Miracle-dz/UniFAR-FTUs huggingface dataset:
Cavitational ultrasonic surgical aspiration for the treatment of vaginal intraepithelial neoplasia.

OBJECTIVE The aim of this study is to determine whether cavitational ultrasonic surgical aspiration (CUSA) is effective and safe for treating vaginal intraepithelial neoplasia (VAIN). METHODS We conducted a retrospective chart review of 46 patients who were treated with CUSA for VAIN in a single gynecologic oncology practice between 1981 and 1999. RESULTS At initial presentation, 39% of treated patients had grade I VAIN, 20% had grade II, and 41% had grade III. The mean duration of follow-up from initial CUSA treatment was 21 months. Twenty-nine patients (63%) were initially treated with CUSA, 7 patients (15%) with laser vaporization, 7 patients (15%) with surveillance by Papanicolaou smear, 1 patient (2%) with partial vaginectomy, 1 patient (2%) with 5-fluorouracil, and 1 patient (2%) with loop excision. Patients initially treated with CUSA had a higher percentage of grade III VAIN at diagnosis (48%) than did patients initially treated with other methods (29%). A significantly greater proportion of patients initially treated with CUSA had no recurrence of VAIN (66%) compared with patients initially treated with other methods (0%) (P < 0.0001). A significantly greater proportion of patients who were treated for recurrent disease with CUSA had no further recurrence (52%) compared with patients treated for recurrent disease with other methods (9%) (P < 0.001). No patient treated with CUSA reported adverse effects; 7 patients treated with other methods reported dysuria, burning, and pain. CONCLUSION These initial data suggest that CUSA is a safe and effective method for treating VAIN and may be an appropriate treatment for many patients.
Phytochemical-induced reduction of pulmonary inflammation during Klebsiella pneumoniae lung infection in mice.

INTRODUCTION Curcumin, a polyphenol derived from the herb Curcuma longa, has number of antioxidant, anti-inﬂammatory, antimicrobial, and anti-carcinogenic activities. Its anti-inflammatory property was here studied alone and in combination with clarithromycin in a mouse model of acute inflammation. METHODOLOGY A total of 80 mice divided into four groups were used. Mice receiving curcumin and/or clarithromycin were fed orally with curcumin (150 mg/kg/day) for 15 days prior to infection, whereas clarithromycin was administered orally (30 mg/kg/day) 12 hours post infection. Simultaneously, the control group receiving only infection but no treatment was also set up. Bacterial load estimation, histopathological examination and analysis of inflammatory parameters was performed on various days for all groups. RESULTS Intranasal inoculation of bacteria resulted in significant increase in neutrophil infiltration along with increased production of various inflammatory mediators (malondialdehyde, myeloperoxidase, nitric oxide, TNFα) in lung tissue. Clarithromycin treatment significantly decreased the bacterial load and other inflammatory components in infected mice, but animals receiving curcumin alone or in combination with clarithromycin showed a much more significant (p < 0.05) reduction in neutrophil influx along with reduced levels of various inflammatory parameters. Though treatment with curcumin did not reduce the bacterial load, in combination with clarithromycin, both bacterial proliferation and lung tissue damage were checked. CONCLUSIONS Though clarithromycin, because of its associated side effects, may not be the preferred treatment, it can be used in conjunction with curcumin. The latter as an adjunct therapy will help to down regulate the exaggerated state of immune response during acute lung infection.
Long-term effects of depot-medroxyprogesterone acetate on lipoprotein metabolism.

