Halogen Bond Structure and Dynamics from Molecular Simulations.
Halogen bonding has emerged as an important noncovalent interaction in a myriad of applications, including drug design, supramolecular assembly, and catalysis. The current understanding of the halogen bond is informed by electronic structure calculations on isolated molecules and/or crystal structures that are not readily transferable to liquids and disordered phases. To address this issue, we present a first-principles simulation-based approach for quantifying halogen bonds in molecular systems rooted in an understanding of nuclei-nuclei and electron-nuclei spatial correlations. We then demonstrate how this approach can be used to quantify the structure and dynamics of halogen bonds in condensed phases, using solid and liquid molecular chlorine as prototypical examples with high concentrations of halogen bonds. We close with a discussion of how the knowledge generated by our first-principles approach may inform the development of classical empirical models, with a consistent representation of halogen bonding.


Anti-Aβ Autoantibodies in Amyloid Related Imaging Abnormalities (ARIA): Candidate Biomarker for Immunotherapy in Alzheimer's Disease and Cerebral Amyloid Angiopathy.
Amyloid-related imaging abnormalities (ARIA) represent the major severe side effect of amyloid-beta (Aβ) immunotherapy for Alzheimer's disease (AD). Early biomarkers of ARIA represent an important challenge to ensure safe and beneficial effects of immunotherapies, given that different promising clinical trials in prodromal and subjects at risk for AD are underway. The recent demonstration that cerebrospinal fluid (CSF) anti-Aβ autoantibodies play a key role in the development of the ARIA-like events characterizing cerebral amyloid angiopathy-related inflammation generated great interest in the field of immunotherapy. Herein, we critically review the growing body of evidence supporting the monitoring of CSF anti-Aβ autoantibody as a promising candidate biomarker for ARIA in clinical trials.


Instance Weighted Incremental Evolution Strategies for Reinforcement Learning in Dynamic Environments.
Evolution strategies (ESs), as a family of black-box optimization algorithms, recently emerge as a scalable alternative to reinforcement learning (RL) approaches such as Q-learning or policy gradient and are much faster when many central processing units (CPUs) are available due to better parallelization. In this article, we propose a systematic incremental learning method for ES in dynamic environments. The goal is to adjust previously learned policy to a new one incrementally whenever the environment changes. We incorporate an instance weighting mechanism with ES to facilitate its learning adaptation while retaining scalability of ES. During parameter updating, higher weights are assigned to instances that contain more new knowledge, thus encouraging the search distribution to move toward new promising areas of parameter space. We propose two easy-to-implement metrics to calculate the weights: instance novelty and instance quality. Instance novelty measures an instance's difference from the previous optimum in the original environment, while instance quality corresponds to how well an instance performs in the new environment. The resulting algorithm, instance weighted incremental evolution strategies (IW-IESs), is verified to achieve significantly improved performance on challenging RL tasks ranging from robot navigation to locomotion. This article thus introduces a family of scalable ES algorithms for RL domains that enables rapid learning adaptation to dynamic environments.


Enhancement-procedure outcomes in patients implanted with the Precisight multicomponent intraocular lens.
Eyes that have undergone phacoemulsification with implantation of a multicomponent intraocular lens (MCIOL) may further undergo an enhancement procedure for correction of residual refractive errors. The enhancement procedure is accomplished by exchanging the front lens used in the primary surgery with another lens containing the correct dioptric power. We evaluated the efficacy and safety of enhancement procedures among eyes that received an MCIOL. A total of 25 eyes that had undergone phacoemulsification with implantation of an MCIOL were found to have a residual error of refraction (spherical equivalent ≥0.75 D) 3 months after primary cataract surgery, and underwent further enhancement surgery. The main study outcomes were uncorrected and corrected distance visual acuity, subjective refraction, anterior-chamber depth, pachymetry, and endothelial cell count. There was a statistically significant improvement in uncorrected distance visual acuity of approximately two lines after enhancement surgery (0.20±0.20-0.02±0.08 logMAR, P<0.001) and a significant decrease in residual spherical equivalent from 1.3±1.1 D to 0±0.38 D (P<0.001). There were no statistically significant changes in pre- and postenhancement corrected distance visual acuity, anterior-chamber depth, pachymetry, or keratometry. There was a statistically significant decrease (2.6%) in endothelial cell count (P<0.01), which could have been endothelial equilibration from the primary procedure. All enhancement surgeries were uneventful, and no major complications were observed. The MCIOL-enhancement procedure demonstrates statistical and clinical improvement in uncorrected distance visual acuity and correction of postoperative refractive errors. The Precisight IOL may be a useful choice for patients with high risk of having significant residual refractive errors after primary cataract surgery.


[A rapid method for intragastric pH-metry].
An original technique of basal topographic pH-metry of the stomach, making use of new pH-microtubes, was employed in mass prophylactic check-ups. The suggested method of intragastric pH-metry is superior to the currently used one and may be employed for the screening of subjects who are in need of an x-ray endoscopic examination of the stomach and for outpatient measurements of the gastric pH values, as well as for the choice and monitoring of the pH-regulating therapy.


α-1-antitrypsin variants and the proteinase/antiproteinase imbalance in chronic obstructive pulmonary disease.
The excessive activities of the serine proteinases neutrophil elastase and proteinase 3 are associated with tissue damage in chronic obstructive pulmonary disease. Reduced concentrations and/or inhibitory efficiency of the main circulating serine proteinase inhibitor α-1-antitrypsin result from point mutations in its gene. In addition, α-2-macroglobulin competes with α-1-antitrypsin for proteinases, and the α-2-macroglobulin-sequestered enzyme can retain its catalytic activity. We have studied how serine proteinases partition between these inhibitors and the effects of α-1-antitrypsin mutations on this partitioning. Subsequently, we have developed a three-dimensional reaction-diffusion model to describe events occurring in the lung interstitium when serine proteinases diffuse from the neutrophil azurophil granule following degranulation and subsequently bind to either α-1-antitrypsin or α-2-macroglobulin. We found that the proteinases remained uninhibited on the order of 0.1 s after release and diffused on the order of 10 μm into the tissue before becoming sequestered. We have shown that proteinases sequestered to α-2-macroglobulin retain their proteolytic activity and that neutrophil elastase complexes with α-2-macroglobulin are able to degrade elastin. Although neutrophil elastase is implicated in the pathophysiology of emphysema, our results highlight a potentially important role for proteinase 3 because of its greater concentration in azurophil granules, its reduced association rate constant with all α-1-antitrypsin variants studied here, its greater diffusion distance, time spent uninhibited following degranulation, and its greater propensity to partition to α-2-macroglobulin where it retains proteolytic activity.


A supercooled imidazolium iodide ionic liquid as a low-viscosity electrolyte for dye-sensitized solar cells.
A series of allyl-functionalized imidazolium salts are reported, including 1-allyl-3-ethylimidazolium iodide and 1-allyl-3-propylimidazolium iodide, which have melting points close to room temperature and show typical properties of supercooled fluids if heated above their melting points. Their viscosities in the liquid state are considerably lower than the benchmark ionic liquid used in solar cells, viz., 1-propyl-3-methylimidazolium iodide. Electrolytes containing these new liquids provide excellent efficiencies and good stability in dye-sensitized solar cells when subjected to an accelerated-light soaking test at 60 degrees C. The structures of three of the new salts have been established in the solid state by single-crystal X-ray analysis.


First-principles calculation of the bulk photovoltaic effect in the polar compounds LiAsS2, LiAsSe2, and NaAsSe2.
We calculate the shift current response, which has been identified as the dominant mechanism for the bulk photovoltaic effect, for the polar compounds LiAsS2, LiAsSe2, and NaAsSe2. We find that the magnitudes of the photovoltaic responses in the visible range for these compounds exceed the maximum response obtained for BiFeO3 by 10-20 times. We correlate the high shift current response with the existence of p states at both the valence and conduction band edges, as well as the dispersion of these bands, while also showing that high polarization is not a requirement. With low experimental band gaps of less than 2 eV and high shift current response, these materials have potential for use as bulk photovoltaics.


No Other Safe Care Option: Nursing Home Admission as a Last Resort Strategy.
Nursing homes are intended for older adults with the highest care needs. However, approximately 12% of all nursing home residents have similar care needs as older adults who live in the community and the reasons they are admitted to nursing homes is largely unstudied. The purpose of this study was to explore the reasons why lower-care nursing home residents are living in nursing homes. A qualitative interpretive description methodology was used to gather and analyze data describing lower-care nursing home resident and family member perspectives regarding factors influencing nursing home admission, including the facilitators and barriers to living in a community setting. Data were collected via semistructured interviews and field notes. Data were coded and sorted, and patterns were identified. This resulted in themes describing this experience. The main problem experienced by lower-care residents was living alone in the community. Residents and family members used many strategies to avoid safety crises in the community but experienced multiple care breakdowns in both community and health care settings. Nursing home admission was a strategy used to avoid a crisis when residents did not receive the needed support to remain in the community. To successfully remain in the community, older adults require specialized supports targeting mental health and substance use needs, as well as enhanced hospital discharge plans and improved information about community-based care options. Implications involve reforming policies and practices in both hospital and community-based care settings.


Neurology referrals to a liaison psychiatry service.
The objective of the present study was to assess the activity of the Liaison Psychiatry service of Cork University Hospital in relation to all in-patient neurology referrals over a 12-month period. Of 1685 neurology admissions, 106 (6%) were referred to liaison psychiatry for assessment. 91 referrals (86%) met criteria for a psychiatric disorder according to DSM-IV, the commonest being major depression (24%) and somatoform disorder (23%). Patients with multiple sclerosis or epilepsy comprised nearly half of all referrals (48 cases; 45%). Approximately 20% of M.S. in-patients (21 cases) were referred for psychiatric assessment, with the corresponding figure in epilepsy being 25% (18 cases). Although only 106 (6%) neurology in-patients were referred to liaison psychiatry, psychiatric diagnoses were documented in 327 (20%) discharge forms, presumably reflecting previous diagnosis. The above findings indicate that psychiatric illness is common among neurology inpatients screened by liaison psychiatry yet referral rates are relatively low in terms of the overall number of neurology in-patients. Psychiatric disorders were diagnosed in 86% of referrals indicating high concordance between neurologists and liaison psychiatry regarding the presence of a psychiatric disorder.


