Miracle-dz/UniFAR-FTUs huggingface dataset:
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase

Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-d-aspartate–receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the γ-aminobutyric acid–producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.
Torsional loads in the early postoperative period following total hip replacement

Torques generated in one subject during the early postoperative period were measured with a telemeterized total hip component. The patient was examined during gait, stair ascent, rising from a chair, and single‐limb stance. The torques were plotted against both the resultant joint contact force and the force component directed along the stem axis. During gait, the maximum torque was 35 Nm, recorded at a walking velocity of 1.7 m/sec. The peak torques during stair ascent and during rising from a seated position were found to be 23 and 15 Nm, respectively. The maximum value for torque measured in this study was 37 Nm during one attempt at single‐limb stance. Comparison of plots for torque versus stem‐axis component for the four activities shows that the torque increased more rapidly for chair exits than for gait up to resultant contact force values of as much as 1,000 N. For stair ascent, the same was true to values of 1,400 N. Within any given activity, the relationship between stem torque and resultant or stem‐axis force showed considerable variability. These results indicate that experiments evaluating the stability of femoral components in total hip arthroplasty should incorporate a component directed along the stem axis, as well as a component normal to the plane of the prosthesis. The results also suggest that theoretical stress analysis models should consider the broad variability in the orientation of the joint force at the hip.
Equalization for Outdoor mmW Deployments

Millimeter wave (mmW) frequencies are considered to be indispensable for next generation wireless systems, both cellular and Wi-Fi, primarily due to the large amounts of spectrum available in these bands. However, the higher frequency-dependent path loss at these frequencies needs to be overcome by the use of high-gain directional antenna arrays at both transmitter and receiver. Due to the complexity and peak to average power ratio (PAPR) requirements of OFDM, single-carrier is being considered for the physical layer, which brings up the question of appropriate equalization. In this paper we present a simulation study of equalization structures specifically for a mmW outdoor system, using realistic ray tracing simulation software to generate multipath channels depending on the transmit and receive antenna beam-widths. We then compare decision feedback equalization (DFE) with linear equalization (LE) for these channels and show that in an urban multipath environment the use of DFEs can offer significant gains even with very narrow antenna beams, while the gains are smaller in a suburban environment with less multipath.
Mechanistic Insights to the Cytotoxicity of Amaryllidaceae Alkaloids

With over 500 individual compounds, the Amaryllidaceae alkaloids represent a large and structurally diverse group of phytochemicals. Coupled to this structural diversity is the significant array of biological properties manifested by many of its members, of which their relevance in motor neuron disease and cancer chemotherapy has attracted considerable attention. To this extent, galanthamine has evolved into a successful commercial drug for Alzheimer's disease since its approval by the FDA in 2001. Concurrently, there have been several positive indicators for the emergence of an anticancer drug from the Amaryllidaceae due to the potency of several of its representatives as cell line specific antiproliferative agents. In this regard, the phenanthridones such as pancratistatin and narciclasine have offered most promise since their advancement into clinical trials, following which there has been renewed interest in the cytotoxic properties of these alkaloids. Given this background, this review seeks to highlight the various mechanisms which have been invoked to corroborate the cytotoxic effects of Amaryllidaceae alkaloids.
Measurement of serum hyaluronic acid in patients with rheumatoid arthritis: correlation with disease activity.

OBJECTIVE To examine serum concentrations of hyaluronic acid (HA) in patients with rheumatoid arthritis (RA) and to investigate the relationship between clinical measures of disease activity and serum HA concentrations in these patients. METHODS Sixty-five patients with established RA were enrolled and RA disease activity was measured by clinical variables. Serum samples obtained at the time of the clinical evaluation were assayed for serum HA, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP), and correlations between these laboratory variables and clinical disease activity were sought. RESULTS Concentrations of serum HA were higher in patients with RA than in healthy controls. There was statistically significant correlation between patient age and serum HA and between serum HA and disease activity measured by physician assessment and number of swollen joints. Correction for age strengthened the correlation between serum HA and measures of disease activity. ESR did not correlate with any measure of clinical disease activity. CRP concentrations correlated with physician assessment of disease activity, and number of swollen joints and tender joints, but the correlation was not as strong as the correlation between serum HA and disease activity variables. CONCLUSION Measurement of serum HA may be a useful measure of disease activity in patients with RA. Measurement of serum HA appears to be a better correlate of clinical disease activity in patients with RA than ESR or CRP.
In Vitro Investigation of DNA Damage Induced by the DNA Cross-Linking Agents Oxaliplatin and Satraplatin in Lymphocytes of Colorectal Cancer Patients

Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can induce mutations, chromosomal rearrangements, and cell death. Many DNA interstrand crosslinks lesions can be generated by platinum-based chemotherapeutic agents. Satraplatin is a novel orally administered platinum-based chemotherapeutic agent. In the present study, we investigated DNA interstrand crosslinks lesions induced by oxaliplatin and satraplatin in lymphocytes obtained from colorectal cancer patients and healthy volunteers. Satraplatin demonstrated an increase in interstrand crosslinks in a dose-dependent manner in the Comet assay (p in vitro. Here, to the best of our knowledge we report for the first time evidence of DNA double strand breaks formation as a possible molecular mechanism of action for satraplatin.
The impact of sonography on the management of extratesticular abnormalities of the scrotum

The results of scrotal sonography performed in a recent one‐year period (1987) were retrospectively reviewed to assess the role of sonography in the management of patients with extratesticular abnormalities. The study included 226 examinations performed in 204 men. In extratesticular abnormalities, scrotal sonography confirms the clinical impression of the referring physicians, monitors the progress of conservative treatment, and guides the surgical approach. Patients with sonographically classic cystic extratesticular abnormalities rarely come to surgery. Those with complicated cystic abnormalities are usually followed clinically but have a higher incidence of surgery. Those with solid‐appearing echogenic abnormalities usually have surgical removal.
Proposed association between the COL1A1 and COL1A2 genes and otosclerosis is not supported by a case‐control study in Spain

Otosclerosis (OTSC) is one of the most common causes of hearing loss in white adults. The COL1A1 and COL1A2 genes coding for type‐I collagen have been proposed as candidate genes in the development of OTSC. The COL1A1 gene was recently reported to be associated with the condition on the basis of a population‐based case‐control study. We report here an independent study of association between COL1A1 and COL1A2 gene polymorphisms and OTSC, in a case‐control sample from a population of Caucasian individuals living in Northwest Spain. Specifically, we studied two COL1A1 polymorphisms previously reported to be associated with OTSC, and six COL1A2 polymorphisms. We performed diverse association analyses based on alleles, genotypes, and two‐locus haplotypes. We found no evidence supporting the putative link of COL1A1 and COL1A2 genes with OTSC. © 2004 Wiley‐Liss, Inc.
Incidence of Epstein-Barr virus in astronaut saliva during spaceflight.

BACKGROUND Astronauts experience psychological and physical stresses that may result in reactivation of latent viruses during space-flight, potentially increasing the risk of disease among crewmembers. HYPOTHESIS The shedding of Epstein-Barr virus (EBV) in the saliva of astronauts will increase during spaceflight. METHODS A total of 534 saliva specimens were collected from 11 EBV-seropositive astronauts before, during, and after four space shuttle missions. The presence of EBV DNA in saliva, assessed by polymerase chain reaction (PCR), was used to determine shedding patterns before, during, and after space-flight. RESULTS EBV DNA was detected more frequently before flight than during (p < 0.001) or after (p < 0.01) flight. No significant difference between the inflight and postflight periods was detected in the frequency of occurrence of EBV DNA. CONCLUSIONS The increased frequency of shedding of EBV before flight suggests that stress levels may be greater before launch than during or after spaceflight.
Zidovudine‐induced restoration of cell‐mediated immunity to mycobacteria in immunodeficient HIV‐infected patients

ObjectiveTo describe a localized form of Mycobacterium avium intracellulare (MAI) infection occurring concurrently with the restoration of cutaneous delayed-type hypersensitivity (DTH) responses to mycobacterial antigens after commencement of ziclovudine therapy in immunodeficient HIV-infected patients. PatientsThe first 108 Western Australian patients with a CD4+ T-cell count of <200 $$ 106/1 and/or symptomatic disease to be given zidovudine (ZDV), of whom 72 had adequate DTH data. MethodsDTH responses to seven antigens were measured by the 'Multitest' method before and on at least two occasions during the 6 months after commencing ZDV. All patients were reviewed at regular intervals and clinical events recorded. ResultsOf the 64 patients who were anergic to tuberculin before commencing ZDV, 27 (42%) developed a DTH response to tuberculin after ZDV. Four of the nine patients with a ‘Multitest’ tuberculin response of ≥8mm and one patient who developed a positive Mantoux test to M. avium purified protein derivative developed an illness characterized by localized MAI infection, lymphadenopathy and/or severe fevers after 1–2 weeks. ConclusionThe development of localized MAI infection and/or fevers shortly after commencing ZDV in immunodeficient HIV-infected patients may reflect restoration of cellular immunity to mycobacterial antigens in some patients rather than early failure of therapy or hypersensitivity to ZDV.
Frequent Sampling Reveals Dynamic Responses by the Transcriptome to Routine Media Replacement in HepG2 Cells