To assess the effects of depot-medroxyprogesterone acetate (DMPA) upon serum lipids and lipoproteins, a comparative study in chronic users and new acceptors was undertaken. Two groups of women of reproductive age were included in the study; group I (n = 8) was formed by new acceptors whereas, group II (n = 14) constituted DMPA users of more than five continuous years (7.0 + 2.1 years). Blood samples were taken on the day of injection and 15, 29, 57 and 92 days after the i.m. administration of 150 mg of DMPA for the measurement of total triglycerides (TG), cholesterol (CHOL) and phospholipids (PHL). In addition, the TG and CHOL content in the very low density (VLDL), low density (LDL) and high density (HDL) lipoprotein fractions obtained by ultracentrifugation were also determined. The results demonstrated a moderate increase in the serum total TG concentrations at the expense of the VLDL fraction in the group of chronic DMPA users. In both groups, the administration of DMPA induced a moderate, though not significant, decrease in total CHOL and HDL-chol, an effect that was noticed at the end of the treatment interval; the serum LDL-chol content remained unchanged. In addition, a decrease in the total serum phospholipids content was noticed after DMPA injection in both groups, which resembled the fluctuations observed in the luteal phase of normal ovulating women. The overall data indicate that acute and/or chronic DMPA administration at the dose currently employed for contraception does not induce major abnormalities in lipoproteins in serum.
The effects of age, jaw site, and bone condition on oral implant outcomes.

PURPOSE This paper reviews literature on age and jaw site in relation to jawbone quantity and quality and the osseointegration of endosseous oral implants. RESULTS AND DISCUSSION The condition of jawbone is both age- and site-specific. However, increased age does not appear to affect the clinical potential for osseointegration or the rate of crestal bone resorption observed around oral implants. In contrast, jaw site is related significantly to osseointegration potential; mandibular sites tend to be more successful than maxillary sites. The reason for this may be that jawbone quality and quantity are often more compromised in maxillary than in mandibular sites. However, evaluation of this relationship has been hampered by a lack of evidence to support the validity and reliability of methods used to assess jawbone condition preoperatively. Furthermore, short-term evidence suggests that high rates of implant success can be achieved in maxillary sites, even those with low trabecular density, if an adequate volume of bone exists to accommodate the implants. Although the rate of crestal bone resorption around oral implants is usually low and may not be site-specific, there is some evidence that it may be greater in sites with less preoperative resorption associated with shorter periods of edentulism. This pattern of bone loss could jeopardize long-term implant outcomes especially in younger implant patients. Another concern in young growing patients is that their prosthetic outcome may become compromised because osseointegrated implants cannot keep pace with growth and development in surrounding structures. CONCLUSION To improve our understanding of how the age- and site-specificity of jawbone condition affects oral implant outcomes, research needs to be aimed at establishing reliable and valid measures of preoperative jawbone condition, and at better documenting the effects of jawbone condition on oral implant outcomes.
Association between Toll-like Receptor and Tumor Necrosis Factor Immunological Pathways in Uterine Cervical Neoplasms

Introduction The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inﬂammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. Methods A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-β was measured by immunohistochemistry and graded into low and high levels of expression. Results There was an association between the expression levels of TLR2 and those of TNF-α and TNF-β (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-β expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-β in any of the groups. Conclusions There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-β in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.
Recurrent “Flexispira rappini” Bacteremia in an Adult Patient Undergoing Hemodialysis: Case Report

ABSTRACT A blood culture from a 65-year-old febrile man undergoing hemodialysis revealed, 5 days after inoculation, an unusual gram-negative fusiform rod with darting motility. During another episode of fever 21 days later, this Campylobacter-like organism was again recovered from three blood cultures and subcultured under an H2-enriched microaerobic atmosphere. The organism was catalase negative and oxidase positive and hydrolyzed urea rapidly. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of whole-cell proteins was indistinguishable from that of “Flexispira rappini” LMG 8738 described by Archer et al. in 1988 (J. R. Archer, S. Romero, A. E. Ritchier, M. E. Hamacher, B. M. Steiner, J. H. Bryner, and R. F. Schell, J. Clin. Microbiol. 26:101–105, 1988). The analysis of the 16S ribosomal DNA sequence revealed a similarity of 99.3% between the two strains. The patient recovered completely after a 4-week course of meropenem therapy. This is the first reported case of a recurrent “F. rappini” bacteremia in an adult patient, which confirms that this organism may be an invasive pathogen in immunocompromised patients, like other newly describedHelicobacter species.
Prediction of Pharmacokinetic Drug-Drug Interactions Using Human Hepatocyte Suspension in Plasma and Cytochrome P450 Phenotypic Data. III. In Vitro-in Vivo Correlation with Fluconazole

