Miracle-dz/UniFAR-FTUs huggingface dataset:
The classical Hodgkin's lymphoma microenvironment and its role in promoting tumour growth and immune escape

It has become clear that cancer is not merely a growth of autonomously proliferating cells, but that other non‐malignant cell types are a functional part of the disease. Immune cells, fibroblasts, specialized mesenchymal cells and microvasculature together make up the tumour microenvironment and have functional interactions with tumour cells. Classical Hodgkin's lymphoma (cHL) is characterized by only a few malignant cells and an abundance of inflammatory cells. Hodgkin and Reed–Sternberg (HRS) cells are surrounded by T and B cells admixed with plasma cells, macrophages, eosinophils and mast cells. A constitutive activity of NF‐κB and an altered JAK–STAT signalling pathway are part of the biological background associated with the increased expression of cytokines and cytokine receptors seen in HRS cells. Over‐expression of the members of the TNF receptor family, especially CD30 and CD40, is a hallmark of HRS cells. cHL is a tumour where aberrant cytokine production contributes not only to the proliferation of HRS cells but also to the maintenance of an appropriate environment for the tumour cells. In addition, several chemokines contribute to the composition of the inflammatory background in cHL. This review summarizes updated information on the complex interactions between the HRS cells and their tissue microenvironment and highlights the development of newer therapeutic strategies aimed at targeting the non‐malignant inflammatory/immune cellular components of HL that are involved in cancer cell growth and/or immune escape. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Virus and bacteria enhance histamine production in middle ear fluids of children with acute otitis media.

Histamine levels were measured in 677 middle ear fluid (MEF) samples from 248 children (aged 2 months to 7 years) with acute otitis media (AOM); of these, 116 (47%) had documented viral infection. Histamine content was higher in bacteria-positive than in bacteria-negative MEF samples (P = .007) and higher in samples from patients with viral infection than in those from patients with no viral infection (P = .002). Bacteria and viruses together had an additive effect on histamine content in MEF. Histamine concentration in the initial MEF sample tended to be higher in patients with persistent otitis than in those with good response to treatment (P = .14). Results suggest that viruses, bacteria, or both induce histamine production, which leads to increased inflammation in the middle ear. Antihistaminic drugs may be beneficial. Large, prospective, controlled trials of the effects of antihistamine as an adjunct therapy in bacterial and viral AOM are required before recommendations can be made.
Comparison of Tissue Distribution, Persistence, and Molecular Epidemiology of Parvovirus B19 and Novel Human Parvoviruses PARV4 and Human Bocavirus

Abstract Background. PARV4 and human bocavirus (HBoV) are newly discovered human parvoviruses with poorly understood epidemiologies and disease associations. We investigated the frequencies of persistence, tissue distribution, and influence of immunosuppression on replication of these viruses. Methods. At autopsy, bone marrow, lymphoid tissue, and brain tissue from human immunodeficiency virus (HIV)—infected individuals with acquired immunodeficiency syndrome (AIDS) and those without AIDS and from HIV-uninfected individuals were screened for parvovirus B19, PARV4, and HBoV DNA by means of quantitative polymerase chain reaction analyses. Results. B19 DNA was detected both in HIV-infected study subjects (13 of 24) and in HIV-uninfected study subjects (8 of 8), whereas PARV4 DNA was detected only in HIV-infected study subjects (17 of 24). HBoV DNA was not detected in any study subjects. The degree of immunosuppression with HIV infection did not influence B19 or PARV4 viral loads. B19 or PARV4 plasma viremia was not detected in any study subjects (n = 76; viral load <25 DNA copies/mL). A significantly older age distribution was found for study subjects infected with B19 genotype 2, compared with those infected with B19 genotype 1. Two genotypes of PARV4 were detected; study subjects carrying prototype PARV4 (genotype 1) were younger (all born after 1958) than those infected with genotype 2 (PARV5; study subjects born between 1949 and 1956). Conclusions. Tight immune control of replication of B19 and PARV4 was retained despite profound immunosuppression. Recent genotype replacement of PARV4, combined with absent sequence diversity among genotype 1 sequences, suggests a recent, epidemic spread in the United Kingdom, potentially through transmission routes shared by HIV.
Mass mortality in Pacific oysters is associated with a specific gene expression signature

