Presentation of severe combined immunodeficiency with respiratory syncytial virus and pneumocystis co-infection.
Severe combined immunodeficiency can cause severe, life-threatening viral, bacterial and fungal infections at an early age. We report a case of a 4-month-old boy with co-infection by respiratory syncytial virus and Pneumocystis jiroveci infection that led to recognition of severe combined immunodeficiency.


Sustainable and practical formation of carbon-carbon and carbon-heteroatom bonds employing organo-alkali metal reagents.
Metal-catalysed cross-coupling reactions are amongst the most widely used methods to directly construct new bonds. In this connection, sustainable and practical protocols, especially transition metal-catalysed cross-coupling reactions, have become the focus in many aspects of synthetic chemistry due to their high efficiency and atom economy. This review summarises recent advances from 2012 to 2022 in the formation of carbon-carbon bonds and carbon-heteroatom bonds by employing organo-alkali metal reagents.


Snekmer: a scalable pipeline for protein sequence fingerprinting based on amino acid recoding.
The vast expansion of sequence data generated from single organisms and microbiomes has precipitated the need for faster and more sensitive methods to assess evolutionary and functional relationships between proteins. Representing proteins as sets of short peptide sequences (kmers) has been used for rapid, accurate classification of proteins into functional categories; however, this approach employs an exact-match methodology and thus may be limited in terms of sensitivity and coverage. We have previously used similarity groupings, based on the chemical properties of amino acids, to form reduced character sets and recode proteins. This amino acid recoding (AAR) approach simplifies the construction of protein representations in the form of kmer vectors, which can link sequences with distant sequence similarity and provide accurate classification of problematic protein families. Here, we describe Snekmer, a software tool for recoding proteins into AAR kmer vectors and performing either (i) construction of supervised classification models trained on input protein families or (ii) clustering for de novo determination of protein families. We provide examples of the operation of the tool against a set of nitrogen cycling families originally collected using both standard hidden Markov models and a larger set of proteins from Uniprot and demonstrate that our method accurately differentiates these sequences in both operation modes. Snekmer is written in Python using Snakemake. Code and data used in this article, along with tutorial notebooks, are available at http://github.com/PNNL-CompBio/Snekmer under an open-source BSD-3 license. Supplementary data are available at Bioinformatics Advances online.


Ocular toxoplasmosis in wallabies (Macropus rufogriseus).
We initiated a pathologic investigation of ocular disease in wallabies. Of 21 animals examined, the eyes were investigated histologically in 11; in four of these animals the brains were also available for section and the sera were investigated in three. In ten animals only sera were received. Histologic studies showed bilateral or unilateral cataract in five animals. Eight animals, with or without cataracts, showed various degrees of keratitis, uveitis, choroidoretinitis, or endophthalmitis. In three animals Toxoplasma cysts were found within the retina or brain, or both. Of the 13 cases examined serologically 11 were positive for toxoplasmosis; three reached high titers.


Intimate partner violence, circulating glucose, and non-communicable Disease: Adding insult to injury?
Analyzing data from the 2015-2016 Indian Demographic and Health Survey (N = 41,768), we investigate how women's circulating glucose varies with the severity of intimate partner violence (IPV) they have experienced in the last year and how their likelihoods of corresponding noncommunicable diseases vary with IPV severity in their lifetime. Consistent with a physiological stress response, women who have recently experienced severe IPV exhibit higher glucose levels and are more likely to have extremely high levels-forewarning of disease development-than women who have not experienced IPV. Correspondingly, women who have ever experienced severe IPV in their lifetime have 33%-200% higher probabilities of diabetes, heart disease, thyroid disorders, and cancer and are 70% more likely to have any of these diseases and 175% more likely to have multiple than women who have experienced none.


Characterization of noise in long-term ECG monitoring with machine learning based on clinical criteria.
Noise and artifacts affect strongly the quality of the electrocardiogram (ECG) in long-term ECG monitoring (LTM), making some of its parts impractical for diagnosis. The clinical severity of noise defines a qualitative quality score according to the manner clinicians make the interpretation of the ECG, in contrast to assess noise from a quantitative standpoint. So clinical noise refers to a scale of different levels of qualitative severity of noise which aims at elucidating which ECG fragments are valid to achieve diagnosis from a clinical point of view, unlike the traditional approach, which assesses noise in terms of quantitative severity. This work proposes the use of machine learning (ML) techniques to categorize different qualitative noise severity using a database annotated according to a clinical noise taxonomy as gold standard. A comparative study is carried out using five representative ML methods, namely, K neareast neighbors, decision trees, support vector machine, single-layer perceptron, and random forest. The models are fed by signal quality indexes characterizing the waveform in time and frequency domains, as well as from a statistical viewpoint, to distinguish between clinically valid ECG segments from invalid ones. A solid methodology to prevent overfitting to both the dataset and the patient is developed, taking into account balance of classes, patient separation, and patient rotation in the test set. All the proposed learning systems have demonstrated good classification performance, attaining a recall, precision, and F1 score up to 0.78, 0.80, and 0.77, respectively, in the test set by a single-layer perceptron approach. These systems provide a classification solution for assessing the clinical quality of the ECG taken from LTM recordings. Graphical Abstract Clinical Noise Severity Classification based on Machine Learning techniques towards Long-Term ECG Monitoring.


Xanthogranulomatous cholecystitis: Diagnosis and management.
Xanthogranulomatous cholecystitis (XGC) is a rare form of cholecystitis, characterized by the presence of xanthogranuloma, prominent yellow structures within the gallbladder wall that is very often lithiasic. When XGC presents in its pseudo-tumoral form with occasional adjacent organ involvement, it can mimic gallbladder carcinoma (GBC). The etiopathogenesis of XGC is inflammatory destruction of Rokitansky-Aschoff sinuses containing biliary and cholesterol pigments within the gallbladder wall; this leads to a florid granulomatous histiocytic inflammatory reaction. The prevalence ranges from 1.3% to 8.8% of all cholecystectomies and varies from country to country; XGC occurs predominantly in patients over 50 years of age, and is equally distributed between males and females. Its association with GBC remains a topic of debate in the literature (between 0 and 20%). Symptoms are non-specific and generally similar to those of acute or chronic cholecystitis. XGC, when associated with altered health status, leads to the suspicion of GBC. XGC can also come to light due to an acute complication of cholecystolithiasis, in particular, gallstone migration. Imaging by sonography and CT scan is suggestive, but magnetic resonance imaging is more specific. In difficult cases, biopsy may be necessary to eliminate the diagnosis of tumor. In case of pre- or intra-operative diagnostic doubt, the opinion of a hepatobiliary specialty center can be of help. When diagnosis of GBC has been eliminated, laparoscopic cholecystectomy is recommended, although with a high risk of conversion to laparotomy and complications.


Safety of fosamprenavir in a cohort of HIV-1-infected patients with co-morbidities.
The hypothesis that fosamprenavir-including highly active antiretroviral therapy (HAART) regimens would be associated with few metabolic and hepatic side-effects was investigated. An observational single-arm retrospective study was set up on a cohort of 139 human immunodeficiency virus (HIV)-infected patients, followed up at A.O.R.N. Cotugno Hospital, Naples, Italy, treated with antiretroviral regimens including fosamprenavir, in order to evaluate the safety of these regimens in relationship to hepatic and metabolic side-effects, also considering co-morbidities and other risk factors. Only seven patients met the criteria to reach the primary end-point (grade ≥ 3 adverse event) and none of them discontinued HAART therapy during the follow-up period. Eighty percent of the patients reached viral load <50 cp/μl at 48 weeks of observation. At the end of follow-up, no patient with fasting serum total cholesterol and/or fasting serum triglycerides above grade 3 was found, while 1 out of 114 (0.88%) cases presented aspartate transaminase and alanine transaminase ≥ grade 3 and 1 out of 114 (0.88%) cases had fasting serum glucose ≥ grade 3. One out of 137 patients developed a malignant neoplasm (0.73%) and 4 (2.92%) displayed newly diagnosed hypertension. Fosamprenavir-based regimens caused a low number of serious metabolic adverse events during a 48 week follow-up period, with a low incidence of co-morbidities and satisfying results in terms of viro-immunological response including for patients with already existing co-morbidities requiring other therapies.


Protoscolicidal effects of curcumin nanoemulsion against protoscoleces of Echinococcus granulosus.
The aim of the present study was to assess in vitro protoscolicidal effects of curcumin nanoemulsion (CUR-NE) against protoscoleces of cystic echinococcosis (CE)/hydatid cysts. The CUR-NE was prepared via spontaneous emulsification of soybean as the oil phase, a mixture of Tween 80 and Tween 85 as the surfactant, ethanol as the co-surfactant and distilled water. Various concentrations of CUR-NE (156, 312, 625 and 1250 µg/ml) were exposed to collected protoscoleces of infected sheep liver hydatid cysts for 10, 20, 30, 60 and 120 min. Viability of the protoscoleces were assessed using eosin exclusion test. Morphological changes of the protoscoleces were observed using differential interference contrast (DIC) microscopy. The mean particle size and zeta potential of CUR-NE included 60.4 ± 14.8 nm and - 16.1 ± 1.1 mV, respectively. Results showed that the viability of the protoscoleces decreased significantly with increases in CUR-NE concentrations (p < 0.001). The mortality rates of protoscoleces with exposure to concentrations of 1250 and 625 µg/ml of CUR-NE for 60 min were 94 and 73.33%, respectively. Mortality of the protoscoleces was 100% after 120 min of exposure to 1250 and 625 µg/ml concentrations of CUR-NE. Using NIC microscopy, extensively altered tegumental surface protoscoleces was observed after protoscoleces exposure to CUR-NE. The findings of the present study revealed the in vitro protoscolicidal potential of CUR-NE. Therefore, CUR-NEs are addressed as novel protoscolicidal agents, which can be used as an alternative natural medicine to kill the protoscoleces, owing to their low toxicity and significant inhibition potency. However, further studies are necessary to investigate pharmacologic and pharmacokinetics of CUR-NEs.


