Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting intracellular Staphylococcus aureus to lower recurrence of orthopaedic infection

Staphylococcus aureus is often found in orthopaedic infections and may be protected from commonly prescribed antibiotics by forming biofilms or growing intracellularly within osteoblasts. To investigate the effect of non‐antibiotic compounds in conjunction with antibiotics to clear intracellular and biofilm forming S. aureus causing osteomyelitis. SAOS‐2 osteoblast‐like cell lines were infected with S. aureus BB1279. Antibiotics (vancomycin, VAN; and dicloxacillin, DICLOX), bacterial efflux pump inhibitors (piperine, PIP; carbonyl cyanide m‐chlorophenyl hydrazone, CCCP), and bone morphogenetic protein (BMP‐2) were evaluated individually and in combination to kill intracellular bacteria. We present direct evidence that after gentamicin killed extracellular planktonic bacteria and antibiotics had been stopped, seeding from the infected osteoblasts grew as biofilms. VAN was ineffective in treating the intracellular bacteria even at 10× MIC; however in presence of PIP or CCCP the intracellular S. aureus was significantly reduced. Bacterial efflux pump inhibitors (PIP and CCCP) were effective in enhancing permeability of antibiotics within the osteoblasts and facilitated killing of intracellular S. aureus. Confocal laser scanning microscopy (CLSM) showed increased uptake of propidium iodide within osteoblasts in presence of PIP and CCCP. BMP‐2 had no effect on growth of S. aureus either alone or in combination with antibiotics. Combined application of antibiotics and natural agents could help in the treatment of osteoblast infected intracellular bacteria and biofilms associated with osteomyelitis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1086–1092, 2018.
Rapid Emergence of Multidrug Resistant, H58-Lineage Salmonella Typhi in Blantyre, Malawi

Introduction Between 1998 and 2010, S. Typhi was an uncommon cause of bloodstream infection (BSI) in Blantyre, Malawi and it was usually susceptible to first-line antimicrobial therapy. In 2011 an increase in a multidrug resistant (MDR) strain was detected through routine bacteriological surveillance conducted at Queen Elizabeth Central Hospital (QECH). Methods Longitudinal trends in culture-confirmed Typhoid admissions at QECH were described between 1998–2014. A retrospective review of patient cases notes was conducted, focusing on clinical presentation, prevalence of HIV and case-fatality. Isolates of S. Typhi were sequenced and the phylogeny of Typhoid in Blantyre was reconstructed and placed in a global context. Results Between 1998–2010, there were a mean of 14 microbiological diagnoses of Typhoid/year at QECH, of which 6.8% were MDR. This increased to 67 in 2011 and 782 in 2014 at which time 97% were MDR. The disease predominantly affected children and young adults (median age 11 [IQR 6-21] in 2014). The prevalence of HIV in adult patients was 16.7% [8/48], similar to that of the general population (17.8%). Overall, the case fatality rate was 2.5% (3/94). Complications included anaemia, myocarditis, pneumonia and intestinal perforation. 112 isolates were sequenced and the phylogeny demonstrated the introduction and clonal expansion of the H58 lineage of S. Typhi. Conclusions Since 2011, there has been a rapid increase in the incidence of multidrug resistant, H58-lineage Typhoid in Blantyre. This is one of a number of reports of the re-emergence of Typhoid in Southern and Eastern Africa. There is an urgent need to understand the reservoirs and transmission of disease and how to arrest this regional increase.
Intravascular large B-cell lymphoma in the United States (US): a population-based study using Surveillance, Epidemiology, and End Results program and National Cancer Database*

Abstract A population-based study of intravascular large B-cell lymphoma (IVLBCL) in the US was conducted to determine incidence, demographic and clinical characteristics, prognostic factors, and survival compared with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS). In the years 2000–2013, the age-adjusted incidence rate of IVLBCL was 0.095 (case/1,000,000). The incidence of IVLBCL increased significantly from 2000 to 2013 (annual percentage change = 9.84, p = 0.002). We identified 344 patients with IVLBCL. The median age at diagnosis was 70 years. The median 1, 3, and 5-year OS rates for IVLBCL were 66.2, 51.8, and 46.3%, respectively. After propensity matching, the 5-year overall survival of IVLBCL was comparable to DLBCL NOS (46.4 versus 46.5%, p = 0.53). On multivariate analysis advanced age, advanced stage and having Medicaid or Medicare insurance predicted worse OS, whereas female gender and use of radiation therapy predicted better OS.
Treatment of Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1: Some Clarity But Continued Controversy.

