Anti N-Methyl-D-Aspartate receptor antibody associated Acute Demyelinating Encephalomyelitis in a patient with COVID-19: a case report.
Anti N-Methyl-D-Aspartate (NMDA) receptor antibody associated ADEM is a diagnosis that was first described relatively recently in 2007 by Dalmau et al. The recent COVID-19 pandemic has resulted in multiple neurological complications being reported. However, there is limited data on Anti-NMDA receptor antibody associated ADEM in COVID-19 patients. Furthermore, the MRI findings in these patients have not been fully elucidated. This case report adds to the growing body of knowledge of neurological complications in COVID-19 patients. A 50 year old Caucasian female with no previous medical co-morbidities presented with symptoms of COVID-19 and subsequently developed neurological symptoms which included confusion, limb weakness and seizures. The patient developed marked behavioural abnormalities which required attention. She was found to have anti NMDA receptor antibodies present in a significant titres, an elevated total protein on lumbar puncture and cytotoxic magnetic resonance imaging (MRI) changes in the brain and spinal cord and was subsequently diagnosed with an anti-NMDA Receptor Antibody associated ADEM. The bilateral symmetric involvement of the corticospinal tract on MRI was considered unusual in our case. She was treated with a combination of corticosteroids and plasmapheresis which halted disease progression. Thereafter she was commenced on intravenous immunoglobulin as maintenance therapy and she has shown continuous improvement with ongoing physiotherapy. The recognition of COVID 19 neurological complications may be difficult in the initial disease as early symptoms of lethargy, weakness and confusion may be very nondescript. However, it is imperative that these complications are sought for as they are imminently treatable. Early institution of therapy is imperative in decreasing long term neurological consequences.


Evaluating a campaign to detect early stage breast tumors in the United States.
Growing concern over failure to detect early stage breast cancer has led communities across the United States to participate in the Breast Cancer Awareness Month program. This program mobilizes local public and private institutions, particularly the media, to reach a large audience each October with information on salutary behaviors, including screening, and on resources that can assist newly motivated audiences to adopt the behaviors. Although the scholarly literature includes no assessments of the effect of the program on the actual detection of early stage breast tumors, similar programs targeting other illnesses (e.g., AIDS) are quickly emerging. We attempt such an assessment by applying time-series designs to 92 quarters (beginning January, 1975) of data obtained from cancer registries in the Atlanta and Detroit metropolitan areas as well as in the San Francisco Bay Area. We find that the detection of in situ and local breast tumors increased in all three communities during the quarters that included Breast Cancer Awareness Month. We conclude that community mobilization may have its intended benefit but suggest that community organizers not ignore unintended costs including the emotional and physical sequelae of false positives.


Fibronectin isoforms in plasma membrane domains of normal and regenerating rat liver.
Plasma membrane fractions were obtained from the three surface domains of normal and regenerating adult rat livers. It was shown by immunoblotting that sinusoidal plasma membranes contained the characteristic 220 and 210 kDa fibronectin doublet, whereas bile canalicular plasma membranes contained a 220 kDa component. In lateral plasma membranes, 180, 190 and 220 kDa fibronectin isoforms were present. Fibronectin in the sinusoidal and canalicular plasma membranes was shown, by detergent/aqueous phase partitioning, to be more hydrophilic than isoforms in lateral plasma membranes. Changes in the distribution of fibronectin between plasma membrane domains occurred during liver regeneration and their significance, especially in relation to cell division, is discussed.


Evaluating Medicaid expansion benefits for patients with cancer: National Cancer Database analysis and systematic review.
Insurance status modifies healthcare access and inequities. The Affordable Care Act expanded Medicaid coverage for people with low incomes in the United States. This study assessed the consequences of this policy change for cancer care after expansion in 2014. National Cancer Database (NCDB) public benchmark reports were queried for each malignancy in 2013 and 2016. Furthermore, a systematic search [PubMed, Embase, Scopus and Cochrane] was performed. Data on insurance status, access to cancer screening and treatment, and socioeconomic disparities in these metrics was collected. Two-tailed analysis of the NCDB revealed that 14 out of 18 eligible states had a statistically significant increase in Medicaid-insured patients with cancer after expansion. The average percentage increase was 51 % (13.2-204 %). From the systematic review, 229 studies were identified, 26 met inclusion. All 21 relevant articles reported lower uninsured rates. The average increase of Medicaid-insured patients was 77 % (9.5-230 %) and the average decrease of uninsured rates was 55 % (13.4-73 %). 15 out of 21 articles reported increased access to care. 16 out of 17 articles reported reductions in inequities. Medicaid expansion in 2014 increased the number of insured patients with cancer. Expansion also improved access to screening and treatment in most oncologic care, and reduced socioeconomic disparities. Further studies evaluating correlative survival outcomes are needed. This study informs debates on expansion of Medicaid in state governments and electorates in the United States, and on health insurance reform broadly, by providing insight into how health insurance can benefit people with cancer while revealing how less insurance coverage could harm patients with cancer before and after their diagnosis. This study also contributes to discussions of health insurance mandates, subsidized coverage for people with low incomes, and covered healthcare services determinations by public and private health insurance providers in other countries.


Optimal sample selection applied to information rich, dense data.
Dense data can be classified into superdense information-poor data (type 1 dense data) and dense information-rich data (type 2 dense data). Arbitrary, random, or optimal thinning may be applied to type 1 dense data to minimise computational burden and statistical issues (such as autocorrelation). In contrast, a prospective or retrospective optimal design can be applied to type 2 dense data to maximise information gain from limited resources (capital and/or time). Here we describe a retrospective optimal selection strategy for quantification of unbound drug concentration from a discrete set of plasma samples where the total drug concentration has been measured.


Evaluation of recovery in iatrogenic evoked acute mediatinitis.
This study attempts to find a prediction method of death risk in patients with acute mediastinitis (AM). There is no such tool described in available literature for this serious disease. The study comprised 37 consecutive cases of iatrogenic AM. General anamnesis and biochemical data were included. Factor analysis was used to extract the risk characteristic for the patients. The most valuable results were obtained for eight parameters, which were selected for further statistical analysis (all collected during a few hours after admission). Three factors reached eigenvalue > 1. Clinical explanations for these combined statistical factors are as follows: Factor 1--proteinic status (serum total protein, albumin, and hemoglobin level), Factor 2--inflammatory status (white blood cells, C-reactive protein, and procalcitonin), and Factor 3--general risk (age and number of coexisting diseases). Threshold values of prediction factors were estimated using statistical analysis (factor analysis, Statgraphics Centurion XVI). The final prediction result for the patients is constructed as simultaneous evaluation of all factor scores. High probability of death should be predicted if factor 1 value decreases with simultaneous increase of factors 2 and 3. The diagnostic power of the proposed method was revealed to be high [sensitivity = 100 %, specificity = 69.2 %]: Factor 1 [SNC = 95.8 %, SPC = 76.9 %]; Factor 2 [SNC = 100 %, SPC = 53.8 %]; and Factor 3 [SNC = 75 %, SPC = 76.9 %]. The described method may turn out to be a valuable prognostic tool for patients with AM.


Characterization of the antigen specificity of T-cell clones from piperacillin-hypersensitive patients with cystic fibrosis.
β-Lactam antibiotics provide the cornerstone of treatment and reduce the rate of decline in lung function in patients with cystic fibrosis, but their use is limited by a high frequency of delayed-type allergic reactions. The objective of this study was to use cloned T-cells expressing a single T-cell receptor from five piperacillin-hypersensitive patients to characterize both the cellular pathophysiology of the reaction and antigen specificity to define the mechanism of activation of T-cells by piperacillin. More than 400 piperacillin-responsive CD4+, CD4+CD8+, or CD8+ T-cell clones were generated from lymphocyte transformation test and ELIspot-positive patients. The T-cell response (proliferation, T helper 2 cytokine secretion, and cytotoxicity) to piperacillin was concentration-dependent and highly specific. Enzyme-linked immunosorbent assay, gel electrophoresis, and mass spectrometry revealed that piperacillin bound exclusively to albumin in T-cell culture. Irreversible piperacillin binding at Lys 190, 195, 199, 432, and 541 on albumin and the stimulation of T-cells depended on incubation time. A synthetic piperacillin albumin conjugate stimulated T-cell receptors via a major histocompatibility complex- and processing-dependent pathway. Flucloxacillin competes for the same Lys residues on albumin as piperacillin, but the resulting conjugate does not stimulate T-cells, indicating that binding of the β-lactam hapten in peptide conjugates confers structural specificity on the activation of the T-cell receptors expressed on drug-specific clones. Collectively, these data describe the cellular processes that underlie the structural specificity of piperacillin antigen binding in hypersensitive patients with cystic fibrosis.


Development of a weighted scoring system for the Electronic Driving Observation Schedule (eDOS).
The electronic Driving Observation Schedule (eDOS) is a novel approach to assessing older drivers' performance in their everyday driving environment on their chosen routes. The original eDOS total score is generated using the count of driving errors, which does not account for distinct risk levels of different types of driving errors made in different complexity of driving environments. This study was conducted to create one score to represent the complexity of driving route during each eDOS observation and one weighted eDOS total score to represent older drivers' performance accounting for the risk of driving errors by their type and the complexity of maneuvers in their corresponding environments. A literature review, a two-round survey with 13 experts in driving evaluation, and iterative discussions between primary investigators were conducted for generating these scores. Two formulae were created to calculate a weighted maneuver/environmental complexity score and a weighted eDOS total score. •An advanced weighted score is created to represent one's on-road driving performance in their everyday driving environment not only using the count of driving errors, but also accounting for the risk level of each error.•The complexity of driving maneuver and environment in each on-road driving trip can be systematically rated.