Appropriate extent of surgery for aspirin-exacerbated respiratory disease.
The current literature lacks strong guidelines regarding surgical management of patients with aspirin-exacerbated respiratory disease (AERD), who present with the clinical triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), bronchial asthma, and aspirin/nonsteroidal anti-inflammatory drug intolerance. To further define the effectiveness of sinus surgery in treating AERD patients, this review article discusses current evidence regarding outcomes associated with more extensive surgery, the benefits of frontal sinus surgery on polyposis, and the role of Draf III intervention. Numerous studies suggest that Draf III frontal sinusotomy may be an efficacious early intervention due to increased neo-ostial patency and subsequent distribution of topical therapies. Future studies that further investigate the efficacy and safety of extensive surgery in AERD patients are warranted.


Clinical experience of a cardio-oncology consultation at a tertiary university hospital in Portugal: An observational study.
Heart disease and cancer are the two leading causes of morbidity and mortality worldwide. Advances in cancer screening and management have led to longer survival and better quality of life. Despite this progress, many cancer patients experience cardiovascular complications during and after cancer treatment. This study describes the experience of a cardio-oncology program at tertiary academic hospital. In this retrospective observational study, cancer patients referred to the CHULN cardio-oncology consultation (COC) between January 2016 and December of 2019 were included. Data collected included: patient demographics, cancer type, reason for referral, cardiovascular risk factors, cardiac and oncologic treatments and clinical outcomes. A total of 520 patients (mean age: 65 ± 14 years; 65% women) were referred to the COC. The main reasons for referral were suspected heart failure (26%), pre-high risk chemotherapy assessment (20%) and decreased LVEF (15%). Pre-existing cardiovascular risk factors were common (79%) and 309 (59%) were taking cardiac medications. The most common type of malignancy was breast cancer (216, 41%) followed by gastrointestinal (139, 27%). More than half received anthracycline-based regimens (303, 58%). Most patients (401; 77%) successfully completed cancer therapy. At the time of last data collection, the majority of patients were alive (430, 83%). Cardiac-related mortality was observed in 16%. The close collaboration between cardiology and oncology teams and timely cardiac monitoring was the key to the majority of patients to completing their prescribed cancer therapy.


DNA mediated water-dispersible graphene fabrication and gold nanoparticle-graphene hybrid.
Water dispersible single- and bilayered graphene sheets are produced by a direct exfoliation from graphite flakes in the presence of pyrene-labeled single stranded DNAs, and the immobilized DNA on the graphene surface is further hybridized with a gold nanoparticle labeled complementary DNA to generate gold nanoparticle-graphene nanocomposites.


Subclinical gait disturbance and postoperative gait improvement in patients with degenerative cervical myelopathy.
This study aimed to evaluate the subclinical gait abnormalities and the postoperative gait improvements in patients with degenerative cervical myelopathy using three-dimensional gait analysis. We reviewed the gait analysis of 62 patients who underwent surgical treatment for degenerative cervical myelopathy. The asymptomatic gait group included 30 patients and the gait disturbance group included 32 patients who can walk on their own slowly or need assistive device on stairs. The step width (17.2 cm vs. 15.9 cm, P = 0.003), stride length (105.2 cm vs. 109.1 cm, P = 0.015), and double-limb support duration (13.4% vs. 11.7%, P = 0.027) improved only in the asymptomatic gait group. Preoperatively, the asymptomatic gait group exhibited better maximum knee flexion angle (60.5° vs. 54.8°, P = 0.001) and ankle plantarflexion angle at push-off (- 12.2° vs. - 6.5°, P = 0.001) compared to the gait disturbance group. Postoperatively, maximum knee flexion angle (62.3° vs. 58.2°, P = 0.004) and ankle plantarflexion angle at push-off (- 12.8° vs. - 8.3°, P = 0.002) were still better in the asymptomatic gait group, although both parameters improved in the gait disturbance group (P = 0.005, 0.039, respectively). Kinematic parameters could improve in patients with gait disturbance. However, temporospatial parameters improvement may be expected when the operative treatment is performed before apparent gait disturbance.


MECOM-related disorder: Radioulnar synostosis without hematological aberration due to unique variants.
The etiology for a considerable proportion of patients with congenital radioulnar synostosis (RUS) remains unclear. This study aimed to investigate the genetic cause of RUS without a known cause. Patients with RUS were investigated. Exome sequencing and/or Sanger sequencing was performed. Bioinformatics analysis was also performed. Pathogenicity was evaluated for variants of interest. We identified unique missense variants in MECOM (encodes EVI1) associated with RUS in 8 families. Of them, 6 families had variants in residue R781, including 3 families with R781C (c.2341C>T), 2 families with R781H (c.2342G>A), and 1 family with R781L (c.2342G>T). Another 2 variants included I783T (c.2348T>C) in 1 family and Q777E (c.2329C>G) in 1 family. All these variants were clustered within the ninth zinc finger motif of EVI1. Phenotype evaluation identified that most of these patients with RUS harboring mutant MECOM had finger malformations, but none of them had identifiable hematological abnormalities. Functional experiments showed that MECOM R781C led to alterations in TGF-β-mediated transcriptional responses. This study examined MECOM variants by focusing on RUS instead of hematological abnormalities. The R781 residue in EVI1 is a hotspot for human RUS variants. Mutant MECOM is the second most common cause for familial RUS.


Impact of Reaction Setting on the Management, Severity, and Outcome of Pediatric Food-Induced Anaphylaxis: A Cross-Sectional Study.
Prompt epinephrine autoinjector (EAI) use is the primary treatment for anaphylaxis. However, limited Canadian data exist on the impact of reaction location on EAI use for food-induced anaphylaxis (FIA). We sought to investigate the setting, management, and severity of pediatric FIA. We recruited children presenting with FIA from 11 Canadian emergency departments. Patient demographics and the setting, management, and symptoms of FIA were collected by standardized questionnaire. Factors associated with prehospital EAI use and reaction severity were determined by logistic regression. We recruited 3,604 children; 60.2% were male and the median age was 5.0 years (interquartile range 1.8-11.0). Among cases with a known location of FIA (85.0%), home was the most common setting (68.1%), followed by school/daycare (12.8%), other locations (11.4%; eg, park, car), and restaurants (7.4%). In the prehospital setting, EAI was administered in 36.7% of reactions at home, 66.7% in school/daycare, 40.2% in other locations, and 44.5% in restaurants. Relative to reactions occurring at school/daycare, prehospital EAI use was less likely at home (adjusted odds ratio [aOR] 0.80; 95% CI 0.76-0.84), in restaurants (aOR 0.81; 95% CI 0.75-0.87), and in other settings (aOR 0.77; 95% CI 0.73-0.83), when data were adjusted for reaction severity, sex, age, comorbidities, and province. The FIA setting was not associated with reaction severity or hospitalization. Prehospital EAI use was higher at school/daycare than in other settings, potentially owing to the presence of policies and training on FIA. Setting-specific interventions including educational programs and policies/laws mandating training and stocking an EAI may improve anaphylaxis recognition and treatment.


Epitope-based minigene vaccine targeting fibroblast activation protein α induces specific immune responses and anti-tumor effects in 4 T1 murine breast cancer model.
Fibroblast activation protein (FAPα) is a tumor stromal antigen expressed by cancer-associated fibroblasts (CAFs) in more than 90 % of malignant epithelial carcinomas. FAPα-based immunotherapy has been reported and showed that FAPα-specific immune response can remold immune microenvironment and contribute to tumor regression. Many FAPα-based vaccines have been investigated in preclinical trials, which can elicit strong and durable cytolytic T lymphocytes (CTL) with good safety. However, epitope-based FAPα vaccines are rarely reported. To break tolerance against self-antigens, analogue epitopes with modified peptides at the anchor residues are typically used to improve epitope immunogenicity. To investigate the feasibility of a FAPα epitope-based vaccine for cancer immunotherapy in vivo, we conducted a preclinical study to identify a homologous CTL epitope of human and mouse FAPα and obtained its analogue epitope in BALB/c mice, and explored the anti-tumor activity of their minigene vaccines in 4 T1 tumor-bearing mice. By using in silico epitope prediction tools and immunogenicity assays, immunodominant epitope FAP.291 (YYFSWLTWV) and its analogue epitope FAP.291I9 (YYFSWLTWI) were identified. The FAP.291-based epitope minigene vaccine successfully stimulated CTLs targeting CAFs and exhibited anti-tumor activity in a 4 T1 murine breast cancer model. Furthermore, although the analogue epitope FAP.291I9 enhanced FAP.291-specific immune responses, improvement of anti-tumor immunity effects was not observed. Check of immunosuppressive factors revealed that the high levels of IL-10, IL-13, myeloid-derived suppressor cells and iNOS induced by FAP.291I9 increased, which considered the main cause of the failure of the analogue epitope-based vaccine. Thus, we demonstrated for the first time that the FAP.291 minigene vaccine could induce mouse CTLs and also function as a tumor regression antigen, providing the basis for future studies of FAPα epitope-based vaccines. This study may also be valuable for further improvement of the immunogenicity of analogue epitope vaccines.


The orientations of transition moments in reaction centers of Rhodopseudomonas sphaeroides, computed from data of linear dichroism and photoselection measurements.
Linear dichroism measurements of reaction centers of Rhodopseudomonas sphaeroides in stretched gelatin films have yielded angles that various optical transition moments make with an axis of symmetry in the reaction center. Photoselection experiments have yielded angles that certain transition moments make with each other. We have combined these data so as to compute the orientations of the Qx and Qy transition moments of the two molecules of bacteriopheophytin and of the bacteriochlorophyll special pair (photochemical electron donor) in the reaction center. Orientations are expressed in spherical polar coordinates with the symmetry axis as the pole. We have also computed additional angles between pairs of transition moments. In this treatment we have assumed that the bacteriopheophytins are independent monomers with little or no exciton coupling.


Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.
Stimulation of macrophages with interferon-γ (IFN-γ) and interleukin 4 (IL-4) triggers distinct and opposing activation programs. During mixed infections or cancer, macrophages are often exposed to both cytokines, but how these two programs influence each other remains unclear. We found that IFN-γ and IL-4 mutually inhibited the epigenomic and transcriptional changes induced by each cytokine alone. Computational and functional analyses revealed the genomic bases for gene-specific cross-repression. For instance, while binding motifs for the transcription factors STAT1 and IRF1 were associated with robust and IL-4-resistant responses to IFN-γ, their coexistence with binding sites for auxiliary transcription factors such as AP-1 generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation in complex environmental conditions.