I. OVERVIEW: MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 Multiple endocrine neoplasia type 1 (MEN1) (prevalence, 1–10/100,000) is the most important inherited pancreatic neuroendocrine tumor (pNET) syndrome causing up to 10% of pNETs including 20% to 25% of gastrinomas, 4% to 5%of insulinomas, and 3% to 15%of nonfunctional pNETs (NF-pNETs). Multiple endocrine neoplasia type 1 is an autosomal dominant disorder classically characterized by neuroendocrine tumors of the parathyroid, pituitary, and pancreas, now known to be due to alterations in the protein, menin, caused by mutations in theMEN1 gene on 11q13. Clinically, patients develop primary hyperparathyroidism (95%–100%), functional pNET (F-pNET) (20%–80%), NF-pNET (80%–100%, symptomatic 0%–13%), and functional/nonfunctional pituitary tumors [mean, 55%–65% (range, 16%–100%)]. The F-pNETs occur in patients with MEN1 with a frequency of gastrinomas (mean, 54%; range, 20%–61%) > insulinomas (18%; range, 7%–31%) > glucagonomas (3%–4%; range, 1%– 5%) > VIPomas, GRFomas, SSomas (<2%). In addition, these patients develop adrenal adenomas/ carcinomas (27%–36%), carcinoids [gastric (7%–35%), lung, and thymic (0%–8%)], and thyroid adenomas (0%–10%), and more recently, it is reported that they also develop nonendocrine tumors of the skin (60%–90%) (angiofibromas and collagenomas), central nervous system (0%–8%) (meningiomas and ependymonas), and smooth muscle (1%–7%) (leiomyomas and leiomyosarcomas). Characteristically, patients with MEN1 present with hyperparathyrodism as the initial manifestation of the disease; however, in a number of more recent series, up to 1 of 3 present with F-pNETs.
The association between radiographic embrasure morphology and interdental papilla reconstruction using injectable hyaluronic acid gel

Purpose The purpose of this study was to evaluate the clinical efficacy of enhancing deficient interdental papilla with hyaluronic acid gel injection by assessing the radiographic anatomical factors affecting the reconstruction of the interdental papilla. Methods Fifty-seven treated sites from 13 patients (6 males and 7 females) were included. Patients had papillary deficiency in the upper anterior area. Prior to treatment, photographic and periapical radiographic standardization devices were designed for each patient. A 30-gauge needle was used with an injection-assistance device to inject a hyaluronic acid gel to the involved papilla. This treatment was repeated up to 5 times every 3 weeks. Patients were followed up for 6 months after the initial gel application. Clinical photographic measurements of the black triangle area (BTA), height (BTH), and width (BTW) and periapical radiographic measurements of the contact point and the bone crest (CP-BC) and the interproximal distance between roots (IDR) were undertaken using computer software. The interdental papilla reconstruction rate (IPRR) was calculated to determine the percentage change of BTA between the initial and final examination and the association between radiographic factors and the reconstruction of the interdental papilla by means of injectable hyaluronic acid gel were evaluated. Results All sites showed improvement between treatment examinations. Thirty-six sites had complete interdental papilla reconstruction and 21 sites showed improvement ranging from 19% to 96%. The CP-BC correlated with the IPRR. More specifically, when the CP-BC reached 6 mm, virtually complete interdental papilla reconstruction via injectable hyaluronic acid gel was achieved. Conclusions These results suggest that the CP-BC is closely related to the efficacy of hyaluronic acid gel injection for interdental papilla reconstruction.
Risk of non-Hodgkin lymphoma subtypes in HIV-infected people during the HAART era: a population-based study