The effect of red blood cell transfusion on platelet function in critically ill patients.
Red blood cell (RBC) transfusion is associated with an increased risk of pro-thrombotic events, but the underlying mechanism is poorly understood. We hypothesized that RBC transfusion modulates platelet activity in critically ill patients with and without sepsis. In a prospective cohort study, 37 critically ill patients receiving a single RBC unit to correct for anemia were sampled prior to and 1 h after transfusion. Platelet exposure of P-selectin, CD63 and binding of PAC-1 as well as formation of platelet-leukocyte complexes were measured by flow cytometry. The ability of plasma from critically ill patients to induce ex vivo platelet aggregation was assessed by flow cytometry after incubation with platelets from a healthy donor. RBC transfusion neither triggered the expression of platelet activation markers nor the formation of platelet-leukocyte complexes. Plasma from critically ill patients induced more spontaneous platelet aggregation prior to RBC transfusion compared to healthy controls, which was further augmented following RBC transfusion. Also collagen-induced platelet aggregation was already increased prior to RBC transfusion compared to healthy controls, and this response was unaffected by RBC transfusion. In contrast, ristocetin-induced platelet agglutination was decreased when compared to controls, suggesting impaired vWF-dependent platelet agglutination, even in the presence of high vWF levels. Following RBC transfusion, ristocetin-induced platelet agglutination further decreased. There were no differences between septic and non-septic recipients in all assays. Ex vivo platelet aggregation is disturbed in the critically ill. Transfusion of a RBC unit may further increase the spontaneous platelet aggregatory response.


Fibronectin-based nanomechanical biosensors to map 3D surface strains in live cells and tissue.
Mechanical forces are integral to cellular migration, differentiation and tissue morphogenesis; however, it has proved challenging to directly measure strain at high spatial resolution with minimal perturbation in living sytems. Here, we fabricate, calibrate, and test a fibronectin (FN)-based nanomechanical biosensor (NMBS) that can be applied to the surface of cells and tissues to measure the magnitude, direction, and strain dynamics from subcellular to tissue length-scales. The NMBS is a fluorescently-labeled, ultra-thin FN lattice-mesh with spatial resolution tailored by adjusting the width and spacing of the lattice from 2-100 µm. Time-lapse 3D confocal imaging of the NMBS demonstrates 2D and 3D surface strain tracking during mechanical deformation of known materials and is validated with finite element modeling. Analysis of the NMBS applied to single cells, cell monolayers, and Drosophila ovarioles highlights the NMBS's ability to dynamically track microscopic tensile and compressive strains across diverse biological systems where forces guide structure and function.


[Integrating patient education in your oncology practice].
Patient education is the process by which health professionals impart information to patients and their caregivers that will alter their health behaviors; improve their health status to better manage their lives with a chronic disease. Patient education implies a profound paradigm shift in the conception of care among health professionals, and should result in structural care changes. Patient education has been promoted by the French Health system for 30years, including in the 2009 HPST law and Cancer Plan 2014-2019. A patient education program was designed in our hospital for breast cancer patients. A multidisciplinary and transversal team of health professionals and resource patients was trained before grant application for funding of the program by the regional health care agency. Management of the project required that a functional unit be built for recording of all patient education related activities. A customized patient education program process was built under the leadership of a coordinator and several patient education project managers during bimonthly meetings, using an accurate timeline and a communication strategy to ensure full institutional support and team engagement. The grant was prepared in four months and the program started within the next four months with the aim to include 120 patients during year 1. The program includes a diagnosis of patient abilities and well-being resources, followed by collective and individual workshops undertaken in 4months for each patient. Patient education is positively evaluated by all participants and may contribute to better health care management in the long term but the financial and human resources allocated to such programs currently underestimate the needs. Sustainability of patient education programs requires that specific tools and more commitment be developed to support health care professionals and to promote patient coping and empowerment in the long term.


Gankyrin promotes osteosarcoma tumorigenesis by forming a positive feedback loop with YAP.
Although gankyrin has been identified as a vital regulator of tumorigenesis, its role and regulatory mechanism in osteosarcoma (OS) remain unclear. QRT-PCR, western blot and IHC staining were conducted to detect the expression of gankyrin in OS. Pearson's χ² test was adopted to examine the associations between gankyrin expression and clinicopathologic characteristics. Kaplan-Meier method was used to investigate the relationship between gankyrin expression and overall survival of patients with OS. Next, a series of in vitro and in vivo assays were performed to determine the positive feedback loop between gankyrin and YAP in OS. We first reported that gankyrin is upregulated in human OS specimens and cell lines and predicts OS progression and poor prognosis. Furthermore, we demonstrated that gankyrin protects miR-200a-mediated yes-associated protein (YAP) downregulation through p53 and establishes a positive feedback loop to regulate YAP signaling in U2OS and MG63 cells. Intriguingly, gankyrin interacts with YAP to promote OS cell growth in vitro. In addition, our results showed that gankyrin promotes OS tumor growth and regulates YAP levels in vivo. Notably, we also observed a positive correlation between gankyrin and YAP expression in human OS tissues, and co-upregulation of gankyrin and YAP indicated a poor prognosis. Our results identify that gankyrin acts as an oncogene in OS by forming a positive feedback loop with YAP, and disrupting the gankyrin-YAP regulation may be beneficial for controlling OS tumorigenesis.


Restoration of mossy fiber projection in slice co-cultures of dislocated dentate gyrus and degranulated hippocampus.
Regional specificity of the mossy fiber projection is a well described feature of hippocampal intrinsic connectivity. Possible mechanisms involved in the formation of this specific projection include attraction molecules localized in the target area or repulsive cues preventing from ingrowth in non-target areas. To test this hypothesis, using organotypic co-cultures of dentate gyrus and irradiated degranulated hippocampal slices, we have disrupted the pathway normally taken by mossy fibers. The dentate gyrus explant was ectopically placed facing the alveus/stratum oriens of the irradiated hippocampal slice forcing the mossy fibers to cross the stratum oriens to reach their target area. Extensive plexuses of labeled mossy fibers were observed in the hilus and adjacent pyramidal cell layer of non-irradiated dentate gyrus explants. A few mossy fibers crossed the border between the co-cultures and reached their specific termination area in the irradiated hippocampus where they formed characteristic multiple synaptic contacts on their target cells. In addition to mossy fibers, numerous thin and varicose non-mossy fibers invade all parts of the co-cultured hippocampus establishing symmetric synapses. From these data we assume that mossy fiber axons emerging from dislocated non-irradiated dentate gyrus explants find their normal termination zone in the co-cultured degranulated hippocampal slice even if they are forced to run an unusual pathway. These results support the idea that an attraction signal arising from the target area is involved in the formation of this specific projection.


Correlation between p38 mitogen-activated protein kinase and human telomerase reverse transcriptase in sarcomas.
One of the major components of telomerase is the human telomerase reverse transcriptase (hTERT) as the catalytic protein. hTERT mRNA expression are reported to be associated with prognosis and tumor progression in several sarcomas. However, there is no clear understanding of the mechanisms of hTERT in human sarcomas. Recent studies have suggested that signals transmitted through p38 mitogen-activated protein kinase (MAPK) can increase or decrease hTERT transcription in human cells. The purpose of this study was to analyse the correlation between p38 MAPK and hTERT in sarcoma samples. We investigated 36 soft tissue malignant fibrous histiocytomas (MFH), 24 liposarcomas (LS) and 9 bone MFH samples for hTERT and p38 MAPK expression. Quantitative detection of hTERT and p38 MAPK was performed by RT-PCR. There was a significant positive correlation between the values of hTERT and p38 MAPK in all samples (r = 0.445, p = 0.0001), soft tissue MFH (r = 0.352, p = 0.0352), LS (r = 0.704, p = 0.0001) and bone MFH samples (r = 0.802, p = 0.0093). Patients who had a higher than average expression of p38 MAPK had a significantly worse prognosis than other patients (p = 0.0036). p38 MAPK may play a role in up-regulation of hTERT, and therefore, p38 MAPK may be a useful marker in the assessment of hTERT and patients' prognosis in sarcomas.


[Deprescription in old people: It's time to take action].
The use of drugs has undeniable benefits to the elderly, but it is not exempt from undesirable effects. Deprescription is the process of systematic medication review with the target of achieving the best risk-benefit ratio based on the best available evidence. This process is especially important for polymedicated elderly patients as well as those overtreated, frail, terminally ill and at the end of life. The deprescription must be done in stages, establishing a close follow-up in case problems appear after withdrawal. In the decision-making process, it is very important to consider the patient and caregivers opinion, assessing the objectives of the treatment according to the clinical, functional and social situation of the patient. There are multiple tools to make it easier for clinicians to select which drugs to deprescribe (Beers criteria, STOPP-START…). The most susceptible to intervention pharmacological groups are: antihypertensives, antidiabetics, statins, benzodiazepines, antidepressants, anticholinergics, anticholinesterase agents, and neuroleptics.


Neocortical synaptogenesis, aging, and behavior: lifespan development in the motor-sensory system of the rat.
Little evidence presently exists on the development and aging of synaptic contacts and their relationship to behavior, particularly in nonvisual brain areas. To investigate this interrelationship, rats at a series of developmental ages [postnatal day 1 (P1) to P90] were initially examined on a battery of motor tasks. The battery, ranging from simple reflexive tests to tests of complex locomotor capacities, consisted of tactile-induced forelimb placing, chin-induced placing, body righting, climbing an inclined plane, traversing a narrow beam, and keeping up with a revolving wheel. Following completion of the behavioral testing, the animals, together with an additional group of aged (28- to 29-month-old) rats, were killed and their motor-sensory cortex was removed, stained with osmium tetroxide or ethanol phosphotungstic acid (EPTA), and examined under electron microscopy for density of synaptic contacts. Simple motor abilities such as tactile-induced placing was present by the end of the first postnatal week, with locomotor performance reaching a mature level by the end of the third postnatal week, and intermediate task abilities maturing within this range. Paralleling the development of complex locomotor skills was a sharp increase in synaptic density in the molecular layer of the motor-sensory cortex, commencing in the second postnatal week and peaking at P30. After P30 there was a sharp decline in synaptic density as well as a decline in performance on some motor tasks, although these two functions seemed to be occurring independently. There was a continued, but less dramatic synaptic loss evident in the aged rats.


Schizophrenia-like psychosis associated with vein of Galen malformation: a case report.
A 34 year old patient presented with a schizophrenia-like clinical picture, and was later found to have a large vein of Galen Arteriovenous Malformation (AVM). There are reports in the literature suggesting that vein of Galen AVMs are associated with psychiatric symptoms. However, the clinical pictures tend to be non specific. We discuss the relevance of the association of vein of Galen AVMs with schizophrenia-like symptomatology.