Use of nitrofurantoin macrocrystals after transurethral prostatectomy.
A prospective randomized study of 223 consecutive patients with sterile urine undergoing transurethral prostatectomy was undertaken to examine the effects of nitrofurantoin macrocrystals on postoperative urine cultures. Patients were divided into 3 groups; group 1 received no postoperative antibiotics, group 2 received nitrofurantion for 5 days postoperatively and group 3 received nitrofurantoin for 10 days postoperatively. Nitrofurantoin decreases the incidence of short-term (24 hours after catheter removal) postoperative bacteriuria, while having no effect on long-term (4 weeks) bacteriuria following transurethral prostatectomy. The use of postoperative nitrofurantoin is supported by its tendency to reduce the incidence of short-term urinary infection in patients with the same organisms found in cultures of the prostatic tissue. However, there was no long-term advantage in prolonging therapy for greater than 5 days. There was no difference in morbidity in the immediate postoperative period among the 3 groups.


Assay of Monoacylglycerol Lipase Activity.
Monoacylglycerol lipase (MGL/MAGL/MGLL) is a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). 2-AG is the most abundant endogenous lipid agonists for cannabinoid receptors in the brain and elsewhere in the body. In the central nervous system (CNS), MGL is localized to presynaptic nerve terminals of both excitatory and inhibitory synapses, where it controls the regulatory actions of 2-AG on synaptic transmission and plasticity. In this chapter, we describe an in vitro method to assess MGL activity by liquid chromatography/mass spectrometry (LC/MS)-based quantitation of its reaction product. The method may be used to determine basal or altered MGL activity in cells or tissues after pharmacological, genetic, or biological interventions. In addition, the assay can be used for MGL inhibitor screening using purified recombinant enzyme or MGL-overexpressing cells.


[Action of lipases on low-density serum lipoproteins].
It was shown that the action of phospholipase A2 on low density serum lipoproteins (LDL) in the presence of serum albumin led to decrease in the floatation coefficient. Lipase hydrolyzed LDL triglycerides after pretreatment of the latter with phospholipase A2. Due to the action of lipases the LDL residue loses its solubility and the cholesterol-rich precipitate forms. The loss of solubility of lipoproteins treated with lipases and proteinases may occur in vivo, underlying athermao formation, i.e. can thus serve as one of the factors in the pathogenesis of atherosclerosis.


Expression patterns of ABCG2, Bmi-1, Oct-3/4, and Yap in the developing mouse incisor.
Recent studies have demonstrated the existence of dental stem cells in the continuously growing tooth. However, much remains to be learned about the complex mechanism involving stem cells during tooth development. We determined the expression patterns of four stem cell markers ABCG2, Bmi-1, Oct-3/4, and Yap in the developing mouse incisors between embryonic day (E) 11 and postnatal day (PN) 20. ABCG2 was localized strongly in the perivascular region of the incisor mesenchyme from E11 to PN20, and in the odontoblasts from E18 to PN20. Bmi-1 was expressed in both the dental epithelium and mesenchyme from E11 to E14. The expression of Bmi-1 was noticeably reduced at E16, and was restricted to the apical bud from E16 to PN20. Oct-3/4 was localized in the nucleus of the cells in the superficial layer and stellate reticulum within the dental epithelium from E11 to E14 and in the apical bud from E16 to PN20. Meanwhile, once the ameloblasts and odontoblasts began to appear at E16, they expressed Oct-3/4 in the cytoplasm. Yap was expressed in most of the basal cells of the incisor dental epithelium from E11 to E14, but was expressed mainly in the transit-amplifying (TA) cells within the basal cell layer from E16 to PN20. The unique and overlapping expression patterns of ABCG2, Bmi-1, Oct-3/4, and Yap suggest the independent and interactive functions of the four stem cell markers in the developing mouse incisor.


Category specific deficits in Alzheimer's disease: fact or artefact?
Impairments in semantic memory commonly occur in Alzheimer's Disease (AD) but do these occur along category-specific lines? We administered a confrontation naming task comprising living and nonliving items to 68 individuals with AD and 59 age-matched control participants, in a study designed to address some of the methodological issues affecting investigation of category effects. In Experiment 1, stimuli were matched for familiarity and word frequency and also visual complexity, and the AD group showed a differential deficit in nonliving things. In Experiment 2, however, living and nonliving stimuli were matched for age-of-acquisition, name agreement, word frequency, and naming accuracy of elderly controls and there was no categorical impairment in the AD group. The AD group was subdivided first into mild and moderate AD, and then into normal or impaired overall naming groups and performance was reanalysed, but there was still no significant category deficit in any group. Converging evidence was provided by hierarchical regressions across items, as age-of-acquisition, name agreement and word frequency were significant predictors of naming performance in mild and moderate AD groups, but category was not. In Experiment 3, stimulus items were matched for familiarity and naming accuracy of elderly controls when their performance was off-ceiling, and again no differential effect of category was found. When we reduced slightly how closely matched stimuli were for familiarity we then found a differential impairment in living things in the AD group. When reviewing the changing pattern of results from use of different stimulus sets, we concluded that the main determinant of whether or not a categorical impairment of either sort is found in AD is which stimulus properties are controlled during stimulus selection. We conclude that AD does not generally lead to a selective category loss in semantic knowledge.


Impact of chronic renal failure and peritoneal dialysis fluids on advanced glycation end product and iNOS levels in penile tissue: an experimental study.
To investigate the impact of chronic renal failure (CRF) on advanced glycation end product and inducible nitric oxide synthase (iNOS) in penile tissue, we examined the advanced glycation end product 5-hydroxy methyl furfural (5-HMF) content and iNOS expression in rats in which uremia had been produced by greater than 85% nephrectomy. In addition, the contribution of peritoneal dialysis (PD) fluids to the elevation of penile tissue 5-HMF levels and iNOS staining scores has been investigated. Adult male Wistar rats, aged between 10 and 12 weeks and weighing 200 to 330 g, were divided into five groups that each included 6 animals. The first group served as a control group. In the second group, CRF was induced and a peritoneal catheter was implanted, but PD was not performed. In group 3, CRF was induced and PD was performed using dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF was also induced and PD was performed using 3.86% glucose and icodextrin. Finally, in group 5, without CRF, an indwelling catheter was implanted, and the PD procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin. The elevation in 5-HMF levels and iNOS staining scores in penile tissue from groups 2, 3, 4, and 5 was significant compared with group 1 (P <0.05). The elevation in 5-HMF levels and iNOS staining scores was also significant between groups 2 and 3, 2 and 4, 3 and 4, 3 and 5, and 4 and 5 (P <0.05). Moreover, the correlation between the 5-HMF levels and iNOS staining scores was statistically significant (r = 0.525, P = 0.003). In the present experimental study, we found that 5-HMF levels and iNOS staining scores were significantly elevated in rat penile tissue in which uremia had been produced compared with the groups without CRF. Additionally, PD fluids containing glucose had an effect on the elevation of penile tissue 5-HMF levels and iNOS staining scores.


Tunneling induced two-dimensional phase grating in a quantum well nanostructure via third and fifth orders of susceptibility.
We study the nonlinear optical properties in an asymmetric double AlGaAs/GaAs quantum well nanostructure by using an external control field and resonant tunneling effects. It is found that the resonant tunneling can modulate the third-order and fifth-order of susceptibilities via detuning frequency of coupling light. In presence of the resonant tunneling and when the coupling light is in resonance with the corresponding transition, the real parts of third-order and fifth-order susceptibilities are enhanced which are accompanied by nonlinear absorption. However, in off-resonance of coupling light, real parts of third-order and fifth-order susceptibilities enhance while the nonlinear absorption vanishes. We investigate also the two-dimensional electromagnetically induced grating (2D-EIG) of the weak probe light by modulating the third-order and fifth-order susceptibilities. In resonance of coupling light, both amplitude and phase grating are formed in the medium due to enhancement of third-order and fifth-order probe absorption and dispersion. When the coupling light is out of resonance, most of probe energy is transferred from zero-order to higher-order directions due to resonant tunneling effect. The efficiency of phase grating for third-order of susceptibility is higher than phase grating for fifth-order susceptibility. Our proposed model may be useful for optical switching and optical sensors based on semiconductor nanostructures.


The mind continues to matter: psychologic and physical recovery 5 years after musculoskeletal trauma.
Posttraumatic psychopathology may complicate recovery from musculoskeletal injury. This article details the 5-year follow-up of a cohort study examining the relationship between posttraumatic psychopathology and recovery after musculoskeletal trauma. A prospective cohort study of patients with musculoskeletal injuries (Grampian Trauma Outcomes Study) assessed 5 years after their injury. Orthopaedic trauma unit, Level I equivalent. One hundred four of the initial group of 200 patients with musculoskeletal injuries. Trauma care and prospective evaluation of physical and psychologic recovery. Development of psychopathology (measured by the General Health Questionnaire [GHQ]) and functional outcome (measured by Short Form-36 [SF-36] and Musculoskeletal Function Assessment [MFA]). Follow-up at 5 years was 104 patients (52%). GHQ caseness was predictive of physical dysfunction (SF-36, MFA), which had not returned to baseline levels by 5 years. Although injury severity was strongly predictive of psychological disturbance (GHQ caseness) at 5 years, linear regression analysis demonstrated that GHQ score was an important predictor of outcome, whereas Injury Severity Score contributed very little. Psychologic disturbance after musculoskeletal trauma is related to adverse functional outcome. This is not influenced by preinjury state, but constitutes a sustained posttraumatic effect that is only weakly related to severity of injury.


Cardioprotective properties of glucagon-like peptide-1 receptor agonists in type 2 diabetes mellitus patients: A systematic review.
Cardiovascular disease is one of the main contributors for the mortality in type 2 diabetes mellitus (T2DM) patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) had shown cardiovascular benefits which may be advantageous to reduce mortality in T2DM patients. This systematic review focused on analyzing the effects of GLP-1 RAs on cardiovascular outcomes. We conducted an extensive search through JSTOR, PubMed, Scopus, EBSCohost, and CENTRAL. All related studies assessing the use of GLP-1 RAs in T2DM patients from inception up to October 2020 were screened. Any cardioprotective properties as the outcomes were obtained. A total of six studies (4 randomized, 2 observational) with a total of 182.205 patients were included in this review. The GLP-1 RAs used were either liraglutide or exenatide in combination with antihypertensive or antilipidemic drugs. All studies showed that GLP-1 RA significantly caused weight loss and improved cardiac functional capacity by increasing left ventricular ejection fraction and reducing end-systolic and end-diastolic left ventricle volume. GLP-1 RA also improved myocardial blood flow without affecting myocardial glucose uptake. However, GLP-1 RA failed to show its effect in reducing blood pressure and improving lipid profiles. Despite the limited number of studies, consistent data showed that GLP-1 RA has several cardioprotective properties.


