1 and 100 mg in F2. Best overall response was stable disease (F1, 6 [54.5%] patients; F2, 11 [64.7%] patients). Pharmacokinetic was dose proportional. Prednisone did not modify PK of crenigacestat, and both F1 and F2 achieved pharmacodynamics effects on evaluable tumor tissue samples. Conclusions This study demonstrated the potential use of prednisone to reduce gastrointestinal (GI) toxicities of a Notch inhibitor without affecting its PK. The safety profile observed was consistent with Notch pathway inhibitors, and the maximum tolerated dose was 75 mg TIW and 100 mg BIW in F1 and F2, respectively. ClinicalTrials.gov: NCT01695005.


Weight-bearing patterns on the knees of preterm infants.
In this study we present a method of monitoring the forces under the knees of preterm infants lying in the prone position. Dual force sensing resistor transducers, connected to optically-isolated amplifiers, were used to monitor the forces. A thermistor airflow sensor was used for the parallel monitoring of the respiratory signal. The measurements were made on ten preterm infants. The average forces were 0.51 and 0.50 N for the left and right knees, respectively. In the frequency domain, the basic harmonic of the force traces was 1.27 Hz approximately, corresponding to the respiratory rhythm. Additional, smaller harmonics, were detected in the force traces at 2.54 and 3.81 Hz. A rather notable power signal could also be seen around 0.1 Hz. The results obtained indicate that the system developed is highly sensitive for providing data on the amplitudes, periods and sequences of oscillations and symmetry of load bearing in preterm infants. Knowledge of the normal and abnormal reaction force patterns may assist in the early diagnosis of abnormal neurodevelopment.


Molecular simulation of the interaction of kappa-conotoxin-PVIIA with the Shaker potassium channel pore.
Molecular simulation techniques were appplied to predict the interaction of the voltage-dependent Shaker potassium channel with the channel-blocking toxin kappa-conotoxin-PVIIA (PVIIA). A structural thee-dimensional model of the extracellular vestibule of the potassium channel was constructed based on structural homologies with the bacterial potassium channel Kcsa, whose structure has been solved by X-ray crystallography. The docking of the PVIIA molecule was obtained by a geometric recognition algorithm, yielding 100 possible conformations. A series of residue-residue distance restraints, predicted from mutation-cycle experiments, were used to select a small set of a plausible channel-toxin complex models among the resulting possible conformations. The four final conformations, with similar characteristics, can explain most of the single-point mutation experiments done with this system. The models of the Shaker-PVIIA interaction predict two clusters of amino acids, critical for the binding of the toxin to the channel. The first cluster is the amino acids R2, I3, Q6 and K7 that form the plug of the toxin that interacts with the entrance to the selectivity filter of the channel. The second cluster of residues, R22, F23, N24 and K25, interacts with a channel region near to the external entrance of the pore vestibule. The consistency of the obtained models and the experimental data indicate that the Shaker-PVIIA complex model is reasonable and can be used in further biological studies such as the rational design of blocking agents of potassium channels and the mutagenesis of both toxins and potassium channels.


Severe anemia from heavy menstrual bleeding requires heightened attention.
The objective of the study was to analyze the behaviors of women that resulted in menstrually related severe anemia (hemoglobin <5 g/dL) from a single public hospital serving indigent women. This was a retrospective cohort study of all women identified as having been treated at Harbor-UCLA Medical Center for excessive menstruation (International Classification of Diseases, ninth revision, codes 285.9, 6256.2) and hemoglobin values less than 5 g/dL in the 6 years from 2008 to 2013. Approvals were obtained from the Human Subjects and Research Committees. This search identified 271 women with those 2 diagnoses; 122 were excluded because their severe anemia had nonmenstrual causes. The remaining 149 women had 168 episodes with hemoglobin levels below 5 g/dL attributed to chronic excessive menstrual bleeding. Mean age was 41 years (range, 19-55 years). Mean body mass index was 28.9 kg/m(2) (range, 18-57 kg/m(2)); 58.2% were actively bleeding at presentation, and 90.4% reported chronic excessive blood loss. Two thirds recognized heavy bleeding that had persisted for more than 6 months without seeking help. However, 7.8% described their bleeding as normal, and 40.5% had received at least 1 previous transfusion. Mean nadir hemoglobin was 4.15 g/dL (range, 1.6-4.9 g/dL). Mean corpuscular volume was 62.2 fL (range, 47.7-99.8 fL) and mean corpuscular hemoglobin concentration was 29.2 g/dL (range, 25.7-33.6 g/dL). Nearly a quarter had reactive thrombocytosis, which might have created a hypercoagulable state. Bleeding was ultimately attributed to leiomyoma in 47.9%; cancer was detected in 4.8%. A total of 33.9% were discharged without being offered any therapy to prevent subsequent bleeding; 3.0% declined any medical therapy; 35.1% were lost to follow-up prior to receiving effective therapy; and 26.8% had multiple subsequent transfusions before seeking/receiving definitive treatments. Even when faced with potentially life-threatening anemia because of chronic, excessive menstrual blood loss, some women are not impressed with the serious nature of their problem. Women will benefit from recognizing the health consequences of chronic excessive blood loss. Chronic excessive blood loss should be treated as both an urgent and potentially recurrent problem; physicians should address this clinical concern proactively.