Compositional variability and antifungal potentials of ocimum basilicum, O. tenuiflorum, O. gratissimum and O. kilimandscharicum essential oils against Rhizoctonia solani and Choanephora cucurbitarum.
The composition of hydrodistilled essential oils of Ocimum basilicum L. (four chemovariants), O. tenuiflorum L., O. gratissimum L., and O. kilimandscharicum Guerke were analyzed and compared by using capillary gas chromatography (GC/FID) and GC-mass spectrometry (GC/MS). Phenyl propanoids (upto 87.0%) and monoterpenoids (upto 83.3%) were prevalent constituents distributed in the studied Ocimum taxa. The major constituents of the four distinct chemovariants of O. basilicum were methyl chavicol (86.3%), methyl chavicol (61.5%)/linalool (28.6%), citral (65.9%); and linalool (36.1%)/citral (28.8%). Eugenol (66.5% and 78.0%) was the major constituent of O. tenuiflorum and O. gratissimum. Eugenol (34.0%), β-bisabolene (15.4%), (E)-α-bisabolene (10.9%), methyl chavicol (10.2%) and 1,8-cineole (8.2%) were the major constituents of O. kilimandscharicum. In order to explore the potential for industrial use, the extracted essential oils were assessed for their antifungal potential through poison food technique against two phytopathogens, Rhizoctonia solani and Choanephora cucurbitarum, which cause root and wet rot diseases in various crops. O. tenuiflorum, O. gratissimum, and O. kilimandscharicum exhibited complete growth inhibition against R. solani and C. cucurbitarum after 24 and 48 h of treatment. O. basilicum chemotypes showed variable levels of growth inhibition (63.0%-100%) against these two phytopathogens.


Incidence of delirium after non-cardiac surgery in the Chinese elderly population: a systematic review and meta-analysis.
POD places a heavy burden on the healthcare system as the number of elderly people undergoing surgery is increasing annually because of the aging population. As a large country with a severely aging population, China's elderly population has reached 267 million. There has been no summary analysis of the pooled incidence of POD in the elderly Chinese population. Systematic search databases included PubMed, Web of Science, EMBASE, Cochrane Library Databases, China Knowledge Resource Integrated Database (CNKI), Chinese Biomedical Database (CBM), WanFang Database, and Chinese Science and Technology Periodicals (VIP). The retrieval time ranged from the database's establishment to February 8, 2023. The pooled incidence of delirium after non-cardiac surgery was calculated using a random effects model. Meta-regression, subgroup, and sensitivity analyses were used to explore the source of heterogeneity. A total of 52 studies met the inclusion criteria, involving 18,410 participants. The pooled incidence of delirium after non-cardiac surgery in the elderly Chinese population was 18.6% (95% CI: 16.4-20.8%). The meta-regression results revealed anesthesia method and year of publication as a source of heterogeneity. In the subgroup analysis, the gender subgroup revealed a POD incidence of 19.6% (95% CI: 16.9-22.3%) in males and 18.3% (95% CI: 15.7-20.9%) in females. The year of publication subgroup analysis revealed a POD incidence of 20.3% (95% CI: 17.4-23.3%) after 2018 and 14.6 (95% CI: 11.6-17.6%) in 2018 and before. In the subgroup of surgical types, the incidence of hip fracture surgery POD was 20.7% (95% CI: 17.6-24.3%), the incidence of non-cardiac surgery POD was 18.4% (95% CI: 11.8-25.1%), the incidence of orthopedic surgery POD was 16.6% (95% CI: 11.8-21.5%), the incidence of abdominal neoplasms surgery POD was 14.3% (95% CI: 7.6-21.1%); the incidence of abdominal surgery POD was 13.9% (95% CI: 6.4-21.4%). The anesthesia methods subgroup revealed a POD incidence of 21.5% (95% CI: 17.9-25.1%) for general anesthesia, 15.0% (95% CI: 10.6-19.3%) for intraspinal anesthesia, and 8.3% (95% CI: 10.6-19.3%) for regional anesthesia. The measurement tool subgroup revealed a POD incidence of 19.3% (95% CI: 16.7-21.9%) with CAM and 16.8% (95% CI: 12.6-21.0%) with DSM. The sample size subgroup revealed a POD incidence of 19.4% (95% CI: 16.8-22.1%) for patients ≤ 500 and 15.3% (95% CI: 11.0-19.7%) for patients > 500. The sensitivity analysis suggested that the pooled incidence of postoperative delirium in this study was stable. Our systematic review of the incidence of delirium after non-cardiac surgery in elderly Chinese patients revealed a high incidence of postoperative delirium. Except for cardiac surgery, the incidence of postoperative delirium was higher for hip fracture surgery than for other types of surgery. However, this finding must be further explored in future large-sample studies. https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42023397883.


Can unilateral, progressive or sudden hearing loss be immune-mediated in origin?
The aim of the present study was to demonstrate that the positivity of nonspecific immunological tests could be found not only in bilateral hearing loss but also in unilateral cases, either sudden or progressive. An observational case series study included subjects suffering from unilateral or bilateral, sudden or progressive, symmetric or asymmetric sensorineural hearing loss (SNHL). All the patients underwent pure tone audiometry and the following battery of blood exams: anti-nuclear antibody (ANA), extractable nuclear antigen (ENA) antibody screening, anti-thyroperoxidase (anti-TPO), anti-thyroglobulin and anti-smooth muscle antibody (ASMA). The positivity to nonspecific immunological test was found in nearly 70% of the study groups. ASMA and ANA were found to be present in both bilateral and unilateral cases, without statistical difference. Considering the correlation between positivity/negativity and systemic autoimmune pathologies, in the bilateral forms of hearing loss, a high incidence of thyroid pathologies has been identified, with a higher percentage of systemic autoimmune diseases in respect to the normal population. The nonspecific autoimmune tests are worth to be performed also when SNHL is not bilateral and progressive, since an immunological mechanism could also underlie unilateral and sudden SNHL cases.


Parental opinions about biomedical research in children in Tours, France.
In order to evaluate parental awareness of the law governing clinical trials in France (Loi Huriet), a study was performed by questionnaire between February and April 1991 in a maternity unit during the days following delivery. The response rate was 59%. 59% of the parents (319/541) were informed of the existence of the law by the media (75%) or their general practitioners (12%). Twenty-one percent (116/541) of the parents would accept the participation of their children in a clinical trial and 74% would refuse. The principal reasons for acceptance were: for the benefit of other children, contribution to medical progress and confidence in physicians. The reasons for refusal were: risk of side effects and unproven efficacy. Parents who would accept had more often received higher education (44%) than parents who would refuse (30%), the latter being less influenced by the explanations of physicians and less willing to accept that a physician should decide for them. Physicians should consider transmitting information directly to parents and indirectly via the media.


Ultrasonic implant site preparation using piezosurgery: a multicenter case series study analyzing 3,579 implants with a 1- to 3-year follow-up.
This multicenter case series introduces an innovative ultrasonic implant site preparation (UISP) technique as an alternative to the use of traditional rotary instruments. A total of 3,579 implants were inserted in 1,885 subjects, and the sites were prepared using a specific ultrasonic device with a 1- to 3-year follow-up. No surgical complications related to the UISP protocol were reported for any of the implant sites. Seventy-eight implants (59 maxillary, 19 mandibular) failed within 5 months of insertion, for an overall osseointegration percentage of 97.82% (97.14% maxilla, 98.75% mandible). Three maxillary implants failed after 3 years of loading, with an overall implant survival rate of 97.74% (96.99% maxilla, 98.75% mandible).


Overall survival of patients with hepatocellular carcinoma treated with sintilimab and disease outcome after treatment discontinuation.
The use of Anti-PD-1 therapy has yielded promising outcomes in hepatocellular carcinoma (HCC). However, limited research has been conducted on the overall survival (OS) of patients with varying tumor responses and treatment duration. This retrospective study analyzed HCC patients who received sintilimab between January 2019 and December 2020 at four centers in China. The evaluation of tumor progression was based on Response Evaluation Criteria in Solid Tumors version 1.1. The study investigated the correlation between tumor response and OS, and the impact of drug use on OS following progressive disease (PD). Out of 441 treated patients, 159 patients satisfied the inclusion criteria. Among them, 77 patients with disease control exhibited a significantly longer OS compared to the 82 patients with PD (median OS 26.0 vs. 11.3 months, P < 0.001). Additionally, the OS of patients with objective response (OR) was better than that of patients with stable disease (P = 0.002). Among the 47 patients with PD who continued taking sintilimab, the OS was better than the 35 patients who discontinued treatment (median OS 11.4 vs. 6.9 months, P = 0.042). In conclusion, the tumor response in HCC patients who received sintilimab affects OS, and patients with PD may benefit from continued use of sintilimab.


[Techniques to Identify Inter-segmental Planes].
There are several different approaches to identify inter-segmental planes in segmentectomy. Inflation-deflation lines can be made by inflating the lung after clumping or resecting the target bronchus, or inflate the target bronchus by jet ventilation, direct tubing, or applying a slip-knot. Indocyanine green can be injected intravenously after resecting or clumping the target pulmonary artery to identify the target segment under an infra-red thoracoscope. Indocyanine green can also be injected through a target bronchus. Virtual-assisted lung mapping (VAL-MAP) is a bronchoscopic multispot dye marking technique. Although VAL-MAP was developed to localize small pulmonary nodules, the multiple marks that provide geometric information on the lung enables application of VAL-MAP to segmentectomy, putting more emphasis on resection margins than accurate identification of intersegmental planes. As such, VAL-MAP is particularly useful in extended or complex segmentectomies. There are advantages and disadvantages in each method. The rapid progress of technology is likely to advance each method further. Taking these into consideration, surgeons need to choose an appropriate technique and possibly combination of these techniques to obtain optimal outcomes in segmentectomy.


The binding of human lysosomal elastase to glomerular basement membrane.
The interaction of purified elastase with glomerular basement membrane and its antigens was studied. There appears to be at least two types of interaction. The first is a weak interaction and the enzyme can be removed simply by extended washing with neutral buffer. The second, stronger interaction is desorbed with high salt concentration at alkaline pH. The different interactions probably represent the binding of isoenzymes. Further experiments demonstrate that all isoenzymes degrade the membrane. Serum proteins prevent binding and inhibit the action of elastase on glomerular basement membrane.