Combined action potential- and dynamic-clamp for accurate computational modelling of the cardiac IKr current.
In the present work Action-Potential clamp (APC) and Dynamic clamp (DC) were used in combination in order to optimize the Luo-Rudy (LRd) mathematical formulation of the guinea-pig rapid delayed rectifier K(+) current (IKr), and to validate the optimized model. To this end, IKr model parameters were adjusted to fit the experimental E4031-sensitive current (IE4031) recorded under APC in guinea-pig myocytes. Currents generated by LRd model (ILRd) and the optimized one (IOpt) were then compared by testing their suitability to replace IE4031 under DC. Under APC, ILRd was significantly larger than IE4031 (mean current densities 0.51±0.01 vs 0.21±0.05pA/pF; p<0.001), mainly because of different rectification. IOpt mean density (0.17±0.01pA/pF) was similar to the IE4031 one (NS); moreover, IOpt accurately reproduced IE4031 distribution along the different AP phases. Models were then compared under DC by blocking native IKr (5μM E4031) and replacing it with ILRd or IOpt. Whereas injection of ILRd overshortened AP duration (APD90) (by 25% of its pre-block value), IOpt injection restored AP morphology and duration to overlap pre-block values. This study highlights the power of APC and DC for the identification of reliable formulations of ionic current models. An optimized model of IKr has been obtained which fully reversed E4031 effects on the AP. The model strongly diverged from the widely used Luo-Rudy formulation; this can be particularly relevant to the in silico analysis of AP prolongation caused by IKr blocking or alterations.


Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells.
The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts. Anisomycin caused the activation of the main stress kinases, phosphorylation of the p53 protein and the eukaryotic initiation factor eIF2α, proteolytic cleavage of protein kinase R, Bid, caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway. All these changes were stronger and more sustained in wtPC12 cells. In the presence of the dominant inhibitory p53 protein, p53- dependent genes involved in the regulation of apoptosis may be less transcribed and this can lead to the decrease of apoptotic processes in p143p53PC12 cells.


[Why do Parkinson patients fall? How can falls be prevented? Etiologic, therpeutic and preventive aspects].
Parkinsonian patients suffer often from falls. There are a lot of causes. Postural instability is an important risk factor for falls in Parkinson's disease. Referring to postural instability and falls the outcome of therapeutic measures using drugs is poor. An interdisciplinary therapeutic approach and general measures can help preventing falls in patients with Parkinson's syndrome.


Developing a Hybrid Four-Prong Approach to Anatomical Education During the COVID-19 Pandemic.
During COVID-19, the anatomy faculty and students at Schulich School of Medicine and Dentistry observed strengths and weaknesses in their transition to online learning. A "four-prong" approach to teaching anatomy was developed. Asynchronous content modules were tailored to specific learning objectives, virtual labs were implemented to work through case-based applications, "live from the lab" review sessions provided the opportunity for interaction and integration, and finally, limited face-to-face laboratory sessions provided an opportunity for supervised consolidation with cadaveric specimens. Our approach may be used by other institutions to enhance anatomical education and student engagement.


Description and validation of a questionnaire for the detection of meteoropathy and meteorosensitivity: the METEO-Q.
There is a growing interest for the effects of weather changes on both healthy and psychiatric individuals. This study aims to validate a short questionnaire (METEO-Q) for the detection of meteoropathy and meteorosensitivity. The METEO-Q was administered to 1099 (528 men, 571 women) healthy subjects. Factor analyses, internal consistency, and item analysis were undertaken to examine the factorial structure of the questionnaire. The METEO-Q has satisfactory factorial structure and internal reliability. Our results demonstrate that women have higher scores than man and, therefore, women mostly have meteoropathy. Our findings support the use of the METEO-Q for collecting information regarding the effects of weather changes on healthy subjects and potentially on psychiatric patients.


An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2.
Soluble forms of angiotensin-converting enzyme 2 (ACE2) have recently been shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We report on an improved soluble ACE2, termed a "microbody," in which the ACE2 ectodomain is fused to Fc domain 3 of the immunoglobulin (Ig) heavy chain. The protein is smaller than previously described ACE2-Ig Fc fusion proteins and contains an H345A mutation in the ACE2 catalytic active site that inactivates the enzyme without reducing its affinity for the SARS-CoV-2 spike. The disulfide-bonded ACE2 microbody protein inhibits entry of SARS-CoV-2 spike protein pseudotyped virus and replication of live SARS-CoV-2 in vitro and in a mouse model. Its potency is 10-fold higher than soluble ACE2, and it can act after virus bound to the cell. The microbody inhibits the entry of β coronaviruses and virus with the variant D614G spike. The ACE2 microbody may be a valuable therapeutic for coronavirus disease 2019 (COVID-19) that is active against viral variants and future coronaviruses.


Risk factors for survival in a university hospital population of dogs with epilepsy.
Although a common neurological disorder in dogs, long-term outcome of epilepsy is sparsely documented. To investigate risk factors for survival and duration of survival in a population of dogs with idiopathic epilepsy or epilepsy associated with a known intracranial cause. One hundred and two client owned dogs; 78 dogs with idiopathic epilepsy and 24 dogs with epilepsy associated with a known intracranial cause. A retrospective hospital based study with follow-up. Dogs diagnosed with epilepsy between 2002 and 2008 were enrolled in the study. Owners were interviewed by telephone using a structured questionnaire addressing epilepsy status, treatment, death/alive, and cause of death. Median life span was 7.6 years, 9.2 years, and 5.8 years for all dogs, and dogs with idiopathic epilepsy or dogs with epilepsy associated with a known intracranial cause (P < .001), respectively. Survival time for dogs with idiopathic epilepsy was significantly (P = .0030) decreased for dogs euthanized because of epilepsy (median: 35 months) compared to dogs euthanized for other reasons (median: 67.5 months). Neutered male dogs with idiopathic epilepsy had a significant (P = .031) shorter survival (median: 38.5 months) after index seizure compared to intact male dogs (median: 71 months). Treatment with two antiepileptic drugs (AED's) did not negatively influence survival (P = .056). Dogs with idiopathic epilepsy can in many cases expect a life span close to what is reported for dogs in general. In dogs where mono-therapy is not sufficient, the need for treatment with two AED's is not linked to a poor prognosis.


Retinal cysts in the eye of the Asian musk shrew, Suncus murinus, (Mammalia, Insectivora).
The development of retinal cysts in the eye primordia of Suncus murinus embryos was studied. Retinal infoldings were first identified in the 17.5-day-old embryo (crown rump length--CRL = 6.3 mm). At this time, the apex of the developing retinal fold could be identified attached to the lens. The pigmented epithelium did not take part in the formation of the cyst. The retinal fold closed, to form a cyst, by day 23 of embryonic development (CRL = 14.0 mm). The newly formed retinal cyst remained continuous with the retina and extended toward the lens where it attached to the lens epithelium. Retinal cysts had an oval, bilaterally symmetrical shape and a narrow lumen, which, lined by the internal limiting membrane, occasionally contained cellular debris. The dimensions of the cysts were usually 100 to 150 microns (diameter) by 200 to 250 microns (length). Retinal cysts appeared in 45 per cent of the embryos examined.


The role of proteomics in dementia and Alzheimer's disease.
Proteomic analysis enables us to identify dementia-related protein profiles of both genetic and environmental origins. In this review, current proteomics technologies are described including many examples of clinical proteomics studies. Many of these studies present only results of the discovery phase. Progression to the validation phase was achieved by developing more advanced proteomics technologies such as fluorescence two-dimensional differential gel electrophoresis or isobaric tagging for relative and absolute protein quantification. These technologies will lead to the design of several new Alzheimer's disease-related protein panels for the analysis of CSF. On these new panels, established markers such as tau and Abeta42 will be used in combination with novel markers, for example beta-2-microglobulin, brain-derived neurotrophic factor 1 and fragments of cystatin C. However, there are still limitations to using proteomic assays. The preparation of homogeneous sample material is difficult due the complexity of brain tissue. Laser capture microdissection and recently developed more sensitive proteomics methods, for example fluorescence saturation labelling, will overcome these limitations. Combining proteomics with approaches at the level of the genome and transcriptome followed by interpretation by systems biology will soon shed further light on dementia-related pathogenesis.


Taxonomy and molecular phylogeny of a new freshwater ciliate Frontonia apoacuminata sp. nov. (Protista, Ciliophora, Oligohymenophorea) from Qingdao, PR China.
The morphology and ciliature of a new freshwater ciliate, Frontonia apoacuminata sp. nov., isolated from an artificial pond in Qingdao, PR China, were investigated using live observation and silver staining methods. The main features separating F. apoacuminata sp. nov. from its congeners are as follows: a broad elliptical body that is slightly pointed at the posterior end, four ophryokineties, one or two spherical micronuclei of a 'compact' type, a dorsally positioned contractile vacuole, and peniculi 1-3 each with five kinetosome rows though the left-most two rows in peniculus 3 are extremely shortened (with only two or three kinetosomes each). Additionally, an improved diagnosis of F. acuminata is provided. Phylogenetic analyses based on the small subunit ribosomal RNA (SSU rRNA) gene show that F. apoacuminata sp. nov. clusters with F. atra, F. minuta, F. acuminata and F. terricola. These five species group with Disematostoma, Marituja and Stokesia rather than with other Frontonia species, causing polyphyly of the genus Frontonia.