Mass mortality events occur in natural and cultured communities of bivalve molluscs. The Pacific oyster, Crassostrea gigas, is a dominant species in many intertidal locations as well as an important aquacultured bivalve species, and for the last 50 years, adult oysters have suffered frequent and extreme mass mortality events during summer months. To investigate the molecular changes that precede these mortality events, we employed a novel nonlethal sampling approach to collect haemolymph samples from individual oysters during the period that preceded a mortality event. Microarray‐based gene expression screening of the collected haemolymph was used to identify a mortality gene expression signature that distinguished oysters that survived the mortality event from those individuals that died during the event. The signature was cross‐validated by comparing two separate episodes of mortality. Here, we report that near‐mortality oysters can be distinguished from longer‐lived oysters by the elevated expression of genes associated with cell death, lysosomal proteolysis, and cellular assembly and organization. These results show the potential utility of nonlethal sampling approaches for investigating the environmental causes of mortality in natural populations in the field, and for predicting when such events could occur and which individuals will be affected.
Increased plasma concentrations of adrenomedullin correlate with relaxation of vascular tone in patients with septic shock.

OBJECTIVE To investigate plasma concentrations of adrenomedullin in patients with septic shock and the potential association of these concentrations with relaxation of vascular tone. DESIGN Prospective, case series. SETTING Department of Emergency and Critical Care Medicine, Nara Medical University. PATIENTS Twelve patients who fulfilled the clinical criteria for severe sepsis or septic shock (as defined by the Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee) and 13 healthy volunteers. INTERVENTIONS Arterial blood samples were obtained via a 20-gauge cannula inserted into each patient's radial artery. MEASUREMENTS AND MAIN RESULTS After extraction and purification, plasma adrenomedullin was measured by radioimmunoassay. Systemic vascular resistance index, pulmonary vascular resistance, cardiac index, and stroke volume index were determined with a thermodilution catheter. The mean plasma concentration of adrenomedullin was markedly higher in patients than in controls (226.1 +/- 66.4 [SEM] vs. 5.05 +/- 0.21 fmol/mL, p < .01). Moreover, these concentrations correlated significantly with cardiac index, stroke volume index, and heart rate values, and correlated significantly with decreases in diastolic blood pressure, systemic vascular resistance index, and pulmonary vascular resistance index values. CONCLUSIONS Enhanced production of adrenomedullin in patients with septic shock may contribute to reduced vascular tone, hypotension, or both. More data are needed to clarify the role of adrenomedullin in the regulation of vascular tone in this patient population.
Poor thiamin and riboflavin status is common among women of childbearing age in rural and urban Cambodia.

BACKGROUND Thiamin deficiency in infancy is the underlying cause of beriberi, which can be fatal without rapid treatment. Reports of thiamin deficiency are common in Cambodia; however, population representative data are unavailable. Because B-complex vitamin deficiencies commonly occur in combination, riboflavin was also investigated. OBJECTIVE We determined the biomarker status of thiamin and riboflavin in women of childbearing age in rural and urban Cambodia. METHODS We measured thiamin (erythrocyte thiamin diphosphate; TDP) and riboflavin (erythrocyte glutathione reductase activity coefficient; EGRac) status in a representative sample of Cambodian women (aged 20-45 y) in urban Phnom Penh (n = 146) and rural Prey Veng (n = 156), Cambodia, and, for comparison purposes, in a convenience sample of women in urban Vancouver, British Columbia, Canada (n = 49). RESULTS Thiamin insufficiency (TDP ≤ 90 nmol/L) was common among both urban (39%) and rural (59%) Cambodian women (P < 0.001), whereas <20% of Vancouver women were thiamin insufficient (P < 0.001). The prevalence of suboptimal and deficient riboflavin status (EGRac ≥ 1.3) was 89%, 92%, and 70% among women in Phnom Penh, Prey Veng, and Vancouver, respectively (P < 0.001). CONCLUSIONS Suboptimal status of both thiamin and riboflavin were common in Cambodian women, with substantially higher rates among women living in rural Prey Veng than in urban Phnom Penh. Strategies may be needed to improve the thiamin and riboflavin status of women in Cambodia. The unexpected finding of high riboflavin inadequacy status in Vancouver women warrants further investigation.
Selective spinal anesthesia versus intravenous propofol in transrectal ultrasound-guided prostate biopsy.