Cultured cell lines are employed extensively for biological research. Large-scale differential gene expression (LSDGE) is being used to study mechanisms of toxicity in such cultures. `Normal' gene expression dynamics could have a major impact on the design and interpretation of these studies. In order to provide understanding of such dynamics, we investigated LSDGE responses to media replacement in human hepatoblastoma cells (HepG2) using 5-minute sampling frequencies for 6 hours post routine media replacement. Each mRNA transcript was found to exhibit a characteristic `operating range' based on signal intensity. Following media replacement, which replenishes nutrients (eg, glucose and glutamate) and removes excretory products (eg, lactate), a complex set of gene expression changes was observed. Some transcripts appeared to switch on from a quiescent state to a very active one (eg, CYP1A1), others exhibited `clocklike' oscillations (eg, asparagine synthetase), or a synchronous burst (chirp) of expression up regulation (eg, timeless). Mathematical analysis (Fourier Transform, Singular Value Decomposition, Wavelets, Phase Analysis) of oscillating expression patterns identified cycle lengths ranging from 11.8 to 210 minutes. There were prominent 36.5- and 17.4-minute cycles, for subsets of genes, and transcript-specific differences in phase angle with respect to these cycles. The functional consequences of these novel observations remain to be determined. It is clear that dense time-course studies provide a valuable approach to the investigation of physiological responses to nutrients, toxicants, and other environmental variables. This research also highlights the need for an understanding of biological dynamics when using cell culture systems. An Excel data file representing individual transcripts from the respective Clontech cDNA arrays referred to in this article is available at http://taylorandfrancis.metapress. com/openurl.asp? genre=journal&issn=0192-6233. Rows represent data for individual transcripts and columns represent the time-points from 0 to 360 minutes. To access this file, click on the issue link for 31(4), then select this article. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath. org.
Survival prognostic factors in patients with glioblastoma: our experience.

AIM Approximate survival for glioblastoma is less than 1 year. Age, histological features and performance status at presentation represent the three statistically independent factors affecting longevity. The purpose of the study was to assess the role of surgery and to analyze prognostic factors in our patients operated for glioblastoma. METHODS We evaluated in 56 patients operated for glioblastoma their depressive and performance status in the preoperative and postoperative time. Moreover we analyzed the extent of surgery, the site and the size of lesions. RESULTS Median overall survival was 17 months. An age of ≥60 years (P<0.03), a preoperative Karnofsky Performance Status KPS≤70 (P=0.04), a subtotal tumor resection (P<0.001), a tumor size >5 cm (P=0.01), and no postoperative adjuvant treatment (P=0.01) were associated with the worst prognosis. Before surgery we found the presence of depression in 10 patients with a significative reduction of mean Back Depression Inventory scores after tumor resection (P=0.03). Finally, a KPS≤70 was significantly associated with an increased incidence of depression in the postoperative time. CONCLUSION Tumor size, total resection and affective disorders were identified as predictors of survival in our series of patients with glioblastoma in addition to age and KPS score. In our opinion an early diagnosis and the use of specific safeguards in the operating room contribute to have an extension of the tumor progression time and median survival.
Patterns of oral cleaning habits and use of fluoride among dentate adults in Finland.

PURPOSE The aim of the present study was to identify the underlying patterns of oral cleaning habits and the use of fluoride, and to investigate their variations by studying the socioeconomic characteristics among Finnish dentate adults aged 30 to 64 years. MATERIALS AND METHODS Participants of the nationwide Health 2000 survey who were dentate, aged 30 to 64 years, and underwent a health interview and a clinical oral examination, were included in the present study (n = 4419). RESULTS In total, 79% of the women and 46% of the men reported to have brushed their teeth twice or more daily; 16% of the women and 14% of the men reported daily use of an electric toothbrush and 14% of the women and 5% of the men reported daily use of dental floss or an interdental brush. Factor analysis revealed five oral cleaning habit patterns, which were named modern, rational, before-breakfast, social and irrational. The modern cleaning pattern was associated with higher levels of education, and the rational cleaning with younger age, female gender and higher levels of education. The before-breakfast cleaning pattern was associated with male gender and lower levels of education, and the social cleaning with older age, female gender and higher levels of education. The irrational cleaning pattern was associated with older age. CONCLUSIONS Adults have various oral cleaning habit patterns, each of which is associated with the subjects' socioeconomic characteristics.
Comparative anatomical and neurohistological observations on the tongues of pigmy and common marmosets