Flexibility of the coordination geometry around the cupric ions in Cu(II)-rat dipeptidyl peptidase III is important for the expression of enzyme activity.
Dipeptidyl peptidase III (DPP III), the zinc peptidase, has a unique helix portion in the metal-binding motif (HELLGH). The enzyme activity of the cupric derivative of rat DPP III (Cu(II)-rat DPP III) for Lys-Ala-β-NA is about 30% of that of the wild-type enzyme. On the other hand, the enzyme activity of Cu(II)-rat del-DPP III, in which Leu453 is deleted from the metal-binding motif, possesses only 1-2% of the enzyme activity of rat del-DPP III. The EPR spectra of Cu(II)-rat DPP III in the presence of various concentrations of the substrate, Lys-Ala-β-NA, changed dramatically, showing formation of the enzyme-metal-substrate complex. The EPR spectra of Cu(II)-rat del-DPP III did not change in the presence of excess Lys-Ala-β-NA. The deletion of Leu453 from the HELLGH motif of rat DPP III leads to a complete loss of flexibility in the ligand geometry around the cupric ions. Under the formation of the enzyme-metal-substrate complex, Glu451 of Cu(II)-rat DPP III is sufficiently able to approach the water molecule via a very different orientation from that of the resting state; however, Glu451 of Cu(II)-rat del-DPP III is not able to access the water molecule.


Neoadjuvant paradigm for accelerated drug development: an ideal model in bladder cancer.
Neoadjuvant cisplatin-based combination chemotherapy for muscle-invasive bladder cancer (MIBC) has been shown to confer a survival advantage in two randomized clinical trials and a meta-analysis. Despite level 1 evidence supporting its benefit, utilization remains dismal with nearly one-half of patients ineligible for cisplatin-based therapy because of renal dysfunction, impaired performance status, and/or coexisting medical problems. This situation highlights the need for the development of novel therapies for the management of MIBC, a disease with a lethal phenotype. The neoadjuvant paradigm in bladder cancer offers many advantages for accelerated drug development. First, there is a greater likelihood of successful therapy at an earlier disease state that may be characterized by less genomic instability compared with the metastatic setting, with an early readout of activity with results determined in months rather than years. Second, pre- and post-treatment tumor tissue collection in patients with MIBC is performed as the standard of care without the need for research-directed biopsies, allowing for the ability to perform important correlative studies and to monitor tumor response to therapy in "real time." Third, pathological complete response (pT0) predicts for improved outcome in patients with MIBC. Fourth, there is a strong biological rationale with rapidly accumulating evidence for actionable targets in bladder cancer. This review focuses on the neoadjuvant paradigm for accelerated drug development using bladder cancer as the ideal model.


Isolated subtalar dislocation.
Little attention has been devoted to subtalar dislocations without an associated bone injury in the literature to date. The aim of this study was to assess the functional and subjective results of a cohort of patients with this injury. A total of ninety-seven patients with a subtalar dislocation were treated at two major university trauma centers from January 1994 to March 2007. Computed tomographic scans indicated a subtalar dislocation without associated bone injury in twenty-three of these patients. Clinical and radiographic examinations were performed on all twenty-three patients at an average of 58.3 months after the completion of treatment. The postoperative clinical examination was supplemented by the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and the degree of arthritis was assessed radiographically. The average score on the AOFAS ankle-hindfoot scale score was 82.3 points. Twenty-one patients achieved a good result, and two patients had a satisfactory result. The range of motion of the subtalar joint was an average of 41.3 degrees. No difference between the results of the medial and lateral subtalar dislocations was observed. Only six patients had minor radiographic changes. The intermediate-term results for a subtalar dislocation without an associated osseous injury are good, and the direction of the dislocation does not appear to make a difference with regard to clinical or radiographic outcome.


Mars inflatable greenhouse analog.
Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design.


Transfusion-induced anergy: skin test as an index for pretransplant transfusions.
Cell-mediated immunity in vivo was studied by delayed cutaneous hypersensitivity (DCH) to seven antigens in 156 chronic haemodialysis (HD) patients, using a disposable multipuncture device. Anergy was found in 46.8 per cent of patients, and a positive correlation was seen between anergy and female sex, time on HD, glomerulonephritis as primary renal disease, younger age and previous blood transfusions (BT). The effect of BT on DCH was studied prospectively in 29 responsive patients. A significant decrease in DCH response was seen. The transfusion-induced anergy remained for a variable time. The pretransplant BT policy suggested by our data would be to periodically undertake skin tests and to transfuse only responsive patients, thereby avoiding the adverse effects of multiple BT.


Biopsy first: Lessons learned from Cancer and Leukemia Group B (CALGB) 140503.
Cancer and Leukemia Group B 140503 is an ongoing, multicenter randomized trial assessing whether sublobar resection is equivalent to lobectomy for the treatment of stage I A non-small cell lung cancer (NSCLC) ≤2 cm in diameter. The objective of this report is to determine the reasons precluding intraoperative randomization. From June 15, 2007, to March 22, 2013, 637 patients were preregistered to the trial. Three hundred eighty-nine were randomized successfully (61%), and 248 patients were not randomized (39%). We analyzed the reasons for nonrandomization among a subset of the nonrandomized patients (208) for whom additional data were available. Of these 208 patients, undiagnosed benign nodules (n =104, 16% of all registered patients) and understaging of NSCLC (n =45, 7% of all registered patients) were the dominant reasons precluding randomization. Granulomas represent one-quarter of the benign nodules. The understaged patients had unsuspected nodal metastases (n =28) or other more advanced NSCLC. The rate of randomization was significantly greater in those patients who had a preoperative biopsy (P <.001). In a carefully monitored cohort of patients with suspected small NSCLC ≤2 cm, a substantial number are misdiagnosed (benign nodules) or understaged. These patients may not have benefited from a thoracic surgical procedure. Preoperative biopsy significantly increased the rate of correct diagnosis. Preoperative biopsy of small suspected NSCLC will reduce the number of nontherapeutic or unnecessary thoracic procedures. Accuracy in preoperative diagnosis is increasingly important as more such small nodules are discovered through lung cancer screening.


Loss-of-function mutants and overexpression lines of the Arabidopsis cyclin CYCA1;2/Tardy Asynchronous Meiosis exhibit different defects in prophase-i meiocytes but produce the same meiotic products.
In Arabidopsis, loss-of-function mutations in the A-type cyclin CYCA1;2/Tardy Asynchronous Meiosis (TAM) gene lead to the production of abnormal meiotic products including triads and dyads. Here we report that overexpression of TAM by the ASK1:TAM transgene also led to the production of triads and dyads in meiosis, as well as shriveled seeds, in a dominant fashion. However, the partial loss-of-function mutant tam-1, an ASK1:TAM line, and the wild type differed in dynamic changes in chromosome thread thickness from zygotene to diplotene. We also found that the pericentromeric heterochromatin regions in male meiocytes in tam-1 and tam-2 (a null allele) frequently formed a tight cluster at the pachytene and diplotene stages, in contrast to the infrequent occurrences of such clusters in the wild type and the ASK1:TAM line. Immunolocalization studies of the chromosome axial component ASY1 revealed that ASY1 was highly expressed at the appropriate male meiotic stages but not localized to the chromosomes in tam-2. The level of ASY1, however, was greatly reduced in another ASK1:TAM line with much overexpressed TAM. Our results indicate that the reduction and increase in the activity of TAM differentially affect chromosomal morphology and the action of ASY1 in prophase I. Based on these results, we propose that either the different meiotic defects or a common defect such as missing ASY1 on the chromosomal axes triggers a hitherto uncharacterized cell cycle checkpoint in the male meiocytes in the tam mutants and ASK1:TAM lines, leading to the production of the same abnormal meiotic products.


No Clear Differences between Organic or Conventional Pig Farms in the Genetic Diversity or Virulence of Campylobacter coli Isolates.
To evaluate the impact of pig farm management on the genetic diversity and on the virulence of Campylobacter coli, we characterized isolates from 19 organic pig farms (62 isolates) and from 24 conventional pig farms (58 isolates). The 120 C. coli isolates were typed using pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) and the presence of nine virulence genes was screened using real-time PCR. The capacity of adhesion and invasion of 61 isolates (32 from organic and 29 from conventional farms) were then tested on human intestinal Caco-2 cells. A total of 59 PFGE types and of 50 sequence types (STs) were identified. Twelve PFGE types and nine STs, accounting for 34 and 41.6% of the isolates, respectively, were common between the two production systems with ST854 dominating (18.3% of the isolates). Twenty-nine PFGE types and 25 STs were only found in isolates from organic farms, and 18 PFGE types and 16 STs from conventional farms. No significant differences were found in diversity despite the differences in rearing systems, except at the locus level for the glnA, gltA, and uncA genes. All isolates, regardless of their origin, carried the ceuE, iam, ciaB, and flaA genes and more than 95% of the isolates carried the cadF and cdtABC genes. No significant differences were found in pathogenicity between the two farming systems. The pathogenicity of the C. coli isolates was low compared to C. jejuni control strains tested. The plasmid gene virb11 was detected in only 13 isolates from organic farms; these isolates showed greater invasion capacity than those without this gene. Our study indicates that pig farm management does not significantly affect the diversity and the virulence of Campylobacter coli isolated from pigs. The common genotypes between conventional and organic farms may indicate that some genotypes are adapted to pigs.


Explorations of Individual Change Processes and Their Determinants: A Novel Approach and Remaining Challenges.
Over the past 40 years there have been great advances in the analysis of individual change and the analyses of between-person differences in change. While conditional growth models are the dominant approach, exploratory models, such as growth mixture models and structural equation modeling trees, allow for greater flexibility in the modeling of between-person differences in change. We continue to push for greater flexibility in the modeling of individual change and its determinants by combining growth mixture modeling with structural equation modeling trees to evaluate how measured covariates predict class membership using a recursive partitioning algorithm. This approach, referred to as growth mixture modeling with membership trees, is illustrated with longitudinal reading data from the Early Childhood Longitudinal Study with the MplusTrees package in R.