Effects of loading methods on rabbit welfare and meat quality.
The effects of different loading methods on the welfare, carcass characteristics and meat quality traits of hybrid commercial rabbits were investigated. 384 male rabbits, 82 days old, were transported from the farm to the slaughterhouse. At the farm, 192 rabbits were loaded onto the truck smoothly (S) and 192 rabbits were loaded roughly (R). The S loading method consisted of carefully placing each rabbit into the transport crates. In the R method, the loading was hurriedly and carelessly executed by the transport operator, throwing each animal into the crates fixed on the truck. Live weight before and after transport as well as slaughter data were recorded for each rabbit, and a subset of 80 carcasses were evaluated for meat quality. Blood samples from 80 rabbits were analysed for haematological and biochemical parameters. A significant neutrophilia (P<0.001), lymphocytopaenia (P<0.001) and an increase in serum aspartate aminotransferase (AST) (P<0.01), alanine aminotransferase (ALT) (P<0.001) and creatine kinase (CK) activities (P<0.001) were recorded in all rabbits after transport, independent of the loading method. A twofold increase in serum corticosterone concentration (6.23 vs. 14.88 ng/mL; P=0.001) was observed in all rabbits following transport. Results suggest that the stress parameters analysed were more influenced by transport and handling itself rather than by the different loading methods. The results showed that there was no adverse effect of loading method on carcass traits. Furthermore, the stress condition evidenced by haematological and biochemical parameters prior to slaughter did not affect meat quality.


In vitro and in vivo studies on cytodifferentiation of pituitary clonal cells derived from the epithelium of Rathke's pouch.
A clonal strain of anterior pituitary cells was derived from Rathke's pouch of the rat. These cells were shown to secrete ACTH, growth hormone and prolactin but no glycoprotein hormones, when grown in vitro. Cells from the 2A8 clone were implanted for one month under kidney capsules or into hypothalami of hypophysectomized female rats. Under the kidney capsule, prominent prolactin cells and poorly developed cells of other types were differentiated as seen in usual pituitary grafts. In hypophysiotrophic areas of the hypothalamus, the grafts were cytodifferentiated into various types of anterior pituitary cells with rich vascularization. These cells had the ultrastructural features indicative of hormone secretion. Increases in body and ovarian weights reflected the secretion of somatotrophic and gonadotrophic hormones. The results obtained indicate that implants of 2A8 clonal cells may differentiate into all types of anterior pituitary cells under the influence of hypothalamic hormones or perhaps some unknown factors present in the general systemic circulation of the rat.


Cocaine increases immunoglobulin heavy chain binding protein and caspase-12 expression in the rat dorsal striatum.
Cocaine increases endoplasmic reticulum (ER) stress protein expression via glutamate and dopamine receptor activation in the dorsal striatum. The present study was performed to investigate ER stress response in the dorsal striatum in response to acute or repeated cocaine stimulation. It was hypothesized that cocaine upregulates the ER stress protein immunoglobulin heavy chain binding protein (BiP) and the ER stress-associated protein caspase-12 via N-methyl-D-aspartate (NMDA) and D1 dopamine receptor activation. Western immunoblot and immunohistochemical analyses were mainly performed to test this hypothesis in the rat dorsal striatum. The results showed that BiP and caspase-12 immunoreactivities were significantly increased at 30, 60, and 120 min after acute or repeated intraperitoneal (i.p.) injections of three doses (10, 20, 40 mg/kg) of cocaine for seven consecutive days. Intrastriatal (i.s.) infusion of the selective NMDA antagonist MK801 (2 nmol) or AP5 (2 nmol) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by repeated, but not acute, cocaine (20 mg/kg) administration. However, i.p. injection of the selective D1 antagonist SCH23390 (0.1 mg/kg) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by both acute and repeated cocaine (20 mg/kg) stimulation. These findings suggest that acute or repeated cocaine administration can cause ER stress response in the dorsal striatum in which NMDA and D1 dopamine receptors participate in the mediation of the process.


Evaluation of lung recovery assay for schistosomula in mice immunized with x-irradiated cercariae of Schistosoma mansoni.
The lung recovery assay for schistosomula has recently been used as a rapid method for measuring the state of immunity of a challenged animal. Its merit rests on the fact that the peak day of schistosomular recovery in the lungs of both normal and immune hosts falls on the same day and the degree of immunity can be measured by the percent of schistosomular recovery on this particular day. An evaluation of this method for mice immunized with highly X-irradiated cercariae of Schistosoma mansoni was made. The results indicate that in the immunized mice the peak day for the schistosomular recovery was delayed and the number of schistosomula recovered on the peak day was decreased. The delay of the peak day was increased by the degree of host immunity, so its identification for a host of an unknown immunologic status was not a simple matter. In addition, this method measured only the immune effect which took place in the skin and on prepeak days in the lungs. It was not as competent as the conventional liver perfusion method which measures the total result of the immune effect of the skin, lungs, and liver. Our conclusion is that for measuring the immunizing effect of irradiated cercariae, the lung recovery method is not suitable for the determination of the state of immunity induced.


High-power, short-duration ablation in the coronary sinus: clinical cases and preliminary observations on swine hearts.
Coronary sinus-related arrhythmias are common; however, it is difficult to perform radiofrequency (RF) ablation at these sites efficiently and safely. High-power, short-duration ablation (HPSD) is a proven alternative strategy for pulmonary vein isolation (PVI); whether it can be applied to ablation of the coronary sinus is unknown. The purpose of this preliminary study was to evaluate the feasibility and safety of HPSD ablation in the coronary sinus. Firstly, we demonstrated 4 clinical cases of 3 types of arrhythmias who had unsuccessful ablation with standard power initially, but received successful ablations with HPSD. Secondly, RF ablation was performed in the coronary sinus ostium (CSO) and middle cardiac vein (MCV) of 4 in vitro swine hearts. Two protocols were compared: HPSD (45 W/5 S×5 rounds) and a conventional strategy that used low-power, long-duration ablation (LPLD: 25 W/10 S ×5 rounds). The total duration of HPSD protocol was 25 s, and which of LPLD was 50 s. A total of 28 lesions were created. HPSD can produce longer, wider, deeper, and larger lesions than LPLD. This difference was more pronounced when the ablation was in the MCV. One instance of steam pop occurred during LPLD in the MCV. HPSD is an effective alternative strategy for ablation in coronary sinus according to clinical applications and preliminary animal study. However, the safety needs to be further evaluated based on more animal and clinical studies.


Knowledge, attitude and preparedness to combat COVID-19 infection among dental professionals: A student-centric pilot study.
In the COVID-19 age, attempts are being made to raise student awareness and improve best practices to contain the outbreak. The target population was interns and 3rdyear undergraduate students from JSS Dental College and Hospital, Mysuru. COVID-19 knowledge, awareness and attitude of the students and interns and the preparedness to tackle the current COVID 19 pandemic were assessed. 120 respondents responded via a contented validated self-administered questionnaire with regard to knowledge, attitude and practices and preparedness to address the COVID 19 pandemic by undergraduates and interns. The student participants irrespective of their years into practice were aware of the guidelines being issued by Health care authorities and to address the COVID 19 pandemic. Among the respondents, 57.5% were 3rd year dental students and 42.5% were interns. Regarding knowledge about COVID infection, 42.9% (3rd year students) and 57.1% of the interns were aware of the recent developments, 34.1% of the III year students were aware of the safe distance to be maintained between patients, 42.4% of the students and 57.6% of interns were aware of the authority to be contacted with suspected COVID 19 infections. The participants were also aware of the vaccine trial which was conducted. Most of the respondents (64.3% of the students and 78.6% of the interns) were aware of fumigation in clinical or high-contact areas on a daily basis and biweekly in nonclinical areas. The results suggest a strong need to encourage the current training program among students in health care-related fields.


Outcomes of extremely low risk prostate cancer following radical prostatectomy.
The optimal management of men with very favorable clinicopathological factors who develop biochemical recurrence (BCR) after radical prostatectomy (RP) has not been previously reported. Both local and systemic recurrences are unlikely in this cohort. This study examines their management and outcomes. Between October 2000 to March 2010, 1627 men underwent open RP by a single surgeon. In all, 448 (27.5%) met the following criteria for extremely low risk disease: preoperative PSA level <10 ng ml(-1), clinical stage T1c/T2a, Gleason score 6, estimated cancer volume in the surgical specimen 5% and no evidence for positive surgical margin. Undetectable PSA was defined as 0.04 ng ml(-1). BCR was defined as PSA 0.2 ng ml(-1) or initiation of salvage radiation therapy (SRT) for progressively rising PSA. At 54 months mean follow-up (range 3-114 months), 9 (2%) of the 448 men developed BCR. Mean time to BCR was 63 months (range 12-93) and mean PSA doubling time was 15 months (range 6-27). Six underwent SRT, two elected surveillance and one was lost to follow-up. All men undergoing SRT exhibited more than 75% reduction in pre-SRT PSA, indicating the presence of local disease recurrence. All men undergoing SRT maintained PSA levels <0.1 at last follow-up. The BCR of 2% confirmed that we selected a cohort with extremely low risk for BCR after RP. We demonstrated that men fulfilling our criteria who develop BCR all harbor local disease based on favorable response to SRT. These men should be managed with SRT if recurrence is felt to be biologically significant.


Towards the understanding of the enzymatic cleavage of polyisoprene by the dihaem-dioxygenase RoxA.
Utilization of polyisoprene (natural rubber) as a carbon source by Steroidobacter cummioxidans 35Y (previously Xanthomonas sp. strain 35Y) depends on the formation and secretion of rubber oxygenase A (RoxA). RoxA is a dioxygenase that cleaves polyisoprene to 12-oxo-4,8-dimethyl-trideca-4,8-diene-1-al (ODTD), a suitable growth substrate for S. cummioxidans. RoxA harbours two non-equivalent, spectroscopically distinguishable haem centres. A dioxygen molecule is bound to the N-terminal haem of RoxA and identifies this haem as the active site. In this study, we provide insights into the nature of this unusually stable dioxygen-haem coordination of RoxA by a re-evaluation of previously published together with newly obtained biophysical data on the cleavage of polyisoprene by RoxA. In combination with the meanwhile available structure of RoxA we are now able to explain several uncommon and previously not fully understood features of RoxA, the prototype of rubber oxygenases in Gram-negative rubber-degrading bacteria.


