Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct proliferative and differentiated stages of murine MC3T3‐E1 cells in culture: An in vitro model of osteoblast development

We examine clonal murine calvarial MC3T3‐E1 cells to determine if they exhibit a developmental sequence similar to osteoblasts in bone tissue, namely, proliferation of undifferentiated osteoblast precursors followed by postmitotic expression of differentiated osteoblast phenotype. During the initial phase of developmental (days 1–9 of culture), MC3T3‐E1 cells actively replicate, as evidenced by the high rates of DNA synthesis and progressive increase in cell number, but maintain a fusiform appearance, fail to express alkaline phosphatase, and do not accumulate mineralized extracellular collagenous matrix, consistent with immature osteoblasts. By day 9 the cultures display cuboidal morphology, attain confluence, and undergo growth arrest. Downregulation of replication is associated with expression of osteoblast functions, including production of alkaline phosphatase, processing of procollagens to collagens, and incremental deposition of a collagenous extracellular matrix. Mineralization of extracellular matrix, which begins approximately 16 days after culture, marks the final phase of osteoblast phenotypic development. Expression of alkaline phosphatase and mineralization is time but not density dependent. Type I collagen synthesis and collagen accumulation are uncoupled in the developing osteoblast. Although collagen synthesis and message expression peaks at day 3 in immature cells, extracellular matrix accumulation is minimal. Instead, matrix accumulates maximally after 7 days of culture as collagen biosynthesis is diminishing. Thus, extracellular matrix formation is a function of mature osteoblasts. Ascorbate and β‐glycerol phosphate are both essential for the expression of osteoblast phenotype as assessed by alkaline phosphatase and mineralization of extracellular matrix. Ascorbate does not stimulate type I collagen gene expression in MC3T3‐E1 cells, but it is absolutely required for deposition of collagen in the extracellular matrix. Ascorbate also induces alkaline phosphatase activity in mature cells but not in immature cells. β‐glycerol phosphate displays synergistic actions with ascorbate to further stimulate collagen accumulation and alkaline phosphatase activity in postmitotic, differentiated osteoblast‐like cells. Mineralization of mature cultures requires the presence of β‐glycerol phosphate. Thus, MC3T3‐E1 cells display a time‐dependent and sequential expression of osteoblast characteristics analogous to in vivo bone formation. The developmental sequence associated with MC3T3‐E1 differentiation should provide a useful model to study the signals that mediate the switch between proliferation and differentiation in bone cells, as well as provide a renewable culture system to examine the molecular mechanism of osteoblast maturation and the formation of bone‐like extracellular matrix.
T-Cell Receptor:CD3 Down-Regulation Is a Selected In Vivo Function of Simian Immunodeficiency Virus Nef but Is Not Sufficient for Effective Viral Replication in Rhesus Macaques

ABSTRACT We investigated the function of severely truncated simian immunodeficiency virus (SIV) Nef proteins (tNef) in vitro and in vivo. These variants emerged in rhesus monkeys infected with SIVmac239 containing a 152-bp deletion in the nef-unique region and have been suggested to enhance SIV virulence (E. T. Sawai, M. S. Hamza, M. Ye, K. E. Shaw, and P. A. Luciw, J. Virol. 74:2038-2045, 2000). We found that the tNef proteins were unable to down-regulate the cell surface expression of major histocompatibility complex class I proteins, CD4, and CD28 and neither stimulated SIV replication nor enhanced virion infectivity. The tNef proteins did efficiently down-regulate T-cell receptor (TCR):CD3 cell surface expression. Nevertheless, the SIVmac239 tnef variants were strongly attenuated in six infected juvenile rhesus macaques. Thus, while the ability of SIV Nef to down-modulate TCR:CD3 cell surface expression apparently confers a selective advantage in vivo, it is insufficient for efficient viral replication in infected macaques. Additional mutations elsewhere in SIVmac239 tnef genomes are required for a virulent phenotype.
A Randomized Trial

