Streptomyces tremellae sp. nov., isolated from a culture of the mushroom Tremella fuciformis.
A novel actinomycete strain, designated Js-1T, was isolated from Tremella fuciformis collected from Gutian, Fujian Province, in southeastern China. The taxonomic status of this strain was determined by a polyphasic approach, which demonstrated that the novel strain was a member of the genus Streptomyces. The cell walls of this strain were found to contain ll-diaminopimelic acid, muramic acid and glycine. An analysis of whole-cell hydrolysates revealed that no characteristic sugar was present. The key identified menaquinones were MK-9 (H6) and MK-9 (H8), while the diagnostic polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylmethylethanolamine and phosphatidylglycerol. The main cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0, C16 : 0 and iso-C16 : 0. An analysis of an almost complete 16S rRNA gene sequence showed that the strain shared the highest levels of sequence similarity with Streptomyces sannanensisKC-7038T (97.87 %), Streptomyces hebeiensis YIM 001T (97.84 %), Streptomyces pathocidini NBRC 13812T (97.80 %), Streptomyces cocklensis BK168T (97.25 %), Streptomyces coerulescens NBRC 12758T (97.12 %), Streptomyces aurantiogriseus NBRC 12842T (97.06 %) and Streptomyces rimosussubsp. rimosus ATCC 10970T (97.04 %). The DNA G+C content of the genomic DNA of strain Js-1T was 70.1 mol%. Furthermore, DNA-DNA hybridization tests revealed that the relatedness values between strain Js-1T and the most closely related species ranged from 15.10 to 47.20 %. Based on its phenotypic and genotypic characteristics, strain Js-1T (=CCTCC M 2011365T=JCM 30846T) is considered to represent a novel species within the genus Streptomyces, which we classified as Streptomycestremellae sp. nov.


REMCARE: Pragmatic Multi-Centre Randomised Trial of Reminiscence Groups for People with Dementia and their Family Carers: Effectiveness and Economic Analysis.
Joint reminiscence groups, involving people with dementia and family carers together, are popular, but the evidence-base is limited. This study aimed to assess the effectiveness and cost-effectiveness of joint reminiscence groups as compared to usual care. This multi-centre, pragmatic randomised controlled trial had two parallel arms: intervention group and usual-care control group. A restricted dynamic method of randomisation was used, with an overall allocation ratio of 1:1, restricted to ensure viable sized intervention groups. Assessments, blind to treatment allocation, were carried out at baseline, three months and ten months (primary end-point), usually in the person's home. Participants were recruited in eight centres, mainly through NHS Memory Clinics and NHS community mental health teams. Included participants were community resident people with mild to moderate dementia (DSM-IV), who had a relative or other care-giver in regular contact, to act as informant and willing and able to participate in intervention. 71% carers were spouses. 488 people with dementia (mean age 77.5)were randomised: 268 intervention, 220 control; 350 dyads completed the study (206 intervention, 144 control). The intervention evaluated was joint reminiscence groups (with up to 12 dyads) weekly for twelve weeks; monthly maintenance sessions for further seven months. Sessions followed a published treatment manual and were held in a variety of community settings. Two trained facilitators in each centre were supported by volunteers. Primary outcome measures were self-reported quality of life for the person with dementia (QoL-AD), psychological distress for the carer (General Health Questionnaire, GHQ-28). Secondary outcome measures included: autobiographical memory and activities of daily living for the person with dementia; carer stress for the carer; mood, relationship quality and service use and costs for both. The intention to treat analysis (ANCOVA) identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes (self-reported QoL-AD mean difference 0.07 (-1.21 to 1.35), F = 0.48, p = 0.53). Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a General Health Questionnaire-28 sub-scale at the ten month end-point (mean difference 1.25 (0.25 to 2.26), F = 8.28, p = 0.04). Compliance analyses suggested improved autobiographical memory, quality of life and relationship quality for people with dementia attending more reminiscence sessions, however carers attending more groups showed increased care-giving stress. Economic analyses from a public sector perspective indicated that joint reminiscence groups are unlikely to be cost-effective. There were no significant adverse effects attributed to the intervention. Potential limitations of the study include less than optimal attendance at the group sessions--only 57% of participants attended at least half of the intervention sessions over the 10 month period, and a higher rate of study withdrawal in the control group. This trial does not support the clinical effectiveness or cost-effectiveness of joint reminiscence groups. Possible beneficial effects for people with dementia who attend sessions as planned are offset by raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions. ISRCTN Registry ISRCTN42430123.


MINRbase: a comprehensive database of nuclear- and mitochondrial-ribosomal-RNA-derived fragments (rRFs).
We describe the Mitochondrial and Nuclear rRNA fragment database (MINRbase), a knowledge repository aimed at facilitating the study of ribosomal RNA-derived fragments (rRFs). MINRbase provides interactive access to the profiles of 130 238 expressed rRFs arising from the four human nuclear rRNAs (18S, 5.8S, 28S, 5S), two mitochondrial rRNAs (12S, 16S) or four spacers of 45S pre-rRNA. We compiled these profiles by analyzing 11 632 datasets, including the GEUVADIS and The Cancer Genome Atlas (TCGA) repositories. MINRbase offers a user-friendly interface that lets researchers issue complex queries based on one or more criteria, such as parental rRNA identity, nucleotide sequence, rRF minimum abundance and metadata keywords (e.g. tissue type, disease). A 'summary' page for each rRF provides a granular breakdown of its expression by tissue type, disease, sex, ancestry and other variables; it also allows users to create publication-ready plots at the click of a button. MINRbase has already allowed us to generate support for three novel observations: the internal spacers of 45S are prolific producers of abundant rRFs; many abundant rRFs straddle the known boundaries of rRNAs; rRF production is regimented and depends on 'personal attributes' (sex, ancestry) and 'context' (tissue type, tissue state, disease). MINRbase is available at https://cm.jefferson.edu/MINRbase/.


Do PPAR-Gamma Agonists Have a Future in Parkinson's Disease Therapy?
Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor (PPAR)-γ agonists commonly used as insulin-sensitizing drugs for the treatment of type 2 diabetes. In the last decade, PPAR-γ agonists have received increasing attention for their neuroprotective properties displayed in a variety of neurodegenerative diseases, including Parkinson's disease (PD), likely related to the anti-infammatory activity of these compounds. Recent studies indicate that neuroinflammation, specifically reactive microglia, plays important roles in PD pathogenesis. Moreover, after the discovery of infiltrating activated Limphocytes in the substantia nigra (SN) of PD patients, most recent research supports a role of immune-mediated mechanisms in the pathological process leading to chronic neuroinflammation and dopaminergic degeneration. PPAR-γ are highly expressed in cells of both central and peripheral immune systems, playing a pivotal role in microglial activation as well as in monocytes and T cells differentiation, in which they act as key regulators of immune responses. Here, we review preclinical evidences of PPAR-γ-induced neuroprotection in experimental PD models and highlight relative anti-inflammatory mechanisms involving either central or peripheral immunomodulatory activity. Specific targeting of immune functions contributing to neuroinflammation either directly (central) or indirectly (peripheral) may represent a novel therapeutic approach for disease modifying therapies in PD.


Analysis of human tear fluid by Fourier transform infrared spectroscopy.
The purpose of this research is to find some useful spectroscopic factors in human tear fluid contents to monitor diurnal changes of the physicochemical ocular conditions noninvasively. All tear fluid samples were collected with glass microcapillary tubes from both eyes of three donors and analyzed by Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR). We measured the peak intensities at 2852, 1735, 1546, and 1242 cm(-1), and the peak intensity ratios among those peaks in the second derivative spectra. We found significant diurnal and individual variations in those peak intensities for tear fluid obtained from right and left eyes. Among these variations, we observed significant changes in tear samples between right and left eyes. In this case the peak intensity ratio between 1242 (phosphate ester) and 2852 cm(-1) (fatty acid methylene) of right eye tear fluid was increased in the afternoon (1600 to 1900 h), while that of left eye tear fluid did not change significantly. In the ratio between 1242 (phosphate ester) and 1546 cm(-1) (amide II), the difference was not observed between both eyes. We conclude that the difference in diurnal variations of biochemical constituents between right and left eye tear fluids could be monitored noninvasively and nondestructively by FTIR technique and this method could be useful in the future for tear diagnoses.


The sandwich generation copes with elder care.
The "sandwich generation" refers to the demographic age group of individuals who are caring for young children and elder parents at the same time. The increasing number of employees who must care for children and parents alike is a trend that is projected to continue. This is a burdensome responsibility that can cause stress and result in loss of productivity, accompanied by higher cost, to employers. The author discusses elder-care services that employers can offer to enhance productivity and gives case examples of companies that are making elder-care benefits available to employees.


Robust size control of bovine serum albumin (BSA) nanoparticles by intermittent addition of a desolvating agent and the particle formation mechanism.
In polymeric nanoparticle preparation, despite similar conditions, large fluctuations in particle size distributions are usually observed. Herein, we demonstrate that the intermittent addition of a desolvating agent can improve reproducibility in the preparation of polymeric bovine serum albumin (BSA) nanoparticles. Using this modification, BSA nanoparticles of controlled size can be manufactured with narrow particle size distributions. In our study, ethanol as a desolvating agent was added intermittently to 1% BSA solutions at different pHs with stirring at 700rpm. The effect of the preparation parameters on size and optical density of the fabricated nanoparticles were studied. The average particles sizes of BSA nanoparticles prepared at pH values of 6, 7 and 9 were approximately 100, 200 and 300nm, respectively. As ethanol addition increased, desolvation of BSA molecules resulted in formation of loose-structured particles with pH-dependent size. Beyond that, only particle density increased, but size remained unchanged with further addition of ethanol. Consistently uniform particle size distribution was achieved by adding ethanol intermittently.


Adapting symptom validity testing to evaluate suspicious complaints of amnesia in medicolegal evaluations.
Symptom validity testing was adapted to assess suspicious complaints of amnesia. In the adaptation, two-alternative, forced-choice memory questions were generated for subject matter claimed to be forgotten. The number of questions correctly answered was then compared to the expected number of questions to be correctly answered if no knowledge actually existed. Three case studies are presented, two of competency-to-stand-trial evaluees and one of an insurance medical examinee. In each case, the use of this procedure generated the conclusion that the knowledge claimed to be forgotten was actually remembered; however, not all individuals were classified as malingerers.


