Increased sensitivity to IL-4 in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.
Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus allergens and a hyper-immunoglobulin (Ig)E state compared with cystic fibrosis patients without ABPA. We hypothesize that one reason for this response is increased sensitivity to interleukin (IL)-4 in ABPA resulting in increased expression of CD23 and CD86 and leading to a positive amplification mechanism that increases Th2 CD4+ T cell responses. Peripheral blood mononuclear cells (PBMC) were isolated from seven ABPA CF and 19 non-ABPA CF patients and 16 nonatopic controls and stimulated with rIL-4 (range 0.1-10 ng/ml) and rIL-13 (range 1-10 ng/ml) for 48 h. The number of CD23 molecules and percentages of CD23+ B cells were quantified by flow cytometry. Both phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO) and antigen stimulated, toxoid and Asp f2/f3/f4, PBMC were examined for cytoplasmic cytokine synthesis enumerated by cytokine staining using flow cytometry to measure Th2 and Th1 CD3+ T cells. The numbers of CD23 molecules on B-cells were significantly elevated at time 0 in ABPA CF patients compared with both non-ABPA CF patients and nonatopic controls. Following IL-4 stimulation in vitro, the numbers and percentages of CD23 expression on B cells were significantly up-regulated in ABPA CF patients compared with non-ABPA CF patients and controls. The IL-13 stimulation up-regulated CD23 expression; however, there was no significant difference in ABPA CF patients compared with non-ABPA CF patients and controls. The percentages of interferon (IFN)-gamma+ CD3+T cells following PMA/IO stimulation were significantly decreased in both ABPA and non-ABPA CF patients compared with controls. There were no significant differences of IL-4+ and IL-13+ CD3+ T cells between ABPA and non-ABPA CF patients. When tetanus toxoid stimulated T cells were examined, both ABPA and non-ABPA CF patients had significantly decreased IFN-gamma+ CD3+ T cells compared with controls. In Asp f2/f3/f4 stimulated T cells, ABPA CF patients had significantly increased IL-4+ CD3+ T cells compared with non-ABPA CF patients and controls. ABPA CF patients have increased sensitivity to IL-4 but not to IL-13 up-regulation of CD23 molecules compared with non-ABPA CF patients. There were decreased percentages of IFN-gamma+ and IL-2+ Th1 T cells in CF patients compared with nonatopic controls but similar percentages of IL-4+ Th2 T cells in all three groups. However, ABPA CF patients had increased frequency of Aspergillus-stimulated Th2 T cells. This indicated that there is skewing of Th2 T cells in ABPA CF patients. Thus, in CF ABPA patients there is increased Th2 T cells and increased sensitivity to IL-4.


Simultaneous occurrence of large B-cell non-Hodgkin lymphoma and acute myeloid leukaemia in an elderly patient: complete remissions of both diseases by rituximab-bendamustine regimen combined to hypomethylating therapy.
The case of an elderly and frail patient affected by simultaneous large B-cell non-Hodgkin lymphoma and acute myeloid leukaemia is reported. The complete remissions of both diseases by azacitidine and rituximab-bendamustine regimen were achieved.


Sexual size dimorphism predicts the frequency of multiple mating in the sex-role reversed pipefish Syngnathus typhle.
The sex-role reversed pipefish Syngnathus typhle is a member of the Syngnathidae, a family of fishes in which males brood embryos on their body surface. As in most ectotherms, embryonic development is highly temperature dependent in syngnathids and male brooding periods are extended when water temperatures are reduced. The influence of temperature on reproduction is expected to effectively truncate the breeding season and reduce fecundity in cold waters, potentially enhancing the opportunity for both fecundity and sexual selection. We studied spatial variation in the morphology and reproductive biology of S. typhle in five European populations which vary in latitude and water temperature. Microsatellite analyses indicated that the average number of male mates per population ranged between 1.3 and 3.7. The frequency of multiple mating by males was negatively correlated with the degree of sexual size dimorphism in each population, suggesting that disproportionate increases in female fecundity may be able to compensate for increased male brood pouch capacity. Both sexes were larger and males had an increased brood size where water temperatures during the breeding season were lower. Morphological variation among populations may be mediated by differences in fecundity selection associated with different optimal reproductive strategies in cold and warm water environments.