Socioeconomic barriers to informed decisionmaking regarding maternal serum screening for down syndrome: results of the French National Perinatal Survey of 1998.
We sought to evaluate socioeconomic disparities in serum screening for Down syndrome and assess whether such disparities are more likely to reflect limits in access or information or, rather, informed decisionmaking. A nationally representative sample of 12 869 French women completed interviews after giving birth. We found substantial disparities in the likelihood of (1) women not being offered screening, (2) screening not being offered as a result of late prenatal care, and (3) women not knowing whether or not they had undergone screening. Except in the case of nationality, there was essentially no evidence of differences in refusal of testing. Rather than representing informed decisionmaking, socioeconomic disparities in screening for Down syndrome are mostly due to limits in access or to information.


Duodenitis in children: clinical, endoscopic, and pathological aspects.
In a retrospective study of 320 gastroduodenoscopies performed on children in the last 2 years, 32 cases of duodenal damage, either isolated or associated with esophagitis, gastritis, or both, were selected. Twenty matched children with dyspeptic symptoms but an endoscopically normal duodenum were chosen as controls. Histological sections of fiberoptic biopsy specimens were submitted to double-blind examination by two observers: only four fulfilled accepted criteria for histological duodenitis. The concordance between endoscopic and histological results in our patients was 13.8%. No changes of duodenal endoscopic appearance predictive of duodenitis were identified. In 8 more cases (6 patients and 2 controls) the histological examination showed an isolated lymphocyte and plasma cell infiltration of the lamina propria without any additional damage. We called this picture "minimal change duodenitis" and considered it as a variation of normal. In 17 patients and 11 controls, basal and maximal acid outputs were calculated and no significant differences were found. We concluded that duodenitis in children may be present, although rare, and its diagnosis requires histological examination of duodenal mucosa.


Risk stratification of individuals with the Brugada electrocardiogram: a meta-analysis.
We performed a meta-analysis of prognostic studies of patients with a Brugada ECG to assess predictors of events. The Brugada syndrome is an increasingly recognized cause of idiopathic ventricular fibrillation; however, there is wide variation in the prognosis of patients with the Brugada ECG. We retrieved 30 prospective studies of patients with the Brugada ECG, accumulating data on 1,545 patients. Summary estimates of the relative risk (RR) of events (sudden cardiac death [SCD], syncope, or internal defibrillator shock) for a variety of potential predictors were made using a random-effects model. The overall event rate at an average of 32 months follow-up was 10.0% (95% CI 8.5%, 11.5%). The RR of an event was increased (P < 0.001) among patients with a history of syncope or SCD (RR 3.24 [95% CI 2.13, 4.93]), men compared with women (RR 3.47 [95% CI 1.58, 7.63]), and patients with a spontaneous compared with sodium-channel blocker induced Type I Brugada ECG (RR 4.65 [95% CI 2.25, 9.58]). The RR of events was not significantly increased in patients with a family history of SCD (P = 0.97) or a mutation of the SCN5A gene (P = 0.18). The RR of events was also not significantly increased in patients inducible compared with noninducible by electrophysiologic study (EPS) (RR 1.88 [95% CI 0.62, 5.73], P = 0.27); however, there was significant heterogeneity of the studies included. Our findings suggest that a history of syncope or SCD, the presence of a spontaneous Type I Brugada ECG, and male gender predict a more malignant natural history. Our findings do not support the use of a family history of SCD, the presence of an SCN5A gene mutation, or EPS to guide the management of patients with a Brugada ECG.


