Miracle-dz/UniFAR-FTUs huggingface dataset:
Ha‐ras mutations in N‐nitrosomorpholine‐induced lesions and inhibition of hepatocarcinogenesis by antisense sequences in rat liver

To evaluate the application of Ha‐ras mRNA antisense oligonucleotide therapy for liver tumors, we examined the frequency and types of mutation in codon 61 of the Ha‐ras oncogene in preneoplastic lesions and hepatocellular carcinomas induced by N‐nitrosomorpholine (NNM) in rats. Thirty‐seven percent of preneoplastic lesions and 50% of hepatocellular carcinomas contained mutations, mostly CAA‐CTA and CAA‐AAA transversions. We also investigated the effects on NNM‐induced lesions of an antisense oligonucleotide directed against a point mutation (CAA‐CTA) in codon 61 of Ha‐ras mRNA. In this experiment, Sprague‐Dawley rats were given free access to water containing NNM for 8 weeks and received twice‐weekly i.p. injections of a mutated Ha‐ras antisense oligonucleotide with a 5′ phosphorothioate linkage or a sense oligonucleotide in oligonucleotide‐liposome complexes. At week 16, rats that had received the mutated Ha‐ras antisense oligonucleotides had significantly fewer and smaller preneoplastic lesions positive for glutathione‐S‐transferase, placental type, and had smaller hepatocellular carcinomas than rats that had received the sense oligonucleotide. Mean cellular fluorescence in the liver was found to increase with higher doses of mutated, fluorescein‐isothiocyanate‐labeled antisense or sense oligonucleotides. Moreover, mutated Ha‐ras antisense oligonucleotide decreased the expression of mutated Ha‐ras mRNA (CAA‐CTA). Our findings indicate that mutated Ha‐ras antisense oligonucleotide significantly inhibits hepatocarcinogenesis in rats and could be an effective therapy against liver tumors. Int. J. Cancer 72:815–820, 1997. © 1997 Wiley‐Liss, Inc.
Characterization of a novel NCAM ligand with a stimulatory effect on neurite outgrowth identified by screening a combinatorial peptide library

The neural cell adhesion molecule, NCAM, plays a key role in neural development and plasticity mediating cell adhesion and signal transduction. By screening a combinatorial library of synthetic peptides with NCAM purified from postnatal day 10 rat brains, we identified a nonapeptide, termed NCAM binding peptide 10 (NBP10) and showed by nuclear magnetic resonance analysis that it bound the NCAM IgI module of NCAM. NBP10 modulated cell aggregation as well as neurite outgrowth induced specifically by homophilic NCAM binding. Moreover, both monomeric and multimeric forms of NBP10 stimulated neurite outgrowth from primary hippocampal neurons. The neurite outgrowth response to NBP10 was inhibited by a number of compounds previously shown to inhibit neurite outgrowth induced by homophilic NCAM binding, including voltage‐dependent calcium channel antagonists, suggesting that NBP10 induced neurite outgrowth by activating a signal transduction pathway similar to that activated by NCAM itself. Moreover, an inhibitor of intracellular calcium mobilization, TMB‐8, prevented NBP10‐induced neurite outgrowth suggesting that NCAM‐dependent neurite outgrowth also requires mobilization of calcium from intracellular calcium stores in addition to calcium influx from extracellular sources. By single‐cell calcium imaging we further demonstrated that NBP10 was capable of inducing an increase in intracellular calcium in PC12E2 cells. Thus, the NBP10 peptide is a new tool for the study of molecular mechanisms underlying NCAM‐dependent signal transduction and neurite outgrowth, and could prove to be a useful modulator of regenerative processes in the peripheral and central nervous system.
When an event sparks behavior change: an introduction to the sentinel event method of dynamic model building and its application to emergency medicine.

Experiencing a negative consequence related to one's health behavior, like a medical problem leading to an emergency department (ED) visit, can promote behavior change, giving rise to the popular concept of the "teachable moment. " However, the mechanisms of action underlying this process of change have received scant attention. In particular, most existing health behavior theories are limited in explaining why such events can inspire short-term change in some and long-term change in others. Expanding on recommendations published in the 2009 Academic Emergency Medicine consensus conference on public health in emergency medicine (EM), we propose a new method for developing conceptual models that explain how negative events, like medical emergencies, influence behavior change, called the Sentinel Event Method. The method itself is atheoretical; instead, it defines steps to guide investigations that seek to relate specific consequences or events to specific health behaviors. This method can be used to adapt existing health behavior theories to study the event-behavior change relationship or to guide formulation of completely new conceptual models. This paper presents the tenets underlying the Sentinel Event Method, describes the steps comprising the process, and illustrates its application to EM through an example of a cardiac-related ED visit and tobacco use.
Consequences of multiple mating‐system shifts for population and range‐wide genetic structure in a coastal dune plant

