Miracle-dz/UniFAR-FTUs huggingface dataset:
Mediating Effect of Repeated Tuberculosis Exposure on the Risk of Transmission to Household Contacts of Multidrug-Resistant Tuberculosis Patients

Abstract. Primary Mycobacterium tuberculosis transmission is an important driver of the global epidemic of resistance to tuberculosis drugs. A few studies have compared tuberculosis infection in contacts of index cases with different drug-resistant profiles, suggesting that contacts of multidrug-resistant (MDR) tuberculosis cases are at higher risk. Repeated tuberculosis exposure in contacts of MDR tuberculosis patients through recurrent tuberculosis may modify this relationship. We compared tuberculosis infection in household contacts of MDR and drug-susceptible (DS) tuberculosis patients from six cities in southeastern China and investigated whether repeated tuberculosis exposure was a mediating factor. Tuberculosis infection was defined as a tuberculin skin test induration ≥ 10 mm. In all, 111 (28.0%) of 397 household contacts of MDR tuberculosis patients and 165 (24.7%) of 667 contacts of DS tuberculosis index cases were infected with tuberculosis. In a multivariate model not including the previous tuberculosis exposure, contacts of MDR tuberculosis patients had a higher likelihood of tuberculosis infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.01–1.84; P = 0.041). In a separate multivariate model adjusted for the previous tuberculosis exposure, the odds ratio of tuberculosis infection flipped and contacts of MDR cases were now at lower risk for tuberculosis infection (AOR = 0.55; 95% CI = 0.38–0.81; P = 0.003). These findings suggest prior tuberculosis exposure in contacts strongly mediates the relationship between tuberculosis infection and the index drug resistance profile. Prior studies showing lower risk of developing tuberculosis among contacts of MDR tuberculosis patients may be partially explained by a lower rate of tuberculosis infection at baseline.
Absolute Bioavailability and Pharmacokinetic Comparability of Sirukumab Following Subcutaneous Administration by a Prefilled Syringe or an Autoinjector

This phase 1, randomized, open‐label study assessed the absolute bioavailability and pharmacokinetic comparability of sirukumab, a human anti–interleukin‐6 monoclonal antibody, following subcutaneous (SC) administration via Prefilled Syringe‐UltraSafe Passive® Delivery System (PFS‐U) or Prefilled Syringe‐SmartJect® Autoinjector (PFS‐AI; Janssen Research & Development, LLC, Spring House, Pennsylvania). A total of 144 healthy male subjects were randomized to 5 single‐dose treatment groups: sirukumab 50 mg and 100 mg (each by PFS‐U and PFS‐AI) and sirukumab 100 mg intravenous (IV) infusion. Pharmacokinetic parameters were calculated using noncompartmental analysis. Following SC administration, maximum serum concentrations (Cmax) and area under the concentration‐vs‐time curve (AUC) increased in an approximately dose‐proportional manner. Median time to reach Cmax was 5 days, and mean half‐life ranged from 16 to 19 days. Mean absolute bioavailability of sirukumab by PFS‐AI and PFS‐U, respectively, was estimated at 92.4% and 81.4% with 100 mg and 88.4% and 94.7% with 50 mg. Ratios of geometric means (90% confidence intervals) of Cmax and AUC0‐77d for PFS‐AI:PFS‐U were 1.13 (1.03, 1.25) and 1.14 (1.05, 1.24), respectively, indicating comparable systemic exposures of sirukumab following a single 100‐mg SC dose by PFS‐U or PFS‐AI. The incidence of antibodies to sirukumab was low (1.4%). No new safety concerns associated with sirukumab were identified at either dose.
Visual Impairment and Dysfunction in Combat-Injured Servicemembers With Traumatic Brain Injury

