Miracle-dz/UniFAR-FTUs huggingface dataset:
Conventional and pretargeted radioimmunotherapy using bismuth-213 to target and treat non-Hodgkin lymphomas expressing CD20: a preclinical model toward optimal consolidation therapy to eradicate minimal residual disease.

Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (²¹³Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)(4)SA fusion protein (FP), followed by a dendrimeric clearing agent and [²¹³Bi]DOTA-biotin. After 90 minutes, tumor uptake for 1F5(scFv)₄SA was 16.5% ± 7.0% injected dose per gram compared with 2.3% ± . 9% injected dose per gram for the control FP. Mice treated with anti-CD20 PRIT and 600 μ Ci [²¹³Bi]DOTA-biotin exhibited marked tumor growth delays compared with controls (mean tumor volume .01 ± .02 vs. 203.38 ± 83.03 mm³ after 19 days, respectively). The median survival for the 1F5(scFv)₄SA group was 90 days compared with 23 days for the control FP (P < .0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with ²¹³Bi-labeled anti-CD20 PRIT.
Interobserver reliability of the italian version of the geriatric mental state examination

The Italian version of the Geriatric Mental State Examination (GMS) was tested for interrater agreement (interobserver). Thirty geriatric patients form psychiatry, neurology and general medical facilities were interviewed by four raters. The mean values of kappa and phi for the analysable items were 0.80 and 0.81. ‘Organic’ and ‘functional’ items produced very similar coeffcient values.
Decreased renal excretion of soluble interleukin-2 receptor α after treatment with daclizumab

Decreased renal excretion of soluble interleukin-2 receptor α after treatment with daclizumab. Background Daclizumab (±150 kD), a humanized monoclonal antibody (mAb) against the alpha-chain of the membrane-bound interleukin-2 (IL-2) receptor (IL-2R) also binds soluble interleukin-2R α (sIL-2Rα; ±45 kD), and thus may influence the glomerular filtration of sIL-2Rα. Methods We have studied the influence of daclizumab on the renal excretion of sIL-2Rα in 38 recipients of a renal transplant (32 treated with daclizumab and six controls). sIL-2Rα was measured every 2weeks after transplantation in serum and urine with Immulite® IL-2R, a solid-phase enzyme-linked immunosorbent assay (ELISA). Results In the control population, the fractional excretion of sIL-2Rα was relatively constant with a median value of 1.7%± 0.5%. In daclizumab-treated patients, sIL-2Rα was not detectable in the urine immediately after the administration of daclizumab. sIL-2Rα became detectable in the urine at a mean of 8 ± 3weeks after transplantation. In additional experiments, serum compounds were separated by size-exclusion chromatography and sIL-2Rα was measured in the collected fractions. In the control patients, sIL-2Rα was only present in the low-molecular-weight fractions of serum. In contrast, in daclizumab-treated patients evaluated several weeks after transplantation, sIL-2Rα was merely detected in the high-molecular-weight fractions of serum. During follow-up there was a relative shift of sIL-2Rα from the high- to the low-molecular-weight fractions and this coincided with normalization of sIL-2Rα excretion. Conclusion Daclizumab inhibits the renal excretion of sIL-2Rα by the formation of a complex with sIL-2Rα in serum, which is too large for glomerular filtration. Measurement of urinary sIL-2Rα may provide information on the concentration of anti-IL-2Rα mAb in serum.
In Vitro Activity of Cefdinir and Comparison Agents Against β-Lactamase-Producing Pathogens

Abstract: The in vitro activities of the oral agents, cefdinir, ceftibuten, cefixime, cefprozil, cefuroxime, cefpodoxime, cephalexin, loracarbef, ampicillin, and amoxicillin/clavulanate with ceftriaxone were compared against a panel of 210 bacterial strains chosen to represent a diverse range of types of β-lactamase expression. Ceftriaxone was included in the study as a representative parenteral cephalosporin. Activities were determined by NCCLS microdilution methodology. Cefdinir was the most active agent overall in terms of its activity against Enterobacteriaceae, Haemophilus influenzae, Moraxella catarrhalis, and methicillin-susceptible Staphylococcus aureus, with greatest activity against community-acquired pathogens. Cefdinir was significantly more resistant to hydrolysis by β-lactamases than cefprozil, cephalexin, cephalothin, cephaloridine, and loracarbef, and generally comparable to cefixime, cefpodoxime, cefuroxime, ceftibuten, and ceftriaxone. Therefore, cefdinir has a spectrum of activity and resistance to β-lactamases suiting it for therapy for infections caused by a wide range of gram-positive and gram-negative pathogens, particularly those encountered in outpatient settings.
Bees under stress: sublethal doses of a neonicotinoid pesticide and pathogens interact to elevate honey bee mortality across the life cycle.