Evolutionary transitions from outcrossing to selfing can strongly affect the genetic diversity and structure of species at multiple spatial scales. We investigated the genetic consequences of mating‐system shifts in the North American, Pacific coast dune endemic plant Camissoniopsis cheiranthifolia (Onagraceae) by assaying variation at 13 nuclear (n) and six chloroplast (cp) microsatellite (SSR) loci for 38 populations across the species range. As predicted from the expected reduction in effective population size (Ne) caused by selfing, small‐flowered, predominantly selfing (SF) populations had much lower nSSR diversity (but not cpSSR) than large‐flowered, predominantly outcrossing (LF) populations. The reduction in nSSR diversity was greater than expected from the effects of selfing on Ne alone, but could not be accounted for by indirect effects of selfing on population density. Although selfing should reduce gene flow, SF populations were not more genetically differentiated than LF populations. We detected five clusters of nSSR genotypes and three groups of cpSSR haplotypes across the species range consisting of parapatric groups of populations that usually (but not always) differed in mating system, suggesting that selfing may often initiate ecogeographic isolation. However, lineage‐wide genetic variation was not lower for selfing clusters, failing to support the hypothesis that selection for reproductive assurance spurred the evolution of selfing in this species. Within three populations where LF and SF plants coexist, we detected genetic differentiation among diverged floral phenotypes suggesting that reproductive isolation (probably postzygotic) may help maintain the striking mating‐system differentiation observed across the range of this species.
Managing amyotrophic lateral sclerosis: Slowing disease progression and improving patient quality of life

It is now possible to slow the disease progression of amyotrophic lateral sclerosis (ALS), but documented improvement in the quality of life of ALS patients has been difficult to quantitate. Putative mechanisms involved in motor neuron degeneration in ALS include oxidative damage, mitochondrial dysfunction, neuroinflammation, growth factor deficiency, and glutamate excitotoxicity. Several pharmacological agents that target these potential targets have demonstrated therapeutic potential in animal models with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Many treatments that have been moderately effective in this animal model have not been successfully translated into effective treatments for humans with ALS. Only the glutamate modulator riluzole has demonstrated efficacy in clinical trials and is approved for treating ALS. Combination treatments may represent a potential therapeutic strategy to more robustly prolong life and preserve function, but only vitamin E with riluzole has been formally studied in clinical trials, and to date, no combination treatments have been found to be more effective than currently available single agents. Ann Neurol 2009;65 (suppl):S17–S23
Detection of BK virus and simian virus 40 in the urine of healthy children

Seroprevalence studies indicate that most primary infections with BK virus (BKV) and JC virus (JCV) occur in the first and second decades of life, respectively. Relatively little is known about the transmission of these agents, including the primary source of human exposure, the portal of entry, and the pathophysiology of life‐long viral persistence. We sought to determine if simian virus 40 (SV40) excretion could be detected in the urine of healthy children and to define the age‐related prevalence of polyomavirus shedding in this population. A point prevalence study of polyomavirus shedding was conducted in healthy children using rigorous enrollment criteria. Urine samples were collected from healthy children, age from 3 to 18 years, during routine evaluation at two urban pediatric clinics. Qualitative PCR analysis was performed using primers that detect a conserved region of the T‐antigen gene of BKV, JCV, and SV40. The identity of polyomaviruses detected was determined by DNA sequence analysis and/or PCR amplification of other regions of the viral genomes. Seven of 72 (9.7%) urine samples were positive for polyomaviruses: three with BKV (ages 4, 6, 13), two with SV40 (ages 6, 16), two with BKV and SV40 co‐excretion (ages 6, 15), and none with JCV. DNA sequence analysis confirmed the identity of viruses detected. These results suggest that the timing of SV40 infections in humans may be similar to that of BKV and that urine from healthy children could contribute to the ubiquity of BKV infection early in life. J. Med. Virol. 75:447–454, 2005. © 2005 Wiley‐Liss, Inc.
Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity.
Thermoregulatory Model of Sleep Control: Losing the Heat Memory