BACKGROUND Selective spinal anesthesia (SSA) focuses on the use of minimal doses of intrathecal agents with greater precision and selectivity so that return of function occurs rapidly. OBJECTIVE The authors compared the efficacy of 1.25 mg of hyperbaric bupivacaine intrathecally with propofol anesthesia in terms of hemodynamic stability, surgical conditions and ability to bypass the post anesthetic care unit (PACU). MATERIAL AND METHOD Seventy male patients, 45-85 years old, ASA physical status I-III, were randomly allocated into two groups. Group 1 (n=35) received intrathecal 1.25 mg hyperbaric bupivacaine plus patients cerebrospinal fluid 0.75 ml. Group 2 (n=35) received propofol 1-1.5 mg/kg IV bolus dose and 6-10 mg/kg/hr infusion to maintain surgical anesthesia. RESULTS The patients in group 1 had adequate anesthesia and were able to walk and bypass the PACU (100%). The need of supplemental oxygen and airway maneuver; the incidence of hypotension and bradycardia were found only in group 2. The surgical conditions were rated as excellent 100% in group 1 and 57.1% in group 2. CONCLUSION SSA is superior to propofol anesthesia in terms of hemodynamic stability, surgical conditions and recovery profiles. Even elderly patients were able to walk out from the operating theatre immediately after the procedure.
Can Intraoperative Motor‐Evoked Potentials Predict All the Spinal Cord Ischemia During Moderate Hypothermic Beating Heart Descending Thoracic or Thoraco‐Abdominal Aortic Surgery?

Abstract Background and aim of the study: Paraplegia is a serious complication of descending thoracic or thoraco‐abdominal aortic aneurysm (DTAA or TAAA, respectively) surgery. The functional integrity of the spinal cord can be monitored with intraoperative motor‐evoked potentials (MEPs). Herein, we evaluated the results and adequacy of MEP monitoring. Methods and Results: Between March 2006 and April 2009, 33 patients (24 males and 9 females) were monitored with MEPs and reviewed retrospectively. The mean age was 50.7 ± 15.2 years. Eighteen and 15 patients underwent TAAA and DTAA repairs, respectively. We routinely used femoro‐femoral partial bypass and cerebrospinal fluid (CSF) drainage. If the MEP demonstrated a significant change, prompt protective interventions were performed. During the procedure, 31 patients (93.9%) had a detectable MEP, of whom four had significant MEP changes and only one had an accompanying alteration in the somatosensory‐evoked potential. In‐hospital mortality occurred in two patients (6.0%) because of mesenteric ischemia and sepsis, respectively. Postoperative paraplegia developed in two patients (6.0%), one with an undetectable MEP and another with no significant intraoperative MEP change. Both patients had hypotensive events and impaired CSF drainage in the immediate postoperative period. Permanent paraplegia persisted in one patient. In four patients with intraoperative MEP changes, paraplegia did not occur. Conclusions: Although intraoperative monitoring of MEP has been shown to be effective in detecting cord ischemia during DTAA or TAAA surgery, it is not definitive and cannot predict all neurologic deficits. Other postoperative preventive strategies such as CSF drainage and maintaining a high blood pressure are important to prevent paraplegia. (J Card Surg 2010;25:542‐547)
Neuronal correlates of visual time perception at brief timescales

