Miracle-dz/UniFAR-FTUs huggingface dataset:
The vulvar epithelium differs from the skin: implications for cutaneous testing to address topical vulvar exposures

Vulvar tissue is more permeable than exposed skin due to differences in structure, occlusion, hydration and susceptibility to friction. The safety assessment of products that contact the vulva should account for this potentially heightened permeability. Standard clinical patch tests may not sufficiently mimic vulvar exposures. Because testing on the vulva is not routinely feasible, we are investigating new and modified cutaneous test methods to increase the degree of conservatism of the safety assessment. To this end, we have 1) developed a method to assess chemical and frictional effects by means of repeated application to the popliteal fossa (the behind‐the‐knee test); 2) modified the quantitative risk assessment for the induction of allergic contact dermatitis; and 3) proposed a modified human repeat insult patch test for assessing materials intended for vulvar contact. Modification of the traditional 4‐day, irritation patch test by using wet samples or compromized skin sites failed to enhance test sensitivity. Future studies will evaluate testing in subjects with heightened susceptibility to chemical and sensory irritation, in order to increase test sensitivity to chemical irritants. These approaches can be employed to augment the margin of safety when cutaneous test methods are applied to agents that contact the vulva.
Variant genotypes and haplotypes of the epidermal growth factor gene promoter are associated with a decreased risk of gastric cancer in a high‐risk Chinese population

Epidermal growth factor (EGF), a ligand of the EGF receptor, plays a critical role in the development of gastric cancer. Genetic variants in its promoter region may influence transcription activity and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped three EGF promoter polymorphisms (G61A, G‐1380A, and A‐1744G) in a case–control study of 675 gastric cancer cases and 704 cancer‐free controls. We found that the variant genotypes of EGF 61GA/AA were associated with a significantly decreased risk of gastric cancer (OR = 0.77, 95% CI = 0.61–0.95), when compared with wild‐type homozygote 61GG. In the combined analysis with all three loci of EGF, subjects carrying one or more variant loci had a significantly decreased risk of gastric cancer in a dose–response manner (adjusted OR = 0.58, 95% CI = 0.42–0.80 for subjects carrying one variant locus and OR = 0.46, 95% CI = 0.32–0.66 for those carrying two to three variant loci, respectively; trend test: χ2 = 16.14, P < 0.001). Compared with the most common haplotype GGA, haplotypes AGA, GGG and GAA (each containing one variant allele) were associated with 33%, 29% and 34% significantly decreased risk of gastric cancer (adjusted OR = 0.67, 95% CI = 0.55–0.82 for AGA; OR = 0.71, 95% CI = 0.57–0.88 for GGG and OR = 0.66, 95% CI = 0.52–0.84 for GAA, respectively). Our findings indicate that variant genotypes and haplotypes of EGF promoter might play a role in gastric carcinogenesis. (Cancer Sci 2007; 98: 864–868)
Effect of exercise training on physical fitness in type II diabetes mellitus.

UNLABELLED Few studies have compared changes in cardiorespiratory fitness between aerobic training only or in combination with resistance training. In addition, no study to date has compared strength gains between resistance training and combined exercise training in type II diabetes mellitus (T2DM). PURPOSE We evaluated the effects of aerobic exercise training (A group), resistance exercise training (R group), combined aerobic and resistance training (A + R group), and sedentary lifestyle (C group) on cardiorespiratory fitness and muscular strength in individuals with T2DM. METHODS Two hundred and fifty-one participants in the Diabetes Aerobic and Resistance Exercise trial were randomly allocated to A, R, A + R, or C. Peak oxygen consumption (V O(2peak)), workload, and treadmill time were determined after maximal exercise testing at 0 and 6 months. Muscular strength was measured as the eight-repetition maximum on the leg press, bench press, and seated row. Responses were compared between younger (aged 39-54 yr) and older (aged 55-70 yr) adults and between sexes. RESULTS VO(2peak) improved by 1.73 and 1.93 mL O(2)*kg(-1)*min(-1) with A and A + R, respectively, compared with C (P < 0.05). Strength improvements were significant after A + R and R on the leg press (A + R: 48%, R: 65%), bench press (A + R: 38%, R: 57%), and seated row (A + R: 33%, R: 41%; P < 0.05). There was no main effect of age or sex on training performance outcomes. There was, however, a tendency for older participants to increase VO(2peak) more with A + R (+1.5 mL O(2)*kg(-1)*min(-1)) than with A only (+0.7 mL O(2)*kg(-1)*min(-1)). CONCLUSIONS Combined training did not provide additional benefits nor did it mitigate improvements in fitness in younger subjects compared with aerobic and resistance training alone. In older subjects, there was a trend to greater aerobic fitness gains with A + R versus A alone.
Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study.