Thermoregulatory mechanisms were hypothesized to provide primary control of non-rapid-eye-movement sleep (NREM). On the basis of this hypothesis, we incorporated the thermoregulatory feedback loops mediated by the “heat memory,” heat load, and loss processes associated with sleep-wake cycles, which were modulated by two circadian oscillators. In addition, hypnogenic warm-sensitive neurons (HWSNs) were assumed to integrate thermoregulation and NREM control. The heat memory described above could be mediated by some sleep-promoting substances. In this paper, considering the possible carrier of the heat memory, its losing process is newly included in the model. The newly developed model can generate the appropriate features of human sleepwake patterns. One of the special features of the model is to generate the bimodal distribution of the sleepiness. This bimodality becomes distinct, as the losing rate of the heat memory decreases or the amplitude of the Y oscillator increases. The theoretical analysis shows the losing rate of the heat memory control's rapidity of model response to a thermal perturbation, which is confirmed by simulating the responses with various losing rates to transient heat loads (“heat load pulse”). The sleepiness exhibits large responses to the heat load pulses applied in the early and late phases of wake period, while the response is significantly reduced to the pulse applied in the supposed wake-maintenance zone. This bimodality of the response appears to reflect the sensitivity of the HWSNs. In addition, the early pulse raises the immediate sleepiness rather than the nocturnal sleepiness, while the heat load pulse applied in the later phase of waking period significantly raises the sleepiness during a nocturnal sleep. In simulations of sleep deprivation, the discontinuous relationship between recovery sleep length and deprivation time is reproduced, where the critical sleep deprivation time at which the recovery sleep length jumps is extended as the losing rate increases. This is possibly due to the dissipation of the heat memory accumulated by the sleep deprivation. The simulation results here qualitatively reproduce the experimental observations or predict the intriguing phenomena of human circadian rhythms. Therefore, our model could provide a novel framework for investigating the relationship between thermoregulation and sleep control processes.
Colpocleisis: A Safe, Minimally Invasive Option for Pelvic Organ Prolapse

Objective This study aimed to describe the morbidity and mortality associated with colpocleisis and factors associated with improved outcomes. Methods We used University HealthSystem Consortium database, which included inpatient data from US hospitals. We included all women who underwent colpocleisis from 2002 to 2012. Centers were categorized geographically and by annual case volume. Cases were grouped by age and provider specialty. Outcome and readmission data from participating hospitals were compared between groups by analysis of variance and Tukey statistics. Average length of stay (LOS), intensive care unit (ICU) admission rate, complication rate, mortality rate, and readmission rate were calculated for each hospital and compared. Results Colpocleisis procedures (4776) were performed at 145 US medical centers. Forty-three percent of procedures were done on women older than 80 years, 52% on women 60 to 79 years, 3% on women 40 to 59 years, and 0.9% on women 20 to 39 years. Overall, rates of complications, ICU admission, and mortality were low with average rates of 6.82%, 2.80%, and 0.15%, respectively. High-volume centers had lower ICU admission and complications rates as well as a shorter LOS. Younger women had higher ICU admission and complication rates as well longer LOS. Stratification by provider specialty demonstrated higher ICU admission rates among cases performed by urologists as compared to cases performed by urogynecologists and general obstetrician-gynecologists. Complication rates were also higher among obstetrician-gynecologists and urologists as compared to urogynecologists. Length of stay was significantly longer when colpocleisis was performed by urologists rather than a urogynecologists. Conclusions Colpocleisis is a safe minimally invasive procedure and outcomes are influenced by provider specialty and hospital volume.
Pit Membrane Porosity and Water Stress-Induced Cavitation in Four Co-Existing Dry Rainforest Tree Species

Aspects of xylem anatomy and vulnerability to water stress-induced embolism were examined in stems of two drought-deciduous species, Brachychiton australis (Schott and Endl.) A. Terracc. and Cochlospermum gillivraei Benth. , and two evergreen species, Alphitonia excelsa (Fenzal) Benth. and Austromyrtus bidwillii (Benth.) Burret. , growing in a seasonally dry rainforest. The deciduous species were more vulnerable to water stress-induced xylem embolism. B. australis andC. gillivraei reached a 50% loss of hydraulic conductivity at −3.17 MPa and −1.44 MPa, respectively; a 50% loss of hydraulic conductivity occurred at −5.56 MPa in A. excelsa and −5.12 MPa in A. bidwillii. To determine whether pit membrane porosity was responsible for greater vulnerability to embolism (air seeding hypothesis), pit membrane structure was examined. Expected pore sizes were calculated from vulnerability curves; however, the predicted inter-specific variation in pore sizes was not detected using scanning electron microscopy (pores were not visible to a resolution of 20 nm). Suspensions of colloidal gold particles were then perfused through branch sections. These experiments indicated that pit membrane pores were between 5 and 20 nm in diameter in all four species. The results may be explained by three possibilities: (a) the pores of the expected size range were not present, (b) larger pores, within the size range to cause air seeding, were present but were rare enough to avoid detection, or (c) pore sizes in the expected range only develop while the membrane is under mechanical stress (during air seeding) due to stretching/flexing.
[Language and aphasias].