Lipoprotein(a) in patients treated by continuous ambulatory peritoneal dialysis.
Lipoprotein(a) [Lp(a)] has been identified as an independent, inherited risk factor for atherosclerotic vascular disease. An elevation of Lp(a) plasma levels has been documented in several series of uremic patients submitted to maintenance dialysis treatment methods or after renal transplantation. We have measured the plasma levels of Lp(a) using an enzyme-linked immunosorbent enzyme method in 19 patients treated with continuous ambulatory peritoneal dialysis (CAPD). Mean (+/- SD) concentration of Lp(a) was significantly higher in the patients than in the 19 healthy controls (51 +/- 48 mg/dL v 16 +/- 15 mg/dL, P < 0.005). No significant differences in Lp(a) levels were found between diabetic patients (n = 5) and nondiabetic patients (n = 14) or between patients who had (n = 6) or had not (n = 13) suffered a previous major cardiovascular complication. No correlation was evident between Lp(a) levels and the patients' ages, period of time on CAPD treatment, or any other lipid-lipoprotein investigated parameter. The mechanisms accounting for the elevation of Lp(a) levels in CAPD patients as well as the specific value of increased Lp(a) concentration as a cardiovascular risk predictor in uremic patients remain thus far speculative. Additional experimental and clinical studies are warranted before the administration of drugs to attempt to lower Lp(a) levels in CAPD patients can be recommended.


The methanol-ethyl acetate partitioned fraction from Chinese olive fruits inhibits cancer cell proliferation and tumor growth by promoting apoptosis through the suppression of the NF-κB signaling pathway.
Chinese olives (Canarium album L.) have historically been used for medicinal purposes rather than commercially for oil. In this report, we reveal that the methanol-ethyl acetate partitioned fraction from Chinese olive fruits (MEO), of which ellagic acid accounted for 12%, exhibited profound anti-proliferative activities in the human colon cancer cell line, HCT116. Additionally, oral administration of MEO remarkably inhibited the tumor growth of subcutaneously implanted CT26 cells, a mouse colon carcinoma cell line, in BALB/c mice. Treatment with MEO induced a significant increase in the percentage of apoptotic cells and resulted in poly(ADP-ribose) polymerase (PARP) cleavage, suggesting that MEO inhibits cancer cell proliferation by promoting apoptosis. Our study also showed that MEO exerted the most potent effect on the inhibition of NF-κB-mediated signaling among the partitioned fractions from Chinese olives. This process employed the use of reporter-based bio-platforms that are capable of detecting the activation of NF-κB. In addition, phosphorylation of NF-κB signaling-associated proteins, IKKα/β, IκBα, and p65, was reduced in MEO-incubated cancer cells, indicating that MEO suppresses NF-κB activation. Moreover, MEO treatment significantly suppressed lipopolysaccharide (LPS)-induced cancer cell proliferation, demonstrating that MEO promotes cancer cell apoptosis through the inhibition of the NF-κB signaling pathway. In summary, our findings demonstrate that the methanol-ethyl acetate partitioned fraction from Chinese olive fruits inhibits cancer cell proliferation and tumor growth by promoting apoptosis through the suppression of NF-κB signaling. Therefore, the Chinese olive fruit has promising potential in cancer treatment.


Biodegradable screw presents as a loose intra-articular body after anterior cruciate ligament reconstruction.
We report a case of intra-articular movement of a broken piece of a poly-L-lactide (PLLA) bioabsorbable interference screw from the femoral tunnel in anterior cruciate ligament (ACL) reconstruction with quadrupled semi-tendinosus and gracilis tendon grafts. Eleven months after initially successful ACL surgery, the patient felt a sudden locking of the knee without associated trauma or injury. The patient experienced pain and swelling episodes after heavy lifting with knee flexion at work, but without symptoms of giving way or locking. On revision arthroscopy, a broken part of a bioabsorbable interference screw was seen in the lateral compartment, which was subsequently removed without incident. The semitendinosus-gracilis graft appeared intact without disruption. After revision surgery, the patient's recovery was uneventful, with return to activity within a few months. This case further shows the problem of biointerference screw breakage in ACL reconstructive surgery and the need to bury the femoral bioabsorbable interference screw on graft fixation.


HCV Treatments and Their Integration Into Rheumatology.
Hepatitis C virus (HCV) has been associated with distinct rheumatic syndromes including arthritis, sialadenitis, and cryoglobulinemic vasculitis (CV). The therapy of these HCV-associated syndromes includes antiviral therapy with or without the addition of immunosuppressives while clinical response is mainly seen in patients who clear the virus after antiviral therapy. Despite significant therapeutic advances, existing antiviral therapies with interferon-a (IFNa)-based schemes achieve viral eradication only in approximately half the patients. Recently, oral antivirals that target specific HCV proteins referred as direct acting antivirals (DAAs) have been developed and approved. Short-term (12-24 weeks) combination schemes with or without IFN ("IFN-free" regimens) including these inhibitors clear the virus in more than 90 % of treated patients. Here, we review current therapeutic options in HCV-associated rheumatic syndromes and the potential role of the newly available antivirals in an integrated therapeutic approach.