Psychiatric issues in cosmetic plastic surgery.
The objective of cosmetic surgery is increased patient self-esteem and confidence. Most patients undergoing a procedure report these results post-operatively. The success of any procedure is measured in patient satisfaction. In order to optimize patient satisfaction, literature suggests careful pre-operative patient preparation including a discussion of the risks, benefits, limitations and expected results for each procedure undertaken. As a general rule, the patients that are motivated to surgery by a desire to align their outward appearance to their body-image tend to be the most satisfied. There are some psychiatric conditions that can prevent a patient from being satisfied without regard aesthetic success. The most common examples are minimal defect/Body Dysmorphic Disorder, the patient in crisis, the multiple revision patient, and loss of identity. This paper will familiarize the audience with these conditions, symptoms and related illnesses. Case examples are described and then explored in terms of the conditions presented. A discussion of the patient's motivation for surgery, goals pertaining to specific attributes, as well as an evaluation of the patient's understanding of the risks, benefits, and limitations of the procedure can help the physician determine if a patient is capable of being satisfied with a cosmetic plastic surgery procedure. Plastic surgeons can screen patients suffering from these conditions relatively easily, as psychiatry is an integral part of medical school education. If a psychiatric referral is required, then the psychiatrist needs to be aware of the nuances of each of these conditions.


A 3D stacked corrugated pore structure composed of CoNiO2 and polyaniline within the tracheids of wood-derived carbon for high-performance asymmetric supercapacitors.
A novel 3D stacked corrugated pore structure of polyaniline (PANI)/CoNiO2@activated wood-derived carbon (AWC) has been successfully constructed to prepare high-performance electrode materials for supercapacitors. AWC functions as a supporting framework that provides ample attachment sites for the loaded active materials. The CoNiO2 nanowire substrate, consisting of 3D stacked pores, not only serves as a template for subsequent PANI loading, but also acts as an effective buffer to mitigate the volume expansion of the PANI during ionic intercalation. The distinctive corrugated pore structure of PANI/CoNiO2@AWC facilitates electrolyte contact and significantly enhances the electrode material properties. The PANI/CoNiO2@AWC composite materials exhibit excellent performance (14.31F cm-2 at 5 mA cm-2) and superior capacitance retention (80% from 5 to 30 mA cm-2), owing to the synergistic effect among their components. Finally, PANI/CoNiO2@ AWC//reduced graphene oxide (rGO)@AWC asymmetric supercapacitor is assembled, which has a wide operating voltage (0 ∼ 1.8 V), high energy density (4.95 mWh cm-3 at 26.44 mW cm-3) and cycling stability (90.96% after 7000 cycles).


Aucubin, a naturally occurring iridoid glycoside inhibits TNF-α-induced inflammatory responses through suppression of NF-κB activation in 3T3-L1 adipocytes.
Obesity is closely associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and activation of inflammatory signaling pathways in adipose tissue. Tumor necrosis factor (TNF)-α is chronically elevated in adipose tissues of obese rodents and humans. Increased levels of TNF-α are implicated in the induction of atherogenic adipokines, such as plasminogen activator inhibitor (PAI)-1, adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6. Aucubin, an iridoid glycoside existing in medicinal plants, has been reported to show an anti-inflammatory activity by suppression of TNF-α production in murine macrophages. The present study is aimed to investigate the effects of aucubin on TNF-α-induced atherogenic changes of the adipokines in differentiated 3T3-L1 cells. Aucubin significantly inhibited TNF-α-induced secretion and mRNA synthesis of the atherogenic adipokines including PAI-1, MCP-1, and IL-6. Further investigation of the molecular mechanism revealed that pretreatment with aucubin suppressed extracellular signal-regulated kinase (ERK) activation, inhibitory kappa Bα (IκBα) degradation, and subsequent nuclear factor kappa B (NF-κB) activation. These findings suggest that aucubin may improve obesity-induced atherosclerosis by attenuating TNF-α-induced inflammatory responses.


Association of glutathione S-transferase M1 and T1 null/present polymorphism with physical performance in the Korean population.
Human physical performance is a highly complex phenotype that is influenced by various factors. In particular, genetic factors related to muscle fiber type, bone density, muscle performance, and metabolic processes are known to contribute in varying degrees to athlete status and physical performance in various ethnic groups. To investigate the relationship between these genetic factors and physical performances, we genotyped five genetic polymorphisms (ACE Ins/Del, ACTN3 R577X, ER-α C/T, GSTM1 null/present, and GSTT1 null/present) in 111 Korean athletes and 145 controls. We examined genotype and allele frequency differences between athletes and control groups, along with the odds ratios, using Chi square. One-way analysis of variance (ANOVA) was used to test the significance of differences in continuous variables between the multiple genetic polymorphisms and physical performance test results. The GSTM1 polymorphism exhibited a highly significant association in athletes (p = 0.017). Combined analysis of GSTM1 and GSTT1 also revealed significant differences between athletes and controls (p < 0.05). In the analysis of physical performance within athletes, the ER-α gene polymorphism was associated with the sargent jump and the side-step (p < 0.05), and the GSTM1 gene polymorphism was significantly associated with the 20 m shuttle run and sit-up (p < 0.05). Thus, our data imply that GSTM1 and ER-α gene polymorphisms were associated with physical performance in Korean athletes, although functional studies with larger sample sizes are necessary to elaborate upon these findings.


What is a disease? What is the disease clinical benign prostatic hyperplasia (BPH)?
Though clinical benign prostatic hyperplasia (BPH) is a common disease worldwide, there is still much confusion in the literature and the many clinical guidelines as to its definition. Often the disease is associated with lower urinary tract symptoms (LUTS) and managed according to only symptoms. This leads to undertreatment in some patients with severe bladder outlet obstruction (BOO) with no symptoms, and overtreatment in patients with LUTS but no clinical BPH. Fundamentally, a disease can be defined as an abnormal structure or function or a condition which may cause harm to the organism. Thus, clinical BPH can be defined as prostate adenoma/adenomata, causing a varying degree of BOO, which may eventually cause harm to the patients. With this definition, we are then able to differentiate the disease clinical BPH from the many other less common causes of LUTS, and then treat it according to its severity. Clinical BPH can be diagnosed with non-invasive ultrasound in the clinic, grading it according to the shape (intravesical prostatic protrusion) and size of the prostate. Treatment can then be planned according to the disease severity using our staging system that classifies severity according to the presence or absence of significant obstruction and bothersomeness of symptoms. This would lead to better individualised and cost-effective management of the disease clinical BPH.


Mesentery vascular metabolism of substance P.
Dipeptidylpeptidase IV (EC 188.8.131.52), an enzyme which metabolizes substance P, is present in crude homogenates of hog mesenteric artery and aorta. Its subcellular localization is closely correlated with the plasma membrane marker enzyme 5'-nucleotidase (EC 22.214.171.124) in addition to the kinin and angiotensin metabolizing enzymes angiotensin I converting enzyme (EC 188.8.131.52) and aminopeptidase M (EC 220.127.116.11). The highest level of dipeptidylpeptidase IV is found on the surface membrane-enriched fraction and is immunologically identical to the kidney brush border-bound enzyme. Vascular dipeptidylpeptidase IV sequentially removes the N-terminal Arg1-Pro2 and Lys3-Pro4 dipeptides of substance P and exposes the biologically active C-terminal heptapeptide product to rapid degradation by vascular aminopeptidases.


An unusual trigonal D3 assembly composed of molybdate anions and multiply bonded dimolybdenum units.
Oxidation of the molybdate-linked pair having two quadruply bonded Mo(2)(4+) units, [Mo(2)(DAniF)(3)](2)(micro(2)-MoO(4)), (DAniF = N,N'-di-(p-anisyl)formamidinate) leads to the formation of a species consisting of three oxidized Mo(2)(5+) units connected by two micro(3)-MoO(4)(2-) dianions, {[Mo(2)(DAniF)(3)](3)(micro(3)-MoO(4))(2)}(2+). This cation displays overall D(3) point group symmetry due to a slight twisting of the three Mo(2)(5+) units about the threefold symmetry axis. This distortion removes all mirror symmetry but preserves all C(2) axes orthogonal to the unique C(3) axis. Cyclic voltammetry of {[Mo(2)(DAniF)(3)](3)(micro(3)-MoO(4))(2)}(2+) in CH(2)Cl(2) reveals three reversible one-electron redox processes, corresponding to successive reduction of each of the three Mo(2)(5+) units, with DeltaE(1/2) separations of 0.36 V and 0.41 V.


Social integration and mental health in a biracial community.
The study investigated the relationship between social integration and mental health, with a particular interest in social integration in a minority group context. The study involved a home interview with 33 white and 30 black women who resided in a residentially integrated working-class community in Austin, Texas. Although blacks reported significantly more psychological symptoms than whites, the race effect was explained by an underlying interaction between race and social integration. Blacks low in social integration showed more symptoms than either white respondents or blacks with a high level of integration. The Race X Social integration interaction is considered in the light of societally based prejudice and the potential social stress associated with minority group status.


Effects of leptin gene expression in mice in vivo by electroporation and hydrodynamics-based gene delivery.
In vivo electroporation and hydrodynamics-based gene delivery were utilized to test the effect of leptin gene transfer on food intake, and body and fat weights of mice. Gene transfer of pVRmob by electroporation caused a significant reduction in body weight compared with the control counterpart (p<0.05), although a lesser effect was found in food intake, and the weights of interscapular brown and epididymal fat by electroporation. As might be expected, the hydrodynamics-based transfection method significantly reduced body weight over 1 week post-transfection (p<0.05). Furthermore, epididymal fat was decreased by 50% at 1 week after gene transfer (p<0.001). These results suggest that both electroporation and hydrodynamics-based gene delivery may be effective approaches for systemic delivery of recombinant leptin to the central nervous system, and that the efficiency of gene transfer in hydrodynamics-based gene delivery was markedly higher than that in electroporation at least within the first week after transfection.


A case of osmotic demyelination syndrome occurred after the correction of severe hyponatraemia in hyperemesis gravidarum.
Osmotic demyelination syndrome (ODS) may be observed as a result of a rapid change in serum osmolarity, such as that induced by an overly rapid correction of serum sodium levels in hyponatraemic patients. We describe the case of a 21-year-old woman who was hospitalized at week 10 of gestation because of severe hyperemesis. At admission the patient appeared restless and confused and severe hyponatraemia (serum sodium 107 mmol/L) and hypokalemia (serum potassium 1.1 mmol/L) were detected. Active and simultaneous correction of these imbalances led to an overly rapid increase of serum sodium levels (17 mmol/L in the first 24 hours). Isotonic saline solution was stopped and replaced by 5% dextrose solution infusion. However, the neurological alterations worsened and the radiological features were consistent with the diagnosis of extra-pontine ODS. Steroids were administered intravenously with progressive improvement of biochemical and clinical abnormalities. At the time of discharge, 20 days later, the patient was able to walk and eat autonomously with only minimal external support. This report illustrates an unusual case of ODS, occurred after an excessive rate of correction of hyponatraemia obtained with isotonic saline infusion. Hypokaliemia and its active correction very likely played a crucial role in facilitating the onset of ODS. This interesting aspect will be explained in detail in the article. A more cautious and thoughtful correction of electrolyte alterations, would have probably prevented the onset of ODS in this patient. Physicians should be aware of the possibly fatal consequences that an exceedingly rapid change of serum osmolarity may have and should strictly follow the known safety measures in order to prevent it to occur.