Background: Several combinations of oral or intravenous methotrexate plus vaginal misoprostol have been used for early abortion with success rates varying widely. So far, any study has evaluated the efficacy and safety of lower doses of oral methotrexate followed by vaginal misoprostol for early abortion. Objectives: To evaluate the efficacy and safety of methotrexate 25 or 50 mg orally and 800 Ìg of misoprostol vaginally 7 days after the methotrexate for abortion at ^56 days of gestation. Study Design: Three-hundred and ten pregnant women seeking elective abortion were randomly allocated to receive 25 mg (group I) or 50 mg (group II) of methotrexate orally and 800 Ìg of misoprostol vaginally 7 days after the methotrexate. The misoprostol dose was repeated 48 and 96 h later if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), side effects and vaginal bleeding. Relative risks were used for the comparison between the outcomes from both treatment regimens. Results: In group I aborted 135/148 cases (91%, 95% CI 85, 95%), and 139/154 cases (90%, 95% CI 84, 94%) aborted in group II (relative risk [RR] = 1.01, RR 95% CI 0.94, 1.09). Conclusions: The two treatment regimens showed the same efficacy and safety, so it would be advisable at least to use the smaller methotrexate dose, i.e. 25 mg.
Understanding the relative contributions of direct environmental effects and passive genotype–environment correlations in the association between familial risk factors and child disruptive behavior disorders

Background Previous work reports an association between familial risk factors stemming from parental characteristics and offspring disruptive behavior disorders (DBDs). This association may reflect (a) the direct effects of familial environment and (b) a passive gene–environment correlation (r GE), wherein the parents provide both the genes and the environment. The current study examined the contributions of direct environmental influences and passive r GE by comparing the effects of familial risk factors on child DBDs in genetically related (biological) and non-related (adoptive) families. Method Participants were 402 adoptive and 204 biological families. Familial environment was defined as maternal and paternal maladaptive parenting and antisociality, marital conflict and divorce; offspring DBDs included attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Mixed-level regressions estimated the main effects of familial environment, adoption status and the familial environment by adoption status interaction term, which tested for the presence of passive r GE. Results There was a main effect of maternal and paternal maladaptive parenting and marital discord on child DBDs, indicating a direct environmental effect. There was no direct environmental effect of maternal or paternal antisociality, but maternal and paternal antisociality had stronger associations with child DBDs in biological families than adoptive families, indicating the presence of a passive r GE. Conclusions Many familial risk factors affected children equally across genetically related and non-related families, providing evidence for direct environmental effects. The relationship of parental antisociality and offspring DBDs was best explained by a passive r GE, where a general vulnerability toward externalizing psychopathology is passed down by the parents to the children.
Communication and Learning in an Aboriginal School: The Influence of Conductive Hearing Loss

Otitis media (middle ear infection) is one of the most common childhood diseases all over the world and is very prevalent in many indigenous populations including Australian Aborigines. When children have otitis media they often have a hearing loss that can range from slight to moderately severe. This hearing loss is often hard to identify and can come and go. The problem often starts in infancy and can continue for years; hearing returns to normal in some children but some have permanent hearing loss. Even a mild hearing loss in early childhood can seriously affect communication development and learning. This can make it very difficult for children to succeed in the classroom — even when they no longer have active otitis media or hearing loss.
The creation and assessment of a social integration predictive model for a large suburban community college

The purpose of this predictive correlation study was to create and assess a model of programs and activities to predict student social integration at a large suburban community college. This study’s model was based upon Tinto’s student integration theory (1975, 1987, 1993) and employed hierarchical multiple regression to analyze the data. The data for this study was archival Community College Survey of Student Engagement (CCSSE) self-report data from students at a large suburban community college in Florida. Predictor variables included participation in extended orientation programs and student success courses, participation with classmates inside and out of class on academic related projects, and participation in co-curricular student activity programs and student clubs/organizations. Control variables included sex, age, hours worked per week and caring for dependents. The criterion variable was student self reports of social integration. The model was significant (p < .01) and demonstrated a medium effect size. The final overall model accounted for 14.2% of the variation in student self-reports of their social integration. Additional community college social integration factors to be considered for future research models are discussed. Strategies to maximize social integration are provided for practitioners.
Polymorphism and regulation of the spxB (pyruvate oxidase) virulence factor gene by a CBS‐HotDog domain protein (SpxR) in serotype 2 Streptococcus pneumoniae