Macroscopic and neurohistological observations of the tongues of the pigmy and common marmosets are described. On the dorsum, there are three circumvallate papillae arranged in an inverted V‐shape. Through the magnifying glass the foliate papillae with a few clefts are found anterior to the attachment of the glossopalatine fold. The fungiform papillae can be seen with a lens. The vallate papillae are supplied with abundant nerves. The taste buds are located only in the lateral non‐cornified wall of the papilla, closely associated with the subgemmal nerve plexus. The lingual glands of the serous type are present deep in the muscle of this region. The ganglion cells composing the ganglion are located inside and below the papilla. The foliate papillae consist of a few furrows with many taste buds and are supplied with abundant nerves and a few ganglion cells. The serous glands are not plentiful. Infiltration of the lymphoid cells in the foliate papilla region should be regarded as the lingual follicle of the primitive type. The fungiform papillae are supplied with abundant nerve fibers which terminate free and are furnished with many taste buds having an embryonic appearance. The papillae are comparable to those of the human fetal or newborn tongue. The “sublingua” is a rudimentary structure having neither sensory nerves nor taste buds. The ganglion cells lying on the nerve fiber bundles in the apical region probably are cells migrating from the submandibular ganglion. No apical glands of Nuhn are present.
In silico augmentation of the drug development pipeline: examples from the study of acute inflammation

The clinical translation of promising basic biomedical findings, whether derived from reductionist studies in academic laboratories or as the product of extensive high‐throughput and high‐content screens in the biotechnology and pharmaceutical industries, has reached a period of stagnation in which ever higher research and development costs are yielding ever fewer new drugs. Systems biology and computational modeling have been touted as potential avenues by which to break through this logjam. However, few mechanistic computational approaches are used in a manner that is fully cognizant of the inherent clinical realities in which the drugs developed through this ostensibly rational process will be ultimately used. This article presents a translational systems biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism. Drug Dev Res 72: 187–200, 2011. © 2010 Wiley‐Liss, Inc.
Altered Neurotrophin, Neuropeptide, Cytokines and Nitric Oxide Levels in Autism

Abstract Introduction: Modifications in neurotrophins, neuropeptides, cytokines and nitric oxide (NO) levels in autism may represent different biological aspects of the disease. In the present study we investigate simultaneously all these variables as an attempt to clarify their interrelationships in autism. Methods: Plasma levels of vasoactive intestinal peptide (VIP), neurotrophin-3 (NT-3), cytokines and nitric oxide (NO) were determined in children with DSM-IV autistic disorder (n=24) and in age- and gender-matched healthy controls (n=24). VIP, NT-3, IFN-γ and IL-1β levels were measured by ELISA, TNF-α, IL-10, IL-6, IL-4, IL-2 were evaluated by flow cytometry, and NO by Griess reaction. Results: Plasma levels of VIP, IFN-γ and NO were significantly higher and NT-3 plasma levels were significantly lower in children with autism, compared to the healthy subjects. In children with autism there was a positive correlation between plasma levels of NO and IFN-γ. Discussion: Our results indicate the presence of altered levels of neurotrophin and neuropeptide in infantile autism and provide additional evidence that higher levels of IFN-γ may be associated with increased oxidative stress in autism.
A pseudo‐outbreak of disseminated cryptococcal disease after orthotopic heart transplantation

Cryptococcal infection is the third most common invasive fungal infection (IFI) among solid‐organ transplant (SOT) recipients and is considered an important opportunistic infection due to its significant morbidity and mortality. To determine whether a cluster of cryptococcosis in heart transplant patients was of nosocomial nature, three cases of orthotopic heart transplant recipients with postoperative disseminated cryptococcal infection were investigated and paired with an environmental survey in a tertiary care hospital. The infection prevention department conducted a multidisciplinary investigation, which did not demonstrate any evidence of health care‐associated environmental exposure. Moreover, multilocus sequence typing showed that one isolate was unique and the two others, although identical, were not temporally related and belong to the most common type seen in the Southern US. Additionally, all three patients had preexisting abnormalities of the CT chest scan and various degrees of acute and chronic rejection. Reactivation was suggested in all three patients. Screening methods may be useful to identify at risk patients and trigger a prophylactic or preemptive approach. However, more data is needed.