A method of MRI-based thermal modelling for a RF phased array.
Magnetic Resonance Imaging (MRI) is an attractive method of temperature monitoring in vivo due to its non-invasive nature. The natural extension of this temperature monitoring is to implement temperature control. This work outlines a method of MRI-based thermal modelling for multi-source phased array heating systems that can potentially be employed, in the future, for real time temperature prediction and control. This method is based on Pennes bioheat equation. It employs the superposition of an empirically acquired basis set of temperature distributions that define the heating system's temperature response. MR thermal images based on the proton resonance frequency shift (PRFS) technique are used to acquire this basis set. The feasibility of this approach is tested in phantom using a radiofrequency (RF) heating system. The results show that this method can accurately reproduce measured temperature distributions outside of the basis set.


Recurrent aphthous stomatitis as an expression of pathergy in atopics.
Recurrent Aphthous Stomatitis (RAS) may be part of the "atopic background". Recently it has been reported that aphtous stomatitis could be an expression of atopic diathesis. The aim of this study is to verify whether the prevalence of posttraumatic aphthae is higher in patients with RAS and atopic diathesis than in patients with RAS without atopy. In the past three years 39 new patients between 14 and 56 years of age and affected by idiopathic RAS have been observed. Atopic status and history of posttraumatic aphthosis were evaluated in all patients. The results appear to show that in our population the prevalence of posttraumatic aphthae is higher among atopic patients. Not only RAS but also pathergy could be considered an expression of the rich clinical/ symptomatic constellation of atopic diathesis.


Consequences of intensive therapy of acute lymphoblastic leukemia in children in initial complete remission lasting more than five years.
Complex clinical, neurological and psychological examination was carried out in 23 children with acute lymphoblastic leukemia (ALL), being in complete initial remission from 5 to 12 years and without medication following the successful intensive therapy according to the protocol 0171 from 2 1/2 to 9 years. Somatic deficiency was observed in 2 children. Slightly hypoplastic bone marrow haemopoesis was found in 2 children. All children had normal haemogram. In 7 children lowered values of E-rosettes and in 3 children lowered levels of serum IgA were detected. Two children were HBsAg positive, in one of them with mild fibrosis was found at biopsy. Pathological neurological findings occurred in 7 children; pathological electromyogram (EMG) and electroencephalogram (EEG) in 8 and 5 children, respectively. Deviations of intellectual development were observed in 13 children. Deviations found can be connected in particular with long-term antileukemic therapy, especially with neurotoxic effects of some components of therapeutic regimen used (methotrexate, brain irradiation).


The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain.
The cell cycle-regulated B-Myb transcription factor is required for early embryonic development and is implicated in regulating cell growth and differentiation. In addition to its transcriptional regulatory properties, recent data indicate that B-Myb can release active cyclin/Cdk2 activity from the retinoblastoma-related p107 protein by directly interacting with the p107 N terminus. As this p107 domain has homology to the cyclin-binding domains of the p21(Waf1/Cip1) family of cyclin-dependent kinase inhibitors (CKIs), we investigated in this study whether B-Myb could also interact with these CKIs. No in vivo interaction was found with either p21(Waf1/Cip1) or p27(KIP1), however, binding to p57(KIP2) was readily detectable in both in vivo and in vitro assays. The B-Myb-interacting region of p57(KIP2) mapped to the cyclin-binding domain. Consistent with this, B-Myb competed with cyclin A2 for binding to p57(KIP2), resulting in release of active cyclin/Cdk2 kinase. Moreover, B-Myb partially overcame the ability of p57(KIP2) to induce G1 arrest in Saos-2 cells. Despite similarities with previous p107 studies, the B-Myb domains required for interaction with p57(KIP2) were quite different from those implicated for p107. Thus, it is evident that B-Myb may promote cell proliferation by a non-transcriptional mechanism that involves release of active cyclin/Cdk2 from p57(KIP2) as well as p107.