INTRODUCTION AND OBJECTIVE Approximately 400,000 years ago men started to use language. Initially it was probably poor with few phonemes. With social evolution it became more complex, with the appearance of new phonemes and a more complete grammatical structure. The current concept of the processing of language dates, with little change, from the nineteenth century. DEVELOPMENT With the birth of phrenology language began to be studied. This lead to the hypothesis of Wernicke, with two main areas joined by the fasciculo arcuato, which is still held to be valid with modifications by Gerchwind and Damasio, amongst others. Important advances in the study of language are due to Chomsky and his transformational grammar. This supports the universal structure of language, since one learns it following genetically determined laws. Language has three main aspects: creativity which makes both the transmitter and the receiver active participants in communication, the form from which words are constructed and the content of the message. Aphasia is an alteration in the comprehension and understanding of language, which may be the clinical expression of many different aetiologies. They help us to localize the lesion topographically. They are divided depending on the clinical signs, into motor or Broca's aphasia, in which understanding is conserved but the patient uses a language with poor grammatical structure, although the semantic content is acceptable: sensitive or Wernicke's aphasia, with inability to understand and language which is fluid but unintelligible; conduction aphasia due to limitation in the transmission of impulses from Wernicke's area to that of Broca, with acceptable understanding and fluid language and the trans-cortical aphasias where the main characteristic is indemnity of the capacity of repetition. CONCLUSIONS The aphasias, as the expression of an alteration of language are an important support in the topographical localization of lesions, even before these can be shown on computerized tomography.
Plasticity‐related regulation of the hippocampal proteome

Plasticity of glutamatergic synapses is considered to be a pivotal mechanism underlying the ability of the CNS to reconfigure its neural circuits. A large number of studies have focused on investigating how individual proteins, biochemical pathways and structural processes alter both the induction and maintenance of synaptic plasticity. However, it is likely that synaptic plasticity involves temporally and spatially coordinated regulation of multiple protein complexes within the activated neural circuit. By using a global proteomics‐based approach we have now been able to reveal that highly diverse protein classes exhibit altered expression in response to both the activation of glutamate receptors and the induction of long‐term potentiation (LTP) of glutamatergic synaptic strength in the hippocampus; a brain area where plastic synaptic modification is believed to be key to cognitive processes, such as spatial learning. Of the 2946 resolvable protein spots detected in this study, 79 (2.7%) were significantly altered in abundance in response to 100 µm glutamate application (all P < 0.05). The majority (56 out of 79) of these changes were due to the activation of the N‐methyl‐d‐aspartate (NMDA) subtype of glutamate receptor. Likewise, the induction of LTP was associated with an altered abundance of 2.4% of the detectable proteome during the early (10 min) phase and 1.7% during the late (4 h) phase of its development. Observed changes in temporal and protein class‐specific patterns of expression depict a widespread shift from metabolic to structural protein alteration as the plasticity process matures.
Day surgery laparoscopic cholecystectomy: initial experience in 43 consecutive patients.

AIM Analyze the results of an early experience in day-case LC (laparoscopic cholecystectomy) in a single laparoscopic unit, in terms of clinical outcome, unexpected admissions, readmissions, patients satisfaction. MATERIALS AND METHODS During three years, 200 consecutive patients underwent LC. Emergency procedures (32pts) and patients scheduled for cholecystectomy plus other surgical procedures (21pts) were excluded. Thus, 147 patients underwent elective LC and 43 were scheduled for DSLC (day-surgery laparoscopic cholecystectomy). RESULTS Six patients (13,9%) were considered not eligible for a same day discharge and admitted to the inpatients ward for overnight observation. The re-admission rate was 2,3% and 41 patients (95.3%) were completely satisfied. DISCUSSION Patients satisfaction was complete in 95.3% of cases, related to a correct preoperative information and the reduction in hospital costs amounted approximately to 41%. Despite the evidence of feasibility and safety of the daycase procedure, the Italian cultural background is nowadays inadequate for a clean acceptance of the DSLC. The provision of adequate staff education and training prior to full DSLC introduction is mandatory to the success of this organizational model. CONCLUSIONS LC can be performed safely in an outpatient setting if there's a careful education of patients and the surgical and anesthesiologist team is well-trained. Besides, good results can be achieved considering inclusion criteria. For the admission to be kept to a minimum, postoperative pain and nausea management has to be carefully planned such as discharge criteria evaluated. For selected patients, day-case LC is feasible and safe and can provide a reduction in hospital costs.