The impact of unacceptable wait time on health care patients' attitudes and actions.
A great deal of time is spent by patients waiting for health care services in doctors' offices. The literature points to a negative impact of wait time on patients' perceptions of health care services, and on patients' subsequent behavior. A survey of 200 patients suggests wait time affects perceptions of quality, satisfaction and likeability, as well as likelihood of recommendations and repeat visits. In addition, response to unacceptable wait time was found to be significantly related to income. These findings indicate a cultural shift in patients' perceptions of wait time, and underline the need for providers to retain patients' loyalty through more timely service.


Metasurface cutoff perfect absorber in a solar energy wavelength band.
We report a metasurface cutoff perfect absorber (MCPA) in the solar energy wavelength band based on the double Mie resonances generated from the silicon and gallium arsenide nanoring arrays grown on the Al layer in the solar energy wavelengths. A high average absorption of 0.910 in the absorption band and almost eliminated absorption in the nonabsorption band are realized within only 120 nm thick structures. The MCPA is of a sharp cutoff between the absorption and nonabsorption band, whose extinction ratio, extinction difference, and cutoff slope are 9.4 dB, 0.8, and 0.0019n m -1, respectively. The proposed MCPA suggests an efficient way to design a solar thermal absorber, which is of great importance in renewable energy, such as for solar thermal applications.


Evolutionary dynamics on networks of selectively neutral genotypes: effects of topology and sequence stability.
Networks of selectively neutral genotypes underlie the evolution of populations of replicators in constant environments. Previous theoretical analysis predicted that such populations will evolve toward highly connected regions of the genome space. We first study the evolution of populations of replicators on simple networks and quantify how the transient time to equilibrium depends on the initial distribution of sequences on the neutral network, on the topological properties of the latter, and on the mutation rate. Second, network neutrality is broken through the introduction of an energy for each sequence. This allows to study the competition between two features (neutrality and energetic stability) relevant for survival and subjected to different selective pressures. In cases where the two features are negatively correlated, the population experiences sudden migrations in the genome space for values of the relevant parameters that we calculate. The numerical study of larger networks indicates that the qualitative behavior to be expected in more realistic cases is already seen in representative examples of small networks.


Chemokines in innate and adaptive granuloma formation.
Granulomas are cellular inflammations that vary widely in histologic appearance depending upon the inciting agent and immunologic status of the responding host. Despite their heterogeneity, granulomas are at their core an ancient innate sequestration response characterized by the accumulation of mononuclear phagocytes. In fact, this innate cellular response was first observed by Metchnikov in simple invertebrates. Among higher vertebrates, environmental pressures have resulted in the evolution of more sophisticated adaptive immune responses which can be superimposed upon and modify the character of granulomatous inflammation. Compared to immune responses that rapidly neutralize and eliminate infectious agents, the granuloma represents a less desirable "fall back" response which still has value to the host but can be co-opted by certain infectious agents and contribute to bystander organ damage. Understanding granulomas requires an analysis of the complex interplay of innate and adaptive molecular signals that govern the focal accumulation and activity of their cellular components. Among these signals, small molecular weight chemoattractant proteins known as chemokines are potentially important contributors as they participate in both directing leukocyte migration and function. This tract will discuss the contribution of chemokines to the development of innate and adaptive granuloma formation, as well as describe their relationship to more recently evolved cytokines generated during adaptive immune responses.


Structural models for the protein family characterized by gamete surface protein Pfs230 of Plasmodium falciparum.
Ps230 is the largest representative of a 10-member family of proteins found in all Plasmodium species. The family is defined by partially conserved, cysteine-rich double domains that are approximately 350 aa in length and have one to three predicted disulfide bridges in each half. In Plasmodium falciparum, the most dangerous human malaria, Pf12 is the smallest member of the family, comprising just one double domain. Pfs230, with 7 double domains, and Pfs48/45 and Pfs47, with 1.5 double domains each, are found on the gamete surfaces and are thus potential candidates for a transmission-blocking vaccine. Fold prediction analyses of the double domains in Pfs230 reveal structural resemblance to SAG1 (surface antigen 1), a surface protein with a double beta-sandwich structure from another apicomplexan parasite, Toxoplasma gondii. Template-directed modeling onto SAG1 clearly establishes the structural link between SAG1 and Pfs230 and produces positions for the cysteines that accord with the disulfide-bonding arrangement predicted for the Pfs230 family in earlier work. A highly clustered region of polymorphisms within the second double domain in Pfs230 maps to one side of the sandwich surface. This observation suggests that this region may be functional and reinforces the validity of these molecular models for the core domains of the Pfs230 family of proteins.


ISG15 Modulates Type I Interferon Signaling and the Antiviral Response during Hepatitis E Virus Replication.
Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals, especially in solid-organ transplant recipients. Innate immunity, via the type I interferon (IFN) response, plays an important role during the initial stages of a viral infection. IFN-stimulated gene 15 (ISG15), an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role and can have a direct antiviral effect on a wide spectrum of virus families. In the present study, we investigated the antiviral effect as well as the potential immunomodulatory role of ISG15 during HEV replication. The results revealed that HEV induced high levels of ISG15 production both in vitro (Huh7-S10-3 liver cells) and in vivo (liver tissues from HEV-infected pigs); however, ISG15 is not required for virus replication. We also demonstrated that ISG15 silencing potentiates enhanced type I IFN-mediated signaling, resulting in an increase in the type I IFN-mediated antiviral effect during HEV replication. This observed enhanced type I IFN signaling correlated with an increase in IFN-stimulated gene expression levels during HEV replication. Furthermore, we showed that PKR and OAS1 played important roles in the ISG15-mediated type I IFN sensitivity of HEV. Taken together, the results from this study suggest that ISG15 plays an important immunomodulatory role and regulates HEV sensitivity to exogenous type I IFN.IMPORTANCE Hepatitis E virus (HEV) infection typically causes self-limiting acute viral hepatitis. However, chronic HEV infection has recently become a significant clinical problem in immunocompromised patients. Pegylated interferon (IFN) has been used to treat chronic HEV infection in solid-organ transplant patients with some success. However, the mechanism behind the type I IFN-mediated antiviral effect against HEV remains unclear. This report demonstrates that ISG15 induced by HEV replication in Huh7-S10-3 human liver cells plays an immunomodulatory role by negatively regulating type I IFN signaling and, thus, HEV sensitivity to type I IFN. Our results also show that PKR and OAS1 play important roles in the ISG15-mediated type I IFN sensitivity of HEV.


Molecular targets for anti-oxidative protection of green tea polyphenols against myocardial ischemic injury.
Ischemic heart disease is the leading cause of death worldwide. An improved understanding of the mechanisms involved in myocardial injury would allow intervention downstream in the pathway where certain drugs including natural products could be efficiently applied to target the end effectors of the cell death pathway. Green tea polyphenols (GTPs) have potent anti-oxidative capabilities, which may account for their beneficial effects in preventing oxidative stress associated with ischemia injury. Although studies have provided convincing evidence to support the protective effects of GTPs in cardiovascular system, the potential end effectors that mediate cardiac protection are only beginning to be addressed. Proteomics analyses widely used to identify the protein targets for many cardiovascular diseases have advanced the discovery of the signaling mechanism for GTPs-mediated cardio-protection. This review focuses on putative triggers, mediators, and end effectors for the GTPs-mediated cardio-protection signaling pathways engaged in myocardial ischemia crisis, allowing a promising natural product to be used for ameliorating oxidative stress associated with ischemic heart diseases.


Relation between lateralization and loudness in asymmetrical hearing losses.
The purpose of these experiments was to study the role of interaural intensity and loudness differences in median-plane lateralization. Observers who either wore an earplug in one ear or had an asymmetrical hearing loss varied the intensity of simultaneous tone bursts at the two ears to center a sound image inside their heads. Hard-of-hearing Ss with conductive and cochlear losses centered the tone bursts by setting them somewhere between equal intensity and equal loudness at the two ears. Although Ss with the simulated loss first centered the tones on the basis of equal loudness, after several days of wearing the ear plug, they centered in the same manner as observers with long-term hearing losses.


An effect of continuous contextual filling in the filled-space illusion.
In the filled-space (or Oppel-Kundt) illusion, the filled part of the stimulus for most observers appears longer in comparison with the empty one. In the first two experimental series of the present study, we investigated the illusory effect as a function of continuous filling (by a shaft-line segment) of the reference spatial interval of the three-dot stimulus. It was demonstrated that for the fixed length of the reference interval, the magnitude of the illusion increases non-linearly with the shaft length. For the fixed length of the shaft, the illusion magnitude gradually decreases with the lengthening of the reference interval. In the third series, psychophysical examination of the conventional Oppel-Kundt stimulus with different number of equally spaced elements (dots) subdividing its filled part was performed. Based on the analysis of the functional dependencies established, we have proposed a simple computational model that was successfully applied to fit the experimental data obtained in the present study.


Comprehensive analysis of competitive endogenous RNAs network: Identification and validation of prediction model composed of mRNA signature and miRNA signature in gastric cancer.
Gastric cancer (GC), one of the most lethal malignant tumors, is highly aggressive with a poor prognosis, while the molecular mechanisms underlying it remain largely unknown. Although advanced imaging techniques and comprehensive treatment facilitate the diagnosis and survival of some GC patients, the precise diagnosis and prognosis are still a challenge. The present study used publicly available gene expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus datasets including mRNA, micro (mi)RNA and circular (circ)RNA of GC to establish a competing endogenous RNA network (ceRNA). Further, the present study performed least absolute shrinkage and selector operator regression analysis on the hub RNAs to establish a prediction model with mRNA and miRNA. The ceRNA network contained 109 edges and 56 nodes and the visible network contains 13 miRNAs, 9 circRNAs and 34 mRNAs. The five mRNA-based signature were CTF1, FKBP5, RNF128, GSTM2 and ADAMTS1. The area under curve (AUC) value of the diagnosis training cohort was 0.9975. The prognosis of the high-risk group (RiskScore >4.664) was worse compared with that of the low-risk group (RiskScore ≤4.664; P<0.05) in the training cohort. The five miRNA-based signature were miR-145-5p, miR-615-3p, miR-6507-5p, miR-937-3p and miR-99a-3p. The AUC value of the diagnosis training cohort was 0.9975. The prognosis of the high-risk group (RiskScore >1.621) was worse compared with that of the low-risk group (RiskScore ≤1.621; P<0.05) in the training cohort. The validation cohorts indicated that both five mRNA and five miRNA-based signatures had strong predictive power in diagnosis and prognosis for GC. In conclusion, a ceRNA network was established for GC and a five mRNA-based signature and a five miRNA-based signature was identified that enabled diagnosis and prognosis of GC by assigning patient to a high-risk group or low-risk group.