Whereas ketoconazole is often used to study the worst-case scenario for clinical pharmacokinetic drug-drug interactions (DDIs) for drugs that are primarily metabolized by CYP3A4, fluconazole is considered to be a moderate inhibitor of CYP3A4, providing assessment of the moderate-case scenario of CYP3A-based DDIs. Fluconazole is also a moderate inhibitor of CYP2C9 and CYP2C19. For predicting clinical DDIs using conventional approaches, determining the in vivo inhibitor concentration at the enzymatic site [I], a critical parameter, is still not practical. In our previous study, a novel method involving hepatocyte suspension in plasma was used to circumvent the need to determine the elusive [I] value. In this study, the CYP1A2, 2C9, 2C19, 2D6, and 3A4 activities remaining in the presence of fluconazole were determined in human hepatocytes suspended in human plasma, covering a range of fluconazole clinical plasma concentrations (Cavg and Cmax). Because the protein-binding effect of fluconazole is expected to be close to that in vivo, the inhibition observed in vitro will be similar to that in vivo. This inhibition information was then applied to the cytochrome P450 (P450) phenotypic data to predict DDIs. Using the available P450 phenotypic information on theophylline, tolbutamide, omeprazole, S-warfarin, phenytoin, cyclosporine, and midazolam and that determined in this study for sirolimus and tacrolimus, we found that the predictions for area under the curve increases for most of these drugs in the presence of fluconazole were remarkably similar (within 35%) to the observed clinical values. This study proves the general applicability of our approach using human hepatocyte incubation in human plasma to predict DDIs.
IFN-&ggr;–related mRNA profile predicts clinical response to PD-1 blockade

Programmed death-1–directed (PD-1–directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-&ggr; is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti–PD-1 therapies, including pembrolizumab. However, whether quantifying T cell–inflamed microenvironment is a useful pan-tumor determinant of PD-1–directed therapy response has not been rigorously evaluated. Here, we analyzed gene expression profiles (GEPs) using RNA from baseline tumor samples of pembrolizumab-treated patients. We identified immune-related signatures correlating with clinical benefit using a learn-and-confirm paradigm based on data from different clinical studies of pembrolizumab, starting with a small pilot of 19 melanoma patients and eventually defining a pan-tumor T cell–inflamed GEP in 220 patients with 9 cancers. Predictive value was independently confirmed and compared with that of PD-L1 immunohistochemistry in 96 patients with head and neck squamous cell carcinoma. The T cell–inflamed GEP contained IFN-&ggr;–responsive genes related to antigen presentation, chemokine expression, cytotoxic activity, and adaptive immune resistance, and these features were necessary, but not always sufficient, for clinical benefit. The T cell–inflamed GEP has been developed into a clinical-grade assay that is currently being evaluated in ongoing pembrolizumab trials.
Connoisseurship Consumption Community and Its Dynamics

Purpose – What is the dynamics of the connoisseurship consumption community? What are the forces that drive this serious leisure consumption community? Design/methodology/approach – Adopting a naturalistic inquiry approach, we immersed ourselves in the field, visiting and observing consumers and professionals in independent coffee shops in North America: Toronto, Montreal, Seattle, and New York from August 2013 to July 2014. Findings – The research describes the connoisseurship consumption community and explains its forces, which are education, emulation and tensions between the members of the community. Originality/value – Our findings explain the amateur consumer’s behavior and the relationship of these amateurs with professionals and with the public during their consumption practices. We help to advance the study of heterogeneous consumption communities by revealing the tensions between the members of the community and the production of subcultural and social capital. Our research contributes to the consumer culture field by increasing knowledge of this social consumption phenomenon.
Relationship of leukemia risk to radiation dose following cancer of the uterine corpus.