spxB‐encoded pyruvate oxidase is a major virulence factor of Streptococcus pneumoniae. During aerobic growth, SpxB synthesizes H2O2 and acetyl phosphate, which play roles in metabolism, signalling, and oxidative stress. We report here the first cis‐ and trans‐acting regulatory elements for spxB transcription. These elements were identified in a genetic screen for spontaneous mutations that caused colonies of strain D39 to change from a semitransparent to an opaque appearance. Six of the seven opaque colonies recovered (frequency ≈ 3 × 10−5) were impaired for SpxB function or expression. Two mutations changed amino acids in SpxB likely required for cofactor or subunit binding. One mutation defined a cis‐acting adjacent direct repeat required for optimal spxB transcription. The other three spontaneous mutations created the same frameshift near the start of the trans‐acting spxR regulatory gene. The SpxR protein contains helix–turn–helix, CBS and HotDog domains implicated in binding DNA, adenosyl compounds, and CoA‐containing compounds respectively, and suggest that SpxR positively regulates spxB transcription in response to energy and metabolic state. Microarray analyses unexpectedly demonstrated that SpxR also positively regulates the strH exoglycosidase gene, which, like spxB, has been implicated in colonization. Finally, SpxR is required for full virulence in a murine model of infection.
Comparison of median and ulnar sensory nerve action potentials in the diagnosis of the carpal tunnel syndrome

Recording of median and ulnar digital sensory nerve action potentials in normal subjects showed that the ratio of the median (index finger) to ulnar (little finger) potential amplitude was consistently greater than one. In 15 patients with the carpal tunnel syndrome (seven bilateral) this ratio was found to be less than one for all but two of the 22 clinically affected hands, including three of the four hands with a normal motor latency to threshold stimulation and four of the five hands with a normal sensory conduction. It is concluded that the estimation of the ratio of the median to ulnar sensory potential amplitude is a sensitive test in the diagnosis of the carpal tunnel syndrome and is particularly useful in those patients who show a normal motor latency and sensory conduction.
Patient Perspectives of Recovery in Adolescent Onset Anorexia Nervosa

The aim of this qualitative study was to describe the patients' perspective of the recovery process from anorexia nervosa. On average 16 years after initial assessment at child and adolescent psychiatric clinics, 68 women were interviewed about what they attributed as important factors in the recovery process of their adolescent onset anorexia nervosa. The answers were coded using content analysis. Those having recovered (n = 58) were able to describe clear turning points in their history and mentioned as most important aspects in their recovery: friends, own decisions, activities, treatment, family of origin, and own family.
Smokers’ reactions to the new larger health warning labels on plain cigarette packs in Australia: findings from the ITC Australia project

Objectives This study examined whether larger sized Australian cigarette health warning labels (HWLs) with plain packaging (PP) were associated with increased desirable reactions towards the HWLs postimplementation. Methods Data were from the International Tobacco Control (ITC) longitudinal cohort survey assessing Australian smokers one wave prior to the policy change in 2011 (n=1104) and another wave after the policy change in 2013 (n=1093). We assessed initial attentional orientation (AO) to or away from warnings, plus other reactions, including cognitive reactions towards the HWLs and quit intentions. Results As expected, AO towards the HWLs and reported frequency of noticing warnings increased significantly after the policy change, but not more reading. Smokers also thought more about the harms of smoking and avoided the HWLs more after the policy change, but frequency of forgoing cigarettes did not change. The subgroup that switched from initially focusing away to focusing on the HWLs following the policy change noticed and read the HWLs more, and also thought more about the harmful effects of smoking, whereas the subgroup (5.4%) that changed to focusing away from the HWLs showed opposite effects. We tested the mediational model of Yong et al and confirmed it for predicting quit intentions, with larger effects post-policy. Conclusions Increasing the size of HWLs and introducing them on PP in Australia appears to have led to an overall increase in desired levels and strength of some reactions, but evidence of reactance was among a small minority.
The Disposal of an Oral Glucose Load in Healthy Subjects: A Quantitative Study