Successful interaction with the world depends on accurate perception of the timing of external events. Neurons at early stages of the primate visual system represent time-varying stimuli with high precision. However, it is unknown whether this temporal fidelity is maintained in the prefrontal cortex, where changes in neuronal activity generally correlate with changes in perception. One reason to suspect that it is not maintained is that humans experience surprisingly large fluctuations in the perception of time. To investigate the neuronal correlates of time perception, we recorded from neurons in the prefrontal cortex and midbrain of monkeys performing a temporal-discrimination task. Visual time intervals were presented at a timescale relevant to natural behavior (<500 ms). At this brief timescale, neuronal adaptation—time-dependent changes in the size of successive responses—occurs. We found that visual activity fluctuated with timing judgments in the prefrontal cortex but not in comparable midbrain areas. Surprisingly, only response strength, not timing, predicted task performance. Intervals perceived as longer were associated with larger visual responses and shorter intervals with smaller responses, matching the dynamics of adaptation. These results suggest that the magnitude of prefrontal activity may be read out to provide temporal information that contributes to judging the passage of time.
Reducing electrostatic charge on spacer devices and bronchodilator response.

AIMS Plastic spacers are widely used with pressurized metered dose inhalers (pMDI). Reducing electrostatic charge by washing spacers with detergent has been shown to greatly improve in vitro and in vivo drug delivery. We assessed whether this finding is associated with an improved bronchodilator response in adult asthmatics. METHODS Twenty subjects (age 18-65 years) with a known bronchodilator response inhaled in random order salbutamol from a pMDI (Ventolin) through an untreated new spacer (Volumatic) and through a detergent washed spacer. Patients received the following doses of salbutamol via pMDI at 20 min intervals: 100 microg, 100 microg, 200 microg, 400 microg, 800 microg. Spirometry, heart rate and blood pressure were checked prior to each dose and 20 min after the last dose. RESULTS There were no differences between baseline forced expiratory volume in 1 s (FEV1) using either spacer (2.61+/-0.56 and 2.52+/-0.45 l, untreated and treated with detergent, respectively; mean +/- s.d.). The provocation dose required to cause a clinically significant improvement of 10% in FEV1 (PD10) was significantly lower when the detergent treated spacer was used (1505 +/-1335 and 430+/-732 microg, untreated and treated, respectively, P<0.002). CONCLUSIONS We have demonstrated an improvement in bronchodilator response, in adult asthmatics, after reducing the electrostatic charge in a spacer device by washing it with ordinary household detergent. This finding stresses the importance of an optimal choice of delivery device for asthma medication.
Ligand‐independent activation of MET through IGF‐1/IGF‐1R signaling

The receptor tyrosine kinase, MET, has been implicated in tumorigenesis and metastasis of many solid tumors, by multiple mechanisms, including cross talk with epidermal growth factor receptor. In this study, we examined the role of insulin‐like growth factor receptor‐1 (IGF‐1R) signaling in MET activation, focusing on prostate cancer cells. Stimulation of the prostate cancer cell line PC3 with IGF‐1 induces a delayed phosphorylation of MET at multiple sites (indicative of full activation), reaching a maximum 18 hr after IGF‐1 addition. MET activation does not require the sole MET ligand hepatocyte growth factor (HGF), but does require transcription to occur. Furthermore, direct injection of IGF‐1 is sufficient to induce MET activation in vivo, in a PC3 xenograft model. Pharmacologic or genetic inhibition of the tyrosine kinase, Src, abolishes MET phosphorylation, and expression of activated Src is sufficient to induce Met phosphorylation in the absence of IGF‐1 stimulation. Activated MET is essential for IGF‐1‐mediated increased migration of PC3 cells, demonstrating an important biologic effect of IGF‐1‐mediated MET activation. Finally, we demonstrate that IGF‐1‐induced delayed MET activation occurs in multiple cell lines which express both the receptors, suggesting that IGF‐1R‐mediated MET activation may contribute to tumorigenic properties of multiple cancer types when both growth factor receptors are expressed. The results further suggest that MET may be activated by multiple receptor tyrosine kinase receptors, and dual targeting of these receptors may be important therapeutically.
Vaccinia virus inoculation in sites of allergic skin inflammation elicits a vigorous cutaneous IL-17 response