Microbial pathogens are thought to have a profound impact on insect populations. Honey bees are suffering from elevated colony losses in the northern hemisphere possibly because of a variety of emergent microbial pathogens, with which pesticides may interact to exacerbate their impacts. To reveal such potential interactions, we administered at sublethal and field realistic doses one neonicotinoid pesticide (thiacloprid) and two common microbial pathogens, the invasive microsporidian Nosema ceranae and black queen cell virus (BQCV), individually to larval and adult honey bees in the laboratory. Through fully crossed experiments in which treatments were administered singly or in combination, we found an additive interaction between BQCV and thiacloprid on host larval survival likely because the pesticide significantly elevated viral loads. In adult bees, two synergistic interactions increased individual mortality: between N. ceranae and BQCV, and between N. ceranae and thiacloprid. The combination of two pathogens had a more profound effect on elevating adult mortality than N. ceranae plus thiacloprid. Common microbial pathogens appear to be major threats to honey bees, while sublethal doses of pesticide may enhance their deleterious effects on honey bee larvae and adults. It remains an open question as to whether these interactions can affect colony survival.
Hepatocyte growth factor (HGF) in jreiodontal disease: detection of HGF in gingival crevicular fluid

Hepatocyte growth factor (HGF) acts as a mitogen, motogen, morphogen, anti-apoptotic factor, and scatter factor for various kinds of epithelial cells. It is a protein secreted by mesenchymal cells such as fibroblasts, and promotes motility and matrix invasion of epithelial cells. To clarify whether HGF is involved in periodontal disease, this study was conducted to determine whether HGF is present in gingival crevicular fluid (GCF) and to investigate the relationship between levels of HGF and the clinical parameters of periodontal disease, probing depth (PD), gingival index (GI) and bleeding on probing (BOP). We examined and collected GCF samples from 80 sites in 38 subjects with periodontal or other oral diseases. The concentrations of HGF, IL-1beta and PGE2 were determined by ELISA, and active collagenase activity was determined by functional assay. The HGF level correlated positively with PD and GI, and was significantly higher in specimens from BOP-positive sites and those where PD exceeded 4 mm compared with those from sites that were BOP-negative or with a PD less than 3 mm. There was a significant positive correlation between the concentrations of HGF and IL-1beta. These results indicate that the HGF level in GCF correlates well with clinical parameters of periodontal disease, and suggest that HGF may be involved in epithelial invasion through its role as a scatter factor.
THE NORMAL RANGE OF GASTRIC ACIDITY FROM YOUTH TO OLD AGE: AN ANALYSIS OF 3,746 RECORDS

At first glance it would seem inconceivable that for sixty years physicians could have gone on studying gastric acidity in the sick, without, somewhere along the way, pausing to secure standards of normal. There are two explanations for this peculiar behavior of the medical profession: one, that we have always been more ready to study disease and to treat it than to make the basic anthropologic and statistical studies that would enable us to say where normal ends and disease begins; and the other, that it is not easy to get several thousand normal persons to submit to gastric intubation. Much work has been done with medical students and with infants, but, unfortunately, most of the published reports of these studies are useless for statistical analysis because distribution tables were not supplied, and measurements from several age groups were averaged together. Although the literature on gastric analysis is enormous, we
Tobacco Use in California An Evaluation of the Tobacco Contol Program, 1989-1993

Evaluation of the California Tobacco Control Program Progress from 1988 through 1993 1. Protection of Nonsmokers form Environmental Tobacco Smoke (ETS) (a) Children at Home: 80% of children younger than 17 years protected by 1993 (b) Nonsmokers at Work: 23% decrease in the number of nonsmokers exposed to ETS during 1990-1993 2. Reduction in Smoking Prevalence (a) Tobacco consumption declined 27% between 1988 and 1993. (b) Smoking prevalence declined 28% from an estimated 26.5% in 1988 to a best estimate of 19.1% in 1993. (c) The observed decline in consumption and prevalence resulted from an increase in successful quitting among California adults. (d) No decline in adolescent smoking was observed after 1990. The Program appears to have halted the increases in adolescent smoking observed during 1988-1990. Forecast to Year 1999 1. As currently implemented, the Tobacco Control Program will not meet the legislatively set goal of a 75% reduction in smoking prevalence. 2. To achieve the set goal, the Program should emphasize effective interventions in order to increase its annual impact by 50% for the period 1994 through 1999.
Mucosa-associated lymphoid tissue lymphoma: a perspective on current and future therapeutic strategies