Although it is an established concept that the liver is important in the dispositionof glucose, the quantitative contribution of the splanchnic and peripheral tissues, respectively,to the disposal of an oral glucose load is still controversial. In the present investigation, we have employed the hepatic venous catheter technique in combination with a double-tracer approach(in which the glucose pool is labeled with 3H-glucose and the oral glucose load is labeled with 14C-glucose) to quantitate the four determinants of oral glucose tolerance: rate of oral glucose appearance, splanchnic glucose uptake, peripheral glucose uptake, and suppression of hepatic glucose production. Studies were carried out in 11 normal volunteers in the overnight-fasted state and for 3.5 h after the ingestion of glucose (1 g/kg body wt; range, 55–93 g). In the postabsorptive state, the rate of endogenous (hepatic) glucose production, evaluated from the 3H-glucose infusion, was 2.34 ± 0.06 mg/min · kg. Glucose ingestion was accompanied by a prompt reduction of endogenous glucose output, which reached a nadir of 0.62 ± 0.23 mg/min kg at 45 min and remained suppressed after 3.5 h (0.85 ±0.22 mg/ min · kg). The average inhibition of hepatic glucose output during the absorptive period was 53 ± 5%. The appearance of ingested glucose in arterial blood, as derived from the 14C-glucose measurements after correction for recycling 14C radioactivity, reached a peak after 15–30 min, and 14C-glucose continued to enter the systemic circulation throughout the observation period. The rate of appearance of ingested glucose was 2.47 ± 0.45 mg/min kg at 3.5 h. A total of 73 ± 4% of the oral load was recovered in the systemic circulation within 3.5 h. The cumulative net output of glucose from the splanchnic area, measured directly with the hepatic vein catheter technique, was 46 ± 5 g over 3.5 h. This net splanchnic glucose balance resulted from the appearance of 50 ± 5 g of the glucose load plus a residual hepatic production of 15 ± 2 g, minus a splanchnic glucose uptake of 19 ± 4 g. Splanchnic fractional extraction of glucose (basal = 2.7 ± 0.7%) failed to increase in response to glucose ingestion. Splanchnic glucose uptake, however, was significantly (P < 0.001) higher during the absorptive period (19 ± 4 g/3.5 h) than in the basal state (5 ± 1 g/3.5 h). Peripheral glucose uptake (48 ± 6 g/3.5 h) was also enhanced by glucose ingestion (P < 0.001 versus a basal value of 27 ± 2 g/3.5 h) and accounted for over 70% of total glucose disposal. It is concluded that, after the ingestion of a glucose load in healthy subjects: (1) endogenous glucose production is suppressed by approximately 50%, (2) both splanchnic and peripheral uptake of glucose are stimulated, (3) the rise in splanchnic uptake is achieved primarily by augmented glucose availability rather than by increased splanchnic fractional extraction of glucose, and (4) peripheral glucose uptake accounts for the majority Of total glucose disposal.
The Effects of Botulinum Toxin A on Survival of Rat TRAM Flap With Vertical Midline Scar