Objective:HIV-infected people have greatly elevated risk of non-Hodgkin lymphoma (NHL), particularly the AIDS-defining NHL subtypes: diffuse large B-cell lymphoma, Burkitt lymphoma and primary lymphomas arising in the central nervous system. The goals of this analysis were to comprehensively describe risks of NHL subtypes, especially those not well studied, among HIV/AIDS patients; examine risks specifically in the HAART era; and distinguish risks in HIV-infected individuals prior to diagnosis with AIDS. Design:Population-based registry linkage study. Methods:We used data from the US HIV/AIDS Cancer Match Study from 1996 to 2010 (N = 273 705) to calculate standardized incidence ratios (SIRs) comparing subtype-specific NHL risks in HIV-infected people to those in the general population, and used Poisson regression to test for differences in SIRs between the HIV-only and AIDS periods. Results:NHL risk was elevated 11-fold compared to the general population, but varied substantially by subtype. AIDS-defining NHL subtypes comprised the majority, and risks were high (SIRs ≥17), but risks were also increased for some T-cell lymphomas (SIRs = 3.6–14.2), marginal zone lymphoma (SIR = 2.4), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR = 3.6), and acute lymphoblastic leukemia/lymphoma (SIR = 2.4). Conclusion:HIV-infected people in the HAART era continue to have elevated risk of AIDS-defining NHL subtypes, highlighting the contribution of moderate and severe immunosuppression to their cause. Whereas non-AIDS-defining subtypes are much less common, immunosuppression or other dysregulated immune states likely play a role in the cause of some T-cell lymphomas, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, and acute lymphoblastic leukemia/lymphoma.
Caries outcome following an intensive fluoride varnish treatment regimen for children at high risk for early childhood caries

PURPOSE To evaluate the caries relapse rate for a cohort of 2- to 4-year-old children at high risk of early childhood caries when treated with an intensive fluoride varnish (FV) regimen. METHODS Eighty paediatric patients were recruited. Forty of these patients were high risk and received the FV treatment (three applications within 2 weeks and additional applications at 1 and 3 months) during 2009-2010. Mutans streptococci (MS) levels in the saliva were evaluated during the treatment period. A comparative group of 40 children, selected from an electronic record search at the New York University College of Dentistry to be of similar age, gender, and ethnicity, but not at elevated risk for ECC, received the standard of care (semi-annual FV treatment). Detailed caries examination and treatment records were obtained for all patients from 2009 to 2014. RESULTS A significant reduction (P < 0.001) in MS levels was observed in the intensive FV treatment group at the 3-month visit compared with baseline. There was no effect of the intensive FV treatment on caries outcome in the anterior teeth, and the overall caries scores were significantly increased on the posterior teeth. CONCLUSION The intensive FV regimen appears insufficient to prevent caries relapse in children at high risk for caries.
Feedlot Performance, Carcass Characteristics, and Muscle CLA Concentration of Lambs Fed Diets Supplemented with Safflower Seeds and Vitamin E

Summary Sixty-eight Rambouillet ram lambs were used to evaluatethe effects of safflower seed and vitamin-E supplementation onfeedlot performance, carcass characteristics, and muscle-conju-gated, linoleic-acid concentration. Lambs were fed finishingdiets that were iso N and similar in estimated TDN containingsafflower seed (SAFF) or no safflower seed (NOSAFF) in com-bination with 0 IU/d or 400 IU/d of supplemental vitamin E(NOVITE and VITE, respectively). Safflower seeds contained43 percent oil with 79 percent linoleic acid, therefore SAFFdiets were considered to contain 6 percent safflower oil. FinalBW, DMI, ADG, and longissimus muscle area as measured byultrasound did not differ ( P > 0.10 ) between lambs fed SAFFand NOSAFF, or VITE and NOVITE. Gain:feed was lower ( P= 0.06 ) for lambs fed SAFF compared to lambs fed NOSAFF(16.3 vs 14.3), but there was no difference ( P = 0.45 ) in G:Fbetween lambs fed VITE and NOVITE. Final weight, HCW,and fat thickness of slaughtered lambs were greater (
Real-World Health Care Costs Based on Medication Adherence and Risk of Stroke and Bleeding in Patients Treated with Novel Anticoagulant Therapy