Disinfection of bacterial biofilms in pilot-scale cooling tower systems.
The impact of continuous chlorination and periodic glutaraldehyde treatment on planktonic and biofilm microbial communities was evaluated in pilot-scale cooling towers operated continuously for 3 months. The system was operated at a flow rate of 10,080 l day(-1). Experiments were performed with a well-defined microbial consortium containing three heterotrophic bacteria: Pseudomonas aeruginosa, Klebsiella pneumoniae and Flavobacterium sp. The persistence of each species was monitored in the recirculating cooling water loop and in biofilms on steel and PVC coupons in the cooling tower basin. The observed bacterial colonization in cooling towers did not follow trends in growth rates observed under batch conditions and, instead, reflected differences in the ability of each organism to remain attached and form biofilms under the high-through flow conditions in cooling towers. Flavobacterium was the dominant organism in the community, while P. aeruginosa and K. pneumoniae did not attach well to either PVC or steel coupons in cooling towers and were not able to persist in biofilms. As a result, the much greater ability of Flavobacterium to adhere to surfaces protected it from disinfection, whereas P. aeruginosa and K. pneumoniae were subject to rapid disinfection in the planktonic state.


Myeloid ATP Citrate Lyase Regulates Macrophage Inflammatory Responses In Vitro Without Altering Inflammatory Disease Outcomes.
Macrophages are highly plastic, key regulators of inflammation. Deregulation of macrophage activation can lead to excessive inflammation as seen in inflammatory disorders like atherosclerosis, obesity, multiple sclerosis and sepsis. Targeting intracellular metabolism is considered as an approach to reshape deranged macrophage activation and to dampen the progression of inflammatory disorders. ATP citrate lyase (Acly) is a key metabolic enzyme and an important regulator of macrophage activation. Using a macrophage-specific Acly-deficient mouse model, we investigated the role of Acly in macrophages during acute and chronic inflammatory disorders. First, we performed RNA sequencing to demonstrate that Acly-deficient macrophages showed hyperinflammatory gene signatures in response to acute LPS stimulation in vitro. Next, we assessed endotoxin-induced peritonitis in myeloid-specific Acly-deficient mice and show that, apart from increased splenic Il6 expression, systemic and local inflammation were not affected by Acly deficiency. Also during obesity, both chronic low-grade inflammation and whole-body metabolic homeostasis remained largely unaltered in mice with Acly-deficient myeloid cells. Lastly, we show that macrophage-specific Acly deletion did not affect the severity of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis. These results indicate that, despite increasing inflammatory responses in vitro, macrophage Acly deficiency does not worsen acute and chronic inflammatory responses in vivo. Collectively, our results indicate that caution is warranted in prospective long-term treatments of inflammatory disorders with macrophage-specific Acly inhibitors. Together with our earlier observation that myeloid Acly deletion stabilizes atherosclerotic lesions, our findings highlight that therapeutic targeting of macrophage Acly can be beneficial in some, but not all, inflammatory disorders.


Evaluating Non-operative Robotic Skills in Colorectal Surgical Training.
Robotic-assisted surgery has become a common platform for performing colorectal procedures. Educators must determine how best to teach and train residents to use the technology safely. There is a paucity of literature on how non-operative skills are being taught and integrated into colorectal training. Herein we describe the implementation and assessment of a pilot simulation-based Robotic Colorectal Surgery Non-Technical Skills curriculum. Since 2017 six colon and rectal surgery residents participated in two scenarios: pelvic bleeding and CO2 embolism. The scenarios were administered in a simulated operating room twice during the academic year (fall and spring), and audio-video recorded. In addition to self-assessment, videos were evaluated by faculty utilizing the validated Interpersonal and Cognitive Assessment for Robotic Surgery system. To understand the role of scenario difficulty with respect to perceived cognitive workload and performance residents completed a NASA-Task Load Index assessment form. Between the fall and spring sessions residents significantly improved in intraoperative leadership skills for both the CO2 embolism and bleeding scenarios, and decision-making and situational awareness for the embolism case. Assessment between resident (self) and expert (faculty) did not correlate (P < 0.05) for either scenario during the fall session. A correlation for both scenarios was appreciated following the spring session revealing resident non-technical skills improved over time. Other than for physical demand, NASA-Task Load Index scores were similar for both scenarios. We were able to successfully develop and implement a pilot Robotic Colorectal Surgery Non-Technical Skills curriculum in a risk-free simulated environment. Non-technical skill curriculums should be considered for both training and assessment in robotic surgery.


Effects of a single nucleotide polymorphism in the chicken NK-lysin gene on antimicrobial activity and cytotoxicity of cancer cells.
NK-lysin is an effector protein of the innate immune system and an important component of host protection. We isolated a SNP in the NK-lysin coding sequence among different chicken breeds. This A to G substitution at the position 271 nucleotide in the ORF results in an Asn (N) to Asp (D) amino acid alteration. We synthesized two 30-aa peptides (N29N and N29D) to compare the biological activity of the helix 2-loop-helix 3 region of NK-lysin resulting from the polymorphic gene. Both peptides were found to be cytotoxic in bacteria and tumor cell cultures at micromolar concentrations. The N29N peptide, however, exhibited greater antibacterial and anticancer activity than the N29D peptide. Circular dichroism spectroscopy of the two peptides in negatively charged single unilamellar vesicles showed spectra typical of α-helical peptides. The helical profile of N29D was reduced substantially compared with that of N29N. However, no structural change was observed in neutral vesicles. ζ-Potential measurements of liposomes incubated with increasing peptide concentrations allowed surface charge neutralization with a negatively charged lipid, but not with a zwitterionic lipid. This result suggests that a difference in electrostatic interaction between lipid membranes and the helical peptides results from the polymorphic gene and is subsequently an important factor in cell lytic activity of variant NK-lysin peptides.


Rebates to Incentivize Healthy Nutrition Choices in the Supplemental Nutrition Assistance Program.
Price incentives, or rebates, have been proposed as one promising strategy for improving diet quality among Supplemental Nutrition Assistance Program participants. This paper explores the existing evidence on effectiveness of rebates in this program. In particular, this paper considers findings from a recent RCT of Supplemental Nutrition Assistance Program rebates, the U.S. Department of Agriculture Healthy Incentives Pilot, in the context of the broader literature on rebate strategies. The paper concludes that rebates have a moderate impact on food intake, at moderate cost relative to alternative interventions. There is further evidence that implicit promotional effects may contribute to impacts of rebate interventions, beyond the impacts of price effects alone. However, existing studies on complementary effects of explicit promotion have been limited by relatively small sample sizes and correspondingly low power to detect differences. This appears to be a promising area for future research.


Highly Stable Perovskite Solar Cells Based on the Efficient Interaction between Pb2+ and Cyano Groups of 4-Aminophthalonitrile.
Defects present on the top surface of perovskite films have a pronounced detrimental impact on the photovoltaic performance and stability of perovskite solar cells (PSCs). Consequently, the development of effective defect passivation strategies has become key in enhancing both the power conversion efficiency (PCE) and stability of PSCs. In this study, a small molecule material, 4-Aminophthalonitrile (4-APN), was introduced as a means to mitigate surface defects within perovskite films. Obviously, 4-APN effectively passivates the defects at grain boundaries by combining cyano groups (-C≡N) with Pb2+ , significantly reducing the density of defect states, inhibiting non-radiative recombination at the interface, and promoting the charge transfer efficiency from the perovskite layer to the hole transport layer. The 4-APN modification led to a significant upswing in the PCE, while concurrently bolstering the overall device stability. Importantly, the devices on 4-APN as passivation additive exhibited negligible performance degradation aging for 1200 h.


Post-meal endogenous insulin secretion was significantly lower in head than in body/tail cancer of the pancreas.
Pancreatic cancer, a rapidly progressive malignancy, is often diagnosed in patients with diabetes. The incidence of pancreatic cancer has risen dramatically over recent decades. Early diagnosis of this malignancy is generally difficult because the symptoms do not become apparent until the disease has progressed, generally leading to a poor outcome. To achieve earlier diagnosis, we analyzed the clinical characteristics of pancreatic cancer patients showing deterioration of plasma glucose levels while hospitalized. Thirty-six cases were divided into 2 groups;those diagnosed with diabetes more than a year prior to identification of pancreatic cancer and diabetes secondary to pancreatic cancer. These 2 groups were further subdivided according to the tumor site (head or body/tail), allowing analysis of 4 subgroups. Anthropometric measurements, laboratory values were determined. Both groups with diabetes lost at least 4 kg and showed HbA1c deterioration of at least 1% within 5 months of the pancreatic cancer diagnosis. The post-meal elevation of serum C-peptide immunoreactivity (CPR) was significantly decreased in the group with cancer of the pancreatic head, and this was unrelated to tumor size. Characteristically, pancreatic head cancer was associated with decreased endogenous insulin secretion as compared to body/tail cancer. J. Med. Invest. 70 : 350-354, August, 2023.


Fluorescence behaviour of 2-, 3- and 4-amino-1,8-naphthalimides: effects of the substitution positions of the amino functionality on the photophysical properties.
The absorption and fluorescence spectra of a series of 1,8-naphthalimide derivatives incorporating the amino functionality at the 2-, 3- and 4-positions of the naphthalene ring (2APNI, 3APNI and 4APNI, respectively) were systematically investigated in various solvents and in the solid state. The fluorescence spectra of 2APNI were insensitive to solvent polarity and intermolecular hydrogen-bonding even in a protic medium such as methanol. Thus, 2APNI displayed blue fluorescence with a moderate fluorescence quantum yield (λFmax = 420-445 nm, ΦF 0.2-0.3) in the solvents investigated. In contrast, the fluorescence spectra of 3APNI and 4APNI were strongly solvent dependent showing positive solvatofluorochromism with large Stokes shifts. Upon increasing the solvent polarity, the fluorescence colours changed from blue in hexane (λFmax = 429 nm) to orange-yellow in methanol (λFmax = 564 nm) for 3APNI, and from blue in hexane (λFmax = 460 nm) to yellow in methanol (λFmax = 538 nm) for 4APNI. The fluorescence quantum yields of 3APNI and 4APNI decreased with increasing solvent polarity. In the solid state, APNIs displayed red-shifted fluorescence emission compared to that in solution (λFmax = 541 nm for 2APNI, 575 nm for 3APNI, and 561 nm for 4APNI) and the fluorescence quantum yields in the solid state were lower than those in solution.