AbstractThe transverse rectus abdominis musculocutaneous (TRAM) flap has been widely used in various reconstructive surgeries. Recently, there have been reports regarding the positive effect of botulinum toxin A (BoTA) on flap survival. We hypothesized that pretreatment with BoTA could augment the survival of pedicled TRAM flaps with a vertical midline scar.Twenty-four Sprague-Dawley rats were randomly divided into 2 groups, namely, control group and BoTA group. Five days after a vertical midline incision, the BoTA group was pretreated with BoTA, whereas the control group was pretreated with normal saline. Ten days after the initial incision, the TRAM flap was harvested.We evaluated the gross flap survival and analyzed the overall histologic change, lumen area of pedicle, and microvessel density with immunohistochemistry. Reverse transcription polymerase chain reaction was performed for the evaluation of angiogenesis-related factors.In the BoTA group, the gross flap survival rate was significantly higher than that in the control group on both ipsilateral and contralateral sides (P < 0.001). In the BoTA group, a significant increase in pedicle lumen area was observed (P < 0.001). In the control group, mild to moderate epidermal necrosis was seen; microvessels were relatively small compared with those of the BoTA group. According to immunohistochemistry, the number of CD31 positively stained vessels was significantly higher on the contralateral side in the control group compared to that in the BoTA group (P < 0.001). The relative messenger RNA (mRNA) expression of CD31 was significantly lower in the BoTA group than that in the control group on both ipsilateral and contralateral sides (P < 0.001). Meanwhile, the relative mRNA expression of VEGF was significantly higher in the BoTA group than in the control group on both ipsilateral and contralateral sides (P < 0.001). We believe that preoperative BoTA therapy is a feasible method to improve circulation of the rat TRAM flap with a vertical midline incision scar.
Interactions between short‐interval intracortical inhibition and short‐latency afferent inhibition in human motor cortex

Transcranial magnetic stimulation (TMS) allows the testing of various inhibitory processes in human motor cortex. Here we aimed at gaining more insight into the underlying physiology by studying the interactions between short‐interval intracortical inhibition (SICI) and short‐latency afferent inhibition (SAI). SICI and SAI were examined in a slightly contracting hand muscle of healthy subjects by measuring inhibition of a test motor‐evoked potential conditioned by a sub‐threshold motor cortical magnetic pulse (S1) or an electrical pulse (P) applied to the ulnar nerve at the wrist, respectively. SICI alone and SAI alone had similar magnitude when S1 intensity was set to 90% active motor threshold and P intensity to three times the perceptual sensory threshold. SICI was reduced or even disinhibited when P was co‐applied, and SAI was reduced or disinhibited when S1 was co‐applied. These interactions did not depend on the exact timing of arrival of P and S1 in motor cortex. A control experiment with a S1 intensity lowered to 70% active motor threshold excluded a contribution by short‐interval intracortical facilitation. Finally, SICI with co‐applied P correlated linearly with SICI alone with a slope of the regression line close to 1 whereas SAI did not correlate with SAI when S1 was co‐applied with a slope of the regression line close to zero. Data indicate that S1 largely eliminates the effects of P when applied together, suggesting dominance of S1 over P. Findings strongly support the idea that SICI and SAI are mediated through two distinct and reciprocally connected subtypes of GABAergic inhibitory interneurons with convergent projections onto the corticospinal neurons. Furthermore, dominance of S1 over P is compatible with the notion that the SICI interneurons target the corticospinal neurons closer to their axon initial segment than the SAI interneurons.
Range of antinuclear antibodies in "healthy" individuals.

OBJECTIVE To determine the range of antinuclear antibodies (ANA) in "healthy" individuals compared with that in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatism (STR). METHODS Fifteen international laboratories experienced in performing tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above. Except for the stipulation that HEp-2 cells should be used as substrate, each laboratory used its own in-house methodology so that the data might be expected to reflect the output of a cross-section of worldwide ANA reference laboratories. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320. RESULTS In healthy individuals, the frequency of ANA did not differ significantly across the 4 age subgroups spanning 20-60 years of age. This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320. In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specificity) could have diagnostic value, since it would classify virtually all patients with SLE, SSc, or SS as ANA positive. Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensitivity) would be useful to confirm the presence of disease in only a portion of cases, but would be likely to exclude 95% of normal individuals. CONCLUSION It is recommended that laboratories performing immunofluorescent ANA tests should report results at both the 1:40 and 1:160 dilutions, and should supply information on the percentage of normal individuals who are positive at these dilutions. A low-titer ANA is not necessarily insignificant and might depend on at least 4 specific factors. ANA assays can be a useful discriminant in recognizing certain disease conditions, but can create misunderstanding when the limitations are not fully appreciated.