A Novel Technique of Saddle Rhizotomy Using Thermal Radiofrequency for Intractable Perineal Pain in Pelvic Malignancy: A Pilot Study.
The prevalence of pain in advanced pelvic cancer may reach up to 95%. Control of such pain is often difficult owing to a variety of neuroanatomical and functional peculiarities. Different modalities have been utilized to treat this pain including saddle chemical rhizolysis with the potential for jeopardizing the neural control of the sphincters. The aim of this pilot study is to determine the feasibility of using selective thermal radiofrequency as an alternative to saddle chemical rhizolysis in patients with refractory perineal pain associated with pelvic malignancies. Pilot study. Pain Relief Department of the National Cancer Institute, Cairo University. Forty patients, 18 years of age or older, who had pelvic malignancy and were complaining of moderate or severe perineal pain not controlled with maximum tolerable doses of morphine sulfate for at least 4 weeks were randomly allocated to receive selective saddle rhizotomy using thermal radiofrequency ablation of S3 on one side and bilateral ablation of S4 and S5 (RF group, n = 20) or conventional chemical rhizotomy using hyperbaric 6% phenol in glycerin (Phenol group, n = 20). Patients were assessed for the intensity of pain, daily consumption of analgesics, functional improvement, overall patient satisfaction, degree of disability and occurrence of procedure-related side effects at 1,4, and 12 weeks. The results were comparable in both groups regarding the control of pain and functional improvement. The incidence of specific procedure-related adverse outcomes was also equivalent for both interventions, although per-patient incidence of major complications was significantly higher in the phenol group. Small sample size to demonstrate statistical significance of the relatively small frequency of events, and the patients could not be blinded to the intervention they received owing to the technical uniqueness of either intervention. Selective thermal radiofrequency ablation of the S3 root on one side, S4 root on both sides, and S5 roots could serve as a feasible alternative to conventional saddle rhizotomy using hyperbaric phenol. Perineal cancer pain, chemical rhizotomy, thermal radiofrequency.


Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder.
There is strong evidence from family and twin studies that genetic determinants play an important role in the etiology of obsessive-compulsive disorder (OCD). In the only genome scan of OCD to date that we are aware of, suggestive linkage was reported to the chromosomal region 9p24, a finding that was subsequently replicated. This region contains the gene encoding the neuronal glutamate transporter, SLC1A1. SLC1A1 represents an excellent candidate gene for OCD based on evidence from neuroimaging and animal studies that altered glutamatergic neurotransmission is implicated in the pathogenesis of this disorder. To determine whether sequence variants in SLC1A1 are associated with transmission of the OCD trait. A family-based candidate gene association study. A specialized anxiety disorders outpatient clinic. One hundred fifty-seven white probands with DSM-IV OCD recruited from consecutive referrals and their first-degree relatives (476 individuals in total). Nine single nucleotide polymorphisms spanning SLC1A1 were genotyped. Single-locus and haplotype analyses were performed using the Family-Based Association Test and the Transmission Disequilibrium Test. Traits examined included DSM-IV OCD diagnosis and highest lifetime symptom severity as measured using the Yale-Brown Obsessive-Compulsive Scale. Correction for multiple comparisons was performed using permutation tests. After correction for multiple comparisons, 2 variants, rs301434 (chi 2 = 12.04; P = .006) and rs301435 (chi 2 = 9.24; P = .03), located within a single haplotype block were found to be associated with transmission of OCD. Furthermore, a specific 2-marker haplotype within this block was significantly associated with OCD (chi 2 = 12.60; P = .005). This haplotype association was statistically significant in transmissions to male but not female offspring. Although requiring replication in larger samples, these findings provide preliminary evidence that sequence variation in SLC1A1 is associated with susceptibility to OCD, particularly in males. Furthermore, these results provide support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.


Changing trends in human immunodeficiency virus and acquired immunodeficiency syndrome in the population aged 50 and older.
To alert persons in the public and private healthcare professions to the increasing trends in higher proportions of persons aged 50 and older who are newly diagnosed with human immunodeficiency virus (HIV) and who are living with HIV and acquired immunodeficiency syndrome (AIDS). Data from the period 1992 through 2004 from the HIV/AIDS Reporting System (HARS) were analyzed. New Jersey is the eleventh-most-populous state, with the highest density of persons per square mile. It also has the fifth-highest number of AIDS cases. All persons residing in New Jersey and reported to HARS with HIV infection or who are considered to have AIDS. Trends in persons aged 50 and older were compared with those in the population younger than 50 during 1992 through 2004 for the numbers of persons living with HIV/AIDS and the number of persons newly diagnosed with HIV infection. The proportion of all persons aged 50 and older living with HIV/AIDS in 2004 was significantly greater than the comparable proportion of persons in 1992. Proportionally, more persons were newly diagnosed with HIV who were aged 50 and older according to sex and for each of the three major race or ethnicity groups (white non-Hispanic, black non-Hispanic, and Hispanic) than were persons younger than 50. Each of these increases was statistically significant. HIV/AIDS social marketing campaigns should include images and issues related to older persons in educational and prevention efforts. New methods that reach older populations should be considered. Physicians and other healthcare providers should be made aware of their role in prevention and education about HIV. Testing of older populations with risk factors should be encouraged.