Introduction: Helicobacter pylori-eradication is the defined standard care for patients with H. pylori-associated gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, to date there is no clearly defined consensus on treatment of eradication-refractory, relapsed or extragastric MALT lymphoma. Areas covered: The authors have conducted a computerized search in MEDLINE to identify recent publications of relevance for current treatment options of MALT lymphoma patients with a special focus on systemic treatment strategies. Therapeutic strategies covered in this article include antibacterial treatment beyond H. pylori-eradication, that is, doxycycline and clarithromycin for orbital MALT lymphoma, respectively; anti-CD20-antibody monotherapy with rituximab (R) for gastric and extragastric patients; further immunomodulatory approaches for example, lenalidomide and everolimus; and finally new data on chemotherapy-containing treatments plus/minus R (chlorambucil ± R, cladribine ± R, bendamustine + R). The aim of this article is to provide the reader with a concise overview with implications for daily practice. Expert opinion: Recently, systemic treatment strategies have been increasingly applied in MALT lymphoma and particularly regimens with a favorable toxicity profile are of interest. Beside chemotherapies with or without R, immunomodulatory substances and antibiotics beyond H. pylori-eradication are also being tested. In conclusion, systemic treatment appears to be safe and feasible not only for systemic but also for localized disease.
Aptidão cardiorrespiratória de adolescentes de Florianópolis, SC

Suitable levels of cardiorespiratory fitness during adolescence are closely concerned with a healthy lifestyle in adulthood. The objective of this study was to identify cardiorespiratory fitness behavior during adolescence and describe the prevalence of adolescents who fulfilled or not the healthy fitness criterion by sex, age and socioeconomic status (SES). The sample was composed by 963 adolescents (513 males and 450 females) aged 10-15 years old. A questionnaire was answered for attainment of the SES (A + B, C, D + E). To have the cardiorespiratory fitness measured, the PACER test (Progressive Aerobic Cardiovascular Endurance Run) was conducted. The number of laps completed in the test and the maximal oxygen uptake - VO2max (ml/kg/min) were used as cardiorespiratory performance parameters. The statistical analysis included means and standard deviations, two-way variance analysis with Tukey post-hoc test, and chi-squared test (p < 0.05). While the number of laps increased from 10 to 15 years, the VO2max diminished, with no sex differences. Low SES adolescents presented lower fitness than the ones from the other SES. 68% of males and 37.2% of females did not reach the healthy fitness criterion. It was verified the majority of the adolescents who did not fulfill the healthy fitness criterion was in the low SES. These findings show that, approximately 2/3 of males and 1/3 of females did not reach the healthy fitness criterion. Low SES adolescents presented the lowest levels of cardiorespiratory fitness.
Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort.

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Créteil newborn SCA cohort (n = 217 SS/Sβ(0)), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigen-genoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L × 10(9)/L increase, 95% CI 1.000-1.006; P = . 04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P = .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention.
Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study.

Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy. Eliglustat tartrate improved clinical manifestations in patients who received 50 or 100 mg twice daily for 1 year during an open-label phase 2 study (Blood. 2010;116(6):893-899). We report further improvements after 2 years of treatment in 20 patients (11 females, 9 males; mean age, 33 years) with baseline splenomegaly and thrombocytopenia and/or anemia. Statistically significant (P < .001) percentage improvements from baseline occurred in platelet count (mean ± SD, 81% ± 56%), hemoglobin level (20% ± 15%), spleen volume (-52% ± 11%), and liver volume (-24% ± 13%). Mean platelet count increased ∼ 50 000/mm(3). Mean hemoglobin level increased 2.1 g/dL overall and 3.1 g/dL in 10 patients with baseline anemia. Organ volume reductions were greatest in patients with severe baseline organomegaly. Seventeen (85%) patients met established therapeutic goals for ≥ 3 of the 4 parameters. Lumbar spine bone mineral density increased 7.8% ± 10.6% (P = .01) and T-score 0.6 ± 0.8 (P = .012), with major gains in osteoporotic and osteopenic patients. Magnetic resonance imaging assessment showed that bone marrow infiltration by Gaucher cells was decreased (8/18 patients) or stable (10/18 patients). No safety-related trends emerged during 2 years of treatment. This multisite, open-label, single-arm phase 2 study is registered at www.clinicaltrials. gov as NCT00358150.
Fungicide efflux and the MgMFS1 transporter contribute to the multidrug resistance phenotype in Zymoseptoria tritici field isolates.