BACKGROUND: With the lack of real-world evidence, the challenge for drug reimbursement policy decision makers is to understand medication adherence behavior among users of novel oral anticoagulants (NOACs) and its effect on overall cost savings. No study has examined and quantified the burden of cost in high-risk patients taking NOAC therapy. OBJECTIVE: To examine the association of cost with adherence, comorbidity, and risk of stroke and bleeding in patients taking NOACs (rivaroxaban and dabigatran). METHODS: A retrospective cohort study used deidentified data from a commercial managed care database affiliated with Optum Clinformatics Data Mart (January 1, 2010-December 31, 2012). Patients aged 18 years and older with ≥ 1 diagnosis of atrial fibrillation/flutter, > 1 NOAC prescription, 6-month pre-index and 12-month post-index continuous enrollment, and CHA2DS2-VASc score ≥ 1 were included. Adherence was calculated using proportion of days covered (PDC ≥ 80%) over an assessment period of 3, 6, and 12 months and compared based on level of comorbidity, stroke, and bleeding risk. The adjusted annual health care costs per patient (drug, medical, and total) were calculated using multivariable gamma regression controlling for demographic and clinical characteristics and compared across groups based on adherence over 12 months, baseline level of comorbidity, and risk of stroke and bleeding. RESULTS: Of 25,120 NOAC patients, 2,981 patients were included in the final cohort. Based on a PDC threshold of ≥ 80%, the adherence rate over 3, 6, and 12 months was 72%, 65%, and 54%, respectively. For all time periods, the level of adherence significantly increased (P < 0.001), with an increase in stroke risk (based on CHA2DS2VASc scores of 1, 2-3, and 4+); comorbidity (Charlson Comorbidity Index scores of 0, 1-2, and 3+); and risk of bleeding (HAS-BLED scores of 0-1, 2, and 3+). Adjusted all-cause total cost calculated for a 12-month period was significantly lower ($29,742 vs. $33,609) among adherent versus nonadherent users. Drug cost was higher ($5,595 vs. $2,233) among adherent versus nonadherent patients but was offset by lower medical costs ($23,544 vs. $30,485) costs. The overall cost significantly increased for patients with a high risk of bleeding and a high level of comorbidity. CONCLUSIONS: Adherence to NOAC therapy led to a reduction in overall health care cost, since higher drug costs were offset by lower medical (inpatient and outpatient) costs among adherent patients. Cost information based on adherence and risk of stroke and bleeding can help formulary decision makers to assess risk-benefit and help clinicians in developing interventions to reduce patient burden.
Measurement of Choroidal Thickness Following Caffeine Intake in Healthy Subjects

Abstract Purpose: The aim of this study is to investigate the effect of 200 mg caffeine on subfoveal choroidal thickness (CT) in the macular area as measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in healthy subjects. Materials and methods: Fifty healthy individuals (study group) and 50 healthy individuals (control group) were enrolled in study. In the study group, participants received a 200 mg caffeine capsule and the control group consisted of subjects who received plasebo capsule. The subfoveal CT was measured by EDI-OCT before the caffeine intake and at 30 min, 1 h, 2 h, 3 h, 4 h and 6 h following caffeine intake. Results: SFCT after caffeine intake was significantly decreased at 30 min, 1 h, 2 h, 3 h and 4 h compared to the baseline measurement, while the difference between baseline and 6 h was not statistically significant in the study group. There were no significant differences between the baseline and the other measurement times in the control group (p > 0.05). Conclusion: The thinning of CT begins about 30 min after the oral ingestion of 200 mg of caffeine and lasts for about four hours.
Authenticity in teaching and teachers’ emotions: a hermeneutic phenomenological study of the classroom reality

ABSTRACT This study probed the conceptualization of authenticity in teaching and its link to teachers’ emotional life through critical emotional praxis because emotions are integral to discovering who we really are (McCarthy, E. D. 2009. “Emotional Performances as Dramas of Authenticity.” In Authenticity in Culture, Self, and Society, edited by P. Vannini, and J. P. Williams, 241–255. London: Ashgate). The participants were 20 Iranian university teachers. Data were collected using interviews, field notes, and observation and were analyzed through the lens of hermeneutic phenomenology. The results revealed that authenticity in teaching consisted of themes of being one’s own self, horizon of significance, and contestation resulted from the sense of responsibility, authentic relations, and de-constructive thinking which confirmed the dialogical nature of authenticity. The emotions connected to authenticity in teaching were Transition-Anger, love, and caring indicating that authenticity in teaching was a practice toward socially just teaching.
Life in an extreme environment: a historical perspective on the influence of temperature on the ecology and evolution of woodrats