Purpose. The purpose of this study was to determine the frequencies of visual impairment and dysfunction among combat-injured Polytrauma Rehabilitation Center (PRC) inpatient and Polytrauma Network Site (PNS) outpatient military personnel with traumatic brain injury (TBI). Methods. A retrospective analysis of data from vision screenings of 68 PRC-inpatients with moderate to severe levels of TBI and 124 PNS-outpatients with mild TBI at the VA Palo Alto Health Care System was conducted. Results. Eighty-four percent of PRC-inpatients and 90% of PNS-outpatients had TBIs associated with a blast event. The majority of patients in both the PRC and PNS populations had visual acuities of 20/60 or better (77.8% PRC, 98.4% PNS). Visual dysfunctions (e.g., convergence, accommodative, and oculomotor dysfunction) were common in both PRC and PNS populations. In the PRC-inpatient population, acuity loss of 20/100 to no light perception (13%) and visual field defects (32.3%) were found. In the PNS-outpatient population, acuity loss of 20/100 to no light perception (1.6%) and visual field defects (3.2%) were infrequently found. In both the PRC and PNS populations, visual field defects were more often associated with blast than non-blast events. Conclusions. Blast events were the most frequent mechanism of injury associated with TBI in combat-injured servicemembers. The vision findings suggest that combat troops exposed to blast with a resulting mild TBI are at risk for visual dysfunction, and combat troops with polytrauma injuries are at risk for visual dysfunction and/or visual impairment. The visual consequences of such injuries necessitate further study and support the need for appropriate evaluation and treatment in all severities of TBI.
In vitro evaluation of cefepime and other broad-spectrum beta-lactams in 22 medical centers in Japan: a phase II trial comparing two annual organism samples. The Japan Antimicrobial Resistance Study Group.

An antimicrobial resistance surveillance study in Japan is presented representing the second year (Phase II) results from 22 medical centers. Each participant laboratory tested (Etest, AB BIODISK, Solna, Sweden) 100 organisms, 10 strains each from 10 species groups including Escherichia coli, Klebsiella spp. , Enterobacter spp. , Citrobacter spp. , indole-positive Proteae, Serratia spp. , Acinetobacter spp. , Pseudomonas aeruginosa, and oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci. Generally only modest variations in the activity of the studied broad-spectrum beta-lactams was observed compared to the study a year before. Specifically, extended spectrum beta-lactamase (ESBL) rates in E. coli increased (2.9 to 8.1%), but the ESBL rate in Klebsiella spp. fell (8.6 to 5.0%). Overall the resistance to the beta-lactams varied from a 4.7% decrease (ceftazidime as a consequence of a modified staphylococcal breakpoint criteria) to a 1.0% increase (cefepime, not significant). The rank order of spectrums in 1998 only changed for cefoperazone-sulbactam (6.1% resistance) that was active against more strains than cefpirome (6.8% resistance). The overall spectrum rank order for the 1998 Japan sample (% resistance) was: cefepime (3.2%) > imipenem (4.1%) > cefoperazone-sulbactam (6.1%) > cefpirome (6.8%) > ceftazidime (8.4%) > piperacillin (19.9%). As with a similar study in 1997, imipenem-resistant isolates of P. aeruginosa and Serratia spp. were discovered with metalloenzymes, usually found in the same medical centers. These results demonstrate the continued in vitro activity and potential sustained clinical efficacy of several broad-spectrum beta-lactams in Japan. Rapid emergence of new or novel resistance were not wide spread using a precise quantitative MIC system. Continued surveillance in this nation would be prudent to document the activity of this clinically valuable class of safe, antimicrobial agents.
Digital image analysis of growth and starvation responses of a surface-colonizing Acinetobacter sp