Image content is more important than Bouma's Law for scene metamers.
We subjectively perceive our visual field with high fidelity, yet peripheral distortions can go unnoticed and peripheral objects can be difficult to identify (crowding). Prior work showed that humans could not discriminate images synthesised to match the responses of a mid-level ventral visual stream model when information was averaged in receptive fields with a scaling of about half their retinal eccentricity. This result implicated ventral visual area V2, approximated 'Bouma's Law' of crowding, and has subsequently been interpreted as a link between crowding zones, receptive field scaling, and our perceptual experience. However, this experiment never assessed natural images. We find that humans can easily discriminate real and model-generated images at V2 scaling, requiring scales at least as small as V1 receptive fields to generate metamers. We speculate that explaining why scenes look as they do may require incorporating segmentation and global organisational constraints in addition to local pooling.


Electronic Nose Sensor Drift Affects Diagnostic Reliability and Accuracy of Disease-Specific Algorithms.
Sensor drift is a well-known disadvantage of electronic nose (eNose) technology and may affect the accuracy of diagnostic algorithms. Correction for this phenomenon is not routinely performed. The aim of this study was to investigate the influence of eNose sensor drift on the development of a disease-specific algorithm in a real-life cohort of inflammatory bowel disease patients (IBD). In this multi-center cohort, patients undergoing colonoscopy collected a fecal sample prior to bowel lavage. Mucosal disease activity was assessed based on endoscopy. Controls underwent colonoscopy for various reasons and had no endoscopic abnormalities. Fecal eNose profiles were measured using Cyranose 320®. Fecal samples of 63 IBD patients and 63 controls were measured on four subsequent days. Sensor data displayed associations with date of measurement, which was reproducible across all samples irrespective of disease state, disease activity state, disease localization and diet of participants. Based on logistic regression, corrections for sensor drift improved accuracy to differentiate between IBD patients and controls based on the significant differences of six sensors (p = 0.004; p < 0.001; p = 0.001; p = 0.028; p < 0.001 and p = 0.005) with an accuracy of 0.68. In this clinical study, short-term sensor drift affected fecal eNose profiles more profoundly than clinical features. These outcomes emphasize the importance of sensor drift correction to improve reliability and repeatability, both within and across eNose studies.


American Mock World Health Organization: An Innovative Model for Student Engagement in Global Health Policy.
The American Mock World Health Organization (AMWHO) is a model for experiential-based learning and student engagement in global health diplomacy. AMWHO was established in 2014 at the University of North Carolina at Chapel Hill with a mission to engage students in health policy by providing a simulation of the World Health Assembly (WHA), the policy-forming body of the World Health Organization that sets norms and transforms the global health agenda. AMWHO conferences are designed to allow students to take their knowledge of global health beyond the classroom and practice their skills in diplomacy by assuming the role of WHA delegates throughout a 3-day weekend. Through the process of developing resolutions like those formed in the WHA, students have the unique opportunity to understand the complexities behind the conflict and compromise that ensues through the lens of a stakeholder. This article describes the structure of the first 2 AMWHO international conferences, analyzes survey results from attendees, and discusses the expansion of the organization into a multi-campus national network. The AMWHO 2014 and 2015 post-conference survey results found that 98% and 90% of participants considered the conference "good" or "better," respectively, and survey responses showed that participants considered the conference "influential" in their careers and indicated that it "allowed a paradigm shift not possible in class."


Strategies for Maintaining Mouse Mutations.
Rules for naming a new mutation are provided. The majority of new mutations are recessive and thus easily maintained in a mouse strain. Considerations on the choice of genetic background are given, depending on how the mutant was produced and how you intend to analyze it. General information on maintaining a mutant colony to perpetuate the mutation and to efficiently produce homozygous mutant mice for analysis is provided. Also discussed are special breeding techniques to delete a selection cassette in vivo, if you produced the mutation in embryonic stem (ES) cells, and to maintain a mutant with a balancer chromosome. In the event of either male or female infertility in the heterozygotes, assisted reproductive techniques may be necessary.


Extraction methods and test techniques for detection of vegetable proteins in meat products. I. Qualitative detection of soya derivatives.
Extracts of 3 soya bean preparations, used commercially in certain countries to replace part of the meat in popular meat products, were made by treatment with (i) sodium dodecyl sulphate, (ii) Triton-X100 or (iii) n-Butanol. Similar extracts were made from beef and pork. All extracts were examined by electrophoretic and immunological techniques. Stained polyacrylamide gels revealed distinctive protein bands after electrophoresis. The migration rates of corresponding bands differed between beef and pork extracts. However, the migration rates of vegetable bands revealed certain similarities, but differed very greatly from those of animal origin. Characteristic fast-migrating S-bands were distinguishable only in extracts of vegetable protein. Immunodiffusion tests, using antisera produced in rabbits against each extract, revealed varying degrees of similarity between extracts of vegetable origin, but the antisera were specific for either vegetable or animal protein.


Scattered lamellar microholes as a complication of epiretinal membranes.
The authors present two cases of an unusual pattern of the fundus corresponding to multiple "scattered lamellar microholes" located at the periphery of thick and contractile idiopathic epiretinal membranes. The retinal defects were documented with blue reflectance fundus photographs and three-dimensional spectral domain optical coherence tomography. They seem to correspond to multiple small areas of partial-thickness or lamellar disruptions of the retina. The authors suggest that the contraction of the epiretinal membrane may have caused tangential traction on the adjacent inner retina, creating disruptions in the internal limiting membrane and inner retina.


Identification of dendritic cell precursor from the CD11c+ cells expressing high levels of MHC class II molecules in the culture of bone marrow with FLT3 ligand.
Dendritic cells (DCs) are readily generated from the culture of mouse bone marrow (BM) treated with either granulocyte macrophage-colony stimulating factor (GM-CSF) or FMS-like tyrosine kinase 3 ligand (FLT3L). CD11c+MHCII+ or CD11c+MHCIIhi cells are routinely isolated from those BM cultures and generally used as in vitro-generated DCs for a variety of experiments and therapies. Here, we examined CD11c+ cells in the BM culture with GM-CSF or FLT3L by staining with a monoclonal antibody 2A1 that is known to recognize mature or activated DCs. Most of the cells within the CD11c+MHCIIhi DC gate were 2A1+ in the BM culture with GM-CSF (GM-BM culture). In the BM culture with FLT3L (FL-BM culture), almost of all the CD11c+MHCIIhi cells were within the classical DC2 (cDC2) gate. The analysis of FL-BM culture revealed that a majority of cDC2-gated CD11c+MHCIIhi cells exhibited a 2A1-CD83-CD115+CX3CR1+ phenotype, and the others consisted of 2A1+CD83+CD115-CX3CR1- and 2A1-CD83-CD115-CX3CR1- cells. According to the antigen uptake and presentation, morphologies, and gene expression profiles, 2A1-CD83-CD115-CX3CR1- cells were immature cDC2s and 2A1+CD83+CD115-CX3CR1- cells were mature cDC2s. Unexpectedly, however, 2A1-CD83-CD115+CX3CR1+ cells, the most abundant cDC2-gated MHCIIhi cell subset in FL-BM culture, were non-DCs. Adoptive cell transfer experiments in the FL-BM culture confirmed that the cDC2-gated MHCIIhi non-DCs were precursors to cDC2s, i.e., MHCIIhi pre-cDC2s. MHCIIhi pre-cDC2s also expressed the higher level of DC-specific transcription factor Zbtb46 as similarly as immature cDC2s. Besides, MHCIIhi pre-cDC2s were generated only from pre-cDCs and common DC progenitor (CDP) cells but not from monocytes and common monocyte progenitor (cMoP) cells, verifying that MHCIIhi pre-cDC2s are close lineage to cDCs. All in all, our study identified and characterized a new cDC precursor, exhibiting a CD11c+MHCIIhiCD115+CX3CR1+ phenotype, in FL-BM culture.


Rapid Analysis of 239,238Pu, 241Am, and 90Sr for Nasal Smear Samples in Radiation Emergency and Evaluation of Intake Retention Fraction.
The efficiency of the nasal smear method was reviewed to perform a method of sample collection, analysis and initial dose estimation. The screening method of alpha-emitting radionuclides using chemical separation and alpha spectrometry was also studied. To rapidly conduct the appropriate response to victims, special monitoring for Pu, Am, and Sr using sequential analysis was established, and the method was successfully validated through participation in an international inter-comparison program. The duration of the analysis method was evaluated with regard to application in emergency situations because of its relatively rapid treatment and counting time. The intake retention fraction was calculated and evaluated to review the characteristics of each radionuclide in the anterior nasal passage of the extra-thoracic region. No large difference was observed among the four radionuclides. However, the values of the intake retention fraction were affected by age groups because of the different respiratory rates. The effects of the Y ingrowth and particle size were also discussed.


Conscious sedation of children with propofol is anything but conscious.
To determine the depth of sedation required for bone marrow aspiration and intrathecal injection of chemotherapeutic agents in children using a bispectral (BIS) index monitor and clinical assessment by an independent observer. Sixteen children who were undergoing 19 intrathecal chemotherapy and bone marrow aspirations were enrolled in the study. Their ages ranged from 23 months to 190 months with a mean of 79 months. The BIS index was recorded every 5 minutes by an independent observer. The patients received only intravenous propofol for sedation. There were no complications during the procedures. The mean BIS score was 62.8+/- 9.6. The mean low BIS score was 29.7 +/- 13.7, indicating a level of deep sedation and/or general anesthesia was necessary to induce the desired stated of consciousness that would permit the practitioner to perform the procedure. The average dose of propofol was 166 +/- 47 microg/kg/min. Mean Aldrete score for level of consciousness was 0.9 +/- 0.4, indicating a depressed level of consciousness. The mean activity level was 1.0+/- 0.4, indicating impaired movement. Children who undergo conscious sedation with propofol for intrathecal chemotherapy and bone marrow aspiration demonstrate BIS values and clinical assessments consistent with deep sedation. Because of an increased risk of adverse events when children undergo deep sedation, appropriate parental informed consent, age-appropriate resuscitative equipment, and skilled anesthesia personnel should be present for rescue in the event of cardiovascular and respiratory complications from deep sedation.