Alterations in respiratory function and hemodynamics during laparoscopic cholecystectomy under pneumoperitoneum.
Respiratory function and hemodynamics were studied during laparoscopic cholecystectomy (LC) under a 10 mmHg pneumoperitoneum (PP) by carbon dioxide insufflation. Blood-gas analysis and measurement of cardiac function by using a Swan-Ganz catheter were performed. Creatinine clearance rate was measured preoperatively and intraoperatively. Compared with values obtained before the institution of PP, blood-gas analysis showed a significant increase in PCO2 (P < 0.01), and a significant decrease in pH (P < 0.01) and base excess (P < 0.05) during PP. With respect to cardiac function, there was no significant change in cardiac output, pulmonary arterial pressure, and pulmonary arterial wedge pressure. Intraoperative creatinine clearance rate (Ccr) was decreased in 29 of 48 cases, increased in 18 cases, and unchanged in 1 case, resulting in no significant difference overall between the values measured preoperatively and intraoperatively. However, in eight individual cases, the Ccr was found to have decreased significantly. Although alterations in respiratory function were observed, LC at 10 mmHg PP did not cause any crucial problems in respiratory or cardiac function. It should be kept in mind, however, that renal blood flow may decrease in some cases even at intraabdominal pressures under 10 mmHg.


Dual-chamber committed mode pacing.
The proliferation of dual-chamber pacemakers has resulted in several different modalities of DVI pacing. A distinction is made between "committed" and "non-committed" modes, and the differences are presented. In addition, a new hybrid mode has been developed which has been termed "semi-committed" and is currently being introduced. The semi-committed mode divides the AV interval into an early non-physiologic interval and a later "physiologic" interval which enables inhibition of ventricular output following a sensed ventricular event.


Effects of phosphoenolpyruvate, other glycolytic intermediates and methylxanthines on calcium uptake by a mitochondrial fraction from rat pancreatic islets.
45Ca2+-accumulation by a mitochondrial fraction from isolated rat pancreatic islets was stronly stimulated by ATP. The ATP-dependent uptake was inhibited by phosphoenolpyruvate in a dose-dependent manner over a wide variety of conditions. Inhibition by phosphoenolpyruvate was non-completitive with respect to calcium, competitive with respect to magnesium, and antagonised by high Mg-ATP2- concentrations; fructose 1,6-diphosphate also decreased 45Ca2+-uptake. Other glucose metabolites were either less effective or ineffective in diminishing mitochondrial 45Ca2+-accumulation. The ATP-dependent uptake was also inhibited by xanthine derivatives (caffeine and 3-isobutyl-1-methylaxanthine) which potentiate the effects of glucose on insulin secretion. Cyclic AMP had no effect. It is thought that the rate of insulin secretion is a function of the cytosolic calcium concentration in the B-cell. These data show that phosphoenolpyruvate, fructose 1,6-diphosphate and methylxanthines might influence exocytosis by direct effects on mitochondrial calcium accumulation, and thus the intracellular distribution of calcium.


Nicotine and methamphetamine share discriminative stimulus effects.
Nicotine and methamphetamine are both abused in similar settings, sometimes together. Because there are known interactions between central nicotinic acetylcholine receptors and dopamine receptors, it is of interest to characterize the nature of the interaction of these two compounds in vivo. The purpose of this study was to characterize the extent to which these two compounds produce similar discriminative stimulus effects and to identify pharmacological mechanisms for their interaction. Male Sprague-Dawley rats were trained to discriminate methamphetamine or nicotine from saline. First, the ability of methamphetamine and nicotine to cross-substitute in rats trained to the other compound was tested. Subsequently, the ability of a dopamine antagonist (haloperidol) and a centrally acting nicotinic antagonist (mecamylamine) to block the discriminative stimulus effects of methamphetamine and nicotine were also tested. Nicotine fully substituted in methamphetamine-trained rats, but methamphetamine only partially substituted in nicotine-trained rats. In nicotine-trained rats, mecamylamine fully antagonized the discriminative stimulus effects of nicotine, but haloperidol had no effect. The partial substitution of methamphetamine was partially attenuated by haloperidol, but not altered by mecamylamine. In methamphetamine-trained rats, mecamylamine failed to antagonize the discriminative stimulus effects of methamphetamine, but haloperidol fully blocked the methamphetamine cue. Mecamylamine blocked the ability of nicotine to substitute for methamphetamine, but haloperidol had no effect. These results indicate that nicotine and methamphetamine share discriminative stimulus effects in some subjects and that the two compounds do not act at the same site, but produce their interaction indirectly. These findings suggest that these two compounds might be at least partially interchangeable in human users, and that there are potentially interesting pharmacological reasons for the commonly observed co-administration of nicotine and methamphetamine.


The Economic Footprint of Interventional Radiology in the United States: Implications for Systems Development.
Despite the growing presence of interventional radiology (IR) in inpatient care, its global impact on the health care system remains uncharacterized. The aim of this study was to quantitate the use of IR services rendered to hospitalized patients in the United States and the impact on cost. The National Inpatient Sample 2016 was queried. Using the International Classification of Diseases, 10th revision, Clinical Modification/Procedure Classification System, adult inpatients who underwent routine IR procedures were identified. Unadjusted and adjusted analyses were performed. Weighted patient data are presented to provide national estimates. Of the 29.7 million inpatient admissions in 2016, 2.3 million (7.8%) had at least one IR procedure. Patients who needed IR were older (62.8 versus 57.1 years, P < .001), were sicker on the basis of the All Patient Refined Diagnosis Related Groups (27% major or extreme versus 14% for non-IR, P < .001), and had higher inpatient mortality (8.2% versus 1.7%, P < .001). While representing 7.8% of all admissions, this cohort accounted for 18.4% ($68.4 billion) of adult inpatient health care costs and about 3 times higher mean hospitalization cost compared with other inpatients ($29,402 versus $11,062, P < .001), which remained significant even after controlling for age and All Patient Refined Diagnosis Related Group. Approximately 1 in 10 US inpatients are treated by IR during their hospitalizations. These patients are sicker, with about 4 times higher mortality and 2.5 times greater length of stay, accounting for almost one-fifth of all health care costs. These findings suggest that IR should have a voice in discussions of means to save costs and improve patient outcomes in the United States.


Generation of monoclonal antibodies reactive with nuclear proteins of human primary breast tumors.
Nuclear proteins were extracted from purified nuclei of human primary breast tumors (BrT) and bladder tumors and of human normal breast, kidney and lymphocytes by enzymatic treatment. SDS-Polyacrylamide gel electrophoresis of nuclear proteins from breast tumors showed different bands in the molecular weight zones from 25 to 220 kDa which were absent or present only as traces in normal breast tissue. Murine monoclonal antibodies (MAbs) have been produced using nuclear extracts of human primary breast tumors as immunogens. Approximately 2,000 hybridomas were generated from 5 hybridizations. According to their reactivity to BrT nuclear extracts and mammary carcinoma cell line MCF-7, seven hybridomas were selected and cloned. They were further characterized with histological immunoperoxidase assays of formaldehyde-fixed BrT paraffin tissue sections. MAb 6A3 particularly gave strong nuclear staining with all BrT specimens while MAb 1D8 showed both nuclear and cytoplasmic staining with only some of them. Specimens from mammoplasty did not react with these MAbs. Immunoblotting of BrT nuclear extracts as developed with MAbs 6A3 and 1D8 revealed major protein bands with molecular weight of 120 and 130 kDa. The potential use of these MAb-defined BrT-related nuclear proteins as markers for human breast cancer was suggested.


Facile preparation of magnetic metal organic frameworks core-shell nanoparticles for stimuli-responsive drug carrier.
Facile synthesis of core-shell magnetic MOFs for drug delivery is of significance due to the advantages of high drug load and easy separation. In this work, magnetic metal organic frameworks (MOFs, Fe3O4-NH2@MIL101-NH2) core-shell nanoparticles were synthesized rapidly in water phase by microwave irradiation using Fe3+ and 2-amino-1,4-benzenedicarboxylate (BDC-NH2) as metal ions and ligands respectively. The resulting magnetic MOFs exhibit large surface areas (96.04 m2 g-1), excellent magnetic response (20.47 emu g-1) and large mesopore volume (22.07 cm3 g-1) along with spherical morphologies with the diameters ranging from 140-330 nm. Using doxorubicin (DOX) as a model drug, the drug loading capacity of Fe3O4-NH2@MIL101-NH2 could reach 36.02%, substantially higher than pristine MIL101-NH2. Importantly, the release of DOX could be controlled by pH as well as the meso pore size of MOFs. The cytotoxicity assay showed that the magnetic MOFs have low cytotoxicity and good biocompatibility. The results suggest great potential of the magnetic MOFs core-shell nanoparticles fabricated in this study on controlled drug release of DOX.


Understanding the Lung Abscess Microbiome: Outcomes of Percutaneous Lung Parenchymal Abscess Drainage with Microbiologic Correlation.
Lung parenchymal abscesses represent an uncommon pathology with high mortality if untreated. Although most respond well to antibiotics, the optimal therapy for persistent abscesses is unknown. The purpose of this study was to review the outcomes of percutaneous lung parenchymal abscess catheter drainage after broad-spectrum antibiotic therapy failure and correlate with patient microbiologic samples. Retrospective review of patients who underwent percutaneous lung abscess drainage at a tertiary hospital system from 2005 to 2015 was performed. In total, 19 procedures were identified on 16 different patients; six females and ten males. Mean patient age was 55 years (range 22-81). Median follow-up time was 7 months (range <1-78). Technical success was 100%. There was one major complication, a pneumothorax. Follow-up was until tube removal or death in 100% of patients. Catheters were removed with resolution of the abscess cavity in 58% (11/19) or with non-draining abscess cavities in 21% (4/19) for a clinical success rate of 79%. Blood cultures demonstrated no growth in all cases, while 21% (4/19) of sputum or bronchoscopic cultures demonstrated growth. In comparison, the specimens from initial catheter placement isolated a causative organism in 95% (18/19) of case (p < 0.0001). In cases of persistent lung abscess after broad-spectrum antibiotics, percutaneous abscess drainage is highly sensitive for microbiologic sampling compared to sputum/bronchoscopic or blood cultures. Additionally, percutaneous drainage of lung parenchymal abscess cavities may promote resolution of the abscess with high rates of therapeutic success and low complications.