PURPOSE To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. RESULTS Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009). CONCLUSION An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.
Collegiate athletes’ experience of the meaning of sport injury: A phenomenological investigation

Aims: In this study, a phenomenological approach was used to gain an in-depth understanding of the meaning collegiate athletes derive from their injury experience. The integrated model of sport injury developed by Wiese-Bjornstal and colleagues1 served as the conceptual framework for the study. Methods: Elite athletes (n = 5) at one National Collegiate Athletic Association (NCAA) Division I university in the USA participated in phenomenological interviews at three different points post-injury and prior to return to participation in their respective sports. The first interview was conducted within seven days post-injury, while the second and third interviews were conducted 15—20 days post-injury and at least 30 days post-injury, respectively. Results: Inductive analysis of the interview data revealed that while participants’ experiences varied somewhat and fluctuated over time, the meaning they derived from the experience was characterized by four major themes: perspective, emotion, coping and relationships. Subsequent deductive analysis indicated a modest fit of each athlete’s experience within the integrated model of sport injury and rehabilitation developed by Wiese-Bjornstal et al. 1 Conclusion: Participants’ psychological responses to sport injury were generally consistent with the Wiese-Bjornstal et al.1 model but the meaning of the experience was highly individualized and seemed to evolve over the course of the injury and rehabilitation process.
Effects of Germanium Biotite Supplement on Immune Responses of Vaccinated Mini-pigs to Foot-and-Mouth Disease Virus Challenge

Since the outbreaks of foot-and-mouth disease (FMD) in South Korea in 2010–2011, a trivalent vaccine has been used as a routine vaccination. Despite the high efficacy of the trivalent vaccine, low antibody formation was reported in the pig industry and there is considerable concern about the ability of the vaccine to protect against the Andong strain responsible for recent outbreaks in South Korea. To overcome these problems, immunostimulators have been widely used to improve vaccine efficacy in South Korea, although without any scientific evidence. Based on the current situation, the aim of this study was to investigate the effects of germanium biotite, a feed supplement used to enhance the immune system, on the immune responses to FMD vaccination through the Andong strain challenge experiment in trivalent vaccinated pigs. Following the challenge, the germanium biotite-fed pigs showed high levels of IL-8 in serum, and increased cellular immune responses to stimulation with the Andong strain antigen compared to nonsupplemented pigs. In addition, higher FMD virus (FMDV) neutralizing antibody titers were detected in the germanium biotite-fed group than in the nonsupplemented group before the challenge. The findings of this study indicate that germanium biotite supplement might enhance immune responses to the FMD vaccine in pigs.
Update on the Medical Treatment of Primary Open-Angle Glaucoma

AbstractGlaucoma comprises a group of progressive, neurodegenerative disorders characterized by retinal ganglion cell death and nerve fiber layer atrophy. Several randomized controlled trials have consistently demonstrated the efficacy of intraocular pressure lowering to slow or halt the measurable progression of the disease. Medical therapy, in places where it is easily accessible, is often the primary method to lower intraocular pressure. We review the medical options currently available and possible future options currently in development. The 5 contemporary classes of topical agents in use include prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, alpha agonists, and cholinergics. In addition, several fixed combination agents are commercially available. Agents from each of these classes have unique mechanisms of action, adverse effects, and other characteristics that impact how they are used in clinical practice. Despite the plethora of medical options available, there are limitations to topical ophthalmic therapy such as the high rate of noncompliance and local and systemic adverse effects. Alternate and sustained drug delivery models, such as injectable agents and punctal plug delivery systems, may in the future alleviate some such concerns and lead to increased efficacy of treatment while minimizing adverse effects.
Factors Associated With Guideline-recommended KRAS Testing in Colorectal Cancer Patients: A Population-based Study

Objectives: Response to epidermal growth factor receptor inhibitors is poorer among stage IV colorectal cancer (CRC) patients with KRAS mutations; thus KRAS testing is recommended before treatment. KRAS testing was collected by Surveillance, Epidemiology, and End Results (SEER) registries for 2010 CRC cases, and our goal was to provide the first population-based estimates of testing in the United States. Methods: SEER CRC cases diagnosed in 2010 were evaluated (n=30,351). &khgr;2 tests and logistic regression were conducted to determine patient characteristics associated with KRAS testing, stratified by stages I-III versus stage IV. Log-rank tests were used to examine survival by testing status. Results: KRAS testing among stage IV cases ranged from 39% in New Mexico to 15% in Louisiana. In the model, younger age, being married, living in a metropolitan area, and having primary site surgery were associated with greater odds of receiving KRAS testing. Those who received testing had significantly better survival than those who did not (P<0.0001). Among those who received testing, there was no significant difference in survival by mutated versus wild-type KRAS. Five percent of stage I-III cases received testing. Conclusions: Wide variation in documented KRAS testing for stage IV CRC patients exists among SEER registries. Age remained highly significant in multivariate models, suggesting that it plays an independent role in the patient and/or provider decision to be tested. Further research is needed to determine drivers of variation in testing, as well as reasons for testing in stage I-III cases where it is not recommended.
Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics

Significance Contractility in cardiac muscle is finely tuned in response to changing circulatory demands, and phosphorylation of cardiac myosin-binding protein C (cMyBP-C) plays an important role in this regulation of function. The molecular mechanism of this regulation is not well understood because the N-terminal region [domains C0–C2 (C0C2)] containing the phosphorylatable region of cMyBP-C is highly dynamic and disordered, thus inaccessible to standard structural techniques. Therefore, we used site-directed spectroscopic probes (fluorescence and magnetic resonance) and computational simulations that are optimized for analyzing dynamic disorder. We found that phosphorylation makes C0C2 more compact and less disordered in the linker region and phosphorylation motif, and a new binding site simultaneously emerges. Our results provide insight into muscle contraction with implications for heart failure. We have used the site-directed spectroscopies of time-resolved fluorescence resonance energy transfer (TR-FRET) and double electron–electron resonance (DEER), combined with complementary molecular dynamics (MD) simulations, to resolve the structure and dynamics of cardiac myosin-binding protein C (cMyBP-C), focusing on the N-terminal region. The results have implications for the role of this protein in myocardial contraction, with particular relevance to β-adrenergic signaling, heart failure, and hypertrophic cardiomyopathy. N-terminal cMyBP-C domains C0–C2 (C0C2) contain binding regions for potential interactions with both thick and thin filaments. Phosphorylation by PKA in the MyBP-C motif regulates these binding interactions. Our spectroscopic assays detect distances between pairs of site-directed probes on cMyBP-C. We engineered intramolecular pairs of labeling sites within cMyBP-C to measure, with high resolution, the distance and disorder in the protein’s flexible regions using TR-FRET and DEER. Phosphorylation reduced the level of molecular disorder and the distribution of C0C2 intramolecular distances became more compact, with probes flanking either the motif between C1 and C2 or the Pro/Ala-rich linker (PAL) between C0 and C1. Further insight was obtained from microsecond MD simulations, which revealed a large structural change in the disordered motif region in which phosphorylation unmasks the surface of a series of residues on a stable α-helix within the motif with high potential as a protein–protein interaction site. These experimental and computational findings elucidate structural transitions in the flexible and dynamic portions of cMyBP-C, providing previously unidentified molecular insight into the modulatory role of this protein in cardiac muscle contractility.
Structure of the gene coding for the human early lymphocyte activation antigen CD69: A C‐type lectin receptor evolutionarily related with the gene families of natural killer cell‐specific receptors

CD69 is the earliest inducible cell surface glycoprotein acquired during lymphoid activation. CD69 functions as a signal transmitting receptor involved in cellular activation events including proliferation and the induction of specific genes. This molecule is a member of a supergene family of type‐II integral membrane proteins with C‐type lectin domains. We have herein studied the genomic structure of the human gene encoding CD69. The coding sequence is divided into five exons separated by four introns. The first two exons corresponded to separate functional domains of the protein (cytoplasmic tail and the transmembrane region), while the final three exons encoded the carbohydrate‐recognition domain (CRD). The conserved intron position between the exons encoding the CRD indicated that this protein is closely related to other type‐II receptor groups with the C‐type CRD, such as the asialoglycoprotein receptors, the low‐affinity IgE receptor (CD23), and natural killer cell‐specific receptors, NKR‐P1 and Ly49. In contrast to the broad NKR‐P1 and Ly‐49 gene families, CD69 is a single‐copy gene, as demonstrated by Southern blot analyses. The major transcription initiation site has been located, by amplification of cDNA 5′ ends, 30 nucleotides downstream of a consensus TATA box. Comparison of human CD69 and mouse NKR‐P1 gene structures indicates that the first intron maintains a conserved position, suggesting that CD69 and this gene family may diverge from a common ancestor gene. A possible evolutionary pathway of these genes is proposed.
Racial and ethnic disparities in cardiac catheterization for acute myocardial infarction in the United States, 1995--2001.