Closed-loop training of attention with real-time brain imaging.
Lapses of attention can have negative consequences, including accidents and lost productivity. Here we used closed-loop neurofeedback to improve sustained attention abilities and reduce the frequency of lapses. During a sustained attention task, the focus of attention was monitored in real time with multivariate pattern analysis of whole-brain neuroimaging data. When indicators of an attentional lapse were detected in the brain, we gave human participants feedback by making the task more difficult. Behavioral performance improved after one training session, relative to control participants who received feedback from other participants' brains. This improvement was largest when feedback carried information from a frontoparietal attention network. A neural consequence of training was that the basal ganglia and ventral temporal cortex came to represent attentional states more distinctively. These findings suggest that attentional failures do not reflect an upper limit on cognitive potential and that attention can be trained with appropriate feedback about neural signals.


Continuous Glucose Monitoring Integration for Remote Diabetes Management: Virtual Diabetes Care with Case Studies.
Use of telemedicine and remote monitoring technologies can significantly improve glycemic control in patients with type 1 diabetes and type 2 diabetes. Patients' ability to interact remotely with their health care providers via smartphones and other communication devices can increase their access to clinical care and online coaching and support programs. The establishment of metrics for clinical use of continuous glucose monitoring data and standardization of data reporting has enabled clinicians to maintain high-quality diabetes care through remote monitoring and telemedicine visits during the COVID-19 pandemic. This article discusses our experiences using remote monitoring and telemedicine visits during this time.


A synonymous polymorphic variation in ACADM exon 11 affects splicing efficiency and may affect fatty acid oxidation.
In recent studies combining genome-wide association and tandem-MS based metabolic profiling, a single-nucleotide polymorphism (SNP), rs211718C>T, located far upstream of the MCAD gene (ACADM) was found to be associated with serum concentrations of medium-chain acylcarnitines indicating improved beta-oxidation of medium-chain fatty acids. We examined the functional basis for this association and identified linkage between rs211718 and the intragenic synonymous polymorphic variant c.1161A>G in ACADM exon 11 (rs1061337). Employing minigene studies we show that the c.1161A allele is associated with exon 11 missplicing, and that the c.1161G allele corrects this missplicing. This may result in production of more full length MCAD protein from the c.1161G allele. Our analysis suggests that the improved splicing of the c.1161G allele is due to changes in the relative binding of splicing regulatory proteins SRSF1 and hnRNP A1. Using publicly available pre-aligned RNA-seq data, we find that the ACADM c.1161G allele is expressed at significantly higher levels than the c.1161A allele across different tissues. This supports that c.1161A>G is a functional SNP, which leads to higher MCAD expression, perhaps due to improved splicing. This study is a proof of principle that synonymous SNPs are not neutral. By changing the binding sites for splicing regulatory proteins they can have significant effects on pre-mRNA splicing and thus protein function. In addition, this study shows that for a sequence variation to have an effect, it might need to change the balance in the relative binding of positive and negative splicing factors.


[Sanation of biliary system using antiseptic decasan in complex treatment of cholangitis].
Experience of treatment of 17 patients, suffering cholangitis of various genesis, using antiseptic Decasan, is presented. Clinical efficacy of the preparation in complex treatment of cholangitis, confirmed by results of the bile bacteriological investigation, was noted.


Gp91phox contributes to NADPH oxidase activity in aortic fibroblasts but not smooth muscle cells.
Reactive oxygen species (ROS) derived from vascular NADPH oxidase are important in normal and pathological regulation of vessel growth and function. Cell-specific differences in expression and function of the catalytic subunit of NADPH oxidase may contribute to differences in vascular cell response to NADPH oxidase activation. We examined the functional expression of gp91phox on NADPH oxidase activity in vascular smooth muscle cells (SMC) and fibroblasts (FB). As measured by dihydroethidium fluorescence in situ, superoxide (O2-*) levels were greater in adventitial cells compared with medial SMC in wild-type aorta. In contrast, there was no difference in O2-* levels between adventitial cells and medial SMC in aorta from gp91phox-deficient (gp91phox KO) mice. Adventitial-derived FB and medial SMC were isolated from the aorta of wild-type and gp91phox KO mice and grown in culture. Consistent with the observations in situ, basal and stimulated ROS levels were reduced in FB isolated from aorta of gp91phox KO compared with FB from wild-type aorta, whereas ROS levels were similar in SMC derived from gp91phox KO and wild-type aorta. There were no differences in expression of superoxide dismutase between gp91phox KO and wild-type FB to account for these observations. Because gp91phox is associated with membranes, we examined NADPH-stimulated O2-. production in membrane-enriched fractions of cell lysate. As measured by chemiluminescence, NADPH oxidase activity was markedly greater in wild-type FB compared with gp91phox KO FB but did not differ among the SMCs. Confirming functional expression of gp91phox in FB, antisense to gp91phox decreased ROS levels in wild-type FB. Finally, deficiency of gp91phox did not alter expression of the gp91phox homolog NOX4 in isolated FB. We conclude that the neutrophil subunit gp91phox contributes to NADPH oxidase function in vascular FB, but not SMC.


Sirtuin/Sir2 phylogeny, evolutionary considerations and structural conservation.
The sirtuins are a protein family named after the first identified member, S. cerevisiae Sir2p. Sirtuins are protein deacetylases whose activity is dependent on NAD(+) as a cosubstrate. They are structurally defined by two central domains that together form a highly conserved catalytic center, which catalyzes the transfer of an acetyl moiety from acetyllysine to NAD(+), yielding nicotinamide, the unique metabolite O-acetyl-ADP-ribose and deacetylated lysine. One or more sirtuins are present in virtually all species from bacteria to mammals. Here we describe a phylogenetic analysis of sirtuins. Based on their phylogenetic relationship, sirtuins can be grouped into over a dozen classes and subclasses. Humans, like most vertebrates, have seven sirtuins: SIRT1-SIRT7. These function in diverse cellular pathways, regulating transcriptional repression, aging, metabolism, DNA damage responses and apoptosis. We show that these seven sirtuins arose early during animal evolution. Conserved residues cluster around the catalytic center of known sirtuin family members.


Dehydrocorydaline alleviates sleep deprivation-induced persistent postoperative pain in adolescent mice through inhibiting microglial P2Y12 receptor expression in the spinal cord.
During adolescence, a second period of central nervous system (CNS) plasticity that follows the fetal period, which involves sleep deprivation (SD), becomes apparent. SD during adolescence may result in abnormal development of neural circuits, causing imbalance in neuronal excitation and inhibition, which not only results in pain, but increases the chances of developing emotion disorders in adulthood, such as anxiety and depression. The quantity of surgeries during adolescence is also consistently on the rise, yet the impact and underlying mechanism of preoperative SD on postoperative pain remain unexplored. This study demonstrates that preoperative SD induces upregulation of the P2Y12 receptor, which is exclusively expressed on spinal microglia, and phosphorylation of its downstream signaling pathway p38Mitogen-activated protein/Nuclear transcription factor-κB (p38MAPK/NF-κB )in spinal microglia, thereby promoting microglia activation and microglial transformation into the proinflammatory M1 phenotype, resulting in increased expression of proinflammatory cytokines that exacerbate persisting postoperative incisional pain in adolescent mice. Both intrathecal minocycline (a microglia activation inhibitor) and MRS2395 (a P2Y12 receptor blocker) effectively suppressed microglial activation and proinflammatory cytokine expression. Interestingly, supplementation with dehydrocorydaline (DHC), an extract of Rhizoma Corydalis, inhibited the P2Y12/p38MAPK/NF-κB signaling pathway, microglia activation, and expression of pro-inflammatory cytokines in the model mice. Taken together, the results indicate that the P2Y12 receptor and microglial activation are important factors in persistent postoperative pain caused by preoperative SD in adolescent mice and that DHC has analgesic effects by acting on these targets.


The genetics of extreme longevity: lessons from the new England centenarian study.
The New England Centenarian Study (NECS) was founded in 1994 as a longitudinal study of centenarians to determine if centenarians could be a model of healthy human aging. Over time, the NECS along with other centenarian studies have demonstrated that the majority of centenarians markedly delay high mortality risk-associated diseases toward the ends of their lives, but many centenarians have a history of enduring more chronic age-related diseases for many years, women more so than men. However, the majority of centenarians seem to deal with these chronic diseases more effectively, not experiencing disability until well into their nineties. Unlike most centenarians who are less than 101 years old, people who live to the most extreme ages, e.g., 107+ years, are generally living proof of the compression of morbidity hypothesis. That is, they compress morbidity and disability to the very ends of their lives. Various studies have also demonstrated a strong familial component to extreme longevity and now evidence particularly from the NECS is revealing an increasingly important genetic component to survival to older and older ages beyond 100 years. It appears to us that this genetic component consists of many genetic modifiers each with modest effects, but as a group they can have a strong influence.


Pregnancy rate after timed artificial insemination in early post-partum dairy cows after Ovsynch or specific synchronization protocols.
The present study was designed to compare the reproductive performance of pre-synchronized post-partum dairy cows subjected, either to the Ovsynch protocol without screening for ovarian status (control group), or to a specific oestrous synchronization protocol applied according to their ovarian status, as determined by transrectal ultrasound (experimental group). The study was conducted on 428 lactating dairy cows. Cows in the Ovsynch group (n = 205) were synchronized and time inseminated after receiving the Ovsynch protocol treatment. Cows in the specific synchronization (Ssynch) group (n = 223) were weekly subjected to transrectal ultrasound exams for 4 weeks, or until AI or starting treatment, and divided into four subgroups according to their ovarian status: (i). corpus luteum (CL) subgroup (n = 130), cows with a CL; (ii). natural oestrus (NE) subgroup (n = 58), cows showing NE; (iii). anovulatory follicles (AF) subgroup (n = 26), cows considered to have AF; and (iv). ovarian cysts (OC) subgroup (n = 9), cows with OC. Cows in the Ssynch group were synchronized and time inseminated following a specific oestrous synchronization protocol, or inseminated at NE. Logistic regression analysis was carried out for the dependent variables ovulation and pregnancy rates to first and to second AI (second AI: first AI + return AI). Cows subjected to Ssynch were 2.1 times more likely to become pregnant at first and at second AI compared with those synchronized using the Ovsynch protocol (P < 0.0001). Our results show that the response of post-partum pre-synchronized cows to a specific oestrous synchronization protocol applied according to their ovarian status is more effective than the response to the Ovsynch protocol applied without taking into account the ovarian status of the animals.