Surface growth of an Acinetobacter sp. cultivated under several nutrient regimens was examined by using continuous-flow slide culture, phase-contrast microscopy, scanning confocal laser microscopy, and computer image analysis. Irrigation of attached coccoid stationary-phase Acinetobacter sp. cells with high-nutrient medium resulted in a transition from coccoid to bacillar morphology. Digital image analysis revealed that this transition was biphasic. During phase I, both the length and the width of cells increased. In contrast, cell width remained constant during phase II, while both cell length and cell area increased at a rate greater than in phase I. Cells were capable of growth and division without morphological transition when irrigated with a low-nutrient medium. Rod-shaped cells reverted to cocci by reduction-division when irrigated with starvation medium. This resulted in conservation of cell area (biomass) with an increase in cell number. In addition, the changes in cell morphology were accompanied by changes in the stability of cell attachment. During phase I, coccoid cells remained firmly attached. Following transition in high-nutrient medium, bacillar cells displayed detachment, transient attachment, and drifting behaviors, resulting in a spreading colonization pattern. In contrast, cells irrigated with a low-nutrient medium remained firmly attached to the surface and eventually formed tightly packed microcolonies. It is hypothesized that the coccoid and bacillar Acinetobacter sp. morphotypes and associated behavior represent specialized physiological adaptations for attachment and colonization in low-nutrient systems (coccoid morphotype) or dispersion under high-nutrient conditions (bacillar morphotype).
End points and United States Food and Drug Administration approval of oncology drugs.

PURPOSE To summarize the end points used by the United States Food and Drug Administration (FDA) to approve new cancer drug applications over the last 13 years. MATERIALS AND METHODS The FDA granted marketing approval to 71 oncology drug applications between January 1, 1990, and November 1, 2002. The end points used as the approval basis for each application are presented, and the rationale for each end point is discussed. RESULTS The FDA grants either regular marketing approval or accelerated marketing approval for oncology drug applications. Regular approval is based on end points that demonstrate that the drug provides a longer life, a better life, or a favorable effect on an established surrogate for a longer life or a better life. Accelerated approval (AA) is based on a surrogate end point that is less well established but that is reasonably likely to predict a longer or a better life. Tumor response was the approval basis in 26 of 57 regular approvals, supported by relief of tumor-specific symptoms in nine of these 26 regular approvals. Relief of tumor-specific symptoms provided critical support for approval in 13 of 57 regular approvals. Approval was based on tumor response in 12 of 14 AAs. CONCLUSION End points other than survival were the approval basis for 68% (39 of 57) of oncology drug marketing applications granted regular approval and for all 14 applications granted accelerated approval from January 1, 1990, to November 1, 2002.
Effects of acupuncture on pain and inflammation in pediatric emergency department patients with acute appendicitis: a pilot study.

OBJECTIVE Acupuncture has been shown to treat various medical conditions, including acute and chronic pain, and there is limited evidence that acupuncture produces anti-inflammatory effects. This pilot study evaluated the use of acupuncture to treat pain and determine if acupuncture can reduce the inflammatory response in pediatric patients diagnosed with acute appendicitis. DESIGN This pilot study used convenience sampling and was conducted in the Pediatric Emergency Department (PED) of an urban tertiary care children's hospital. Patients conventionally evaluated and definitively diagnosed with appendicitis were eligible to voluntarily participate. INTERVENTION The diagnostic homogeneity of the target population allowed for a standardized intervention protocol. A licensed acupuncturist performed a specific form of Japanese acupuncture known as the Kiiko Matsumoto Style on all study patients. OUTCOME MEASURES Subjective pain was assessed immediately before the intervention and 20 minutes postintervention, using 3 measures: Faces Pain Scale-Revised (FPS-R), colored analog scale (CAS), and visual analog scale (VAS). Evidence of inflammation was assessed using two biomarkers: white blood cell (WBC) count and C-reactive protein (CRP). WBC and CRP were drawn and recorded 3 times: before the intervention, 2 minutes before removal of needles, and 30 minutes after needling. RESULTS Six Latino/Hispanic patients (4 males, 2 females, median age=15 years) with no previous acupuncture experience participated in the study. Median pre/postacupuncture pain scores were as follows: FPS-R, 5 vs. 4; CAS, 6.1 vs. 4.8; VAS, 46 vs. 32. Median WBC (10(3)/μL) and CRP (mg/dL) across time were as follows: WBC, 13.2, 11.8, and 11.4; CRP, 4.5, 4.9, and 5.1. Median acupuncture duration was 28.5 minutes (range 22-32) and no complications were observed. CONCLUSIONS Pilot data suggest that acupuncture may be a feasible and effective treatment modality for decreasing subjective pain and inflammation as measured by WBC. Acupuncture may be a useful nonpharmacological PED intervention for treating patients with acute appendicitis pain.
Brain Aromatase Modulates Serotonergic Neuron by Regulating Serotonin Levels in Zebrafish Embryos and Larvae

Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB), cyp19a1b, is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1) estradiol (E2) exposure and (2) morpholino (MO)-mediated AroB knockdown. When embryos were exposed to E2, the effects were biphasic. The low dose of E2 (0.005 µM) significantly increased serotonin (5-HT) positive area at 48 hour post-fertilization (hpf) detected by immunohistochemistry and relative mRNA levels of tryptophan hydroxylase isoforms (tph1a, tph1b, and tph2) at 96 hpf measured by semi-quantitative PCR. To test the effects on serotonin transmission, heart rate and thigmotaxis, an indicator of anxiety, were analyzed. The low dose also significantly increased heart rate at 48 hpf and decreased thigmotaxis. The high dose of E2 (1 µM) exhibited opposite effects in all parameters. The effects of both low and high doses were reversed by addition of estrogen receptor (ER) blocker, ICI 182,780, thereby suggesting that the effects were mediated through ER. When AroB MO was injected to fertilized eggs, 5-HT-positive area was significantly decreased, while the significant decrease in relative tph mRNA levels was found only with tph2 but not with two other isoforms. AroB MO also decreased heart rate and increased thigmotaxis. All the effects were rescued by co-injection with AroB mRNA and by exposure to E2. Taken together, this study demonstrates the role of brain aromatase in development of serotonergic neuron in zebrafish embryos and larvae, implying that brain-formed estrogen is an important factor to sustain early development of serotonergic neuron.
Impact of hospital nursing care on 30-day mortality for acute medical patients.

AIM This paper reports on structures and processes of hospital care influencing 30-day mortality for acute medical patients. BACKGROUND Wide variation in risk-adjusted 30-day hospital mortality rates for acute medical patients indicates that hospital structures and processes of care affect patient death. Because nurses provide the majority of care to hospitalized patients, we propose that structures and processes of nursing care have an impact on patient death or survival. METHOD A model hypothesizing the impact of nursing-related hospital care structures and processes on 30-day mortality was tested. Patient data from the Ontario, Canada Discharge Abstract Database 2002-2003, nurse data from the Ontario Nurse Survey 2003, and hospital staffing data from the Ontario Hospital Reporting System 2002-2003 files were used to develop indicators for variables hypothesized to impact 30-day mortality. Two multiple regression models were implemented to test the model. First, all variables were forced to enter the model simultaneously. Second, backward regression was implemented. FINDINGS Using backward regression, 45% of variance in risk-adjusted 30-day mortality rates was explained by eight predictors. Lower 30-day mortality rates were associated with hospitals that had a higher percentage of Registered Nurse staff, a higher percentage of baccalaureate-prepared nurses, a lower dose or amount of all categories of nursing staff per weighted patient case, higher nurse-reported adequacy of staffing and resources, higher use of care maps or protocols to guide patient care, higher nurse-reported care quality, lower nurse-reported adequacy of manager ability and support, and higher nurse burnout. CONCLUSION Just as hospitals and clinicians caring for patients focus carefully on completing accurate diagnosis and appropriate and effective interventions, so too should hospitals carefully plan and manage structures and processes of care such as the proportion of Registered Nurses in the staff mix, percentage of baccalaureate-prepared nurses, and routine use of care maps to minimize unnecessary patient death.
Worldwide Epidemiology of Atrial Fibrillation: A Global Burden of Disease 2010 Study

Background— The global burden of atrial fibrillation (AF) is unknown. Methods and Results— We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5–22.2 million] and 12.6 million women [95% UI, 12.0–13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8–19.3) in men and 18.9% (95% UI, 15.8–23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8–612.7) and 359.9 in women (95% UI, 334.7–392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2–78.5) and 43.8 in women (95% UI, 35.9–55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4–636.7) in men and 373.1 (95% UI, 347.9–402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2–95.4) in men and 59.5 (95% UI, 49.9–74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0–2.2) and 1.9-fold (95% UI, 1.8–2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data. Conclusions— These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.
Accurate Evaluation of 1,2‐Diacylglycerol in Gerbil Forebrain Using HPLC and In Situ Freezing Technique