Purification of thymidine phosphorylase from Escherichia coli and its photoinactivation in the presence of thymine, thymidine, and some halogenated analogs.
Isoelectric focusing was used as the final step in the isolation of thymidine phosphorylase which was found to have an isoelectric point of 4.1. Analytical acrylamide gel electrophoresis showed the purified enzyme preparation contained one major protein band which stained for thymidine phosphorylase activity and usually a minor, faster migrating band devoid of activity. Inactivation of thymidine phosphorylase alone or in the presence of sensitizers by ultraviolet light, primarily at 253.7 nm, followed first order inactivation kinetics. The rate of inactivation of the enzyme was the same at pH 5 and 7.4 and the addition of various pyrimidine bases and nucleosides enhanced the inactivation rate at both pH values, but to a greater extent at pH 5. Linear plots of inactivation rates versus concentrations of thymidine or thymine were the same. At 7.8 mM thymidine or thymine, 11- and 4.4-fold increases in photoinactivation of thymidine phosphorylase were observed at pH 5 AND 7.4 RESPECTIVELY. Parabolic curves were obtained with increasing concentrations of either 5-iodo-2'-deoxyuridine or 5-iodouracil. 5-Iodouracil at 5.2 mM caused 212- (pH 5) and 100- (pH 7.4) FOLD INCREASES IN THE RATES OF PHOTOINACTIVATION OF THYMIDINE PHOSPHORYLASE. However, 5-iodo-2'-deoxyuridine at 5.0mM only enhanced the photoinactivation of enzyme by factors of 83 (pH 5) and 21 (pH 7.4). Neither 5-bromo-2'-deoxyuridine or 5-bromo-uracil was as potent in sensitizing the enzyme as the iodo analogs. Combinations of 5-iodouracil or 5-iodo-2'-deoxyuridine with thymine resulted in higher inactivation rates than the additive inactivation rates of individual compounds, whereas combinations of either iodo analog with thymidine resulted in lower inactivation rates. Increasing concentrations of phosphate or NaCl lessened the photoinactivation rate of thymidine phosphorylase alone and protected the enzyme from the sensitization caused by the different bases and nucleosides. No quantitative changes in the number of primary amino groups in thymidine phosphorylase was evident as a result of irradiation in the presence or absence of 5-iodouracil or 5-iodo-2'-deoxyuridine. Examination of the irradiated enzyme on Sephadex G-150 indicated that a larger protein species is formed and that 5-iodouracil promotes this process.


Key points of development of motor skills in childhood embodied in gait parameters.
To observe changes of correlations of gait parameters of four sets of body in children aged 3-6. A cross-sectional observational study. Dong Gang kindergarten in Suzhou, China. A total of 89 children between 3 and 6 years old. A total of 37 three-dimensional (3-D) gait parameters assessed with a wearable gait analysis system in 2-min walking test, for 3 times. There were significant differences in gait speed, stride length and sagittal range of motion (ROM) of trunk among children of 3-6 years old (P < 0.05). The left and right toe out angle, sagittal ROM of waist, coronal ROM of trunk and arm swing velocity of male were significantly greater than those of female children (P < 0.05). Most gait parameters were symmetrical (P < 0.01). Canonical correlations of Upper Limbs Set vs. Trunk and Waist Sets increased by ages (P < 0.05). Canonical correlation of Trunk Set vs. Waist Set decreased by ages. Canonical correlations of Lower Limbs Set to any other sets were not significant (P > 0.05). Values and symmetry of gait parameters cannot reflect the development of motor skill during ages of 3-6. Proper trunk movement coordinating with upper limbs and isolating from waist is the key point of development of motor skill in walking. It is built during preschool period and girls develop better. Before the preschool period, lower limbs' isolating movements from the other segments have already developed well. These key points of motor skills in walking should be considered when motor tasks for segment isolation and coordination are given to children with motor dysfunction.


Immunotherapy for Management of Thymic Epithelial Tumors: A Double-Edged Sword.
Thymic epithelial tumors (TETs) are rare thoracic cancers that are broadly classified as thymomas and thymic carcinomas. Surgery is the cornerstone of management for early-stage disease. There are a limited number of effective treatment options for patients with advanced or recurrent disease. The occurrence of paraneoplastic autoimmune disorders in patients with TETs, especially thymomas, creates significant challenges for the development of immunotherapy, including immune checkpoint inhibitors, as a feasible treatment option. In addition, patients with TETs are at increased risk for the development of immune-mediated toxicity with a predilection for musculoskeletal and neuromuscular adverse events upon treatment with immunotherapy. The identification of biomarkers of response and toxicity is expected to play a key role in harnessing the benefits of immunotherapy for patients with TETs. In this paper we review the biology of TETs and the potential effects on the tolerability of immunotherapy. The results of clinical trials of immune checkpoint inhibitors for the treatment of advanced TETs are described to understand the potential risks and benefits of immunotherapy. We also provide an overview of future avenues for treatment with novel immunotherapeutic modalities and opportunities to develop biomarkers to improve the safety and tolerability of immunomodulatory treatments in patients with TETs.


Are snoRNAs and snoRNA host genes new players in cancer?
Small nucleolar RNAs (snoRNAs) have long been considered important but unglamorous elements in the production of the protein synthesis machinery of the cell. Recently, however, several independent lines of evidence have indicated that these non-coding RNAs might have crucial roles in controlling cell behaviour, and snoRNA dysfunction could consequently contribute to oncogenesis in previously unsuspected ways.


The role of professional judgment in chemical hazard assessment and communication.
Most hazard assessment guidelines and regulatory requirements--both nationally and internationally--explicitly advocate the use of professional judgment in hazard assessment. However, the practical application of such judgment (i.e., how and when that judgment should be applied) is often left to the assessor's discretion. This can lead to inconsistent guidance on the use, handling, and disposal of chemicals and can ultimately result in ineffective hazard communication and chemical management. This paper traces the regulatory rationale and legislative conventions for applying professional judgment in hazard assessment to key global regulations and professional standards. A series of guidelines for applying professional judgment are drawn from these regulations and standards, consistent with sound toxicological concepts and principles. The guidelines are illustrated by cogent examples drawn from the experiences of professional toxicologists and industrial hygienists charged with complying with the norms of hazard assessment. We contend that these guidelines and supporting examples are fully compliant with international regulations, decision-neutral with regard to the stringency of the assessment, and reflective of the harmonized efforts to develop more effective and complete hazard communications. We discuss the regulatory ramifications and needs for better definition of professional judgment in hazard assessments under GHS and REACH.


[Comparative study of sympathetic and parasympathetic discharges in the autonomic nerves during stimulation of different structures of the cat hypothalamus].
Simultaneous recordings of hypothalamo-parasympathetic and hypothalamo-sympathetic evoked discharges in anesthetized cats demonstrated that both parasympathetic discharges in the pelvic nerve and sympathetic discharges in the splanchnic nerve of the lowest threshold and shortest latency could be obtained from stimulation of the posterior hypothalamus. The focus of the maximal neuronal activated elicited by stimulation of afferent fibres of visceral nerves and the focus evoking maximal efferent reactions of parasympathetic and sympathetic nerves were located in the same region of the postero-lateral hypothalamus. It is supposed (as a working hypothesis) that convergent polysensory neurons of the hypothalamus are also polyeffector divergent elements of the hypothalamo-visceral reflex system.


A strict test of the phonological loop hypothesis with Libyan data.
In Arabic, there are two ways, differing in length, of pronouncing each digit. This feature of word pairs that are conceptually identical but of different length allows for a stricter test of the phonological loop hypothesis than has been reported previously. Libyan schoolchildren, both boys and girls, of two grades took part in a quasi-experimental study in which shorter and longer digits and shorter and longer words were presented in recall and pronunciation tasks. The results confirmed the validity of the phonological loop model in that memory span was longer for shorter stimuli. Analysis of the data with structural equation modeling showed that only 17% of the individual-level variation in memory span could be explained by pronunciation speed. In an analysis of covariance, it was determined that pronunciation speed could account for a substantial proportion of the variation found across age (8-year-olds vs. 10-year-olds), stimulus modality (digits vs. words), and stimulus length (short vs. long), but not for gender differences.


Evolution of the Bacillus Calmette-Guérin scar Russia and Moreau strains in newborns: A brazilian cohort.
In Brazil, in 1925, the Moreau strain was introduced, and since its implementation, it has been the routine vaccine for health services. Since 2013, many countries, including Brazil, have been experiencing problems with the production of vaccines. As of January 2018, the country started to use the BCG vaccine with Russia strain, developed by the Serum Institute India. To describe the evolution of the vaccine scar in neonates vaccinated by BCG-Russia compared to BCG-Moreau. This was a cohort study was conducted in Salvador city, northeast Brazil. The study population consisted of newborns from the reference maternity hospital, who were vaccinated with BCG-ID strains Moreau or Russia, followed up to assess vaccine lesion evolution. It was observed that regardless of the vaccine strains, the evolution of the lesion was the same: wheal, reddish macula, induration, pustule, ulcer, and scar. The proportion of vaccine scar in the group vaccinated with BCG Russia was lower than that of BCG Moreau, 62.5 % and 90.9 %, respectively, with a statistically significant difference. The evolution of the scar by BCG-Russia was similar to the Moreau scar, however different proportions were observed in different stages of lesion between the groups.