Cultural hair practices, physical activity, and obesity among urban African-American girls.
Hair holds cultural meaning and value for women of African descent. The values placed on hair type and hair style date back to preslavery days. There is a small body of literature that addresses the relationship between cultural hair practices and physical inactivity among black women. Understanding this is important because inactivity during childhood and adolescent years contributes to increased weight-related morbidity and mortality during adult years. The purpose of this study was to determine the relationship between cultural hair practices, physical activity, and obesity among urban African-American adolescent girls. A convenience sample of 50 African-American girls completed questionnaires and were weighed and measured for body mass index (BMI) calculation. Cultural hair practices such as the amount of money (p = .047) and time (p = .015) spent on hair maintenance were associated with decreased physical activity but were not associated with BMI. Inactivity during adolescence can result in obesity, a major cause of chronic health conditions that contribute to morbidity and mortality as an adult. When nurse practitioners understand and appreciate the cultural differences and beliefs around cultural hair practices they will be able to develop culturally appropriate strategies that will aid in weight loss.


Interference in dichotic listening: the effect of contralateral noise on oscillatory brain networks.
Coupling of thalamocortical networks through synchronous oscillations at gamma frequencies (30-80 Hz) has been suggested as a mechanism for binding of auditory sensory information into an object representation, which then becomes accessible for perception and cognition. This study investigated whether contralateral noise interferes with this step of central auditory processing. Neuromagnetic 40-Hz oscillations were examined in young healthy participants while they listened to amplitude-modulated sound in one ear and a multi-talker masking noise in the contralateral ear. Participants were engaged in a gap-detection task, for which their behavioural performance declined under masking. The amplitude modulation of the stimulus elicited steady 40-Hz oscillations with sources in bilateral auditory cortices. Analysis of the temporal dynamics of phase synchrony between source activity and the stimulus revealed two oscillatory components; the first was indicated by an instant onset in phase synchrony with the stimulus while the second showed a 200-ms time constant of gradual increase in phase synchrony after phase resetting by the gap. Masking abolished only the second component. This coincided with masking-related decrease of the P2 wave of the transient auditory-evoked responses whereas the N1 wave, reflecting early sensory processing, was unaffected. Given that the P2 response has been associated with object representation, we propose that the first 40-Hz component is related to representation of low-level sensory input whereas the second is related to internal auditory processing in thalamocortical networks. The observed modulation of oscillatory activity is discussed as reflecting a neural mechanism critical for speech understanding in noise.


Postoperative endophthalmitis due to Burkholderia cepacia complex from contaminated anaesthetic eye drops.
To report the clinical presentation and outcomes of cluster postcataract Burkholderia cepacia complex endophthalmitis, the source of infection and clonal relatedness of the isolates. This was a retrospective study on 13 patients who developed acute postoperative endophthalmitis, along with an infiltrate at the corneal section, after an uneventful cataract surgery with intraocular lens implantation. Aqueous aspirates, vitreous aspirates and environmental surveillance specimens were sampled. Genotypic diversity was determined by PCR using BOX-PCR for each strain, and the clonal relationship was established between clinical and eye drops isolates. Vitreous samples showed B. cepacia in cultures in all 13 eyes. Among the samples from various surveillance specimens cultured, topical anaesthetic eye drops grew B. cepacia. The isolates from the patients and the eye drops solution revealed matching banding patterns in BOX-PCR. Isolates from the patients and eye drops were susceptible to cefotaxime and piperacillin/tazobactam only. 9 (69%) patients out of 13 had a final visual acuity of 6/60 or better. Among the remaining four patients, three had a vision of perception of light and one had final vision of 1/60. Microbiology culture and BOX-PCR results revealed contamination of local anaesthetic eye drops and the same organism was cultured from a group of patients with acute-onset postoperative endophthalmitis after an uneventful cataract surgery. Outbreaks may occur in the most vigilant settings, and any sterile consumable may be a common link.


Brucellosis and veterinary surgeons.
Forty-six veterinary surgeons were given a full clinical examination, serological examinations with estimates of immunoglobulins, and supplementary haematological and radiological investigations. Thirty-five complained of one or more symptoms, and eight had abnormal physical signs which might have been caused by infection with Brucella abortus, but neither sereological tests results nor immunoglobulin estimates bore any special relation to the clinical features. The soundest way of assessing ill health which had possibly been caused by brucellosis seemed to be thorough clinical examination and disregard of serologican findings. Interpreting results by the usual serological tests in the absence of a clinical examination is probably of doubtful value and may even be misleading.


Theory of the Topological Spin Hall Effect in Antiferromagnetic Skyrmions: Impact on Current-Induced Motion.
We demonstrate that the nontrivial magnetic texture of antiferromagnetic Skyrmions (AFM Sks) promotes a nonvanishing topological spin Hall effect (TSHE) on the flowing electrons. This effect results in a substantial enhancement of the nonadiabatic torque and, hence, improves the Skyrmion mobility. This nonadiabatic torque increases when decreasing the Skyrmion size, and, therefore, scaling down results in a much higher torque efficiency. In clean AFM Sks, we find a significant boost of the TSHE close to the van Hove singularity. Interestingly, this effect is enhanced away from the band gap in the presence of nonmagnetic interstitial defects. Furthermore, unlike their ferromagnetic counterpart, the TSHE in AFM Sks increases with an increase in the disorder strength, thus opening promising avenues for materials engineering of this effect.


Extracellular β-fructofuranosidase from Fusarium graminearum: stability of the spray-dried enzyme in the presence of different carbohydrates.
Microbial enzymes have been used for various biotechnological applications; however, enzyme stabilization remains a challenge for industries and needs to be considered. This study describes the effects of spray-drying conditions on the activity and stability of β-fructofuranosidase from Fusarium graminearum. The extracellular enzyme β-fructofuranosidase was spray dried in the presence of stabilizers, including starch (Capsul) (SC), microcrystalline cellulose (MC), trehalose (TR), lactose (LC) and β-cyclodextrin (CD). In the presence of TR (2% w/v), the enzymatic activity was fully retained. After 1 year of storage, 74% of the enzymatic activity was maintained with the CD stabilizer (10% w/v). The residual activity was maintained as high as 80% for 1 h at 70°C when MC, SC and CD (5% w/v) stabilizers were used. Spray drying with carbohydrates was effective in stabilizing the F. graminearum β-fructofuranosidase, improved enzymatic properties compared to the soluble enzyme and demonstrated a potential use in future biotechnology applications.


A case of prosthetic mitral valve endocarditis caused by Brucella abortus.
Endocarditis is a rare but serious complication of brucellosis. We report here a case of Brucella abortus endocarditis occurring on a prosthetic mitral valve. The diagnosis was established by positive serology, the presence of vegetation on the mitral prosthesis and isolation of B. abortus from the blood and valve cultures. The patient was successfully treated with combined medical and surgical therapy.


Cholorhexidine, octenidine or povidone iodine for catheter related infections: A randomized controlled trial.
Protection of the catheter site by antimicrobial agents is one of the most important factors in the prevention of infection. Povidone iodine and chlorhexidine gluconate are the most common used agents for dressing. The purpose of this study was to compare the effects of povidone iodine, chlorhexidine gluconate and octenidine hydrochloride in preventing catheter related infections. Patients were randomized to receive; 4% chlorhexidine gluconate, 10% povidone iodine or octenidine hydrochlorodine for cutaneous antisepsis. Cultures were taken at the site surrounding catheter insertion and at the catheter hub after removal to help identify the source of microorganisms. Catheter related sepsis was 10.5% in the povidone iodine and octenidine hydrochlorodine groups. Catheter related colonization was 26.3% in povidone iodine group and 21.5% in octenidine hydrochlorodine group. 4% chlorhexidine or octenidine hydrochlorodine for cutaneous disinfection before insertion of an intravascular device and for post-insertion site care can reduce the catheter related colonization.


Systematic review of cardiovascular disease in women: assessing the risk.
Cardiovascular disease is the number one cause of death for women. In an effort to reduce cardiovascular burden for women, identifying risk factors and increasing awareness of sex differences are fundamental. This systematic review examines cardiovascular disease risk for women. A search of the literature was undertaken using key health databases. Search terms used were cardiovascular disease AND women OR gender. Additional references were manually identified from this literature; 58 articles were reviewed in total. On average, cardiovascular disease presents 10 years later in women compared to men. By this time, they are more likely to suffer from more comorbidities, placing them at higher risk. The complexity of cardiovascular disease identification in women is accentuated through atypical symptoms, and has the potential to lead to delayed and/or misdiagnosis. It is clear through identifying sex differentiation in cardiovascular risk factors that there has been an increased awareness of symptom presentation for women. In light of the sex differences in risk factors, sex-specific aspects should be more intensively considered in research/practice to improve clinical outcomes for female cardiovascular disease patients.