Insight into the effect of facet-dependent surface and oxygen vacancies of CeO2 for Hg removal: From theoretical and experimental studies.
The reaction mechanisms of Hg oxidation on CeO2(111) and (110) surface are clarified by a group of designed experiments and density functional theory (DFT) calculations. CeO2 nanorods and nanoparticles with exposure (110) and (111) faces were prepared by hydrothermal methods, and their morphological properties were investigated using XRD, XPS and HRTEM. Combined experimental and DFT results, the nanorods show better activity than nanoparticles. The total oxidation of Hg can be partially prohibited by the high barriers for the incorporated chlorine activation at reduced surfaces, due to the strong electronic repulsion of heavily accumulated charges. The energy barrier profiles suggest Hg oxidation is much more favorable on CeO2(110) surface than that on CeO2(111) surface. In the Hg oxidation via HCl and O2, the role of O2 is not only replenishment of lattice oxygen, but also could generate surface oxygen as active center for HCl active. The complete catalytic cycle can be identified as four parts: (i) HCl activated by lattice oxygen, (ii) Hg oxidation on defect surface, (iii) HCl activated by adsorbed oxygen and (iv) Hg oxidation on stoichiometric surface. The results of this study provide deep insights into the effects of CeO2 nanocatalyst morphology on the Hg oxidation.


Detection of food intake from swallowing sequences by supervised and unsupervised methods.
Studies of food intake and ingestive behavior in free-living conditions most often rely on self-reporting-based methods that can be highly inaccurate. Methods of Monitoring of Ingestive Behavior (MIB) rely on objective measures derived from chewing and swallowing sequences and thus can be used for unbiased study of food intake with free-living conditions. Our previous study demonstrated accurate detection of food intake in simple models relying on observation of both chewing and swallowing. This article investigates methods that achieve comparable accuracy of food intake detection using only the time series of swallows and thus eliminating the need for the chewing sensor. The classification is performed for each individual swallow rather than for previously used time slices and thus will lead to higher accuracy in mass prediction models relying on counts of swallows. Performance of a group model based on a supervised method (SVM) is compared to performance of individual models based on an unsupervised method (K-means) with results indicating better performance of the unsupervised, self-adapting method. Overall, the results demonstrate that highly accurate detection of intake of foods with substantially different physical properties is possible by an unsupervised system that relies on the information provided by the swallowing alone.


Morphological, biochemical, physiological and molecular aspects of the response of Fusobacterium nucleatum exposed to subinhibitory concentrations of antimicrobials.
Subinhibitory concentrations (SICs) of antimicrobials may result in alterations in bacterial biology with implications for its potential aggression. This has considerable importance for the resident microbiota. Our aim was to analyze the effects of SICs of antimicrobials on the morphological, biochemical, physiological and molecular characteristics of the resident anaerobic Fusobacterium nucleatum. Fourteen strains were obtained from F. nucleatum ATCC 25586, selected by culturing on SICs of ampicillin, ampicillin/sulbactam, clindamycin, chloramphenicol, levofloxacin, metronidazole and piperacillin/tazobactam and subsequent culturing in the absence of drugs. Antimicrobial susceptibility, bacterial morphology, biochemical profiles and biofilm formation were evaluated. Genotyping and analysis of protein profiles were also performed. The antimicrobial susceptibility patterns showed that most of the derived strains were less sensitive to the antimicrobials, even after culturing them without drugs. Morphological and cell complexity alterations were observed, mainly in strains grown in SICs of β-lactam; these strains also expressed a reduced ability for biofilm formation. The other strains showed an increase in biofilm formation but no apparent morphological changes. Alterations were observed in the carbohydrate metabolism patterns and in the activity of microbial enzymes. Several proteins were positively or negatively regulated and there was polymorphism in the DNA from all derived strains. Therefore, SICs of antimicrobials induce alterations in F. nucleatum, which directly impact its biology. These results emphasize the risk of inadequate antibioticotherapy, which may have serious implications for clinical microbiology and infectious diseases and also may interfere with the host-bacteria relationship.


Suicide inactivation of peroxidases and the challenge of engineering more robust enzymes.
As the number of industrial applications for proteins continues to expand, the exploitation of protein engineering becomes critical. It is predicted that protein engineering can generate enzymes with new catalytic properties and create desirable, high-value, products at lower production costs. Peroxidases are ubiquitous enzymes that catalyze a variety of oxygen-transfer reactions and are thus potentially useful for industrial and biomedical applications. However, peroxidases are unstable and are readily inactivated by their substrate, hydrogen peroxide. Researchers rely on the powerful tools of molecular biology to improve the stability of these enzymes, either by protecting residues sensitive to oxidation or by devising more efficient intramolecular pathways for free-radical allocation. Here, we discuss the catalytic cycle of peroxidases and the mechanism of the suicide inactivation process to establish a broad knowledge base for future rational protein engineering.


Decreasing intradental nerve activity in the cat with potassium and divalent cations.
Nerve activity was recorded from deep dentinal cavities in the canine teeth to assess the possible influence of potassium and divalent cations in decreasing this activity in hypersensitive teeth. The decreased activity after the topical application of 0.756 mol/l KCl to the cavity was primarily due to the cation. KCl elicited a biphasic response from intradental nerves, an initial transient excitatory response followed by a prolonged inhibitory period. During the inhibitory period 3 mol/l NaCl, an effective excitatory stimulus, failed to evoke intradental nerve activity. However, with time the response to 3 mol/l NaCl eventually recovered to its previous control level. Close, intra-arterial injection of KCl showed the same biphasic response and time-course of intradental nerve activity as with topical application. Therefore, whether KCl was applied topically or injected its effectiveness in altering the nerve activity was similar. Pretreatment of the dentinal cavity with CaCl2, MgCl2 or SrCl2 greatly reduced the response of intradental nerves to KCl. Therefore these divalent cations seem to have a depressant action on pulpal nerve fibres. The mechanism of action of KCl seems to be an alteration of K+ concentration immediately surrounding the intradental nerves which presumably depolarizes the nerve fibre membrane and elicits an initial firing of action potentials. Because of the persisting high levels of extracellular potassium a sustained depolarized state occurs that results in an inactivation of the action potential. Divalent cations appear to depress the excitability of the nerve cell membrane without altering membrane potential. Such ionic agents could be used in conjunction with KCl as a possible treatment for hypersensitive teeth.


Synthetic studies towards marmycins A and B: development of the vinylogous aldol-aza-Michael domino reaction.
The vinylogous aldol-aza-Michael domino reaction between 2-aminobenzaldehydes and prenal was developed to build up the core of natural products marmycin A and B without the need of protective groups.


Reducing Blood Culture Contamination Rates: Experiences of Four Hospital Systems.
Blood cultures (BCs) frequently become contaminated during the pre-analytic phase of collection leading to downstream ramifications. We present a summary of performance improvement (PI) interventions provided by four hospital systems and common factors that contributed to decreased blood culture contamination (BCC) rates. Each hospital independently formed a multidisciplinary team and action plan for implementation of their intervention, focusing on the use of educational and training tools. Their goal was to significantly decrease their BCC rates. Pre- and post-intervention data were compared during the sustainment period to determine their success. All hospitals met their goals of post-intervention BCC rates and with most achieving and sustaining BCC rates ≤ 1.0-2.0%. Our report highlights how four hospitals independently achieved their objective to decrease their BCC rate with the support of a multidisciplinary team. We propose a benchmark for BCC rates of 1.5 to < 2.0% as achievable and sustainable.


Variant enterovirus A71 found in immune-suppressed patient binds to heparan sulfate and exhibits neurotropism in B-cell-depleted mice.
Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease outbreaks with neurological complications and deaths. We previously isolated an EV-A71 variant in the stool, cerebrospinal fluid, and blood of an immunocompromised patient who had a leucine-to-arginine substitution on the VP1 capsid protein, resulting in increased heparin sulfate binding. We show here that this mutation increases the virus's pathogenicity in orally infected mice with depleted B cells, which mimics the patient's immune status, and increases susceptibility to neutralizing antibodies. However, a double mutant with even greater heparin sulfate affinity is not pathogenic, suggesting that increased heparin sulfate affinity may trap virions in peripheral tissues and reduce neurovirulence. This research sheds light on the increased pathogenicity of variant with heparin sulfate (HS)-binding ability in individuals with decreased B cell immunity.


Metallothionein production: similar responsiveness of avian liver and kidney to chronic cadmium administration.
The accumulation of hepatic and renal Cd, Zn, Cu, and metallothionein (MT) was investigated in ringed turtle doves (Streptopelia risoria) chronically exposed to 3 different concentrations of dietary Cd. When only tissue-Cd was considered as an inducer of MT, kidney was found to be 35% as responsive as liver in producing MT. However, when all potentially relevant inducing metals (Cd + Zn + Cu) were taken into account, kidney was found to be 85% as responsive as liver. The greater production of MT/mol Cd in liver was accounted for mainly by a greater co-accumulation of Zn/mol Cd in liver than in kidney. We conclude that the apparent tissue specificity in expression of MT may be overestimated by failure to consider fluctuations in multiple inducers. Variability in tissue-MT concentrations after chronic dietary Cd administration is best accounted for by a consideration of tissue-Cd, -Zn, and -Cu, rather than tissue-Cd alone.


Life-threatening pneumonitis after first-line treatment with osimertinib for primary T790M mutated non-small cell lung cancer.
Epithelial growth factor receptor (EGFR) directed tyrosine kinase inhibitor (TKI) treatment is the standard approach in patients with advanced, EGFR-mutated non-small cell lung cancer (NSCLC). Although benefit/risk ratio is favorable for these TKI and side effects are manageable in the vast majority of patients, severe and even life-threatening side effects have been reported. TKI-induced interstitial lung disease (ILD) has been reported for single cases in modest severity, predominantly in EGFR-TKI pretreated patients. Here, we report a case of successful stabilization of a life-threatening ILD in a de novo T790M mutated NSCLC during first-line treatment with osimertinib. As osimertinib will be used more often in many EGFR-positive NSCLC patients in the future, this potentially life-threatening side effect should receive special attention, especially in first-line treatment.