Evolution of a new nonclassical MHC class I locus in two Old World primate species.
HLA-G is a nonclassical major histocompatibility complex (MHC) class I molecule that is expressed only in the human placenta, suggesting that it plays an important role at the fetal-maternal interface. In rhesus monkeys, which have similar placentation to humans, the HLA-G orthologue is a pseudogene. However, rhesus monkeys express a novel placental MHC class I molecule, Mamu-AG, which has HLA-G-like characteristics. Phylogenetic analysis of AG alleles in two Old World primate species, the baboon and the rhesus macaque, revealed limited diversity characteristic of a nonclassical MHC class I locus. Gene trees constructed using classical and nonclassical primate MHC class I alleles demonstrated that the AG locus was most closely related to the classical A locus. Interestingly, gene tree analyses suggested that the AG alleles were most closely related to a subset of A alleles which are the products of an ancestral interlocus recombination event between the A and B loci. Calculation of the rates of synonymous and nonsynonymous substitution at the AG locus revealed that positive selection was not acting on the codons encoding the peptide binding region. In exon 4, however, the rate of nonsynonymous substitution was significantly lower than the rate of synonymous substitution, suggesting that negative selection was acting on these codons.


Low-temperature synthesis of high-ordered anatase TiO2 nanotube array films coated with exposed {001} nanofacets.
High-ordered anatase TiO2 nanotube array films coated with exposed high-reactive {001} nanofacets were fabricated by a modified hydrothermal method using amorphous anodic TiO2 nanotube arrays (ATONAs) as starting materials. It was found that the reaction between gas phase HF and solid ATONAs played a key role in the transformation process from amorphous to anatase TiO2, and the TiO2 tubular structure kept unchanged during the surface modification with an exposed {001} facets up to 76.5%, which could be attributed to the low reaction temperature of 130 °C. Our study provided a novel route for the facile preparation of {001} facets exposed anatase TiO2.


Disease prevention programs for racial and ethnic minorities.
Many studies show a dramatic relationship between socioeconomic status and disease incidence. Clear racial and ethnic disparities also exist in the occurrence of diseases such as acquired immunodeficiency syndrome (AIDS), tuberculosis and syphilis. Consequently, to identify true risk factors for diseases when planning prevention programs, the effect of socioeconomic status must be differentiated from that of race or ethnicity. Further, different cultural heritages and social structures may affect how interventions are perceived or used and this must also be taken into account when planning programs. The Centers for Disease Control, through its National Center for Prevention Services, provides financial and technical assistance to state and local health departments to develop approaches that are culturally sensitive and linguistically appropriate to reach persons in racial and ethnic minority groups.


[Process optimization for extraction of immune active polysaccharides from Fomes fomentarius by introduction of ultrasonication].
To study the optimal extraction process of immune active polysaccharides from Fomes fomentarius by introduction of ultrasonication. An orthogonal experimental design of L9 (3(4)) was used to investigate the effects of ultrasonication time, extraction temperature and extraction time on the extraction ratio, sugar content and immune stimulating activity (mouse splenocyte metabolic activity measured with MTT colorimetry) of the polysaccharides and the optimal extraction process was evaluated. Ultrasonication treatment had the most remarkable effect on the immune stimulating activity of the polysaccharides. The optimal extraction process for extraction of immune active polysaccharides was as follows: ultrasonication for 30min, extraction temperature at 80 degrees C and water extraction time for 2h. Ultrasonication can be used as a useful technique for extraction of immune active polysaccharides from Fomes fomentarius.


Double immunocytochemical evidence for a clonal development of specific antibody-containing cells in the rabbit spleen.
Rabbits were intravenously primed with the antigens human serum albumin (HSA) and bovine gamma globulin (BGG). The antigens were given simultaneously, or at an interval of 1, 2, or 4 days. After 2 months an intravenous booster injection with both antigens was given simultaneously. The localization pattern of anti-HSA-antibody-containing cells and of anti-BGG-antibody-containing cells in the spleen was determined during both the primary and secondary immune response. Anti-HSA-antibody-containing cells and anti-BGG-antibody-containing cells were not distributed randomly but, rather, were found in defined groups during the induction of an immune response. The most probable explanation for this grouping is that lymphoid cells, once triggered to proliferation by a particular antigen, show a clonal development in the spleen. During their proliferation and successive antibody formation, they migrate only slowly, so that they remain close together. Specific-antibody-containing cells were also detected in the popliteal lymph nodes and in the appendix of the rabbits.