Dietary intake and physical activity in a Canadian population sample of male patients with HIV infection and metabolic abnormalities.
Objective was to assess dietary intake and physical activity in a Canadian population sample of male patients with HIV and metabolic abnormalities and to compare the data to Canadian recommendations. Sixty-five HIV-infected men with at least one feature associated with the metabolic syndrome (insulin resistance, dyslipidemia, central obesity, or lipodystrophy) were enrolled. Results from 7-day food records and activity logs were compared to the Dietary Reference Intakes and recommendations of Canada's Physical Activity Guide, respectively. Anthropometric data were also measured. Fifty-two percent of the subjects were overweight, another 15% were obese. However, energy intake (mean+/-SEM) (2153+/-99 kcal/d) was lower than the estimated requirement (2854+/-62 kcal/d; p<0.0001), and 84.5% of the patients reached the recommended minimum of 60 min of mild or 30 min of moderate daily exercise. Intake was adequate for protein, but high for fat and cholesterol in 40% of patients. No patient reached the recommendation for fiber. Intake from diet alone was suboptimal for most micronutrients. Prevalence was highest for low vitamin E (91% of patients) and magnesium (68%) intake, and high sodium intake (72%). In summary, a large proportion of HIV patients with metabolic abnormalities were overweight or obese. However, this was not associated with high energy intake, or reduced physical activity. High fat, low fiber and inadequate micronutrient intakes were prevalent.


In vitro effects of pentoxifylline and coenzyme Q10 on the sperm of oligoasthenoteratozoospermia patients.
The effect of in-vitro sperm incubation with Pentoxifylline (PTX) and Coenzyme Q10 (CoQ10) in Oligoasthenoteratozoospermia (OAT) patients was evaluated. Semen samples were obtained from men with Normozoospermia and men with OAT. Motile sperm from the two groups were subdivided into four subgroups: (i) without incubation with PTX + CoQ10; (ii) incubation with PTX; (iii) Incubation with CoQ10; and (iv) incubation with a combination of PTX + CoQ10. Then, sperm parameters, chromatin, DNA and membrane integrity, protamine deficiency, apoptosis, mitochondrial activity, sperm chromatin dispersion test (SCD), hypo-osmotic swelling test (HOS), chromomycin A3 (CMA3), Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), and diaminobenzidine (DAB) assays were evaluated, respectively. Sperm incubated with CoQ10 and a combination of CoQ10 and PTX resulted in a significant increase in the sperm parameters. Also, a significant decrease was noted with a combination of PTX and CoQ10 in normal men. There was a significant difference between CoQ10 treated and CoQ10 + PTX treated groups in comparison with the OAT group in the percentage of the DNA fragmentation, sperm apoptosis, AB+, HOS test + and sperm mitochondrial activity. Incubated sperm with CoQ10, PTX, and in combination with each other can improve sperm parameters in OAT patients.


Integration of exercise prescription into medical provision as a treatment for non-communicable diseases: A scoping review.
The purpose of this scoping review is to stimulate interest and to raise awareness, among researchers, healthcare practitioners, and policymakers regarding the current scientific literature related to exercise prescription for non-communicable diseases (NCDs). Exercise prescription is a safe and cost-effective method that enables physicians to use exercise as a complementary addition to NCDs management and treatment. This scoping review followed the PRISMA Extension Guidelines for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Using this framework, we considered information from qualitative and quantitative studies to identify research gaps. We provide feasible suggestions to guide future research for the implementation of exercise prescription in the healthcare environment. The literature search was conducted using SPIDER and PICO tools for qualitative, quantitative, and mixed-study designs. Inclusion criteria included articles that investigated patients with NCDs and considered exercise interventions. Systematic searches of PubMed, Web of Science, MEDLINE, EMBASE, and ScienceDirect were undertaken on 26 July 2022 and all reference lists were manually searched. Data processing was performed using EndNote 2.0 software and data charts were used for numerical summary and thematic analysis. There were 10,951 articles retrieved, of which 28 met the inclusion criteria. Based on the evidence, exercise was a feasible, safe, and acceptable method to prevent and manage non-communicable diseases in inpatient and outpatient settings. Six research directions were identified and discussed. In addition, implementation evidence and suggestions for policy-reconfiguration are also provided. This scoping review summarizes the current evidence for the effectiveness of exercise in the treatment of non-communicable diseases. The review provides key findings supporting exercise prescription for the inpatient and outpatient healthcare service. We suggest that governments and healthcare policymakers globally advocate the inclusion of structured exercise prescription within the NCDs treatment setting.


Rab7 mutants associated with Charcot-Marie-Tooth disease exhibit enhanced NGF-stimulated signaling.
Missense mutants in the late endosomal Rab7 GTPase cause the autosomal dominant peripheral neuropathy Charcot-Marie-Tooth disease type 2B (CMT2B). As yet, the pathological mechanisms connecting mutant Rab7 protein expression to altered neuronal function are undefined. Here, we analyze the effects Rab7 CMT2B mutants on nerve growth factor (NGF) dependent intracellular signaling in PC12 cells. The nerve growth factor receptor TrkA interacted similarly with Rab7 wild-type and CMT2B mutant proteins, but the mutant proteins significantly enhanced TrkA phosphorylation in response to brief NGF stimulation. Two downstream signaling pathways (Erk1/2 and Akt) that are directly activated in response to phospho-TrkA were differentially affected. Akt signaling, arising in response to activated TrkA at the plasma membrane was unaffected. However Erk1/2 phosphorylation, triggered on signaling endosomes, was increased. Cytoplasmic phospho-Erk1/2 persisted at elevated levels relative to control samples for up to 24 h following NGF stimulation. Nuclear shuttling of phospho Erk1/2, which is required to induce MAPK phosphatase expression and down regulate signaling, was greatly reduced by the Rab7 CMT2B mutants and explains the previously reported inhibition in PC12 neurite outgrowth. In conclusion, the data demonstrate a mechanistic link between Rab7 CMT2B mutants and altered TrkA and Erk1/2 signaling from endosomes.


p16(INK4a) -mediated suppression of telomerase in normal and malignant human breast cells.
The cyclin-dependent kinase inhibitor p16(INK4a) (CDKN2A) is an important tumor suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal.


Simultaneous Chiral Fixation and Chiral Regulation Endowed by Dynamic Covalent Bonds.
The construction of chiral superstructures through the self-assembly of non-chiral polymers usually relies on the interplay of multiple non-covalent bonds, which is significantly limited by the memory ability of induced chirality. Although the introduction of covalent crosslinking can undoubtedly enhance the stability of chiral superstructures, the concurrent strong constraining effect hinders the application of chirality-smart materials. To address this issue, we have made a first attempt at the reversible fixation of supramolecular chirality by introducing dynamic covalent crosslinking into the chiral self-assembly of side-chain polymers. After chiral induction, the reversible [2+2] cycloaddition reaction of the cinnamate group in the polymer chains can be further controlled by light to manipulate inter-chain crosslinking and decrosslinking. Based on this photo-programmable and dynamic chiral fixation strategy, a novel pattern-embedded storage mechanism of chiral polymeric materials was established for the first time.


Quality of Life in Nursing Professionals: Burnout, Fatigue, and Compassion Satisfaction.
The objective of this research was to analyse the quality of life of nursing professionals and its relationship with socio-demographic variables and the work context. A multi-centre, descriptive, cross-sectional design was used. Questionnaires were administered to 1521 nurses working in the Andalusian Public Health System (APHS), Spain. Professional quality of life (ProQOL v. IV) was measured, as well as several socio-demographic and work-related variables. To this end, a descriptive analysis and multiple exploratory analyses were conducted. The levels of compassion fatigue (CF) and burnout (BO) were elevated. The level of compassion satisfaction (CS) was below the estimated mean. Marital status, the healthcare setting, the area where the centre is located, and the work shift are variables associated with CF. According to the multiple linear regression model, the predicting factors for the occurrence of CF were being married, working in primary care, in urban areas, and working a morning/evening/night shift. The variables related to CS were the professional's age, sex, marital status, the healthcare setting of the centre, the location of the centre, and the work shift. Specifically, according to the exploratory model, the factors that predicted a reduction in CS were working in primary care, in urban areas, and working a morning/evening/night shift. However, being divorced increased CS. BO was influenced only by the work shift. Nursing professionals are exposed to certain factors that may influence professional quality of life. Some of these factors are related to the work context.


The role of perceptual load in negative priming.
Negative priming (NP) effects from irrelevant distractors were assessed as a function of perceptual load in the processing of prime targets. Participants searched for a target letter among a varying number of nontarget letters in the center of the display and ignored an irrelevant peripheral distractor. NP from this distractor was found to depend on the relevant search set size, decreasing as this set size was increased. The authors conclude that exhausting attention in relevant processing reduces irrelevant processing (e.g., N. Lavie, 1995), leaving less distractor processing to produce NP. This conclusion is consistent with recent reactive inhibition views for NP (e.g., G. Houghton, S. P. Tipper, B. Weaver, & D. I. Shore, 1996).


TLR2, TLR3, TLR4, TLR9 and TLR11 expression on effector CD4+ T-cell subsets in Leishmania donovani infection.
T-cells play a central role in cell-mediated immunity. While activation of T-cells is major histocompatibility-restricted, the Toll-like receptors (TLRs)- a family of proteins that recognize conserved molecular patterns present on the pathogens-are not well-studied for their expression and function in T-cells. As any association of TLR expression profiles with an effector T-cell subset is unknown, we analyze BALB/c mice-derived CD4+ and CD8+ T-cells' TLR expression profiles. We report: CD4+t-bet+ T-cells are frequent in TLR2LowTLR3HighTLR4Low subpopulation, CD4+GATA3+ T-cells are frequent within the cells with intermediate expression of TLR2, TLR3, TLR4 and TLR11, CD4+FoxP3+ T-cells in TLR2HighTLR3High cells whereas CD4+RORγt + T-cells are frequent in TLR2LowTLR3LowTLR4LowTLR11Low cells. CD4+ effector T-cell subsets may therefore show association with TLRs- TLR3, in particular-expression. In Leishmania donovani infection in BALB/c mice, TLR3 expression on both CD4+ and CD8+ T-cells is reduced. Poly-I:C, a TLR3 ligand, do not have any distinctive effects on the CD4+ effector T-cell subsets. These data suggest that TLRs on T-cells may not function as a primary receptor that controls T-cell function but their distinctive expression profiles on different T-cell subsets suggest plausible immunomodulatory role.