Anti-endothelial cell antibodies are associated with apoptotic endothelial microparticles, endothelial sloughing and decrease in angiogenic progenitors in systemic sclerosis.
Evidence has accumulated for the role of endothelial damage in systemic sclerosis (SSc) and the anti-endothelial cell antibodies (AECAs) might underlie vascular injury. Since endothelial microparticles (EMPs) and circulating endothelial cells (CECs) reflect endothelial damage, we aimed to investigate their possible relationship with AECAs in SSc. We examined whether AECAs could affect endothelial repair based on the number of endothelial progenitor cells (EPCs). Forty-seven SSc patients were screened. The AECAs were identified in serum by indirect immunofluorescence. EPCs and CECs were isolated from the peripheral blood using anti-CD34-based immunomagnetic separation, whereas EMPs were analyzed in plasma. Flow cytometry was used to quantify EMPs, CECs and EPCs. AECAs were found in 21 (44.7%) SSc patients and were significantly associated with higher levels of total as well as apoptotic (AnnV+ and CD51+) EMPs, whereas activated (CD62E+/AnnV-) EMPs did not differ between groups. Patients with AECAs had significantly elevated total CECs as well as activated CD105+ CECs. Total endothelial progenitors did not differ between patients with or without AECAs; however AECAs was negatively associated with the population of EPCs that express VEGFR2 or Tie2 receptors. We found an association between AECAs and the severity of endothelial damage in SSc based on higher levels of total EMPs and CECs. In our study, AECAs were associated with apoptosis of ECs rather than their activation. We also identified a possible role of AECAs in the impairment of vascular repair in SSc as evidenced by significantly fewer angiogenic EPCs.


How I do it? The surgical resection of the fourth ventricle choroid plexus papilloma.
The surgical resection of the large fourth ventricle choroid plexus papilloma (CPP) is complicated, where the challenge is to minimize the impairment of the vermis and the brainstem and restore the cerebrospinal fluid circulation. We report a case of large CPP that wholly occluded the fourth ventricle, extended to the Luschka foramen, and underwent radical resection via telovelar approach. The intraoperative endoscope was applied to inspect the tumor residue and the aqueduct's opening. This case demonstrates the surgical nuance of the fourth ventricle CPP.


Trends of beta-lactam antibiotic susceptibility in blood-borne methicillin-resistant Staphylococcus aureus (MRSA) and their linkage to the staphylococcal cassette chromosome mec (SCCmec) type.
We investigated trends of beta-lactam antibiotic susceptibility in a total of 218 strains of blood-borne methicillin-resistant Staphylococcus aureus (MRSA) isolated from 1978 through 2002 at a middle-size geriatric hospital in Tokyo; the strains were classified by the MRSA marker, staphylococcal cassette chromosome mec (SCCmec). The minimum growth inhibitory concentration (MIC) of cloxacillin at which 50% of the strains were inhibited (MIC50) was 2 microg/ml in the strains isolated in 1978-1984 and 32 to 64 microg/ml in the strains isolated subsequently. Similarly, the MIC50 values of cefazolin and imipenem in the 1978-1984 isolates were 16 and <or=0.25 microg/ml, respectively, and those in the strains isolated subsequently were 128 and 16 to 32 microg/ml, respectively. These results indicated that the MRSA strains isolated after 1985 had gained high-level resistance to beta-lactam antibiotics. The type of SCCmec was investigated by polymerase chain reaction (PCR). We observed an elevated frequency of type II SCCmec, from about 15% in the strains isolated in 1978-1984 to about 50% in the 1985-1989 isolates, and the frequency reached and remained at about 90% subsequently. These results imply that the high-level beta-lactam antibiotic resistance of the MRSA strains isolated after 1985 is most likely due to the increased integration of type II SCCmec.


Genetics of metabolic syndrome.
Metabolic syndrome (MetS) is a common phenotype, affecting about 24% of the US population. It is associated with an increased risk for type 2 diabetes and cardiovascular disease. Although there is no universally accepted definition for MetS, affected individuals commonly have a cluster of features, including abdominal obesity, hypertension, dyslipidemia, and dysglycemia. Recently, there has been extensive interest in potential genetic contributions to MetS. At present, no single gene or cluster of genes has been consistently replicated for MetS among different populations, likely due to the complex interplay between gene and environment necessary for expression of this phenotype. We review recent studies regarding the genetic contributions to MetS.


Experimental and finite element analysis of the rat ulnar loading model-correlations between strain and bone formation following fatigue loading.
The rat forelimb compression model has been used widely to study bone response to mechanical loading. We used strain gages to assess load sharing between the ulna and radius in the forelimb of adult Fisher rats. We used histology and peripheral quantitative computed tomography (pQCT) to quantify ulnar bone formation 12 days after in vivo fatigue loading. Lastly, we developed a finite element model of the ulna to predict the pattern of surface strains during compression. Our findings indicate that at the mid-shaft the ulna carries 65% of the applied compressive force on the forelimb. We observed large variations in fatigue-induced bone formation over the circumference and length of the ulna. Bone formation was greatest 1-2 mm distal to the mid-shaft. At the mid-shaft, we observed woven bone formation that was greatest medially. Finite element analysis indicated a strain pattern consistent with a compression-bending loading mode, with the greatest strains occurring in compression on the medial surface and lesser tensile strains occurring laterally. A peak strain of -5190 microepsilon (for 13.3N forelimb compression) occurred 1-2 mm distal to the mid-shaft. The pattern of bone formation in the longitudinal direction was highly correlated to the predicted peak compressive axial strains at seven cross-sections (r2 = 0.89, p = 0.014). The in-plane pattern of bone formation was poorly correlated to the predicted magnitude of axial strain at 51 periosteal locations (r2 = 0.21, p < 0.001), because the least bone formation was observed where tensile strains were highest. These findings indicate that the magnitude of bone formation after fatigue loading is greatest in regions of high compressive strain.


Considerations for Addressing the Needs of Culturally and Linguistically Diverse Speech-Language Pathology Praxis Test Takers.
The primary purpose of this article is to explore the speech-language pathology (SLP) Praxis test, a barrier to culturally and linguistically diverse (CLD) individuals entering the profession, by investigating first-time pass rates and mean scores by test taker race/ethnicity. Other potential barriers to licensure and certification, as well as solutions for mitigating these barriers, will also be addressed. SLP Praxis test data from two windows of time, 2008-2011 and 2014-2020, were compared for the following: (a) proportions of test taker race/ethnicity relative to U.S. demographic estimates of racial/ethnic group proportions overall, (b) proportions of racial/ethnic groups, and (c) trends in test-taker mean scores by race/ethnicity. First-attempt pass rates by racial/ethnic groups were also calculated for the 2014-2020 testing window. The percentage of some CLD SLP Praxis test-taker groups increased since the 2008-2011 testing window but is still not representative of U.S. racial/ethnic demographics. The first-attempt pass rates and overall mean scores of CLD test-taker groups remained substantially lower than White non-Hispanic/Latinx test takers. Despite the encouraging trends in SLP Praxis test-taker racial/ethnic diversity, disparities persist between the racial/ethnic makeup of SLP Praxis test takers and the demographic makeup of the United States. Consequently, these disparities have implications for the continued lack of cultural representativeness seen in our workforce.


Diet and development among children aged 36-59 months in low-income countries.
To assess the associations between diet, stimulation and development among children 36-59 months of age in low-income and middle-income countries (LMICs). We pooled Demographic and Health Survey data on 12 126 children aged 36-59 months from 15 LMICs. Child diet indicators included dietary diversity score (DDS, range 0-7), minimum dietary diversity (MDD, defined as DDS ≥4) and animal source foods (ASFs) consumption. Child development was assessed using the Early Childhood Development Index and stimulation by the number of stimulation activities (range 0-6). Associations were assessed using generalised linear models. In our sample, 18% of children met MDD and 50% received ≥4 stimulation activities. The prevalence of suboptimal cognitive, socioemotional, literacy-numeracy and physical development was 24%, 32%, 87% and 11%, respectively. Higher DDS, meeting MDD and consuming ASFs were associated with 8%-13% more stimulation activities. Children who met MDD were slightly less likely to have suboptimal literacy-numeracy development compared with children who did not meet MDD: relative risk 0.97 (95% CI 0.95 to 1.00). DDS, meeting MDD and ASFs consumption were not associated with cognitive, socioemotional or physical development. However, there was evidence of positive associations between MDD and cognitive and literacy-numeracy development among subgroups of children, including those who received ≥4 stimulation activities or attended an early childhood care and education programme. Child diet was associated with more stimulation activities. However, independent of stimulation, socioeconomic status and other factors, child diet appeared to be a prominent determinant only of literacy-numeracy development among children 36-59 months of age.


Locomotion and gait analysis.
Gait analysis can play an important role in exercise physiology, racetrack ergonomics, lameness prophylaxis, and assessment of performance potential in racehorses. This article concentrates on the methods used for gait analysis and considers some basic data on the different gaits of the horse.


Expression of concern: Subfunctionalization reduces the fitness cost of gene duplication in humans by buffering dosage imbalances.
After publication of this article (Fernandez et al., BMC Genomics 2011, 12:604) it was brought to the Editors' attention that the data generated by the first author, Ariel Fernandez, seemed anomalous. One of the author's institutions found that the data were not reproducible from the described methods, but an investigation by the author's other institution did not find the data or their interpretation suspicious. Given the conflicting conclusions of these investigations, the Editors advise the readers to interpret the data with due caution. We apologize to all affected parties.


Medical student subinternships in surgery: characterization and needs assessment.
Medical students commonly enroll in courses known as "subinternships" before residency application. This study investigated the experiences and needs of students completing subinternships in surgery. Electronic surveys were sent to medical students applying to the surgery residency program at our institution and to medical student clerkship directors for distribution nationally. Approximately 700 surveys were distributed with 275 completed (39%). Sixty-one percent of respondents indicated subinternships influenced specialty choice, and 82% of this group applied in general surgery. General surgery applicants rated mentorship (93%) and clerkship experience (92%) as important factors for specialty choice. Technical skills education was rated as beneficial by 89% of respondents, but formal laboratories were included only in 21% of courses. Only 49% received course objectives, and less than 10% were given a reading schedule. Opportunity exists to define a curriculum for surgical subinternships in order to address student needs for specific didactics for residency preparation and technical skill enhancement.