Utilization and Perioperative Outcomes of Partial Cystectomy for Urothelial Carcinoma of the Bladder: Lessons from the ACS NSQIP Database.
We identified predictors of partial cystectomy in the ACS NSQIP® database of more than 400 hospitals across North America. We also reviewed perioperative outcomes. We reviewed the records of patients with an ICD-9 diagnosis of urothelial carcinoma of the bladder who were treated with partial or radical cystectomy from 2007 to 2012. The proportion of patients who underwent partial vs radical cystectomy and the proportion who received neoadjuvant chemotherapy were compared across time. We reviewed 30-day morbidity and mortality, and determined risk factors. Logistic regression was used to identify factors predictive of undergoing partial vs radical cystectomy. A total of 2,393 patients met study inclusion criteria. The ratio of partial to radical cystectomy was low and stable at 0% to 7% (p = 0.36). While patients undergoing radical cystectomy were more likely to receive neoadjuvant chemotherapy in later years (p <0.001), neoadjuvant chemotherapy use before partial cystectomy was consistently low with time (p = 0.68). The 30-day morbidity rate after partial and radical cystectomy was 23.3% and 58.1% (p = 0.001), and the 30-day mortality rate was 1.6% and 2.1%, respectively (p = 0.66). On multivariate regression factors independently associated with partial vs radical cystectomy were cerebrovascular accident history (OR 4.4, p = 0.005), current nonsmoking (OR 0.43, p = 0.032) and lack of trainee participation in the operation (OR 0.28, p <0.001). The ratio of the number of partial to radical cystectomies performed was stable. Cerebrovascular accident history, nonsmoker status and lack of trainee participation were associated with partial cystectomy. Patients treated with radical cystectomy but not those who underwent partial cystectomy were more likely to receive neoadjuvant chemotherapy in later years. Large detailed registries such as ACS NSQIP have important potential use for evaluating trends in urological practice.


Carbocupration-functionalization of arynes: rapid access to variably ortho-substituted ((E)-3-phenylprop-1-enyl)silanes.
A consecutive three-component coupling reaction involving a lithium di[3-(prop-1-enyltrimethylsilyl)]cuprate, variably substituted ortho-arynes, and a selection of common electrophiles is described. The method affords readily functionalized homobenzylic vinylsilanes with exceptional E-diastereoselectivity and allows for in situ incorporation of carbon- or heteroatom-based electrophiles into the arene.


Evaluating educational service quality among dentistry and nursing students with the SERVQUAL model: A cross-sectional study.
This study was aimed at evaluating the quality of educational services among dentistry and nursing students through use of the SERVQUAL model. Additionally, the effects of education sector, country, gender, and academic year on the quality of education services were studied. A convenience sampling technique was used in this cross-sectional study to recruit 528 dentistry and nursing students in governmental and private sectors from Egypt and KSA. Data were collected through two self-administered questionnaires. The first questionnaire included participants' demographic characteristics, whereas the second questionnaire collected data on educational service quality by using the five-dimension SERVQUAL tool. The total mean score for quality of education was 3.65. The mean reliability score was highest among all quality dimensions (3.79). A significant positive linear association was observed between the quality of education and educational sector, field of study, country, and academic year. Students' perceptions of educational service quality were above average. Field of study had the largest main effect on the quality of educational services. Additionally, academic year, educational sectors, and country significantly influenced the quality of educational services.


Structural and binding properties of laminarin revealed by analytical ultracentrifugation and calorimetric analyses.
One of the β-1,3-glucans, laminarin, has been widely used as a substrate for enzymes including endo-1,3-β-glucanase. To obtain quantitative information about the molecular interaction between laminarin and endo-1,3-β-glucanase, the structural properties of laminarin should be determined. The results from pioneering work using analytical ultracentrifugation for carbohydrate analysis showed that laminarin from Laminaria digitata predominantly exists as a single-chain species with approximately 5% of triple-helical species. Differential scanning calorimetry experiments did not show a peak assignable to the transition from triple-helix to single-chain, supporting the notion that a large proportion of laminarin is the single-chain species. The interaction of laminarin with an inactive variant of endo-1,3-β-glucanase from Cellulosimicrobium cellulans, E119A, was quantitatively analyzed using isothermal titration calorimetry. The binding was enthalpically driven and the binding affinity was approximately 10(6) M(-1). The results from binding stoichiometric analysis indicated that on average, E119A binds to laminarin in a 2:1 ratio. This seems to be reasonable, because laminarin mainly exists as a monomer, the apparent molecular mass of laminarin is 3.6 kDa, and E119A would have substrate-binding subsites corresponding to 6 glucose units. The analytical ultracentrifugation experiments could detect different complex species of laminarin and endo-1,3-β-glucanase.