BACKGROUND Radiotherapy has been linked infrequently to secondary leukemia despite extensive exposure of the active bone marrow to ionizing radiation. Few studies include substantial numbers of elderly patients. PURPOSE We evaluated women with cancer of the uterine corpus, the majority of whom were treated at older ages, to gain additional information on cancer risk following partial-body radiotherapy and to examine differences in risk between external-beam therapy and brachytherapy. METHODS A cohort of 110,000 women with invasive cancer of the uterine corpus who survived at least 1 year following their initial cancer was assembled from nine population-based cancer registries. Cancer diagnoses occurred from 1935 through 1985, and most patients were diagnosed during the 1960s and 1970s. Radiation doses were computed to 17 sections of the active bone marrow for 218 women who developed leukemia and for 775 matched control subjects. RESULTS Radiotherapy did not increase the risk of chronic lymphocytic leukemia (CLL) (relative risk [RR] = 0.90; 95% confidence interval [CI] = 0.4-1.9). However, for all leukemias except CLL, a significant risk was identified (RR = 1.92; 95% CI = 1.3-2.9). Overall, the pattern of risk in relation to dose was erratic and was most consistent with a constant increased risk across the entire dose range. The risk following continuous exposures from brachytherapy at comparatively low doses and low dose rates (RR = 1.80; 95% CI = 1.1-2.8; mean dose = 1.72 Gy) was similar to that after fractionated exposures at much higher doses and higher dose rates from external-beam treatment (RR = 2.29; 95% CI = 1.4-3.7; mean dose = 9.88 Gy), indicating a large difference in the estimated risk per unit dose. Risk did not vary by age at first exposure; increased risks were apparent for irradiated patients aged 65 years or older (RR = 1.77; 95% CI = 0.9-3.5). CONCLUSION The leukemia risk associated with partial-body radiotherapy for uterine corpus cancer was small; about 14 excess leukemia cases were due to radiation per 10,000 women followed for 10 years. Women aged 65 years or older had a radiation risk comparable with that found in younger women. The relationship of leukemia risk to radiation dose was found to be complex due to the competing processes of cell killing, transformation, and repair. At very high doses delivered at high rates, destruction of cells likely dominates, and the risk per unit dose is low. In the low dose range, where dose was protracted and delivered at relatively low dose rates, the leukemia risk appears lower than that projected from risk estimates derived from the instantaneous whole-body exposures of atomic bomb survivors.
Efficiency of peptides and lipopeptides for in vivo priming of virus‐specific cytotoxic T cells

Synthetic peptides and a novel type of lipopeptide vaccine, both containing T cell epitopes recognized by Kd‐restricted, influenza virus‐specific cytotoxic T cells (CTL) were compared in their efficiency to induce virus‐specific CTL in vivo. All attempts to induce virus‐specific CTL with synthetic peptide (in the absence of adjuvants) failed. However, a latent immunization was observed, resulting in an increased response to the injected peptide seen only after boosting the recipients with immunogenic virus. In contrast, priming with synthetic lipopeptide vaccine (tripalmitoyl‐S‐glycerylcysteinyl‐seryl‐serine [P3CSS] coupled to peptide) was successful under most conditions, and matched the priming efficiency seen with infectious virus. The requirements for in vivo priming of virus‐specific CTL using lipopeptide suggest that attachment of the lipopeptide to a hydrophobic entity, such as the cell membrane, is responsible for its efficiency.
The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer.