Removal kinetics of antibodies against glutamic acid decarboxylase by various plasmapheresis modalities in the treatment of neurological disorders.
Plasmapheresis is one of the acute treatment modalities for neurological disorders associated with antibodies against glutamic acid decarboxylase (anti-GAD). However, there is little information about the removal kinetics of anti-GAD by various plasmapheresis modalities. Here, we investigated the removal rate of anti-GAD and fibrinogen (Fib) by immunoadsorption (IA), plasma exchange using a conventional plasma separator (OP-PE), and plasma exchange using a high cut-off selective membrane plasma separator (EC-PE) in two cases of anti-GAD-associated neurological diseases. In case 1, IA and OP-PE were used, and the percent reductions were as follows: anti-GAD: 38.2% and 69.1% and Fib: 67.7% and 68.2%, respectively. In case 2, OP-PE and EC-PE were used, and the percent reductions were as follows: anti-GAD: 65.8% and 48.5% and Fib: 68.5% and 19.8%, respectively. OP-PE could remove anti-GAD more efficiently than IA. Further, EC-PE could maintain coagulation factors such as Fib better than IA and OP-PE. It is important to select the appropriate plasmapheresis modality on the basis of the removal kinetics.


Postural adjustments in adolescent idiopathic thoracic scoliosis during walking.
Adolescent idiopathic scoliosis (AIS) is the most common type of three-dimensional spinal deformity. Identifying the postural adjustments or changes for different phases and events is needed for developing programs to improve the AIS gait, but such information has been limited. The current study aimed to fill the gap via three-dimensional motion analysis of quiet standing and level walking in patients with severe thoracic AIS. Sixteen female adolescents with AIS (Lenke 1 or 2, age: 14.9 ± 1.7 years, height: 154.7 ± 5.0 cm, mass: 41.7 ± 7.2 kg) and sixteen sex-, age- and BMI-matched healthy controls (age: 14.8 ± 2.7 years, height: 154.9 ± 5.6 cm, mass: 44.7 ± 6.3 kg) participated in the current study with informed written consent. The kinematic and kinetic changes between the trunk, pelvis, and lower limb segments, and at the lumbosacral level at different gait events were measured during quiet standing and level walking. The homogeneity of the current patient group helped reduce the effects of the level and severity of spinal deformity on inter-subject variability that has been associated with controversies over reported gait variables in AIS. The current results support the hypothesis that postural adjustments involving the trunk, pelvis and lower limb segments were needed in severe thoracic AIS during both quiet standing and level walking, and differed between concave and convex sides at different key gait events during level walking. Although scoliotic spinal deformity occurred mainly in the frontal plane, postural adjustments in all three planes were present at key events during level walking with associated joint loading changes in patients with severe thoracic AIS. Monitoring of such adjustments and the associated joint kinetic changes will be helpful for assessing the disease and treatment outcomes.


AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo.
Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor. Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153's activity in vivo. AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206. Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells.


Interferon-γ induces a tryptophan-selective amino acid transporter in human colonic epithelial cells and mouse dendritic cells.
IDO1, which encodes the immunosuppressive and tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-1 (IDO1), is a target for interferon-γ (IFN-γ). IDO1-mediated tryptophan catabolism in dendritic cells and macrophages arrests T cell proliferation, thereby providing a molecular basis for the immunosuppressive function of IDO1. Whether the entry of tryptophan into IDO1-expressing cells is also regulated by IFN-γ is not known. Here we used a human colonic epithelial cell line (CCD841) and a mouse dendritic cell line (DC2.4) to test the hypothesis that IFN-γ, which induces IDO1, also induces a tryptophan transporter to promote substrate availability to IDO1. Upon treatment with IFN-γ, there was a marked increase in IDO1 mRNA and a concomitant increase in tryptophan uptake in both cell lines. The induced uptake system was selective for tryptophan and saturable with a Michaelis constant of 36±3 μM in CCD841 cells and 0.5±0.1 μM in DC2.4 cells. The induction by IFN-γ and the tryptophan-selectivity of the induced transport system were demonstrable even in the presence of physiologic concentrations of all other amino acids. Since kynurenine, the catabolic end product of IDO1, is a signaling molecule as an agonist for the aryl hydrocarbon receptor (AhR), we examined if AhR signaling induces the tryptophan-selective transporter. Treatment of the cells with kynurenine and other AhR agonists increased tryptophan uptake. The present studies demonstrate that IFN-γ coordinately induces IDO1 and a tryptophan-selective transporter to maximize tryptophan depletion in IDO1-expressing cells and that the process involves a positive feedback mechanism via kynurenine-AhR signaling.


Diadenosine tetraphosphate activates cytosol 5'-nucleotidase.
The rate of hydrolysis of IMP (0.5 mM) by cytosol 5'-nucleotidase from Artemia embryos was increased up to 7-fold by concentrations of around 10 microM diadenosine tetraphosphate (Ap4A). Half maximal activation of the enzyme was accomplished with 5 microM Ap4A. The Km (S 0.5) values of the nucleotidase for IMP, GMP, AMP, XMP and CMP decreased about 10 fold in the presence of 10 microM Ap4A. Maximum velocity of the enzyme was not affected by Ap4A. ATP had been previously described as an activator of the enzyme. However, comparatively with Ap4A, concentrations of ATP two orders of magnitude higher are needed to elicit similar effects on the enzyme. Preliminary results indicate that Ap4A is also an activator of the cytosol 5'-nucleotidase from rat liver.


Effect of interactions among individuals on the chemotaxis behaviours of Caenorhabditis elegans.
In many species, individual social animals interact with others in their group and change their collective behaviours. For the solitary nematode Caenorhabditis elegans strain N2, previous research suggests that individuals can change the behaviour of other worms via pheromones and mechanosensory interactions. In particular, pheromones affect foraging behaviour, so that the chemotactic behaviours of individuals in a group (population) can be modulated by interactions with other individuals in the population. To investigate this, we directly compared the chemotactic behaviours of isolated (single) worms with those of individual animals within a population. We found that worms approached an odour source in a distinct manner depending on whether they were alone or in a population. Analysis of behaviours of the N2 worm and a pheromone production-defective mutant revealed that the 'pirouette' strategy was modulated by interaction of the worms via pheromones. Thus, pheromones play an important role in the characteristic collective behaviours seen in the population condition.


Dysphagia in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease as a surrogate of brain involvement?
Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are demyelinating disorders that typically affect the optic nerves and the spinal cord. However, recent studies have demonstrated various forms of brain involvement indicating encephalitic syndromes, which consequently are included in the diagnostic criteria for both. Swallowing is processed in a distributed brain network and is therefore disturbed in many neurological diseases. The aim of this study was to investigate the occurrence of oropharyngeal dysphagia in NMOSD and MOGAD using flexible endoscopic evaluation of swallowing (FEES) as a surrogate parameter of brain involvement. Thirteen patients with NMOSD and MOGAD (mean age 54.2 ± 18.6 years, six men) who received FEES during clinical routine were retrospectively reviewed. Their extent of oropharyngeal dysphagia was rated using an ordinal dysphagia severity scale. FEES results were compared to a control group of healthy individuals. Dysphagia severity was correlated with the presence of clinical and radiological signs of brain involvement, the Expanded Disability Status Scale (EDSS) and the occurrence of pneumonia. Oropharyngeal dysphagia was present in 8/13 patients, including six patients without other clinical indication of brain involvement. Clinical or subclinical swallowing impairment was significantly more severe in patients with NMOSD and MOGAD compared to the healthy individuals (p = 0.009) and correlated with clinical signs of brain involvement (p = 0.038), higher EDSS (p = 0.006) and pneumonia (p = 0.038). Oropharyngeal dysphagia can occur in NMOSD and MOGAD and might be associated with pneumonia and disability. FEES may help to detect subclinical brain involvement.


Effect of integrated management bundle on 1-year overall survival outcomes and perioperative outcomes in super elderly patients aged 90 and over with hip fracture: non-concurrent cohort study.
Due to concomitant factors like frailty and comorbidity, super elderly (≥90 years) patients with hip fracture differ from patients aged 65-89 years in perioperative complications and mortality. The integrated management bundle referred to bundled application of multiple clinical measures. The aim of this study was to analyze effect of integrated management bundle on 1-year overall survival and perioperative outcomes in super elderly patients with hip fracture, with multidisciplinary management group serving as the control group. In this retrospective cohort study, super elderly patients with hip fracture were included from Jan 2017 to Nov 2020. Patients were retrospectively divided to multidisciplinary management group and integrated management bundle group. The primary outcome was 1- year overall survival, and the secondary outcome was perioperative outcomes. Kaplan-Meier methods was used to compare survival probability. Multivariable Cox's modeling was used to explain the effect of integrated bundle on 1-year overall survival adjusted for confounders. The perioperative outcomes including complications and in-hospital data of two groups were compared. The multivariable logistic regression was used to explain the effect of integrated bundle on the occurrence of perioperative complications adjusted for confounders. Prognostic factors related to survival was identified by multivariable Cox's regression analysis. Ninety-seven patients comprised multidisciplinary management group, and 83 comprised integrated management bundle group. The Kaplan-Meier plots showed that the survival probability of integrated management bundle group was significantly better than multidisciplinary management group (HR:0.435, 95%CI:0.207-0.914, P = 0.039). Multivariable analysis after adjustment for confounders showed a 42.8% lower incidence of mortality integrated management bundle group than multidisciplinary management group (HR:0.428, 95%CI:0.186-0.986, P = 0.046). Incidence of hypoproteinemia, and electrolyte disturbance in integrated management bundle group was significantly lower than multidisciplinary management group (all P < 0.05). In addition, significant reduction was observed in length of stay (P < 0.05) in integrated management bundle group. Multivariable logistic regression showed integrated management bundle was independent protective factor of hypoproteinemia, and electrolyte disturbance. mECM score ≥ 6 and ASA score > 2 were independent risk factors of overall survival (HR: 1.940, 95%CI: 1.067-3.525,P = 0.030; HR: 2.281, 95%CI: 1.113-4.678,P = 0.024). The integrated management bundle improved 1-year overall survival and played positive effects in improving perioperative outcomes. It might be a more suitable management modality for super elderly patients with hip fracture.