Molecular signaling pathways regulating muscle proteolysis during atrophy.
Although a variety of diverse stimuli induce muscle atrophy, there is a surprising number of similarities in the intracellular responses. One prominent response is an increase in muscle proteolysis resulting from stimulation of the ubiquitin-proteasome pathway. Understanding the intracellular signaling pathways that regulate muscle mass should offer insights into the coordination of cellular responses. This review will discuss recent findings on the molecular signaling pathways regulating proteolysis during muscle atrophy. The expression of several muscle-specific E3 ubiquitin ligases is consistently increased in conditions causing muscle atrophy. Insulin and insulin-like growth factor-1 act through the phosphoinositide 3-kinase/AKT pathway to suppress the expression of two of these enzymes, MuRF1 and MAFbx/atrogin-1. Efforts to identify targets of the muscle-specific E3 ligases are yielding interesting information. Insulin and insulin-like growth factor-1 also attenuate wasting by inhibiting caspase-3, which cleaves actin to facilitate its destruction by the ubiqutin-proteasome system. Other signaling systems involved in the regulation of muscle mass include the nuclear factor kappa B pathway. The maintenance of muscle mass requires a delicate balance between catabolic factors and anabolic factors. These signals inversely modulate the activity of several key regulatory pathways including the phosphoinositide-3 kinase/AKT and nuclear factor kappa B systems, which control the transcription of components of the ubiquitin-proteasome proteolytic pathway activity, the activity of caspase-3, and perhaps other proteolytic functions. When levels of insulin or insulin-like growth factor-1 are insufficient or inflammatory cytokine production is increased, muscle atrophy ensues.


Hyperacute Cutibacterium acnes Endophthalmitis Following Cataract Surgery.
Postoperative endophthalmitis is a relatively uncommon, but potentially visually devastating, complication associated with cataract surgery. Specific microbial causes of endophthalmitis are characteristically associated with particular disease time courses. Though Cutibacterium acnes is typically associated with an indolent course of inflammation, we report a case of C. acnes endophthalmitis with onset on postoperative day (POD) 1 and a positive culture from POD 2. Case report. A 56-year-old man underwent cataract extraction and posterior chamber intraocular lens placement in his left eye. On POD 1, he presented with severe discomfort, reduced visual acuity, and significant inflammation. On POD 2, his anterior chamber was tapped and injected with broad-spectrum antibiotics and steroids. The inflammation ultimately resolved, and his visual acuity improved to 20/20. C. acnes is a rare cause of hyperacute onset postoperative endophthalmitis. Maintaining a high clinical suspicion and initiating prompt treatment can help to optimize long-term visual outcomes.


Workplace support and affirming behaviors: Moving toward a transgender, gender diverse, and non-binary friendly workplace.
Background: The experiences of transgender, gender diverse, and non-binary (TGDNB) workers remain poorly understood and under-examined in the extant literature, with workplace support perceptions and affirming behaviors of these workers particularly misunderstood. Aims: We address this gap in the literature by presenting and empirically testing a theoretical model that suggests affirming behaviors are differentially related to various sources of TGDNB worker support. We further suggest these sources of support are differentially related to TGDNB employee satisfaction and gender identity openness at work. Methods: We collected data from trans-related social media groups, inviting TGDNB-identifying employees to participate in the study. Quantitative and qualitative data from 263 TGDNB employees were collected through survey administrations. Results: Supervisor and coworker support are related to job and life satisfaction, with supervisor support strongly connected to job satisfaction. The use of gender-affirming pronouns/titles and discouraging derogatory comments at work were related to perceived TGDNB support. Positive transgender organizational climate was strongly related to gender identity openness at work. Discussion: Results highlight a need for better workplace inclusivity and TGDNB-friendly environments, as well as more diversity training and company policy improvements that directly impact the workplace experiences of TGDNB people.


A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi.
We cloned an aquaporin gene from Trypanosoma cruzi (TcAQP) that encodes a protein of 231 amino acids, which is highly hydrophobic. The protein has six putative transmembrane domains and the two signature motifs asparagine-proline-alanine (NPA) which have been shown, in other aquaporins, to be involved in the formation of an aqueous channel spanning the bilayer. TcAQP was sensitive to endo H treatment, suggesting that the protein is N-glycosylated. Oocytes of Xenopus laevis expressing TcAQP swelled under hyposmotic conditions indicating water permeability, which was abolished after preincubating oocytes with very low concentrations of the AQP inhibitors HgCl(2) and AgNO(3). glycerol transport was detected. No Immunofluorescence microscopy of T. cruzi expressing GFP-TcAQP showed co-localization of TcAQP with the vacuolar proton pyrophosphatase (V-H(+)-PPase), a marker of acidocalcisomes. This localization was confirmed by Western blotting and immunofluorescence staining using polyclonal antibodies against a C-terminal peptide of TcAQP. In addition, there was a strong anterior labeling in a vacuole, close to the flagellar pocket, that was distinct from the acidocalcisomes and that was identified by immunogold electron microscopy as the contractile vacuole complex. Taking together, the presence of an aquaporin in acidocalcisomes and the contractile vacuole complex of T. cruzi, provides support for the role of these organelles in osmotic adaptations of these parasites.


Measured sodium excretion is associated with CKD progression: results from the KNOW-CKD study.
Diet is a modifiable factor of chronic kidney disease (CKD) progression. However, the effect of dietary salt intake on CKD progression remains unclear. Therefore, we analyzed the effect of dietary salt intake on renal outcome in Korean patients with CKD. We measured 24-h urinary sodium (Na) excretion as a marker of dietary salt intake in the prospective, multi-center, longitudinal KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD). Data were analyzed from CKD patients at Stages G3a to G5 (n = 1254). We investigated the association between dietary salt intake and CKD progression. Patients were divided into four quartiles of dietary salt intake, which was assessed using measured 24-h urinary Na excretion. The study endpoint was composite renal outcome, which was defined as either halving the estimated glomerular filtration rate or developing end-stage renal disease. During a median (interquartile range) follow-up of 4.3 (2.8-5.8) years, 480 (38.7%) patients developed the composite renal event. Compared with the reference group (Q2, urinary Na excretion: 104.2 ≤ Na excretion < 145.1 mEq/day), the highest quartile of measured 24-h urinary Na excretion was associated with risk of composite renal outcome [Q4, urinary Na excretion ≥192.9 mEq/day, hazard ratio 1.8 (95% confidence interval 1.12-2.88); P = 0.015] in a multivariable hazards model. Subgroup analyses showed that high-salt intake was particularly associated with a higher risk of composite renal outcome in women, in patients <60 years of age, in those with uncontrolled hypertension and in those with obesity. High salt intake was associated with increased risk of progression in CKD.


Surgical pitfalls in cochlear implantation.
Increasing experience with cochlear implantation has led to the identification of potential surgical pitfalls: improper patient selection, poor flap design and handling, facial nerve injury, improper electrode placement, and improper seating of the receiver stimulator. Each of these areas of potential difficulty are reviewed, emphasizing methods of avoidance and management of adverse outcome.


Greenhouse evaluation of struvite and sludges from municipal wastewater treatment works as phosphorus sources for plants.
Sewage sludge obtained by a conventional aerobic activated sludge process (CSS), P-rich sewage sludge from an enhanced biological P removal process (PRS), and struvite (MgNH 4PO 4 x 6H 2O) recovered from an anaerobic digester supernatant using a low-grade MgO byproduct from the calcination of natural magnesite as a Mg source (STR) were evaluated as P sources for plant growth. For this purpose, a greenhouse pot experiment was conducted using a P-deficient loamy sand soil and perennial ryegrass ( Lolium perenne L.) as the test crop. The P sources were applied at rates equivalent to 0, 9, 17, 26, 34, and 44 mg/kg P. Single superphosphate (SUP) was used as reference for comparison with the other P sources. The results obtained indicated that STR was as effective as SUP in increasing the dry matter yield and supplying P to ryegrass. Compared to SUP and STR, PRS and especially CSS exhibited less agronomic effectiveness as P sources, which may be attributed, at least partially, to greater soil P fixation because of the larger amount of Fe incorporated with these materials.


The role of aging upon β cell turnover.
Preservation and regeneration of β cell endocrine function is a long-sought goal in diabetes research. Defective insulin secretion from β cells underlies both type 1 and type 2 diabetes, thus fueling considerable interest in molecules capable of rebuilding β cell secretion capacity. Though early work in rodents suggested that regeneration might be possible, recent studies have revealed that aging powerfully restricts cell cycle entry of β cells, which may limit regeneration capacity. Consequently, aging has emerged as an enigmatic challenge that might limit β cell regeneration therapies. This Review summarizes recent data regarding the role of aging in β cell regeneration and proposes models explaining these phenomena.


Recurrent impetigo herpetiformis successfully treated with methotrexate: a case report.
Impetigo herpetiformis is a rare disease and its occurrence is specific for pregnancy. The lesions are characterized by sterile, pustular eruptions. The disorder is usually seen in the third trimester, but cases of impetigo herpetiformis appearing in the first trimester have also been reported. The lesions are expected to disappear after birth, but the disorder may recur during subsequent pregnancies. In this case report we discuss a 28-year-old pregnant woman, G3P1011, with a history of impetigo herpetiformis in the first pregnancy, who presented with generalized pustular lesions at 30 weeks' gestation. Her disease responded poorly to corticosteroids and was more severe than in the previous pregnancy. She delivered prematurely at 34 weeks' gestation and then received aggressive postpartum treatment with methotrexate, resulting in a dramatic response. This case supports the current understanding that recurrent impetigo herpetiformis in subsequent pregnancy tends to be more severe and to have an earlier onset. Additionally, it provides additional evidence that methotrexate may be used as an alternative treatment for impetigo herpetiformis in the case of a poor response to corticosteroids.