Abstract The heterogeneous topography of the Great Basin province leads to one of the most climatically variable regions in the Northern Hemisphere. Along the southwestern edge lies Death Valley, an area of even more extreme climate and physiographic relief; Death Valley has the dubious distinction of being the hottest place on earth. Our research investigates the adaptive response of Neotoma (woodrats) to temperature fluctuations over the late Quaternary on the valley floor and along a nearby elevational and environmental gradient. By combining fieldwork on extant animals living on the valley floor with historical information from museum specimens and paleomiddens, we reconstruct the evolutionary histories of 2 species (N. lepida and N. cinerea) differing significantly in size and habitat preferences. Here, at the modern limit of both species' thermal and ecological thresholds, we find fluctuations in body size and range boundaries over the Holocene as climate shifted. Although N. cinerea is extirpated on the east side of the valley today, it was ubiquitous throughout the late Quaternary. Moreover, we find fundamental differences in the adaptive response of woodrats related to elevation and local microclimate. Modern work suggests the mechanism is physiological; exposure to consistently high temperatures leads to high mortality. Thus, high temperatures strongly restrict time available for the essential activities of foraging and mating. Our results illustrate the profound influence temperature has on all aspects of woodrat life history, ecology, distribution, and evolution.
Nerve growth factor regulates the expression of the cholinergic locus and the high‐affinity choline transporter via the Akt/PKB signaling pathway

Nerve growth factor (NGF) is a trophic and survival factor for cholinergic neurons, and it induces the expression of several genes that are essential for synthesis and storage of acetylcholine (ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. We have found previously that the phosphatidylinositol 3′‐kinase pathway, but not the MEK/MAPK pathway, is the mediator of NGF‐induced cholinergic differentiation. Here we demonstrate, in the rat pheochromocytoma cell line PC12 and in primary mouse neuronal cultures, that NGF‐evoked up‐regulation of these three cholinergic‐specific genes is mediated by the anti‐apoptotic signaling molecule Akt/protein kinase B. Inhibition of Akt activation by the pharmacological inhibitor 1L‐6‐hydroxymethyl‐chiro‐inositol 2(R)‐2‐O‐methyl‐3‐O‐octadecylcarbonate (HIMO), or by a peptide fragment derived from the proto‐oncogene TLC1, eliminated NGF‐stimulated increases in cholinergic gene expression, as demonstrated by RT‐PCR and reporter gene assays. Moreover, treatment with HIMO reversed NGF‐evoked increases in choline acetyltransferase activity and ACh production. In co‐transfection assays with the reporter construct, a dominant‐negative Akt plasmid and Akt1‐specific small interfering RNA also attenuated NGF‐induced cholinergic promoter activity. Our data indicate that, in addition to its well‐described role in promoting neuronal survival, Akt can also mediate signals necessary for neurochemical differentiation.
Effects of stimulant medication on growth rates across 3 years in the MTA follow-up.

OBJECTIVE To evaluate the hypothesis of stimulant medication effect on physical growth in the follow-up phase of the Multimodal Treatment Study of Children With ADHD. METHOD Naturalistic subgroups were established based on patterns of treatment with stimulant medication at baseline, 14-, 24-, and 36-month assessments: not medicated (n = 65), newly medicated (n = 88), consistently medicated (n = 70), and inconsistently medicated (n = 147). Analysis of variance was used to evaluate effects of subgroup and assessment time on measures of relative size (z scores) obtained from growth norms. RESULTS The subgroup x assessment time interaction was significant for z height (p <.005) and z weight (p <.0001), due primarily to divergence of the newly medicated and the not medicated subgroups. These initially stimulant-naïve subgroups had z scores significantly >0 at baseline. The newly medicated subgroup showed decreases in relative size that reached asymptotes by the 36-month assessment, when this group showed average growth of 2.0 cm and 2.7 kg less than the not medicated subgroup, which showed slight increases in relative size. CONCLUSIONS Stimulant-naïve school-age children with Combined type attention-deficit/hyperactivity disorder were, as a group, larger than expected from norms before treatment but show stimulant-related decreases in growth rates after initiation of treatment, which appeared to reach asymptotes within 3 years without evidence of growth rebound.