Branched-chain amino acids and neurotransmitter metabolism: expression of cytosolic branched-chain aminotransferase (BCATc) in the cerebellum and hippocampus.
In the brain, catabolism of the branched-chain amino acids (BCAAs) provides nitrogen for the synthesis of glutamate and glutamine. Glutamate is formed through transfer of an amino group from BCAA to alpha-ketoglutarate in reaction catalyzed by branched-chain aminotransferases (BCAT). There are two isozymes of BCAT: cytosolic BCATc, which is found in the nervous system, ovary, and placenta, and mitochondrial BCATm, which is found in all organs except rat liver. In cell culture systems, BCATc is found only in neurons and developing oligodendrocytes, whereas BCATm is the isoform in astroglia. In this study, we used immunohistochemistry to examine the distribution of BCATc in the rat brain, focusing on the well-known neural architecture of the cerebellum and hippocampus. We show that BCATc is expressed only in neurons in the adult rat brain. In glutamatergic neurons such as granule cells of the cerebellar cortex and of the dentate gyrus, BCATc is localized to axons and nerve terminals. In contrast, in GABAergic neurons such as cerebellar Purkinje cells and hippocampal pyramidal basket cells, BCATc is concentrated in cell bodies. A common function for BCATc in these neurotransmitter systems may be to modulate amounts of glutamate available either for release as neurotransmitter or for use as precursor for synthesis of GABA. Particularly striking in our findings is the strong expression of BCATc in the mossy fiber pathway of the hippocampal formation. This result is discussed in light of the effectiveness of the anticonvulsant drug gabapentin, which is a specific inhibitor of BCATc.


Direct observation of the nanocomplex surface reorganization of antifouling silicones containing a highly mobile PEO-silane amphiphile.
While nanocomplexity derived from surface reorganization in aqueous biofouling environments is known to give rise to antifouling behavior, quantification of this process is limited. In this work, the surface of an antifouling polymer matrix - a silicone modified with a highly mobile PEO-silane amphiphile - was characterized while undergoing dynamic surface reorganization in aqueous solution via off-resonance tapping mode atomic force microscopy (AFM) and while monitoring surface changes at a rate >25 μm2 min-1. Utilizing multimodal analysis during incubation in aqueous solution and surface force spectroscopic mapping before and after incubation, we directly observed the nanoscopically complex surface of the matrix and its five distinct stages of surface reorganization. Pre- and post-incubation nanomechanical mapping revealed a marked increase in Young's modulus and surface area, as well as increased adhesion and dissipative properties for the post-incubated surface. The observed topographic and viscoelastic changes are explained in terms of surface-air and surface-water interactions. These findings are compared to the bulk matrix reordering observed by immersion dynamic mechanical analysis (DMA) and enhanced protein resistance with increased submersion times as determined by confocal microscopy.


The quest for new mild and selective modifications of natural structures: laccase-catalysed oxidation of ergot alkaloids leads to unexpected stereoselective C-4 hydroxylation.
Laccase-catalysed oxidation of ergot alkaloids in the absence of chemical mediators allowed the unexpected isolation of the mono-hydroxylated derivatives of compounds 2-7. Structure determination by NMR techniques clearly indicated that hydroxylation took place at the C-4 benzylic position. Quite notably, the proposed protocol allowed, for the first time, functionalisation at the C-4 position of the ergoline skeleton. Depending on the absence or on the presence of a C-10 α-methoxy substituent, hydroxylation was either stereoselective (furnishing C-4α OH derivatives) or gave rise to a C-4α/C-4β OH mixture in a 2:1 ratio, respectively.


Modulation of population density and size of silver nanoparticles embedded in bacterial cellulose via ammonia exposure: visual detection of volatile compounds in a piece of plasmonic nanopaper.
The localized surface plasmon resonance exhibited by noble metal nanoparticles can be sensitively tuned by varying their size and interparticle distances. We report that corrosive vapour (ammonia) exposure dramatically reduces the population density of silver nanoparticles (AgNPs) embedded within bacterial cellulose, leading to a larger distance between the remaining nanoparticles and a decrease in the UV-Vis absorbance associated with the AgNP plasmonic properties. We also found that the size distribution of AgNPs embedded in bacterial cellulose undergoes a reduction in the presence of volatile compounds released during food spoilage, modulating the studied nanoplasmonic properties. In fact, such a plasmonic nanopaper exhibits a change in colour from amber to light amber upon the explored corrosive vapour exposure and from amber to a grey or taupe colour upon fish or meat spoilage exposure. These phenomena are proposed as a simple visual detection of volatile compounds in a flexible, transparent, permeable and stable single-use nanoplasmonic membrane, which opens the way to innovative approaches and capabilities in gas sensing and smart packaging.


Customized vascular catheters for rodents.
Custom arterial and venous catheters were made for rodents from polyurethane tubing. The low thrombogenicity and toxicity index, chemical stability and resiliency of polyurethane made this tubing an ideal catheter material. The tubing is shaped using peanut oil heated to 160 degrees C. Sealing these catheters is accomplished simply by heating the tube end with a hot object and pinching it between the fingers. Chronic catheter patency was maintained using Burr's solution (9:1 mixture of glycerine and heparin). No flushing was necessary.


Transformed cells require continuous activity of RNA polymerase II to resist oncogene-induced apoptosis.
Studies have indicated that deregulated oncogene expression can result in either programmed cell death or proliferation, depending on the cellular microenvironment. However, little is known about whether oncogenic signals in themselves are able to activate a cellular apoptotic program. We have tested the hypothesis that oncogenic signals in the absence of gene expression are sufficient to induce cell death, which would indicate that constitutive expression of antiapoptotic genes is necessary for maintenance of the transformed state. Using two highly specific RNA polymerase (RNAP) II inhibitors, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) and alpha-amanitin, which inhibit RNAP II function by two distinct mechanisms, we found that inhibition of gene expression substantially increased apoptosis in a time- and dose-dependent manner in p53+/+- and p53(-/-)-transformed mouse embryonic fibroblasts and in HeLa cells, demonstrating that this type of apoptosis does not require wild-type p53. Engineered expression of an alpha-amanitin resistance RNAP II gene rendered cells resistant to induction of apoptosis by alpha-amanitin without affecting their sensitivity to DRB, indicating that alpha-amanitin induces apoptosis solely by inhibiting RNAP II function and not by a nonspecific mechanism. DRB-induced apoptosis was independent of the cell cycle or ongoing DNA replication, since DRB induced similar levels of apoptosis in asynchronous cells and cells synchronized by collection at mitosis. Inhibition of RNAP II in untransformed cells like Rat-1 or human AG1522 fibroblasts resulted not in apoptosis but in growth arrest. In contrast, deregulated expression of c-Myc in Rat-1 cells dramatically increased their sensitivity to DRB, directly demonstrating that apoptosis following inhibition of RNAP II function is greatly enhanced by oncogenic expression. The requirement for RNAP II function to prevent oncogene-induced apoptosis implies the need for the constitutive expression of an antiapoptotic gene(s) to maintain the transformed state. The differential sensitivities of untransformed and transformed cells to induction of apoptosis by transcriptional inhibition, coupled with the finding that this type of apoptosis is independent of p53 status, suggest that inhibition of RNAP II may be exploited therapeutically for the design of successful antitumor agents.


Chromophore-modified bisnaphthalimides: DNA recognition, topoisomerase inhibition, and cytotoxic properties of two mono- and bisfuronaphthalimides.
Bisnaphthalimides represent a promising group of DNA-targeted anticancer agents. In this series, the lead compounds elinafide and bisnafide have reached clinical trials, and the search for more potent analogues remains a priority. In the course of a medicinal chemistry program aimed at discovering novel antitumor drugs based on the naphthalimide skeleton, different dimeric molecules containing two tetracyclic neutral DNA intercalating chromophores were synthesized. The naphthalimide unit has been fused to a benzene ring (azonafide derivatives), an imidazole, a pyrazine, or, as reported here, a furan ring which increases the planar surface of the chromophore and enhances its stacking properties. We report a detailed investigation of the DNA binding capacity of the dimeric molecule MCI3335 composed of two furonaphthalimide units connected by a 12 A long amino alkyl linker [(CH(2))(2)-NH-(CH(2))(3)-NH-(CH(2))(2)] identical to that of elinafide. Qualitative and quantitative binding studies, in particular using surface plasmon resonance, establish that the dimer binds considerably more tightly to DNA (up to 1000 times) than the corresponding monomer and exhibits a higher sequence selectivity for GC-rich sequences. DNase I footprinting experiments attest that the dimer, and to a lesser extent the monomer, preferentially intercalate at GC sites. The strong binding interaction between the drugs and DNA perturbs the relaxation of supercoiled DNA by topoisomerases, but the test compounds do not promote DNA cleavage by topoisomerase I or II. Despite the lack of poisoning effect toward topoisomerase II, MCI3335 displays a very high cytotoxicity toward CEM human leukemia cells, with an IC(50) in the low nanomolar range, approximately 4 times inferior to that of the reference drug elinafide. Confocal microscopy observations indicate that the monomer shows a stronger tendency to accumulate in the cell nuclei than the dimer. The extremely high cytotoxic potential of MCI3335 is attributed to its enhanced capacity to bind to DNA and to inhibit DNA synthesis, as evidenced by flow cytometry experiments using the BrdU assay. The results provide novel mechanistic information that furthers the understanding of the structure-activity relationships in the bisnaphthalimide series and identify MCI3335 as a novel lead compound for further preclinical investigations.


Depression as a risk factor for mortality after acute myocardial infarction.
The ENRICHD clinical trial, which compared an intervention for depression and social isolation to usual care, failed to decrease the rate of mortality and recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation for this is that depression was not associated with increased mortality in these patients. The purpose of this study was to determine if depression was associated with an increased risk of mortality in a subsample of the ENRICHD trial's depressed patients compared with a group of nondepressed patients recruited for an ancillary study. Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months. There were 47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk factors, depressed patients were at higher risk for all-cause mortality (hazard ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with nondepressed patients. In conclusion, depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.