Aerobic Exercise Improves Depressive-like Behavior in CUMS-Induced Rats via the SIRT3/ROS/NLRP3 Signaling Pathway.
This study aimed to investigate the effect of exercise on depressive-like behavior induced by chronic unpredictable mild stress (CUMS) in rats and to explore the role of the SIRT3/ROS/NLRP3 signaling pathway in this process. Twenty-nine male 8-week-old Sprague Dawley rats were divided into a control group (CON) (nine rats) and a model group (twenty rats). Thirteen chronic stress stimuli were randomly applied once or twice per day for 35 days to induce depression in the model group rats. After the model was established, the model group rats were randomly divided into the CUMS group (CUMS) and the aerobic exercise + CUMS group (EX + CUMS). The EX + CUMS group received 8 weeks of aerobic exercise intervention for 6 days per week. Behavioral assessments were performed using the sucrose preference test and forced swimming test. The expression of SIRT3, NLRP3, IL-1β, and IL-18 in the hippocampus was detected using RT-PCR. The ROS level in the hippocampus was detected using immunofluorescence. The protein levels of SIRT3 and NLRP3 in the hippocampus were detected using western blotting. The protein levels of IL-1β and IL-18 in the hippocampus were measured using ELISA. After 5 weeks of chronic stress stimuli, the hippocampal function of rats in the CUMS model group was impaired, and their sucrose preference was reduced, while their forced swimming time was prolonged. The expression of SIRT3 decreased, ROS increased, and the expression of NLRP3 and the levels of IL-1β and IL-18 increased. Aerobic exercise increased the sucrose preference of rats, shortened their immobility time, increased the expression of SIRT3, and reduced the levels of ROS, NLRP3, IL-1β, and IL-18. Exercise can improve the depressive behavior of CUMS model rats, and its mechanism may be related to the upregulation of SIRT3 in the hippocampus, which plays an anti-inflammatory role.


Follow-up of probably benign lesions in non-screening breast diagnostics.
Our study addresses at the benefit of surveillance of probably benign lesions, detected outside mammographic screening, during a 3-year period. 28,588 women (mean age 57 ± 12 years) were examined. Two independent radiologists read the mammogram as well as the supplemented ultrasound (in case of breast density ACR type 3 and 4). In the case of discordance a third expert considered whether further examination was indicated or not. 3,266 diagnostic procedures ended with BI-RADS 3 result and 2,512 (76.9 %) women underwent a follow-up examination. 295 (11.7 %) of them received assessment examination (imaging and/or biopsy) and 37 (12.5 %) (none of them palpable) ended with BI-RADS 6. This equals a tumor detection rate of 14.7/1,000. The ratio in situ:invasive was 7:10 (1:1.43) and the mean size was 11.1 ± 4.51 mm. In the total cohort, 536 carcinomas ended with BI-RADS 6 of them 17 % were in situ and 83 % were invasive breast cancers (ratio in situ:invasive 1:4.99), mean size was 13.8 ± 6.3 mm. The cancer detection ratio in these cases was 18.7/1,000. The amount of detected tumors at follow-up of women with preceding BI-RADS 3 equates the associated potential of malignancy.


Target genes used for biosensor development in COVID-19 diagnosis.
In a published review entitled "COVID-19 diagnosis -A review of current methods", the authors considered hemagglutinin esterase as one of the structural proteins of SARS-CoV-2 and also they did not represent ORF3b, ORF9b, and ORF9c in SARS-CoV-2 genome structure. However, according to the scientific evidence, among coronaviruses only some betacoronaviruses (Embecovirus subgenera) contain HE, and the genome of most of the coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV lack the HE gene. In addition, the genome of SARS-CoV-2 contains several accessory proteins ORFs including ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF9c, and ORF10.


PTEN Regulates Renal Extracellular Matrix Deposit via Increased CTGF in Diabetes Mellitus.
Extracellular matrix accumulation and fibrosis are the features of diabetic nephropathy. PI3K (phosphatidylinositol 3-kinase)/Akt (protein kinase B) signal pathway and its inhibitor PTEN (phosphatase and tensin homolog deleted on chromosome 10) are revealed to modulate renal fibrosis. However, the exact mechanism is still not well known. In the present study we found that compared with normal mice, diabetic mice showed decreased PTEN, increased phospho-Akt (Ser 473), phospho-Akt (Thr 308), CTGF (connective tissue growth factor), α-SMA (α-smooth muscle actin), and matricellular protein in kidney. Knocking down of PTEN caused an increase in phospho-Akt (Ser 473), phospho-Akt (Thr 308), CTGF, secreted fibronectin, and secreted Col 3 in HKC cells (human renal tubular epithelial cells). Again, in vitro experiment revealed 1.89, 2.18, 1.92, 3.06, 2.06-fold increases of phospho-Akt (Ser 473), phospho-Akt (Thr 308), CTGF, secreted fibronectin, and secreted Col 3 in high glucose-stimulated HKC cells in comparison with normal control cells. Furthermore, knocking down of CTGF reversed increased secreted fibronectin and Col 3 in high glucose-treated HKC cells. Moreover, transfection of PTEN expression vector prevented high glucose-caused these changes in HKC cells. Especially, CTGF expression, secretion of fibronectin and Col 3 were, respectively, decreased by 38.81, 53.85, and 39.12%. The treatment of LY294002 inhibited phospho-Akt (Ser 473) and phospho-Akt (Thr 308) expression followed by decreased CTGF, secretory fibronectin and secretory Col 3 in high glucose-treated HKC cells. In the end our study suggests that PTEN regulates renal extracellular matrix production via activated Akt and increased CTGF in diabetes mellitus.


2,3,7,8-Tetrachlorodibenzo-p-dioxin reduces high-affinity binding of epidermal growth factor to cell surface receptors in C3H 10T1/2 cells.
The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on epidermal growth factor (EGF)-binding characteristics was studied in a cultured embryonic fibroblast cell line, C3H 10T1/2. At very low concentrations, TCDD was found to cause a persistent decline in EFG binding, the median effective concentration (EC-50) being 10(-12) M. This particular effect was most conspicuous when TCDD was added at the time of medium change with fresh Dulbecco's modified Eagle's medium. Cells at an early stage of confluency were more responsive to TCDD than those at a later stage. Although most reported TCDD-evoked biological changes are recognized to occur slowly during the course of a few days to weeks, the response of C3H 10T1/2 cells to TCDD was swift, showing a sign of decline of EGF binding as early as three hours after TCDD addition. C3H 10T1/2 cells appear to be an excellent in vitro model to study TCDD's biochemical action mechanisms.


Expression of allogeneic MHC class I antigens by transgenic mouse trophoblast does not interfere with the normal course of pregnancy.
Mammalian embryos express paternal histocompatibility antigens which make them potential targets for maternal immune responses. Yet, the histoincompatible fetus survives and develops normally. Down regulation of classical MHC antigen expression by trophoblast cells which are in direct contact with maternal circulation has been repeatedly shown. The trophoblast cells are unable to function properly in antigen presentation and do not induce allogeneic rejection reactions. In the present study we have created transgenic mice that express an allogeneic class I transgene whose transcription is controlled by the transferrin receptor promoter. The expression patterns of the transgene product mice from a single transgenic line were studied in each of the typical placental subpopulations. The allogeneic class I antigen was expressed in the allantoic plate region of the trophoblast, and this expression was not restricted to the endothelial region but extended also to the spongiotrophoblast, as well as the major blood vessels and in the endodermal sinuses. In contrast to the normal class I expression, prominent levels of allogeneic H-2 antigens were detected in the labyrinthine trophoblast. The fetal resorption rate in females mated with these transgenic males was not higher then the normal rate, and the embryos survived and developed normally. These data imply that the unusual expression of allogeneic class I antigens in certain trophoblast subpopulations does not affect fetal development.


A dual-targeting near-infrared biomimetic drug delivery system for HBV treatment.
Hepatitis B virus (HBV) infection is a serious global public health threat. It remains elusive to achieve a functional HBV cure with currently available antivirals. Herein, a photo-responsive delivery vehicle composed of Nd3+ -sensitized core-shell upconversion nanoparticle (UCNP), mesoporous silica nanoparticle (MSN), antisense oligonucleotides (ASOs), and capsid-binding inhibitor C39 was established, which was named UMAC according to the initials of its components. Subsequently, the as-synthesized delivery vehicle was encapsulated by β- D-galactopyranoside (Gal) modified red blood cell (RBC) membrane vesicles, which enabled precise targeting of the liver cells (UMAC-M-Gal). Both in vitro and in vivo experiments demonstrated that this biomimetic system could successfully achieve controlled drug release under light conditions at 808 nm, leading to effective suppression of HBV replication in this dual-targeted therapeutic approach. Together, these results substantiate the system has huge prospects for application to achieve functional HBV cure, and provides a promising novel strategy for drug delivery.


Tuberculous meningitis in children: treatment with isoniazid and rifampicin for twelve months.
Patients with tuberculous meningitis were treated with isoniazid and rifampicin for 12 months. To evaluate the result of treatment, we studied the outcome of patients treated from January 1979 to December 1985. Of the 51 patients, 27 were female, and 5, 25, and 21 patients were in the first, second, and third stages of the disease, respectively. Increased intracranial pressure of greater than 200 mm H2O was observed in 42 patients. Three patients required ventriculostomy, and one of them needed ventriculoperitoneal shunting. Three patients died within the first week of admission, and four patients were lost to follow-up. Forty-four patients were followed for 1 1/2 to 7 years; 31 of them recovered completely. Thirteen patients recovered with neurologic sequelae, which included mental retardation, motor weakness, seizures, and hydrocephalus. No serious side effect of the drugs were observed except for transient elevation of liver enzyme activities in four patients. The combination of isoniazid and rifampicin for 1 year, with appropriate management of increased intracranial pressure, seemed to be safe and effective enough to be used as a routine treatment of tuberculous meningitis in areas where resistance to these drugs is uncommon.


Antibodies to PECAM-1 and glucocorticoids reduce leukocyte adhesion in adjuvant arthritis of the rat knee synovium in vivo.
To demonstrate the effect of monoclonal antibodies to the adhesion-molecule PECAM-1 (CD31) and of prednisolone on leukocyte adhesion in rat adjuvant arthritis. Adjuvant arthritis was induced in male CD-rats (five groups of n = 6) 18 days prior to measurements. Mouse-monoclonal antibody to rat CD-31 at 200 microg/kg or prednisolone at 24 mg/kg were administered i.v. 15 minutes prior to measurements. Venules within the intact rat-knee synovium were focused by confocal laser scanning microscopy. Numbers of rolling and adherent leukocytes were assessed in vivo. Induction of arthritis significantly increased rolling and adherent leukocytes compared to healthy controls. Both monoclonal antibodies to PECAM-1 and prednisolone significantly reduced adherent, but not rolling leukocytes in arthritic animals. The method used is well suited for in vivo quantification of leukocyte adhesion under the influence of antiadhesive therapies. PECAM-1 might be an interesting target for novel therapies in rheumatoid arthritis.