[Case of facial edema and tongue swelling after aortic surgery in the lateral position].
The facial edema and tongue swelling after oral surgery are not rare complications and many case reports were published, but they were limited after anesthesia for surgery of other parts. A 70-year-old woman who had underwent thoraco-abdominal aortic graft surgery showed severe facial edema and tongue swelling after the surgery in the right lateral position. The tongue was largely protruded outside of the mouse when entering ICU and was gradually improved. Twelve hours later, the tongue was shrunken into the mouse. The patient was moved to a general ward without any complications on the 5th postoperative day. The patient had taken anti-hypertensive drugs including candesartan for a long period. She might have become susceptible to angioedema by angiotensin receptor blocker such as angiotensin-converting enzyme inhibitor and stress of surgery, and anesthesia might have induced a complication of the acute tongue swelling. Although, prevention and treatment of angioedema have not been established, careful observation would be required.


Measurements of pelvic floor dyssynergia: which test result matters?
Failure to expel a 60-mL balloon on manometry and abnormal relaxation of anal sphincter on electromyographic testing are frequently used to diagnose pelvic floor dyssynergia. However, the relationship between these 2 test results and their relationship to defecography is poorly characterized. We aimed to describe this relationship and create a predictive model for pelvic floor dyssynergia on defecography. From March 2008 to April 2010 consecutive patients with symptoms suggestive of functional constipation were evaluated at our Pelvic Floor Disorders Center 125 and the results of their workups were collected prospectively. Sixty-three patients with pelvic floor dyssynergia on defecography were compared with 60 patients without dyssynergia in terms of manometry pressures, electromyographic text results, and balloon expulsion testing results (χ, t tests). Of 125 patients meeting Rome II symptom criteria for constipation, 123 patients underwent defecography and, of these, 63 (51.2%) had evidence of pelvic floor dyssynergia. Patients with and without dyssynergia had a slight difference in mean resting pressures (62.8 mmHg vs 49.5 mmHg, P = .02) and no discernable differences in rectal sensitivity and compliance: first sensation (56.5 vs 62.5, P = .34) and maximum tolerated volume (164.2 vs 191.2, P = .09). It appeared that abnormalities in electromyographic relaxation and balloon expulsion occurred in the same patients: 84.1% of patients with abnormal electromyographic results also did not expel the balloon. However, the presence of these abnormalities, in isolation or together, did not predict the presence of dyssynergia on defecography. Normal electromyographic results or the ability to expel a 60-mL balloon does not exclude the presence of pelvic floor dyssynergia on defecography. It is unclear which of these 3 tests should be used to guide the recommendation for (and to then measure response to) biofeedback.


Metabolomic charactetization of yeast cells after dehydration stress.
In this study, we analyzed the metabolite features of the yeasts Saccharomyces cerevisiae, Naumovia castellii, and Saccharomyces mikatae. The three species are closely related genetically but differ in their tolerance of desiccation stress. Specifically, we determined whether certain metabolites correlated with cell viability after stress imposition. The metabolomics profiles of these strains were compared before cell desiccation and after cell rehydration. In S. mikatae, the presence of lysine or glutamine during rehydration led to a 20% increase in survival whereas during dehydration the levels of both amino acids in this yeast were drastically reduced.


[Interatrial communication in patients over 40 years of age].
Surgical treatment of atrial septal defect in patients older than 40 years is a subject of controversy. We compared the outcome in patients medically treated after the age of 40, with the long-term outcome in a similar group of patients after surgical closure. We conclude that surgical closure was superior to medical treatment. According to our results, surgical treatment must be performed as soon as possible, even if the symptoms of the functional status seem to be minimal.


Alterations of gut microbiota in a mouse model with partial small intestinal obstruction.
Changes in the gut microbiota of patients with partial small intestinal obstruction (PSIO) have not been widely clarified. We aimed to explore bacterial diversity in a PSIO mouse model. A PSIO mouse model was established using male C57BL/6 mice, and feces samples from the distal ileum and ileum epithelium tissues were collected. MiSeq sequencing of the 16S rRNA gene was conducted to characterize microbiota diversity and composition. RNA sequencing for differences in transcriptomic programming of the ileum tissue was performed between the PSIO and (Control) Ctrl groups. Bacterial diversity in the PSIO group was significantly lower than that in the controls. Pseudomonadota was predominant in the feces of the PSIO group. Unclassified_Muribaculaceae (p = 0.008) and Akkermansia (p = 0.007) were more abundant in the Ctrl group than those in the PSIO group. Furthermore, Escherichia_Shigella (p = 0.008) was more predominant in the feces of the PSIO group. The Kyoto Encyclopedia of Genes and Genomes pathways related to metabolism were depleted in the PSIO group. Pathways associated with intestinal fibrosis, including extracellular matrix-receptor interaction, focal adhesion, phosphoinositide 3-kinase (PI3K)-Akt signaling pathway and transforming growth factor (TGF)-beta signaling pathway, which were enriched in ileum epithelial tissue in the PSIO group. PSIO can lead to changes in the predominant intestinal bacterial groups. Depleted functional profiles of the gut microbiota were identified in the PSIO group. Functional pathways associated with intestinal fibrosis were activated by PSIO. The potential regulation by the microbiota needs to be explored in the future.


Electromagnetic Trihybrid Ellis Nanofluid Flow Influenced with a Magnetic Dipole and Chemical Reaction Across a Vertical Surface.
The purpose of this study is to evaluate the augmentation of thermal energy transfer in trihybrid Ellis nanofluid flow in the occurrence of magnetic dipole passes over a vertical surface. The ternary hybrid nanofluid is prepared by the dispersion of ternary nanoparticles (Al2O3, SiO2, and TiO2) in the Carreau Yasuda fluid. The velocity and heat transportation has been examined in the existence of the Darcy Forchhemier influence and heat source/sink. The phenomena of fluid flow have been mathematically designed for energy and fluid velocity in the form of a nonlinear partial differential equation (PDE)-based system. The system of PDEs is further refined to the set of ordinary differential equations via suitable similarity substitutions. The acquired dimensionless equations are numerically solved with the help of the HAM. It has been noticed that the energy contour is enhanced versus the variation of viscous dissipation and heat generation. A significant contribution of a magnetic dipole is observed to elevate the production of the thermal energy field, and an opposite trend is noticed versus the flow profile. The accumulation of Al2O3, SiO2, and TiO2 nanomaterials in the base fluid "engine oil" improves the velocity and energy profiles.


Combining serotonin reuptake inhibitors and bupropion in partial responders to antidepressant monotherapy.
Many patients with affective illness show partial or otherwise unsatisfactory responses to standard treatments, encouraging trials of combinations of pharmacologically dissimilar antidepressants. Records of consecutive outpatients with affective disorders only partially responsive to treatment with a serotonin reuptake inhibitor (SRI) or bupropion, alone, were reviewed for changes in specific symptoms and risks of adverse events when an SRI and bupropion were combined. Greater symptomatic improvement was found in 19 (70%) of 27 subjects during a mean +/- SD of 11 +/- 14 months of combined daily use of bupropion (243 +/- 99 mg) with an SRI (31 +/- 16 mg fluoxetine-equivalents) than with either agent alone. Adverse effect risks were similar to those associated with each monotherapy, with a > 10% incidence of sexual dysfunction (N = 11, 41%), insomnia (N = 6, 22%), anergy (N = 4, 15%), and tremor (N = 3, 11%) during combined therapy; there were no seizures. With conservative dosing and close monitoring, combinations of SRIs with bupropion in this uncontrolled clinical series appeared to be safe and often more effective than monotherapy.


Biochemical properties of V91G calmodulin: A calmodulin point mutation that deregulates muscle contraction in Drosophila.
A mutation (Cam7) to the single endogenous calmodulin gene of Drosophila generates a mutant protein with valine 91 changed to glycine (V91G D-CaM). This mutation produces a unique pupal lethal phenotype distinct from that of a null mutation. Genetic studies indicate that the phenotype reflects deregulation of calcium fluxes within the larval muscles, leading to hypercontraction followed by muscle failure. We investigated the biochemical properties of V91G D-CaM. The effects of the mutation on free CaM are minor: Calcium binding, and overall secondary and tertiary structure are indistinguishable from those of wild type. A slight destabilization of the C-terminal domain is detectable in the calcium-free (apo-) form, and the calcium-bound (holo-) form has a somewhat lower surface hydrophobicity. These findings reinforce the indications from the in vivo work that interaction with a specific CaM target(s) underlies the mutant defects. In particular, defective regulation of ryanodine receptor (RyR) channels was indicated by genetic interaction analysis. Studies described here establish that the putative CaM binding region of the Drosophila RyR (D-RyR) binds wild-type D-CaM comparably to the equivalent CaM-RyR interactions seen for the mammalian skeletal muscle RyR channel isoform (RYR1). The V91G mutation weakens the interaction of both apo- and holo-D-CaM with this binding region, and decreases the enhancement of the calcium-binding affinity of CaM that is detectable in the presence of the RyR target peptide. The predicted functional consequences of these changes are consonant with the in vivo phenotype, and indicate that D-RyR is one, if not the major, target affected by the V91G mutation in CaM.


Effect of angiotensin-converting enzyme inhibition on survival in 3773 Chinese type 2 diabetic patients.
We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on survival and cardiorenal outcomes in a consecutive cohort of Chinese type 2 diabetic patients with varying degree of albuminuria, ranging from normoalbuminuria to macroalbuminuria. A total of 3773 consecutive Chinese type 2 diabetic patients were followed prospectively for a mean period of 35.8 months. Clinical end points included all-cause mortality, with cardiovascular end point defined as first hospitalization because of ischemic heart disease, congestive heart failure, revascularization procedures, or cerebrovascular accident as well as renal end point defined as dialysis, doubling of baseline plasma creatinine, or plasma creatinine > or =500 micromol/L. The use of ACE inhibitor was 26.3% in normoalbuminuric (NA), 70.1% in microalbuminuric (MI), and 82.6% in macroalbuminuric (MA) groups. Albuminuria was a major predictor for all-cause mortality with 4-fold difference between NA and MA patients. The 7-year cumulative mortality rate was 7.1%, 10.8%, and 21.7% in the NA, MI, and MA groups, respectively. The use of ACE inhibition was associated with significant reduction of mortality (hazard ratio 0.41 and 95% confidence interval, 0.29, 0.58) in the entire group and was most evident in high-risk patients who had cardiorenal complications or retinopathy at baseline for all albuminuric groups (NA 0.76 [0.31,1.87]; MI 0.32 [0.16, 0.65]; and MA 0.20 [0.13, 0.33]). The prognostic value of albuminuria for death in type 2 diabetes and the beneficial effects of ACE inhibitors in Chinese type 2 diabetic patients with micro- or macroalbuminuria has been confirmed. The effects of ACE inhibitors in type 2 diabetic patients with normoalbuminuria require further evaluation.