Classification of First-Episode Schizophrenia, Chronic Schizophrenia and Healthy Control Based on Brain Network of Mismatch Negativity by Graph Neural Network.
Mismatch negativity (MMN) has been consistently found deficit in schizophrenia, which was considered as a promising biomarker for assessing the impairments in pre-attentive auditory processing. However, the functional connectivity between brain regions based on MMN is not clear. This study provides an in-depth investigation in brain functional connectivity during MMN process among patients with first-episode schizophrenia (FESZ), chronic schizophrenia (CSZ) and healthy control (HC). Electroencephalography (EEG) data of 128 channels is recorded during frequency and duration MMN in 40 FESZ, 40 CSZ patients and 40 matched HC subjects. We reconstruct the cortical endogenous electrical activity from EEG recordings using exact low-resolution electromagnetic tomography and build functional brain networks based on source-level EEG data. Then, graph-theoretic features are extracted from the brain networks with the support vector machine (SVM) to classify FESZ, CSZ and HC groups, since the SVM has good generalization ability and robustness as a universally applicable nonlinear classifier. Furthermore, we introduce the graph neural network (GNN) model to directly learn for the network topology of brain network. Compared to HC, the damaged brain areas of CSZ are more extensive than FESZ, and the damaged area involved the auditory cortex. These results demonstrate the heterogeneity of the impacts of schizophrenia for different disease courses and the association between MMN and the auditory cortex. More importantly, the GNN classification results are significantly better than those of SVM, and hence the EEG-based GNN model of brain networks provides an effective method for discriminating among FESZ, CSZ and HC groups.


Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimens.
The diagnosis of Histoplasma capsulatum infection by serologic testing for the presence of antibodies is limited by a high rate of false positive and false negative results and by the requirement that the patient have a normal immune response. We have developed a radioimmunoassay for the detection of H. capsulatum antigen in urine and serum specimens. Antigenuria was noted in 20 of 22 episodes of disseminated histoplasmosis that occurred in 16 patients, in 6 of 32 patients with self-limited infection, in 2 of 32 patients with cavitary histoplasmosis, and in 4 of 8 patients with a sarcoid-like illness caused by H. capsulatum. The detection of antigen in urine was reproducible in 38 of 41 (93 percent) retests of specimens. H. capsulatum antigen was also detected in the serum during 11 of the 22 episodes of disseminated histoplasmosis, in none of the 12 episodes of other types of histoplasmosis in patients with antigenuria, in 1 of the 33 patients with histoplasmosis who lacked the urinary antigen, and in none of the 50 controls. Antigenemia and antigenuria decreased after initiation of antifungal therapy and recurred in patients who had a relapse. We conclude that this radioimmunoassay for H. capsulatum antigen represents a useful new method for the rapid diagnosis of disseminated histoplasmosis.


Which orthopaedic trauma patients are likely to refuse to participate in a clinical trial? A latent class analysis.
The study aimed to assess systematic differences in the characteristics of patients that consented for the trial compared with the broader pool of eligible patients in a large, pragmatic orthopaedic trauma trial. A retrospective observational study performed from April 2017 to March 2018. Academic trauma centre in Baltimore, USA. There were 642 eligible adult trial participants with an operative fracture to the appendicular skeleton and were indicated for blood clot prophylaxis. The median age of the sample was 50 years (IQR: 31-63), and 60% were male. The primary outcome was the refusal to enrol in the trial. Demographic and injury covariates were included in iterations of latent class models. The final model was selected based on a minimum Bayesian information criterion. The final model identified three clusters with five covariates predictive of cluster membership (age, neighbourhood-based socioeconomic status, alcohol use, multiple fractures, multiple surgeries). The three clusters were associated with 22% (Cluster 1), 38% (Cluster 2) and 62% (Cluster 3) refusal rates, respectively. Members of Cluster 3 (n=84) were most commonly between 66 and 80 years of age (49% vs 6% (Cluster 1) and 21% (Cluster 2)), of high neighbourhood-based socioeconomic status (85% vs 63% (Cluster 1) and 8% (Cluster 2)), with isolated fractures (100% vs 80% (Cluster 1) and 92% (Cluster 2)), and were less likely to have multiple surgeries compared with the other clusters (28% vs 47% (Cluster 1) and 35% (Cluster 2)). In this study, the likelihood of refusing to participate in the trial ranged from 22% to 62% in the three identified clusters. Elderly age, high socioeconomic status, and less severe injuries defined the cluster that was most likely to refuse trial participation. NCT02984384.


Sheep primary cells as in vitro models to investigate Mycoplasma agalactiae host cell interactions.
Appropriate infection models are imperative for the understanding of pathogens like mycoplasmas that are known for their strict host and tissue specificity, and lack of suitable cell and small animal models has hindered pathogenicity studies. This is particularly true for the economically important group of ruminant mycoplasmas whose virulence factors need to be elucidated for designing effective intervention strategies. Mycoplasma agalactiae serves as a useful role model especially because it is phylogenetically very close to M. bovis and causes similar symptoms by as yet unknown mechanisms. Here, we successfully prepared and characterized four different primary sheep cell lines, namely the epithelial and stromal cells from the mammary gland and uterus, respectively. Using immunohistochemistry, we identified vimentin and cytokeratin as specific markers to confirm the typical cell phenotypes of these primary cells. Furthermore, M. agalactiae's consistent adhesion and invasion into these primary cells proves the reliability of these cell models. Mimicking natural infections, mammary epithelial and stromal cells showed higher invasion and adhesion rates compared to the uterine cells as also seen via double immunofluorescence staining. Altogether, we have generated promising in vitro cell models to study host-pathogen interactions of M. agalactiae and related ruminant pathogens in a more authentic manner.


Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations.
To model the three-dimensional structure and investigate the interaction mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c mutants). The three-dimensional complex structures of furin/kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newly published X-ray crystallographical structures of mouse furin and yeast kexin as templates. The electrostatic interaction energy of each complex was calculated and the results were compared with the experimentally determined inhibition constants to find the correlation between them. High quality models of furin/kexin-eglin c mutants were obtained and used for calculation of the electrostatic interaction energies between the proteases and their inhibitors. The calculated electrostatic energies of interaction showed a linear correlation to the experimental inhibition constants. The modeled structures give good explanations of the specificity of eglin c mutants to furin/kexin. The electrostatic interactions play important roles in inhibitory activity of eglin c mutants to furin/kexin. The results presented here provided quantitative structural and functional information concerning the role of the charge-charge interactions in the binding of furin/kexin and their inhibitors.


Invasion activating caveolin-1 mutation in human scirrhous breast cancers.
We looked for mutations in the caveolin-1 gene, encoding a critical molecule for membrane signaling to cell growth, in 92 primary human breast cancers, and we report here the identification of a mutation in caveolin-1 at codon 132 (P132L) in 16% of cases. The mutation-positive cases were mostly invasive scirrhous carcinomas. In cell lines expressing the same mutant of caveolin-1, we observed that the mutant Caveolin-1 expression seemed to induce cellular transformation and activation of mitogen-activated protein kinase-signaling pathway and to promote invasion-ability as well as altered actin networks in the cells. These results provide, for the first time, genetic evidence that a functioning Caveolin-1 mutation may have a role in the malignant progression of human breast cancer.


Hepatoprotective activity of aqueous-methanol extract of Artemisia vulgaris.
The effect of a crude extract of the aerial parts of Artemisia vulgaris (Av.Cr) was investigated against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced hepatitis in mice. Co-administration of D-GalN (700 mg[sol ]kg) and LPS (1 microg[sol ]kg) significantly (p < 0.05) raised the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice in the toxin group compared with the values in the control group. Pre-treatment of mice with different doses of Av.Cr (150-600 mg[sol ]kg) significantly (p < 0.05) reduced the toxin-induced rise in plasma ALT and AST. The hepatoprotective effect was further verified by histopathology of the liver, which showed improved architecture, absence of parenchyma congestion, decreased cellular swelling and apoptotic cells, compared with the findings in the toxin group of animals. These findings scientifically validated the traditional use of Artemisia vulgaris for various liver disorders.


Late results of surgical treatment of transposition of the great arteries.
In summary, many of these patients have achieved a normal working capacity, but as a group there is a statistically significant reduction when compared to healthy children (p < 0.01). There was no significant difference between the group of patients who had their Mustard operation in infancy and later. As yet, there is no suggestion that the older patients, or those with the longest time interval between the operation and the exercise test, have a progressive reduction in working capacity. The decreased working capacity and moderate increase in ventilation suggests restricted cardiac output on exercise. This could be related to the abnormal heart rate response rather than indicating poor ventricular function. Equally, a restricted cardiac output on exercise may be due to inefficiency of atrial transport, tricuspid regurgitation or unmasked pulmonary vascular obstructive disease. Further studies may clarify these points. This study demonstrated that the exercise performance of asymptomatic patients 6-13 years after Mustard's operation was somewhat diminished, compared with a group of normal children. Nevertheless, these patients did lead and enjoy a normal life. Only longitudinal studies may bring the final answer to the important question: How many patients will be alive with normal or near normal exercise tolerance 40-50 years after Mustard's operation? Until such an answer is available, we believe that the Mustard operation should be used in the treatment of TGA, while the alternative techniques are carefully explored.


Therapeutic Algorithm Guided by Sequential 11C-Choline PET/CT in a Patient With Metastatic Castration-Resistant Prostate Cancer.
Antiandrogen therapy alone or combined with radical therapy is the first choice in diagnosis and recurrence of patients with metastatic prostate cancer. However, patients on androgen deprivation frequently show treatment resistance. In recent years, new treatments for metastatic castration-resistant prostate cancer have been developed. Clinical studies with docetaxel have shown its usefulness for first-line therapy, and different therapeutic algorithms with second-line drugs like abiraterone or cabazitaxel have also been proposed. Sequential metabolic study with PET/CT imaging with ¹¹C-choline may be important for assessing the right moment for administration each one of the therapeutic options.


Accurate and economical intracavitary endocurietherapy in the treatment of uterine cervix cancer.
A modified afterloading cervical applicator and intracavitary endocurietherapy application technique eliminates several problems associated with the Henschke cervical applicator, and conventional preloading technique. The Kumar cervical applicator minimizes patient discomfort, and improves patient mobility while reducing the tendency of the applicator to rotate during the 40 to 50 hours of uterine intracavitary endocurietherapy. The use of hygroscopic laminaria tent for gradual cervical dilatation in place of manual cervical dilatation, and the use of inflatable Foley balloon threaded onto the tandem instead of vaginal packing, to separate the 137Cesium sources away from the rectum and bladder, eliminate the need of general anesthesia for the majority of patients undergoing intracavitary endocurietherapy.