BACKGROUND & AIMS Estimates of the frequency of hereditary nonpolyposis colon cancer (HNPCC) based on clinical criteria have varied widely. Recent studies of germline mismatch repair gene mutations have suggested that HNPCC accounts for close to 3% of all colon cancer, but this estimate may have been inflated by inclusion of founder effects peculiar to Finland. We therefore determined by genetic criteria the colon cancer burden associated with HNPCC in a population-based study of 1066 individuals from Utah and California. METHODS The coding regions of mismatch repair genes hMSH2 and hMLH1 were sequenced from the germline of those individuals whose tumors exhibited microsatellite instability. RESULTS Microsatellite instability was present in 16% (171/1066) of tumors. Pathogenic germline mismatch repair gene mutations were identified in 7 individuals, and missense amino acid changes of uncertain significance were identified in another 6 individuals. After adjusting for the availability of sufficient germline DNA for sequencing, the 7 clearly pathogenic mutations accounted for 0.86% of colon cancer at the population level. Individuals with these mutations were significantly younger, more likely to have a family history of colon and endometrial cancer, and more likely to have first-degree relatives with a young-age onset of colon cancer than individuals with unstable tumors but without germline mutations (P < 0.01). CONCLUSIONS We conclude that genetically defined HNPCC accounts for a very small percentage of colon cancer at the population level, a percentage less than that estimated by most previous clinical studies.
Timing of Repeat BMD Measurements: Development of an Absolute Risk‐Based Prognostic Model

This study attempted to address the following questions: for an individual who is at present nonosteoporotic, given their current age and BMD level, what is the individual's risk of fracture and when is the ideal time to repeat a BMD measurement? Nonosteoporotic women (n = 1008) and men (n = 750) over the age of 60 in 1989 from the Dubbo Osteoporosis Epidemiology Study were monitored until one of the following outcomes occurred: (1) BMD reached “osteoporosis” level (i.e., T‐scores ≤ −2.5) or (2) an incident fragility fracture. During the follow‐up period (average, 7 yr), 346 women (34%) and 160 men (21%) developed osteoporosis or sustained a low‐trauma fracture. The risk of osteoporosis or fracture increased with advancing age (women: RR/10 yr, 1.3; 95% CI, 1.1–1.6; men: RR/10 yr, 2.3; 95% CI, 1.7–2.9) and lower BMD levels (women: RR per −0.12 g/cm2, 3.2; 95% CI, 2.6–4.1; RR per −0.12 g/cm2, 2.6; 95% CI, 2.0–3.3). Using the predicted risk (of osteoporosis or fracture) of 10% as a cut‐off level for repeating BMD measurement, the estimated time to reach the cut‐off level varied from 1.5 (for an 80‐yr‐old woman with a T‐score of −2.2) to 10.6 yr (for a 60‐yr‐old man with a T‐score of 0). These results suggest that, based on an individual's current age and BMD T‐score, it is possible to estimate the optimal time to repeat BMD testing for the individual. The prognostic model and approach presented in this study may help improve the individualization and management of osteoporosis.
Assessment of Health-Promoting Behavior and Lifestyle of Adolescents of a North Indian City

Background: Several health-compromising behaviors (e.g., smoking, alcohol) as well as health-enhancing behaviors (e.g., physical exercise, nutrition) are adopted in adolescence and they often persist into adulthood. Thus, there is a definite need to investigate the health behavior of adolescents rather than focus on adults since it will be far more difficult for adults to change their unhealthy habits adopted in their youth. Therefore, the present study was conducted to ascertain health-promoting behavior and lifestyle of university graduates of Chandigarh. Methods: The present cross-sectional pilot study was conducted in Chandigarh during 2009 among university graduates of Chandigarh aged 17-20 years. A semi-structured, pretested questionnaire comprising of 28 items was used to get information from students regarding their involvement in diet, physical exercise, spirituality and philanthropy. Height, weight, waist and hip circumference of the respondents were measured using standardized equipments and procedures. Results: Mean score of health-promoting lifestyle profile of university graduates was found to be 67.5 ± 12.1 (maximum attainable score = 106). Fourteen students were found to be overweight. Frequent intake of fast food and less consumption of fruits and vegetables was reported by the students. Majority of students exercised as part of their daily routine. Conclusions: The result of the study showed that North Indian students had reasonably good orientations toward health behaviors, with a mean score of 67.5. The topics related to diet, physical exercise, spiritual growth and philanthropy promotion should be incorporated within the curriculum of students for their all round personality development.