OBJECTIVE To examine recent trends in racial and ethnic disparities in cardiac catheterization for acute myocardial infarction (AMI) to determine whether disparities documented from the 1980s through mid-1990s persist, and evaluate whether patient and hospital characteristics are associated with any observed disparities METHODS Cross-sectional analyses of 585,710 white, 51,369 black and 31,923 Hispanic discharges from hospitals in the Nationwide Inpatient Sample (which includes data on all discharges from 951 representative hospitals in 23 states) that had performed cardiac catheterization from 1995--2001 with a primary diagnosis of AMI. Adjusted procedure rates and prevalence ratios (PR) were computed to compare catheterization rates by race and ethnicity. MEASUREMENTS AND MAIN RESULTS Catheterization rates were higher for whites than blacks for all years examined; rates among Hispanics increased during this period and approached the rate among whites. After adjustment for age, demographics, comorbidity, year and hospital characteristics, rates (per 100 discharges) were 58.4 for whites, 50.1 for blacks (PR 0.87; 95% CI 0.84-0.91) and 55.2 for Hispanics (PR 0.95; 95% CI 0.90-0.99). CONCLUSIONS These nationwide data suggest blacks remain less likely than whites and Hispanics to undergo catheterization during a hospitalization for AMI. Whether this disparity stems from patient or provider factors remains to be determined.
Prognostic factors for alveolar regeneration: effect of space provision.

OBJECTIVES The role of space provision as an independent prognostic factor for periodontal regeneration remains to be established. The objective of this study was to evaluate the role of space provision on alveolar bone regeneration in periodontal sites. METHODS Critical size, supra-alveolar, periodontal defects were created in 11 young adult Beagle dogs. Six animals received a porous ePTFE device to provide for space provision. Five animals received sham surgery. The animals were euthanized at 8 weeks post-surgery. A histometric analysis assessed vertical regeneration of alveolar bone and the width of the alveolar crest at the base of the defect. Because of the correlation of within-dog measurements, a mixed model anova/ancova was used to analyse the data. RESULTS A significant relationship between the width of the alveolar crest at the base of the defect and bone regeneration was observed with no significant difference between sites receiving the different treatments (p=0.84). Bone regeneration at sites treated with the space-providing device was significantly greater compared with that at sites treated with sham surgery (p=0.0003), and the difference remained significant after adjusting for bone width (p=0.0001). CONCLUSIONS Space provision has a significant effect on alveolar bone regeneration in periodontal sites. The width of the alveolar bone appears to influence space provision effectively supporting bone regeneration.
Carcinoma of the apocrine glands of the anal sac in dogs: 113 cases (1985-1995).

OBJECTIVE To characterize the signalment, clinical signs, biological behavior, and response to treatment of carcinoma of the apocrine glands of the anal sac in dogs. DESIGN Retrospective study. ANIMALS 113 dogs with histologically confirmed carcinoma of the apocrine glands of the anal sac. PROCEDURE Data on signalment, clinical signs, and staging were reviewed and analyzed along with treatment modality for potential association with survival time. RESULTS Sex distribution was approximately equal (54% female, 46% male). One hundred four dogs underwent treatment consisting of surgery, radiation therapy, chemotherapy, or multimodal treatment. Median survival for treated dogs was 544 days (range, 0 to 1,873 days). Dogs treated with chemotherapy alone had significantly shorter survival (median, 212 days) than those receiving other treatments (median, 584 days). Dogs not treated with surgery had significantly shorter survival (median, 402 days) than those that underwent surgery as part of their treatment (median, 548 days). Dogs with tumors > or = 10 cm2 had significantly shorter survival (median, 292 days) than dogs with tumors < 10 cm2 (median, 584 days). Hypercalcemia was identified in 27% (n = 29) of dogs, and those dogs had significantly shorter survival (median, 256 days), compared with those that were normocalcemic (median, 584 days). Dogs with pulmonary metastasis had significantly shorter survival (median, 219 days) than dogs without evidence of pulmonary metastasis (median, 548 days). CONCLUSIONS AND CLINICAL RELEVANCE Unlike most previous reports, this study revealed an approximately equal sex distribution, and results suggest a more favorable prognosis.
Autoantibody-mediated dysfunction of sympathetic neurons in guillain-barre syndrome.

OBJECTIVE To investigate a pathologic immune response to autonomic nerve fibers in Guillain-Barré syndrome (GBS). DESIGN We compared the effects of purified IgG from patients with GBS, multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy on transmitter synthesis and synaptic transmission in an in vitro model of sympathetic neurons and cardiomyocytes. SUBJECTS Three patients with GBS, 2 with chronic inflammatory demyelinating polyradiculoneuropathy, and 2 with relapsing-remitting multiple sclerosis. RESULTS Incubation of sympathetic neurons with GBS-IgG resulted in an upregulation of tyrosine hydroxylase and caused a relative increase of noradrenaline levels. In cocultures of sympathetic neurons and cardiomyocytes, GBS-IgG altered the synaptic transmission, as assessed by changes in the average cardiomyocyte beat rate. These effects could be neutralized by preincubation of sympathetic neurons with intravenous immunoglobulins. CONCLUSION Our findings indicate that in GBS, circulating antibodies directed against sympathetic neurons may contribute to autonomic dysfunction via functionally relevant changes in the noradrenaline synthesis.