Into the void: ECM fungal communities involved in the succession from rockroses to oak stands.
Oak forests accompanied by Cistus species are a common landscape in the Mediterranean basin. It is argued that Cistus dominated fields serve as recruitment areas for Quercus seedlings, as they help in the transmission of the fungal community through vegetative succession in these ecosystems. To test these assumptions, we analyzed the fungal community in terms of its richness and composition, taking into account the effects of host (Oaks vs. Cistus) and forest structure, mainly based on age. Edaphic variables related to the different structures were also analyzed to examine how they evolve through succession and relate to shifts in the fungal community. No differences in fungal richness were observed between old Cistus stands and younger Quercus, while a brief increase in ECM richness was observed. Community composition also showed a greater overlap between old Cistus and young Quercus stands. We suggest that the most important step in fungal transfer from one host to another is the shift from the oldest Cistus fields to the youngest Quercus stands, with the genera Amanita, Cortinarius, Lactarius, Inocybe, Russula, and Tomentella probably playing a major role. In summary, our work has also revealed the network of fungal community structure in the succession of Cistus to Oak stands, it would suggest that the fungi share niches and significantly enhance the ecological setting of the transition from Cistus to Oak stands.


Laparoscopic subtotal cholecystectomy after percutaneous transhepatic gallbladder drainage for grade II or III acute cholecystitis.
Severe adhesions and fibrosis between the posterior wall of the gallbladder and liver bed often render total cholecystectomy after percutaneous transhepatic gallbladder drainage (PTGBD) difficult, leading to high open conversion rates. Since the publication of Tokyo Guidelines 2018 (TG18), our policy has shifted from open conversion to subtotal cholecystectomy (SC) when total laparoscopic cholecystectomy for difficult cases of cholecystitis is not feasible. Recently, SC has been frequently applied as bailout surgery for complicated cholecystitis. Nonetheless, the efficacy and validity of laparoscopic SC after PTGBD remain unclear. This study aimed to evaluate the safety and feasibility of laparoscopic SC after PTGBD for grade II or III acute cholecystitis (AC) by comparing two periods of altered surgical strategies. This retrospective cohort study was conducted between January 2013 and December 2020. A total of 44 eligible patients with grade II or III AC were divided according to the time of cholecystitis onset into the pre-TG18 group (2013-2017, n = 17) and post-TG18 group (2018-2020, n = 27). Patients' background demographics, surgical method, surgical results, and postoperative complications were compared. The interval between PTGBD and surgery was significantly longer in the post-TG18 group than in the pre-TG18 group (15 [interquartile range: 9-42] days vs. 8 [4-11] days; P = 0.010). The frequency of laparoscopic cholecystectomy significantly increased from 52.9% in the pre-TG18 group to 88.9% in the post-TG18 group (P = 0.007), whereas the frequency of SC was 23.5% and 40.7%, respectively, which showed no statistically significant difference (P = 0.241). However, the rate of laparoscopic SC significantly increased from 0 to 90.9% among 15 SC cases, whereas the rate of open SC significantly plummeted from 100 to 9.1% (P = 0.001). Significant differences in the operative time, amount of intraoperative bleeding, and incidence of postoperative complications (wound infection and subhepatic abscess) were not observed. Mortality, bile leakage, and bile duct injury did not occur in either group. For grade II or III AC after PTGBD, aggressive adoption of SC increased the completion rate of laparoscopic surgery. Laparoscopic SC is a safe and feasible treatment option.


A 3D-printed sub-atmospheric pressure electrospray ionization source for robust, facile, and flexible mass spectrometry analysis.
The operation and performance of electrospray ionization (ESI) is affected by the surrounding environment. In this study, a compact sub-atmospheric pressure ESI (SAP-ESI) source was designed and fabricated using the 3D printing method. This source has a simple structure and is easy to operate, as the sample solution and auxiliary gas are continuously sucked into the source through the pressure difference. The compact and enclosed ionization chamber can reduce the fluctuation of the surrounding gas flow to ensure a remarkably stable (< 3%) electrospray. Moreover, the source can offer variable SAP conditions for ESI analysis. The yield of analyte ions increases with decreasing pressure, while the production of background ions is suppressed under these conditions. In the analysis of protein samples, SAP-ESI can increase the yield and charge state of ions, which may be due to the reduction of proton transfer between charged proteins and surrounding gas. The SAP-ESI source was then used to continuously monitor the extract aqueous solution of tea leaves, and to detect the carbendazim residues on the apple surface by coupling with the liquid extraction surface analysis technique. Experimental results demonstrate that the developed SAP-ESI is a stable, practical, and versatile ionization technique.