Negative pressure wound therapy, silver coated foam dressing and conventional bandages in open wound treatment in dogs. A retrospective comparison of 50 paired cases.
To evaluate negative pressure wound therapy (NPWT) for treatment of complicated wounds in dogs. Retrospective multicentre study. Dogs (n = 50) undergoing open wound treatment were classified according to treatment method used: bandage (Group A, n = 7), NPWT (Group B, n = 18), and foam dressing (Group C, n = 25). Pairs of patients matched based on wound conformation, localization, and underlying cause were compared between Group A and C (n = 7 pairs) and between groups B and C (n = 18 pairs) in terms of duration of previous treatment, time to closure, and complications. Signalment, antibiotic medications, antiseptic treatment, and bacterial status of wounds were comparable between groups. The duration of previous treatment was significantly higher in patients assigned to Group B (p = 0.04) compared to Group C, while no significant difference was found between groups A and B. Total time to wound closure was significantly shorter in Group C compared to Group A (p = 0.02) and in Group B compared to Group C (p = 0.003). Wounds treated with NPWT suffered significantly less complications (p = 0.008) and were significantly less septic during treatment (p = 0.016) than wounds treated with a foam dressing. This study shows that time to healing was halved in NPWT treated patients compared to foam dressing treated patients, which in turn healed faster than patients treated with conventional bandage, underlining the value of NPWT therapy for the treatment of complicated wounds.


Cysteine starvation, isoleucyl-tRNAIle, and the regulation of the ilvGEDA operon of Escherichia coli.
The involvement of undermodified tRNA in the regulation of the ilvGEDA operon has been investigated using Escherichia coli C6, a relA-, Cys-, Met- mutant. This strain accumulates thionucleotide-deficient or methyl-deficient tRNA when starved for cysteine or methionine, respectively. The levels of threonine deaminase, the ilvA gene product, and transaminase B, the ilvE gene product, were both lower in cysteine-starved cells, as compared with either growing or methionine-starved cultures. When cysteine was added to cysteine-starved cells, growth ensued promptly and both enzyme activities returned to control levels. Treatment of recovering cultures with valine limited growth by isoleucine limitation, but did not cause a derepression of the ilvGEDA operon. Valine treatment of nonstarved or methionine-starved cells led to the expected increase in threonine deaminase and transaminase B activities. Cysteine-starved cells slowly regained the ability to derepress the operon after 3 h of recovery in complete medium. In contrast, the induction of the lac operon was normal in cysteine-starved cultures, even in the presence of valine. The loss of derepressibility of the ilvGEDA operon was correlated with the presence of a kinetically and chromatographically altered tRNAIle in cysteine-starved cells. No changes in tRNAIle were observed after methionine starvation. Using the periodate method, we found that the charging of tRNAIle increased from the normal level of 60 to 80% or greater after starvation for cysteine. Under conditions where the ilvGEDA operon was fully derepressed in nonstarved cells, the charging of tRNAIle fell to 27%. Unexpectedly, nearly identical results were obtained with cysteine-starved cells after an identical derepression test. These results suggest that factors other than the aminoacylation state of tRNAIle may be important in the regulation of this operon. In particular, modifications to tRNA which involve cysteine may be necessary for controlling the expression of the ilvGEDA operon in E. coli.


Clinical trial of combination chemotherapy and specific active immunotherapy in disseminated melanoma.
Fifty-six patients with disseminated malignant melanoma were randomly allocated to two treatment groups. The first group C received combination chemotherapy consisting of DTIC and ICRF 159. The second group (C+I) received the same chemotherapy but were also immunized with 2 X 10(7) irradiated allogeneic melanoma cells mixed with 50 mug of percutaneous BCG. The survival rates in both treatment groups C and (C+I) were not significantly different, and only minor enhancement of the chemotherapy was found in the (C+I) group. A similar pattern of tissue response was observed in both groups: lymph node, skin and, to some extent liver metastases, respond better than other sites.


[Effect of autologous blood transfusion using UV-irradiated blood on the hemostasis system in patients with stomach and duodenal ulcers].
The effect of autotransfusions of blood irradiated by long-wave UV rays on the system of hemostasis was studied in 22 patients with ulcer disease of the stomach and duodenum. It was shown that transfusion of the autoblood irradiated by long-wave UV rays in a certain dosage decreased the hemostatic potential of blood improving its rheological properties and facilitated the stimulation of reparative processes.


Wounding systemically activates a mitogen-activated protein kinase in forage and turf grasses.
Forage and turf grasses are continually cut and grazed by livestock, however very little is known concerning the perception or molecular responses to wounding. Mechanical wounding rapidly activated a 46 kDa and a 44 kDa mitogen-activated protein kinase (MAPK) in six different grass species. In the model grass species Lolium temulentum, the 46 kDa MAPK was rapidly activated within 5 min of wounding both locally and systemically in an adjacent unwounded tiller. This indicates that wounding generates a rapidly propagated long-distance signal that activates a MAPK in the distal portions of the plant. This 46 kDa MAPK activity was not enhanced by the addition of the pathogen-associated signal salicylic acid (SA) to the wound site nor induced when exposed to methyl jasmonate (MJ), which is a potent inducer of the wound response in dicotyledonous plants. However, pretreatment with MJ increased the wound-induced activity of the 44 kDa MAPK over the activity in control plants.


Significance of nitrogen-fixing actinorhizal symbioses for restoration of depleted, degraded, and contaminated soil.
Atmospheric nitrogen (N2)-fixing legume trees are frequently used for the restoration of depleted, degraded, and contaminated soils. However, biological N2 fixation (BNF) can also be performed by so-called actinorhizal plants. Actinorhizal plants include a high diversity of woody species and therefore can be applied in a broad spectrum of environments. In contrast to N2-fixing legumes, the potential of actinorhizal plants for soil restoration remains largely unexplored. In this Opinion, we propose related basic research requirements for the characterization of environmental stress responses that determine the restoration potential of actinorhizal plants for depleted, degraded, and contaminated soils. We identify advantages and unexplored processes of actinorhizal plants and describe a mainly uncharted avenue of future research for this important group of plant species.


New records of the rare Troschel's Pampas Snake, Phimophis guianensis (Serpentes: Dipsadidae) in Brazil.
The Troschel's Pampas Snake, Phimophis guianensis (Troschel, 1848), is widely distributed in Amazonian Savannas at northern South America and a small portion of southern Central America, being recorded to Brazil based on three historical records, that ranged from 1997 to 2002, in Amapá and Pará states. In this study, we revise all known records of P. guianensis, providing an updated distribution map, and the first record to Roraima state.


Slug Flow Coprecipitation Synthesis of Uniformly-Sized Oxalate Precursor Microparticles for Improved Reproducibility and Tap Density of Li(Ni0.8Co0.1Mn0.1)O2 Cathode Materials.
The microparticle quality and reproducibility of Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) cathode materials are important for Li-ion battery performance but can be challenging to control directly from synthesis. Here, a scalable reproducible synthesis process is designed based on slug flow to rapidly generate uniform micron-size spherical-shape NCM oxalate precursor microparticles at 25-34 °C. The whole process takes only 10 min, from solution mixing to precursor microparticle generation, without needing aging that typically takes hours. These oxalate precursors are convertible to spherical-shape NCM811 oxide microparticles, through a preliminary design of low heating rates (e.g., 0.1 and 0.8 °C/min) for calcination and lithiation. The outcome oxide cathode particles also demonstrate improved tap density (e.g., 2.4 g mL-1 for NCM811) and good specific capacity (202 mAh g-1 at 0.1 C) in coin cells and reasonably good cycling performance with LiF coating.


High-yield production in Escherichia coli and convenient purification of a candidate vaccine against SARS-CoV-2.
The aim of the present work was to identify a time-saving, effective, and low-cost strategy to produce in Escherichia coli a protein chimera representing a fusion anti-SARS-CoV-2 candidate vaccine, consisting of immunogenic and antigenic moieties. We overexpressed in E. coli BL21(DE3) a synthetic gene coding for CRM197-RBD, and the target protein was detected in inclusion bodies. CRM197-RBD was solubilized with 1 % (w/v) of the anionic detergent N-lauroylsarcosine (sarkosyl), the removal of which from the protein solution was conveniently accomplished with Amberlite XAD-4. The detergent-free CRM197-RBD was then separated from contaminating DNA using polyethylenimine (PEI), and finally purified from PEI by salting out with ammonium sulfate. Structural (CD spectrum) and functional (DNase activity) assays revealed that the CRM197-RBD chimera featured a native and active conformation. Remarkably, we determined a yield of purified CRM197-RBD equal to 23 mg per litre of culture. To produce CRM197-RBD, we devised the use of sarkosyl as an alternative to urea to solubilize the target protein from E. coli inclusion bodies, and the easy removal of sarkosyl by means of Amberlite XAD-4.


Disparate Responses in Match Outcome across Competitive Surgical Subspecialties to Pandemic Era Constraints: An Analysis of Impacts of Minimal Auditions.
The Covid-19 pandemic eliminated nearly all visiting sub-internships. We seek to uncover match rate disparities across plastic surgery, otolaryngology, urology, and neurosurgery subspecialties with respect to in-person appraisals. These data aim to highlight the common practices as well as subtle differences that each subspecialty may be displaying in selecting their respective residency candidates. We accessed publicly available online spreadsheets between March 24 to 27 specific to the following surgical subspecialties: plastic surgery, otolaryngology, neurosurgery, and urology. We collected available information including the matched applicants' medical school, the institution at which they matched, and whether they had previous communication with their matched program. This data was then used to record whether the applicant matched at their home institution. N/A PARTICIPANTS: N/A RESULTS: There was a statistically significant increase in the number of plastic surgery and otolaryngology applicants who matched at their home programs during the 2020 to 2021 application cycle. 12.1% and 17.2% of plastic surgery applicants matched at their home program in the 2018 to 2019 and 2019 to 2020 application cycles, compared to 25.0% during the 2020 to 2021 application cycle (p = 0.0345). Overall, 23.4% and 22.2% of otolaryngology applicants matched at their home program in the 2018 to 2019 and 2019 to 2020 application cycles, compared to 31.3% during the 2020 to 2021 application cycle (p = 0.0482). Neurosurgery and urology applicants did not demonstrate statistically significant differences in home match rates during the 2020 to 2021 application cycle (p = 0.164 and p = 0.105, respectively). Covid-19 related restrictions in the 2020 to 2021 match cycle led residency programs to utilize novel selection mechanisms to evaluate applicants. Without visiting sub-internships during the 2020 to 2021 match cycle, some programs appear to have intentionally favored candidates with whom they were previously acquainted. The significantly higher number of international medical graduates and non-senior medical graduates among neurosurgery and urology residencies, respectively, likely washed out the home matching effect among these specialties but does not discount the importance of in-person appraisals.