Septoria leaf blotch is mainly controlled by fungicides. Zymoseptoria tritici, which is responsible for this disease, displays strong adaptive capacity to fungicide challenge. It developed resistance to most fungicides due to target site modifications. Recently, isolated strains showed cross-resistance to fungicides with unrelated modes of action, suggesting a resistance mechanism known as multidrug resistance (MDR). We show enhanced prochloraz efflux, sensitive to the modulators amitryptiline and chlorpromazine, for two Z. tritici strains, displaying an MDR phenotype in addition to the genotypes CYP51(I381V Y461H) or CYP51(I381V ΔY459/) (G460) , respectively, hereafter named MDR6 and MDR7. Efflux was also inhibited by verapamil in the MDR7 strain. RNA sequencing lead to the identification of several transporter genes overexpressed in both MDR strains. The expression of the MgMFS1 gene was the strongest and constitutively high in MDR field strains. Its inactivation in the MDR6 strain abolished resistance to fungicides with different modes of action supporting its involvement in MDR in Z. tritici. A 519 bp insert in the MgMFS1 promoter was detected in half of the tested MDR field strains, but absent from sensitive field strains, suggesting that the insert is correlated with the observed MDR phenotype. Besides MgMfs1, other transporters and mutations may be involved in MDR in Z. tritici.
Perceived psychosocial stress and cardiovascular risk : observations among the Bhutias of Sikkim, India

Psychosocial factors (including psychosocial stress) are documented to be related to morbidity and mortality due to cardiovascular diseases (CVDs) and their risk factors. The present study examines whether perceived psychosocial stress affects blood pressures, blood lipids and obesity among the Bhutias, a tribal population of Sikkim. A total of 428 Bhutias of both sexes aged 20 years and above inhabiting both urban and rural areas participated after providing informed consent. Data on blood pressures, blood lipids, anthropometrics and a variety of lifestyle-related factors including perceived stress level were collected following standard methods. The results clearly indicate that perceived stress significantly affects more than one CVD risk factor selected for study both in males and females. Perceived stress significantly affects diastolic blood pressure, total cholesterol (TC) and ratio of TC and high-density lipoprotein (HDL) cholesterol in males, while in females, although significant effect of stress does not exist on blood pressures, significant effects of stress are discernible on Low-density lipoprotein (LDL) cholesterol, TC/HDL as well as adiposity/obesity measures such as body mass index, waist circumference and waist–hip ratio. Perceived stress remains an independent factor affecting CVD risk factors even after controlling other significant lifestyle-related predictors. Again, hypertension, both systolic and diastolic, overweight and obesity, have also been significantly affected by perceived stress. It appears that contribution of psychosocial stress in addition to other lifestyle-related factors remains substantial among a tribal population inhabiting the eastern Himalaya and experiencing rapid socio-cultural changes. Copyright © 2007 John Wiley & Sons, Ltd.
The Silent World of Doctor and Patient

In this thoughtful and important book, Jay Katz takes us on a journey through medical and legal history to establish convincingly one point— that medical and legal relationships and entitlements up to the 20th century have developed in a manner that has kept patients out of the process of decision in which the harms and benefits of therapeutic alternatives concerning them were weighed and balanced. In medicine, for centuries, such exclusion was justified on the basis of things such as the medical ignorance of patients, their intolerance of uncertainty, the need to maintain the patient's hope that things would improve, the simplicity that unilateral decision making gave to the doctor's life, the painfulness of discussing with patients dreaded events and hopeless prognoses, and the authority that silence in the medical relationship gave to physicians. In the law, too, the rights given to patients up to the mid-20th century were basically
Clinical Observations with Transient Evoked Otoacoustic Emissions with Adults

The measurement system used is the Otodynamic IL088 Analyzer hardware and software developed by Kemp et al., Bray and Kemp et al. This instrument measures transiently evoked otoacoustic emissions (TEOAEs) with an 80-μs rectangular pulse stimulus with a frequency response of 600 to 5000 Hz. Pulse rate was 50/s. Two advantages of using transient stimulation are that the resulting OAEs can provide information over a wide range of frequencies simultaneously and testing time is minimal. Following a pilot investigation, a single-stimulus setting of 80 dB pe SPL with the differential nonlinear test paradigm of the IL088 was chosen for all patient testing. In this paradigm four pulses are subaveraged as an 80-μs stimulus block consisting of three compressional pulses of equal amplitude and one rarefaction pulse three times larger. After each block of stimuli, the summed response in the ear canal is zero unless there is a nonlinear component (the EOAE). Kemp et al. report that this procedure yields a 40-dB reduction in stimulus artifacts with only a 6-dB loss in echo response. The nonlinear stimulus paradigm is far superior to linear stimulation for identification of TEOAEs in a clinical setting. We opted not to search for emission threshold. As previously reported, searching for TEOAE threshold in a clinical setting has limitations. For example, holding audiometric thresholds constant, TEOAE thresholds increase with increasing age above 30 years and ears having spontaneous otoacoustic emissions (SOAEs) have understandably lower TEOAE detection thresholds. Therefore, in our clinical evaluation of TEOAEs we chose to employ a moderate stimulus level