Abstract: Gerbil forebrains were frozen in situ to inactivate the tissues, and 1,2‐diacylglycerols were first measured quantitatively by HPLC. Although 1,2‐diacylglycerols were completely recovered from the HPLC column, the control amount of 1,2‐diacylglycerol in gerbil forebrain was only 79.6 nmol/g wet weight, which is about one‐fourth of that previously reported for gerbil brain inactivated by liquid N2 after decapitation instead of in situ freezing. The fatty acid composition of 1,2‐diacylglycerols in gerbil forebrain was first reported and the control 1,2‐diacylglycerols were richer in palmitic acid than in stearic acid or arachidonic acid, which is rather different from the data previously reported for mouse or rat brain obtained by decapitation and analyzed by traditional TLC methods. The amount of 1,2‐diacylglycerol increased by 82.9% in gerbil forebrain during 5 min of ischemia induced by bilateral carotid ligation. Arachidonic acid and stearic acid were abundant in the 1,2‐diacylglycerols produced by 5 min of ischemia. Thus we were able to obtain accurate values of the amount and the fatty acid composition of 1,2‐diacylglycerols in gerbil forebrains using HPLC and in situ freezing technique.
Alterations in the Renal Excretion of Valproate and Its Metabolites After Chronic Treatment

SUMMARY: Urinary excretion of valproate (VPA, administered as its sodium salt) and its various metabolites was studied in rats before and after 6 weeks of chronic treatment with intraperitoneal (i.p.) injection of 200 mg/kg VPA three times daily. Urinary excretion was determined after i.p. injection of a single dose of 200 mg/kg VPA, to which [14C]labeled VPA had been added to yield a dose of 1 μCi/kg body weight. Unlabeled VPA and metabolites were determined in urine by gas chromatography‐mass spectrometry (GC‐MS). After injection of a single dose of VPA before onset of chronic treatment, ˜40–50% of the dose administered was excreted in the urine within 24 h, mainly in the form of conjugated VPA and ω‐oxidation products, i.e., 5–hydroxy‐VPA and 2–propyl‐glutaric acid. After chronic treatment, urinary excretion of total radioactivity increased ˜75% as compared with activity before chronic treatment, demonstrating a marked increase in elimination rate of VPA during prolonged administration. Determination of VPA and metabolites in urine by GC‐MS indicated that this enhanced elimination resulted mainly from increases in glucuronidation and (β‐oxidation of VPA, whereas ω‐oxidation was apparently not altered or was even reduced. The data strongly indicate that at least in rats VPA produces induction of its own metabolism during prolonged treatment.
Elbow Valgus Stress Radiography in an Uninjured Population

Valgus instability of the elbow joint is a clinical diagnosis. However, many authors describe valgus stress radiographs as an aid in making this diagnosis. We studied valgus stress radiographs of 20 men (40 elbows) and 20 women (40 elbows), none with a history of elbow trauma or instability. The medial ulnohumeral distance was measured with no stress, valgus stress by gravity, and an applied valgus stress of 25 N (approximately 5 pounds). Measurements were made with the elbow positioned in extension and in 30° of flexion. The increase in medial ulnohumeral gapping with either gravity or 5 pounds of stress was statistically significant at both extension and 30° of flexion compared with the unstressed condition. The difference in ulnohumeral gapping between gravity stress and 5 pounds of valgus stress in extension and in 30° of flexion was also significant. We found no differences with regard to hand dominance or sex. We conclude that uninjured elbows have significant medial ulnohumeral gapping on valgus stress radiography. Although this is an important tool in diagnosing valgus instability of the elbow, it may yield a false-positive assessment of valgus instability. Valgus stress radiographs comparing contralateral elbows may reduce the false-positive rate since there appears to be no significant difference in medial ulnohumeral gapping between the two elbows.