Adenosine triphosphate/adenosine guided pulmonary vein isolation does not improve the outcomes of ablation: a meta-analysis of randomized controlled trials.
Successful pulmonary vein isolation (PVI) is the most reliable predictor of success after ablation in patients with atrial fibrillation (AF). Adenosine triphosphate (ATP) unmasks the dormant conduction and can be used to improve the effectiveness of PVI. The impact of ATP guided PVI on clinical outcomes is discordant in various randomized controlled trials (RCTs). To delineate the incremental benefit of ATP during PVI in patients with AF through a meta-analysis. Database searches through January 2017 identified 5 RCTs (enrolling 2839 patients) comparing ATP guided PVI versus standard PVI (non-ATP). Four trials exclusively studied paroxysmal AF while one trial included both paroxysmal and non-paroxysmal AF patients. Baseline characteristics, dose of adenosine and ablation strategies were clearly identified among all the trials. The risk ratio (RR) for AF episodes lasting >30 s after 3-month blanking period was calculated with random effects meta-analysis and showed no difference at a median follow up of 12 months [RR: 1.02, 95 % Confidence interval (CI): 0.85 to 1.25; p = 0.82]. Similarly, the number of repeat ablation was similar in both groups [RR: 1.02, 95 % CI: 0.63, 1.56; p = 0.98]. ATP guided PVI does not decrease the recurrence of AF or the need for repeat ablation at 12 months.


[Surgical therapy of the dissection of the ascending aorta. Experience in the use of the G. R. F. biological glue].
Nine patients with dissecting aneurysm of the ascending aorta (type A dissection) were operated upon. Six cases had an acute dissection, whereas three cases had a chronic type of dissection. The ascending aorta was replaced with a Dacron tubular prosthesis after solidification of the external and the internal layers of the two aortic stumps using a G.R.F. biological glue. Early and late results as well as the possible complications during the post-operative course are reported. Furthermore the advantages in using the G.R.F. glue are discussed in details. They are mainly represented by the excellent solidification of the aortic stumps, by the possibility to correct the aortic regurgitation without valve replacement and particularly by a good hemostasis of the surgical sutures.


[The clinical value of Holter ECG recording].
The Holter ECG is a well established clinical tool to document intermittent arrhythmias. The main indications are palpitations and syncope. However, the occurrence of these events during 24 h recording is very rare. So, it is often a matter of definition, what findings can speculatively "explain" a syncope. Therefore, an event recorder is often more successful. In addition, in patients with organic heart disease and reduced left ventricular function invasive electrophysiologic testing may be more appropriate. In these cases prophylactic implantation of an ICD may be indicated to prevent sudden death. So, in many instances the clinical value of Holter recording is overestimated.


Indian food ingredients and cancer prevention - an experimental evaluation of anticarcinogenic effects of garlic in rat colon.
The major food items of Indian cuisine include rice, wheat, diary products, and abundant fruits and vegetables. Beside these, there are several kinds of herbs and spices as important ingredients, containing many phytochemicals with medicinal properties, adding taste to Indian cuisine. An impressive body of data exists in support of the concept that Indian food ingredients can be used in preventive strategies aimed at reducing the incidence and mortality of different types of cancers because of their antioxidative, antimutagenic and anticarcinogenic properties. Vital ingredients used in Indian cooking include turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic Garlic is an indispensable ingredient of Indian food and this report concerns the chemopreventive efficacy of garlic in an azoxymethane induced rodent colon carcinogenesis model. The effect of garlic was evaluated in terms of aberrant crypt foci, putative preneoplastic lesions in the colon. In addition, cell proliferation and levels of apoptosis were determined and the expression of cyclooxygenase-2 protein was analyzed. Following treatment, significant inhibition of cell proliferation and induction of apoptosis, as well as suppression of cyclooxygenase-2 activity were observed, associated with significant reduction in the incidence of aberrant crypt foci. The study points to combined protective effects of garlic components on colon carcinogenesis.


Stiffness optimization and reliable design of a hip implant by using the potential of additive manufacturing processes.
Due to the steadily increasing life expectancy of the population, the need for medical aids to maintain the previous quality of life is growing. The basis for independent mobility is a functional locomotor system. The hip joint can be so badly damaged by everyday wear or accelerated by illness that reconstruction by means of endoprostheses is necessary. In order to ensure a high quality of life for the patient after this procedure as well as a long service life of the prosthesis, a high-quality design is required, so that many different aspects have to be taken into account when developing prostheses. Long-term medical studies show that the service life and operational safety of a hip prosthesis by best possible adaptation of the stiffness to that of the bone can be increased. The use of additive manufacturing processes enables to specifically change the stiffness of implant structures. Reduced implant stiffness leads to an increase in stress in the surrounding bone and thus to a reduction in bone resorption. Numerical methods are used to demonstrate this fact in the hip implant developed. The safety of use is nevertheless ensured by evaluating and taking into account the stresses that occur for critical load cases. These results are a promising basis to enable longer service life of prostheses in the future.


Prospective Multicenter Feasibility Study of Laparoscopic Sentinel Basin Dissection after Endoscopic Submucosal Dissection for Early Gastric Cancer: SENORITA 2 Trial Protocol.
Although standard radical gastrectomy is recommended after noncurative resection of endoscopic submucosal dissection (ESD) for early gastric cancer in most cases, residual tumor and lymph node metastasis have not been identified after surgery. The aim of this study is to evaluate the feasibility of sentinel node navigation surgery after noncurative ESD. This trial is an investigator-initiated, multicenter prospective phase II trial. Patients who underwent ESD for clinical stage T1N0M0 gastric cancer with noncurative resections were eligible. Qualified investigators who completed the prior phase III trial (SENORITA 1) are exclusively allowed to participate. In this study, 2 detection methods will be used: 1) intraoperative endoscopic submucosal injection of dual tracer, including radioisotope and indocyanine green (ICG) with sentinel basins detected using gamma-probe; 2) endoscopic injection of ICG, with sentinel basins detected using a fluorescence imaging system. Standard laparoscopic gastrectomy with lymphadenectomy will be performed. Sample size is calculated based on the inferior confidence interval of the detection rate of 95%, and the calculated accrual is 237 patients. The primary endpoint is detection rate, and the secondary endpoints are sensitivity and postoperative complications. This study is expected to clarify the feasibility of laparoscopic sentinel basin dissection after noncurative ESD. If the feasibility is demonstrated, a multicenter phase III trial will be initiated to compare laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy in early gastric cancer after endoscopic resection. ClinicalTrials.gov Identifier: NCT03123042.


Improvement of the trivalent inactivated flu vaccine using PapMV nanoparticles.
Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic.


The effect of two different crosslinkers on in vitro characteristics of ciprofloxacin-loaded chitosan implants.
The objective of this study was to determine and evaluate a controlled release implant of ciprofloxacin using bovine hydroxyapatite (BHA)-chitosan composite and glutaraldehyde or genipin as crosslinking agents. Ciprofloxacin implants were prepared using BHA, chitosan, ciprofloxacin at 30:60:10 and using three different concentrations of glutaraldehyde or genipin (0.3, 0.5, or 0.7%) as crosslinkers. Implants were formed as mini-tablet with 4.0 mm diameter weighing 100 mg using compression method. Further, the prepared ciprofloxacin implants were characterized for porosity, density, water absorption capacity, swelling, degradation, compressive strength, compatibility (Fourier transforms-infrared spectroscopy (FT-IR)), morphology (scanning electron microscope (SEM)), X-ray diffraction (X-RD), and in vitro drug release. The addition of glutaraldehyde or genipin as crosslinkers in ciprofloxacin implant showed controlled release profile of ciprofloxacin over a time period of 30 days. SEM photomicrograph revealed low porosity of the implant after crosslinking with glutaraldehyde or genipin. The FTIR study confirmed the formation of covalent imine bonds between chitosan and glutaraldehyde. Moreover, the addition of glutaraldehyde or genipin as crosslinkers caused a decrease in the mechanical strength of the implant. Increased concentration of glutaraldehyde or genipin reduced the crystallinity of BHA and chitosan, which were confirmed by X-RD studies. The results obtained from this study indicated that glutaraldehyde or genipin had the potential effect to retard ciprofloxacin release from BHA-chitosan-ciprofloxacin implant for 30 days.


Media and environmental effects on phenolics production from tobacco cell cultures.
The effects of various factors in culture medium on the phenolics production from cultured tobacco cells (free and immobilized) were studied. It was found that removing the growth hormone from the medium increased the productivities of phenolics for both free and immobilized cultures. Low initial sucrose concentration in the medium restricted growth and resulted in high cellular productivities of the phenolics for freely suspended cells, but not for the immobilized cells. Addition of 1.4% DMSO to standard culture medium greatly increased phenolics productivities without affecting cell viability in both free and immobilized cell cultures. Continuous operation of a packed-column reactor of the immobilized cells was achieved for 500 hours. Aeration was accomplished by diffusing pure oxygen through silicone tubing placed inside the reactor. It was found that prolonged cell viability was contingent upon initially operating the reactor with total recycle for several days, and then introducing fresh feed while maintaining a high recycle rate. Immobilized cells packed in a continuous column reactor achieved productivities more than twice that achieved in any batch run.