Eczema vaccinatum (EV) is a complication of smallpox vaccination occurring in patients with atopic dermatitis. In affected individuals, vaccinia virus (VV) spreads through the skin, resulting in large primary lesions and satellite lesions, and infects internal organs. BALB/c mice inoculated with VV at sites of Th2-biased allergic skin inflammation elicited by epicutaneous ovalbumin (OVA) sensitization exhibited larger primary lesions that were erosive, more satellite lesions, and higher viral loads in skin and internal organs than mice inoculated in saline-exposed skin, unsensitized skin, or skin sites with Th1-dominant inflammation. VV inoculation in OVA-sensitized skin induced marked local expression of IL-17 transcripts and massive neutrophil infiltration compared to VV inoculation in saline-exposed skin. Treatment with anti-IL-17 decreased the size of primary lesions, numbers of satellite lesions, and viral loads. Addition of IL-17 promoted VV replication in skin explants. These results suggest that IL-17 may be a potential therapeutic target in EV.
Adequacy of Colonoscopic Biopsy Specimens for Molecular Analysis: A Comparative Study With Colectomy Tissue

Molecular analyses of tumors are increasingly useful for prognosis and for guiding therapy. Colonoscopic biopsy provides the first source of tissue for most cases of colorectal carcinoma and therefore might become an important source for molecular analyses. We have addressed the question whether molecular analyses of colonoscopic biopsy yield results similar to the findings from the surgical specimen. Further, we analyzed 2 separate areas of the colectomy specimen to assess tumor heterogeneity. We evaluated 3 samples from each of 67 patients for point mutations in the KRAS gene, loss of heterozygosity (LOH) at the Adenomatous Polyposis Coli (APC) and Deleted in Colon Cancer (DCC) genes and for microsatellite instability (MSI) using polymerase chain reaction based techniques. The average time interval between biopsy and surgery was 2.2±0.15 weeks. Lesions were from all colon segments and all surgical stages. The degree of agreement between the biopsy and surgical sites was high for APC LOH, MSI, and KRAS mutations (κ=0.85, 1.00, and 0.93, respectively) but less so for DCC LOH (κ=0.62). Colonoscopic biopsies are an acceptable source of neoplastic DNA for studies of KRAS, APC LOH, and MSI, but less so for DCC LOH, primarily resulting from technical considerations.
Depressive symptoms in adult coeliac disease.

BACKGROUND Psychic symptoms and depression have been reported in coeliac disease (CD). The aim of this study was to explore depression in a large cohort of adult CD patients. METHODS Depressive symptoms were evaluated in 92 adult coeliacs, 100 normal controls (NC), and 48 chronic persistent hepatitis (CPH) patients by means of a modified version of the Zung Self-Rating Depression Scale (M-SDS). CD patients were evaluated for the level of knowledge about CD and the compliance with diet. RESULTS The M-SDS score differentiated CD patients from NC. Age at diagnosis and duration of and compliance with diet did not correlate with depression. Three main factors could be identified with the M-SDS: 'reactiveness', 'pessimism', and 'anhedonic-asthenic'. CONCLUSION Depressive symptoms are a feature of CD; they are present to a similar extent in patients with childhood- and adulthood-diagnosed CD. The results underline the relevance of personal psychologic resources, which play a fundamental role in determining and sustaining depression.
Disclosure Model for Pediatric Patients Living with HIV in Puerto Rico: Design, Implementation, and Evaluation

ABSTRACT. The American Academy of Pediatrics strongly encourages the disclosure of HIV status to school-age children and further recommends that adolescents know their HIV status. Limited information exists on the impact of disclosure. We designed and implemented a disclosure model hypothesized to be associated with healthy psychological adjustment and improved medication adherence. We report the model's design and implementation and results of a quasi-experimental study of the disclosure's effects on health care professionals (n = 16), caregivers (n = 39), and HIV-infected youth (n = 40) in Puerto Rico. Information was collected from youth, caregivers, and professionals by semistructured interviews and questionnaires. Most youth (70%) had feelings of normalcy 6 months post-disclosure, and most also improved their adherence to therapy after disclosure as reported by both patients (58%) and caregivers (59%). Eighty-five percent of youth and 97% of caregivers considered disclosure a positive event for themselves and their families. Fewer health care professionals reported feelings of fear, discomfort, and insecurity after protocol participation.