Exponential increase in age-specific prevalence of ventricular dysrhythmia among males.
Analyzing nine available studies of cardiac dysrhythmia among males shows an exponential increase of the prevalence of dysrhythmia with increased age (16-74 yr). This pattern appears in unselected populations and in populations selected for prior history of myocardial infarction. In 6 of 9 population groups the exponent for the rate of increased prevalence of any ventricular premature contractions (VPCs) with age was statistically indistinguishable from study to study despite variations in length of monitoring, of local interpretations of ECG, or of differences in the composition of these groups. Within each population group the prevalence of "frequent" VPCs or of "complex" VPCs also increased exponentially with age. The precise mathematical expression for the increase suggests an etiologic explanation for cardiac dysrhythmia common to coronary artery disease and myocardial infarctions which exhibit similar behavior.


Investigating grounded conceptualization: Stimulus-response compatibility for tool handles is due to spatial attention.
Brain imaging research shows that viewing tools activates regions of the cortex implicated in performing actions with that tool. Grounded (or embodied) theories of cognition propose that this activity reflects the activation of motor representations that are constitutive of the object concept. Behaviorally, participants respond faster with the hand that is aligned with the handle of an object. This stimulus-response compatibility (SRC) effect is often taken as evidence supporting the hypothesis that motor representations are activated in response to the visual presentation of tools during conceptual processing. To test this hypothesis, we trained participants to use a set of novel tools (manipulation group) or to report spatial information about the tools (spatial group) in preparation for a Martian archeological dig. We investigated compatibility effects in a conceptual judgment task and a visual discrimination task. Compatibility effects were observed for both groups regardless of experience. These effects were predicted by the salient parts of objects specified by task demands and not by motor experience with the objects. This result provides evidence that compatibility effects with tools reflect a general stimulus-response compatibly effect due to visual attention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Influence of smoking on disease activity and prognosis of antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study.
Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are a group of autoimmune diseases characterized by inflammation of small blood vessels. Smoking is a potential trigger for such diseases, however, its link with AAV remains controversial. The aim of this study was to analyze the link between AAV and smoking based on clinical characteristics, disease activity, and mortality. This retrospective study included 223 AAV patients. Their smoking status was assessed at diagnosis and they were classified as ever smokers (ESs), including current or past smokers, and never smokers (NSs). Information regarding clinical presentation, the disease activity, immunosuppressive therapy, and survival was collected. The ESs had similar organ involvement to the NSs, except for significantly greater frequency of renal replacement therapy (31% vs 14%; P = 0.003). Median (interquartile range [IQR]) time from symptom onset to diagnosis was significantly shorter in the ESs than the NSs (4 [2-9.5] vs 6 [3-13] months; P = 0.03), with significantly higher mean (SD) value of the Birmingham Vasculitis Activity Score version 3 (19.5 [7.93] vs 17.25 [8.05]; P = 0.04). The ESs were more likely to receive cyclophosphamide therapy (P = 0.03), and had significantly higher morality than the NSs (hazard ratio, 2.89; 95% CI, 1.47-5.72; P = 0.002). There were no significant differences between the current and past smokers. The multivariable Cox proportional regression analysis found ever smoking and male sex to be independent predictors of mortality in AAV patients. Ever smoking is associated with increased AAV activity and more frequent renal replacement therapy and immunosuppressive treatment, resulting in a poorer survival prognosis in AAV patients. Future multicenter studies are required to further characterize the clinical, biological, and prognostic impact of smoking on AAV.


Monitoring active site alterations upon mutation of yeast pyruvate kinase using 205Tl+ NMR.
The interaction of the monovalent cation with wild type (WT) yeast pyruvate kinase (YPK) and with the T298S, T298C, and T298A mutants was investigated by 205Tl+ NMR to monitor possible structural alterations at the active site by Thr-298 mutation. TlNO3 activates WT YPK with a kcat value similar to that obtained with KCl and an apparent Ka of 0.96 +/- 0.07 mm in the presence of Mn2+ and fructose 1,6-bisphosphate. With the three mutants, Tl+ is a better activator than is K+ based on kcat values. Tl+ activation and inhibition of YPK is affected by mutation of the active site Thr-298. The effect of Mn2+ on the 1/T value of 205Tl+1 in the presence of the WT and mutant YPK complexes was determined at 173 MHz (300 MHz, 1H) and 346 MHz (600 MHz, 1H). For each complex studied, 1/pT2p >> 1/pT1p and 1/pT1p is frequency-dependent suggesting fast exchange conditions. The values of 1/pT1p differ for each mutant. A correlation time of 0.65 +/- 0.35 ns was estimated for the Mn2+-205Tl+ interaction. The Tl+-Mn2+ distances at the active site of YPK were calculated from the paramagnetic contribution of Mn2+ to 1/T1M of YPK-bound 205Tl+. The calculated Tl+-Mn2+ distance for the Thr-298 mutants is decreased by about 1 A from 6.0 +/- 0.2 A observed with WT. The results suggest conformational alterations at the active site of YPK where phosphoryl transfer occurs upon mutation of Thr-298. These conformational changes may, in part, explain the alteration in kcat and kcat/Km,PEP observed with the Thr-298 mutants.


A safe and cost-effective approach to minimally invasive radial artery harvesting.
We describe a minimally invasive, cost effective, and safe method of radial artery harvesting. After obtaining informed consent and completing a preoperative evaluation, 169 radial arteries were harvested. Harvesting was accomplished through a 3-cm proximal mid forearm incision with exposure provided by a modified self-retaining lighted retractor. A total of 169 radial arteries were successfully harvested. The average incision length was 2.9 cm, radial artery length was 15.8 cm, and harvest time was 32.7 minutes. No trauma to the artery or graft spasm was evident. No procedure required conversion to an open technique. Superficial cellulitis occurred in 2 patients (1.2%) and wound infection in 1 (0.6%). Three patients (1.8%) experienced intermittent residual dysesthesia. All of the patients were highly satisfied with the excellent aesthetic results. This approach allowed for a substantial cost savings compared with other minimally invasive techniques. Direct minimally invasive radial artery harvesting is an acceptable alternative approach to radial artery harvesting. This method is safe, cost effective, easily reproducible, and aesthetically pleasing.


Non-flammable fluorobenzene-diluted highly concentrated electrolytes enable high-performance Li-metal and Li-ion batteries.
Lithium-ion batteries with Ni-rich cathode and flammable carbonate electrolytes are breeding severe safety concerns which hinds their application in electric vehicles. Herein, by introducing the fluorobenzene (FB) with low-density and low-cost as a cosolvent and bridge solvents in triethyl phosphate (TEP)-based diluted high-concentration electrolytes (DHCEs) system, we design a non-flammable electrolyte with a special solvation structure containing internal-external flame retardants. This non-flammable electrolyte not only solves successfully the incompatibility problem of TEP-based electrolyte to the Li-metal anode (LMA) and the graphite (Gr) anode, but also ensures the stable cycling of Li||LiNi0.7Co0.1Mn0.2O2 (86% capacity retention after 120 cycles) and Gr|| LiNi0.7Co0.1Mn0.2O2 (75% capacity retention after 200 cycles) full cells. Such design opens up a new window for developing new electrolyte systems and building safer high-energy-density batteries.


Sequential dependencies regulate sensory evoked responses of single units in the rat hippocampus.
Unit activity from 3 major types of hippocampal cells were recorded from the CA1, CA3 and dentate granule cell layers of the hippocampus in awake freely moving rats. Units were classified as complex spike (ComSp), theta and dentate granule cells (G-cell) based on their spontaneous and stimulus-evoked firing characteristics. Single trial records for each cell type were collected during criterion performance of a two-tone discrimination task. Results showed that: tone-evoked discharges of theta- and G-cells, but not ComSp cells, were influenced by the reward status of the tone presented; the firing tendency of all cell types was significantly influenced by the preceding trial sequence; different types of preceding trial sequences including single and double alternation and runs of positive or negative trials significantly affected the firing tendency of all 3 cell types; the pattern of theta- and G-cell discharges differed with respect to latency to peak discharge and the duration of the discharge following long runs of similar trials. These effects were similar to previously described sequential influence on synaptically identified sensory evoked potentials in the dentate gyrus.


Cancer chemotherapy: a critical analysis of its 60 years of history.
Chemotherapy has already proven widely effective in the treatment of cancer, occupying a prominent place in the current therapeutic arsenal. However, in recent years, there has been a plateau in the evolution of the clinical results obtained with this modality treatment. In some cases, the limitations of chemotherapy observed during the early days still apply. These facts forced us to do a thorough analysis of what happened in the past 60years. We have observed that each major advance obtained in this field was based on empirical clinical observations. We thus believe that the current results of old or new agents can only be improved by understanding the natural history of each specific cancer subtype at the clinical level and by overcoming the physiological barriers involved in chemotherapy failure. This strategy will surely allow us to enlarge the list of curable cancers by chemotherapy.


Referral Patterns for Infertile Men: Predictors of Continued Treatment by Reproductive Endocrinologist versus Referral to a Nearby Urologist.
We evaluated fertility clinic management of male factor infertility, including patient education and referral for urological evaluation and care. Using 2015-2018 Centers for Disease Control and Prevention Fertility Clinic Success Rates Reports, 480 operative fertility clinics in the United States were identified. Clinic websites were systematically reviewed for content regarding male infertility. Structured telephone interviews of clinic representatives were performed to determine clinic-specific practices for management of male factor infertility. Multivariable logistic regression models were used to predict how clinic characteristics (geographic region, practice size, practice setting, in-state andrology fellowship, state-mandated fertility coverage, annual in vitro fertilization cycles and percentage of in vitro fertilization cycles for male factor infertility) were associated with reproductive endocrinologist physician management of male infertility and/or referral to a urologist. We interviewed 477 fertility clinics and analyzed available websites (474). The majority of websites (77%) discussed male infertility evaluation, while 46% discussed treatment. Clinics that were academically affiliated, had an accredited embryo laboratory and referred patients to a urologist were less likely to have the reproductive endocrinologist manage male infertility (all p <0.05). Practice affiliation, practice size and website discussion of surgical sperm retrieval were the strongest predictors of nearby urological referral (all p <0.05). Variability in patient-facing education, and fertility clinic setting and size influence fertility clinics' management of male factor infertility.