Mechanisms involved in the processing of the p55 and the p75 tumor necrosis factor (TNF) receptors to soluble receptor forms.
The two tumor necrosis factor (TNF) receptors (TNF-R55 and TNF-R75) can release soluble TNF-binding proteins (TNF-R55-BP and TNF-R75-BP) by proteolytic cleavage. The proteolytic processing of the TNF receptors was investigated in monoblastic THP-1 and promyelocytic HL-60-10 leukemic cell lines. The release of soluble forms of both receptors was rapidly stimulated by staurosporine-sensitive protein kinase C activation by phorbol myristate acetate (PMA) and more slowly stimulated by TNF. No receptor release was seen below a temperature of 16 degrees C. NH4Cl (10 mmol/liter) and monensin (1 mumol/liter), known to increase intracellular pH, inhibited to some extent PMA- and TNF-induced release of both TNF-R55-BP and TNF-R75-BP. The inhibitory effect of monensin might be explained by a diminished translocation of newly synthesized receptor to the plasma membrane. The weak inhibitory effect of NH4Cl on PMA-induced release of soluble receptor forms could be due to effects on a pH-sensitive compartment. PMA-induced down-regulation of receptors was not dependent on acidity as it occurred also in the presence of monensin and NH4Cl when the release of TNF-BPs is partially blocked. Dibutyryl cAMP inhibited the PMA-induced release of TNF-R55-BP but not of TNF-R75-BP in both cell lines investigated. In addition, dibutyryl cAMP alone stimulated the release of both receptors but only in THP-1 cells. Our data show that the generation of soluble forms of both TNF receptors can be regulated by both PKC and PKA.


Laboratory-based cryogenic soft x-ray tomography with correlative cryo-light and electron microscopy.
Here we present a novel laboratory-based cryogenic soft X-ray microscope for whole cell tomography of frozen hydrated samples. We demonstrate the capabilities of this compact cryogenic microscope by visualizing internal subcellular structures of Saccharomyces cerevisiae cells. The microscope is shown to achieve better than 50 nm half-pitch spatial resolution with a Siemens star test sample. For whole biological cells, the microscope can image specimens up to 5 μm thick. Structures as small as 90 nm can be detected in tomographic reconstructions following a low cumulative radiation dose of only 7.2 MGy. Furthermore, the design of the specimen chamber utilizes a standard sample support that permits multimodal correlative imaging of the exact same unstained yeast cell via cryo-fluorescence light microscopy, cryo-soft X-ray microscopy, and cryo-transmission electron microscopy. This completely laboratory-based cryogenic soft X-ray microscope will enable greater access to three-dimensional ultrastructure determination of biological whole cells without chemical fixation or physical sectioning.


[How Charcot got his chair].
Charcot's career, as is well-known, reached a summit with his acquisition of the Faculty clinical chair of diseases of the nervous system inaugurated in 1882. Based upon previously untapped archival materials at the Charcot Library and the National Archives, this paper explores four questions: I. Was "Charcot's chair" really the first specialized chair for neurology?; 2. Was it founded specifically for Charcot?; 3. What role did the Faculty of Medicine play and did it offer any opposition?; 4. How important was the creation of the chair for the flourishing of the Salpêtrière school. Evidence is presented to show that Charcot considered a specialized chair in nervous diseases a high priority for his career and his school. Sometime around 1880, convinced of the importance of this project, he began to assemble arguments in its behalf from French and foreign sources, particularly from his German colleagues, Westphal and Erb. He learned that there were no precedents, not even in Berlin. Charcot's carefully prepared manuscript memoir presented a strong case for the "necessity" of the chair based on the recent progress and theoretical as well as practical importance of his subject. He described psychiatry, which already had a Faculty clinical chair, as but a "small part" of neuropathology and rejected the idea of combining the two disciplines. Although the project encountered opposition from several Faculty colleagues, who claimed that it was a personal favor for Charcot, powerful support from political allies such as Gambetta and Ferry ensured government funding. In fact, government action in behalf of the creation of the chair for Charcot preceded and surprised the medical Faculty. This paper shows the extent to which Charcot's own initiatives and arguments set the agenda and defined the role he envisaged for the new foundation at the center of the clinical research and teaching centre emerging under his direction at the Salpêtrière.


Preparation and characterization of chitosan film incorporated with thinned young apple polyphenols as an active packaging material.
The objective of this study was to characterize the physical, mechanical and bioactive properties of chitosan film incorporated with thinned young apple polyphenols (YAP). The results indicated that the addition of YAP resulted in a significant increase in the thickness, density, swelling degree, solubility and opacity of chitosan film, but the water content, water vapor permeability and mechanical properties of the film were decreased. Besides, the antioxidant and antimicrobial properties of chitosan film were significantly enhanced by YAP. Both the NMR and FTIR spectra indicated the interactions between YAP and chitosan were likely to be non-covalent. Furthermore, the thermal stability of the film was decreased by YAP addition, suggested by DSC. Interestingly, the changing tendency of crystalline degree indicated by X-ray kept pace with that of thermal stability for YAP-chitosan films. Overall, YAP-chitosan film was shown a potential as a bioactive packaging material to extend food shelf-life.


[Current aspects of Goodpasture's syndrome].
Goodpasture's syndrome is an auto-immune disorder with antibodies directed against alveolar and glomerular basement membrane. These antibodies are usually present in the serum but their detection is difficult, requiring a radio-immunological technique which remains uncommon. The fixed antibodies are detected more easily and more constantly in the kidney tissue than in the lung; they appear on a kidney biopsy in the form of linear deposits of immunoglobulins on the basement membrane. Thus, the renal biopsy appears to be the essential requirement to establish a diagnosis of Goodpasture's syndrome, and one should not hesitate to perform a biopsy in the presence of diffuse alveolar haemorrhage without an evident aetiology and even in the absence of any biological evidence of renal disease. Alveolar lavage may be used to confirm a haemorrhage which has been purely alveolar. The treatment for respiratory and renal recovery, using immunological therapy includes corticosteroids, cytotoxic drugs and plasmapheresis. The exact methods are not yet fully defined during the course on certain clinical forms of the disease: for oliguric patients, dialysis is the single treatment; the isolated pulmonary forms have often been treated and improved by corticotherapy alone. The responsible antigen, probably unique, has been recently been identified as collagen type IV of the glomerular basement membrane. The pathogenesis of Goodpasture's syndrome remains unknown. The inhalation of hydrocarbons has been frequently noted. The dismal prognosis in the natural history of the disease and the therapeutic possibilities available make diagnosis an urgency. Currently, renal biopsy represents the most reliable and rapid mean of diagnosis.


Nitric oxide synthase expression in the central nervous system of Sepia officinalis: an in situ hybridization study.
We recently reported the molecular cloning of nitric oxide synthase (NOS) mRNA from Sepia officinalis (SoNOS) using a strategy that involves hybridization of degenerate PCR primers to highly conserved NOS regions, combined with a RACE procedure. Here, in situ hybridization study has been performed on serial sections of the cuttlefish central nervous system to reveal localized specific staining of cell bodies in several lobes of the brain. Staining was found in many lower motor centres, including cells of the inferior and superior buccal lobes (feeding centres); in some higher motor centres (anterior basal and peduncle lobes); in learning centres (vertical, subvertical and superior frontal lobes); and in the visual system [medulla and deep retina (optic lobe)]. Positive staining was also found in the olfactory lobe. NOS-expressing cells have been detected also in the interbasal lobe. Double labelling experiments, performed on consecutive sections, showed that neurons containing NOS immunoreactivity were also positive in in situ hybridization staining. All these data support the presence of NOS in several systems in the cuttlefish brain.


[Effects of selenium and DTPA on cadmium excretion in rats].
Fifty-six male wistar rats were selected to study the effects of selenium and DTPA on cadmium excretion. Cadmium levels in urine, feces and tissues of the rats were determined with graphite stove method, and their kidneys were examined pathohistologically. Results showed selenium had stronger effects on cadmium excretion via feces in rats than DTPA did, and combination of both of them showed synergistic effects on it. Also, selenium could accelerate the recovery from kidney injury caused by cadmium, and combination of both of them showed synergism on it.


A simple and sensitive proteinase assay using Sepharose 4B-coupled fluorescamine-labeled casein as a substrate.
A simple and sensitive method for proteinase assay was developed, which uses fluorescamine-labeled casein-Sepharose 4B as a substrate. Casein-Sepharose 4B was prepared most effectively by coupling casein to cyanogen bromide-activated Sepharose 4B at pH 10.0. Fluorescamine-labeled casein-Sepharose 4B was then prepared by mixing fluorescamine and casein-Sepharose 4B suspension at pH 8.0 and used for the assay as a substrate after removal of the excess reagent and/or its hydrolysis products. The assay can be done by simple measuring the fluorescence (excitation at 390 nm and emission at 475 nm) of the filtrate of the assay mixture after incubation of the substrate with enzyme solution. This method is suited for the assay of proteinases active at neutral to slightly alkaline pH values, and the activity of 3 ng of trypsin or 10 ng of alpha-chymotrypsin can be determined with reasonable accuracy. This method is therefore almost as sensitive as those using radioisotope-labeled proteins as substrates.


Treatment of Acute Antibody-Mediated Rejection.
Acute antibody-mediated rejection (AMR) remains an important challenge in the field of kidney transplantation despite the advances in immunosuppressive strategies, and has been recognized as an important cause of allograft dysfunction and graft loss. The treatments of acute AMR are not standardized and poor evidence is currently available on the effectiveness of therapy regimens with combinations of drugs. Standard treatment for acute AMR is based on 3 cornerstones: removal of donor-specific antibodies (DSAs) from the bloodstream, reduction of DSAs synthesis, and inhibition of the interaction between DSAs and human leukocyte antigen antigens on donor's cells. In this paper, we discuss the mechanism of action of the principal drugs currently in use, the main published studies on this topic, and the future insights related to the treatment of acute AMR.


Investigating Healthcare Providers' Acceptance of Personal Robots for Assisting with Daily Caregiving Tasks.
Robots have potential to provide assistance to healthcare providers in daily caregiving tasks. The healthcare providers' acceptance of assistive robots will mediate the success or failure of implementation of robotic systems in care settings. It is essential to understand why and how providers would accept implementation of a robot in their daily work routines. We identified caregiving tasks with which healthcare providers would or would not accept assistance from a personal robot (Willow Garage's PR2). We also explored preferences for human or robot assistance. The healthcare providers we interviewed were quite open to the idea of receiving robot assistance for certain tasks.