Expandability of haemopoietic progenitors in first trimester fetal and maternal blood: implications for non-invasive prenatal diagnosis.
Selective amplification of rare fetal cells in maternal blood is a potential strategy for non-invasive prenatal diagnosis. We assessed the proliferative potential of first trimester fetal progenitors compared to maternal ones. Fetal and maternal haemopoietic progenitors were cultured separately and in two model mixtures: (i) co-cultures of male fetal nucleated cells mixed with maternal nucleated cells and (ii) co-cultures of malefetal CD34+ cells with maternal CD34+ cells. Cell origin was detected by X-Y fluorescence in situ hybridisation (FISH) RESULTS: The frequency of haemopoietic progenitors in first trimester fetal blood (predominantly CFU-GEMM) differed from those in peripheral blood from pregnant women (predominantly BFU-e). First trimester haemopoietic progenitors formed larger colonies (p=0.0001) and their haemoglobinisation was accelerated compared to those of maternal origin (p<0.001). CD34+ fetal haemopoietic progenitor cells could be expanded four times more than their maternal counterparts (median 235.8-fold, range 174.0-968.0 vs 71.9-fold, range 41.1-192.0; p=0.003). While selective expansion of fetal cells was not observed in the mononuclear cell model, the CD34+ cell rare event mixtures produced a 463.2-fold (range 128.0-2915.0) expansion of fetal cells. Selective expansion of first trimester fetal haemopoietic progenitors may be useful for amplifying fetal cells from maternal blood.


Intravenous Acetaminophen for Postoperative Pain Management in Patients Undergoing Living Laparoscopic Living-Donor Nephrectomy.
Postoperative pain is a common complication of laparoscopic living-donor nephrectomies (LLDNs). To determine whether intravenous (IV) acetaminophen administration post-LLDN influenced length of stay (LOS) when used for pain management. This single-center, retrospective study compared patients undergoing LLDN who had received IV acetaminophen for pain control versus those who did not between June 1, 2011, and November 30, 2015. Patient LOS, 30-day readmissions, frequency of pain assessments, patient-reported pain scores, and opioid administration were assessed. A total of 90 patients were included in the analysis (IV acetaminophen, n = 48; non-IV acetaminophen, n = 42). Patients who did not receive IV acetaminophen were more often older (48.8 ± 12.1 vs 39.3 ± 12.1 years; P = 0.012) and female (71.4% vs 47.9%; P < 0.001). The average LOS was similar between the 2 groups (median = 3.0; interquartile range = [3, 4] vs 3.5 [3, 4]; P = 0.737). The 30-day readmissions were higher in the IV acetaminophen group (16.7%) compared with the group not receiving IV acetaminophen (2.4%; P = 0.033). After the first postoperative day, the frequencies of pain assessments performed were similar among the 2 groups. There was no difference in average pain scores between the groups at any time after LLDN. Patients receiving IV acetaminophen were found to have no improvements in hospital LOS, average pain score, or opioid requirements compared with patients not receiving IV acetaminophen. Patients who received IV acetaminophen were also found to have a higher 30-day readmission rate.


Cost-effectiveness and impact on quality of life of alefacept in the treatment of psoriasis.
Although alefacept was the first biologic agent approved to treat psoriasis, it is used less frequently than other biologic therapies. Alefacept decreases the Psoriasis Area and Severity Index (PASI) score and enhances the quality of life of patients with psoriasis. Unlike other biologics, alefacept can also induce remission of psoriasis. If reports in Pubmed and the package insert are considered to be surrogates for side effects, alefacept appears to be safer than other biologics. Alefacept can be effective against psoriatic arthritis, especially in combination with methotrexate. The response of psoriatics to alefacept, however, is inconsistent and often incomplete. Alefacept also has the highest cost of any biologic agent as measured by patients achieving PASI-75 and cost per patient achieving Dermatology Life Quality Index Minimal Important Difference. Traditional systemic therapies such as spriatane, ciclosporine, as well as phototherapy and TNF-alpha, possess firmer and superior pharmacoeconomic foundations, although some of these apparent cost-benefit disadvantages may take into account the ability of alefacept to induce remission after cessation of treatment.


Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China.
Narcolepsy is caused by the loss of hypocretin/orexin neurons in the hypothalamus, which is likely the result of an autoimmune process. Recently, concern has been raised over reports of narcolepsy in northern Europe following H1N1 vaccination. The study is a retrospective analysis of narcolepsy onset in subjects diagnosed in Beijing, China (1998-2010). Self-reported month and year of onset were collected from 629 patients (86% children). Graphical presentation, autocorrelations, chi-square, and Fourier analysis were used to assess monthly variation in onset. Finally, 182 patients having developed narcolepsy after October 2009 were asked for vaccination history. The occurrence of narcolepsy onset was seasonal, significantly influenced by month and calendar year. Onset was least frequent in November and most frequent in April, with a 6.7-fold increase from trough to peak. Studying year-to-year variation, we found a 3-fold increase in narcolepsy onset following the 2009 H1N1 winter influenza pandemic. The increase is unlikely to be explained by increased vaccination, as only 8 of 142 (5.6%) patients recalled receiving an H1N1 vaccination. Cross-correlation indicated a significant 5- to 7-month delay between the seasonal peak in influenza/cold or H1N1 infections and peak in narcolepsy onset occurrences. In China, narcolepsy onset is highly correlated with seasonal and annual patterns of upper airway infections, including H1N1 influenza. In 2010, the peak seasonal onset of narcolepsy was phase delayed by 6 months relative to winter H1N1 infections, and the correlation was independent of H1N1 vaccination in the majority of the sample.


Isokinetic back testing in the athlete.
With increasing numbers of professional, collegiate, and high school athletes developing low back pain, isokinetic back testing could prove to be a way of preventing the development of severe problems and extended stays on injured lists. Isokinetic testing provides an advantage over other testing procedures by more closely simulating the way muscles perform functional activities. This type of testing allows comparison between patients, normals, preoperative and postoperative status, and pre-rehabilitation and post-rehabilitation protocols.


Enhanced eosinophil luminol-dependent chemiluminescence and complement receptor expression by platelet-activating factor and interleukin-5.
The cytokine interleukin-5 (IL-5) and the lipid mediator platelet-activating factor (PAF) have both been shown to be involved in eosinophil differentiation and activation. We have measured and compared the effect of PAF and IL-5 on human eosinophils in terms of their luminol-dependent chemiluminescence (CL) response and their expression of complement receptors, CR1 and CR3. Both IL-5 and PAF enhanced the eosinophil CL response. The optimal concentrations were 40 U/ml for IL-5, and 10(-6) M for PAF. The priming effect of IL-5 was slow and reached a maximal response after 90 minutes incubation. In contrast, the effect of PAF peaked early and declined during incubation. In the complement receptor study, only PAF was able to enhance CR3 expression (p < 0.05) while the effect of IL-5 on eosinophil complement receptor expression was negligible. These results provide evidence that both inflammatory mediator (PAF) and cytokine (IL-5) can activate eosinophils but the effects of IL-5 and PAF on eosinophil CL response appear to be distinct. The activation of eosinophils by PAF and IL-5 may occur through different mechanisms.


Aerobic and anaerobic bacteriology of cholesteatoma.
Cholesteatoma specimens were obtained from 28 patients undergoing surgery for chronic otitis media and cholesteatoma. All specimens were cultured for aerobic and anaerobic organisms. Bacterial growth was present in specimens of 24 of the 28 patients. A total of 74 bacterial isolates were present (40 aerobes and 34 anaerobes). Aerobes alone were isolated from 8 (33%) of culture positive patients, 4 patients (26.7%) yielded only anaerobes, and 12 (50%) had both aerobic and anaerobic bacteria. Fifty isolates (27 aerobes and 23 aerobes) were present in a concentration greater than 10(6) CFU/gm. The most commonly isolated aerobic organisms were P. aeruginosa (9), Proteus sp. (7), K. pneumoniae (5), S. aureus (5), and E. coli (4). The anaerobic bacteria most commonly isolated were gram-positive anaerobic cocci (12), Bacteroides sp. (12, including 5 B. fragilis group), Clostridium sp. (3), and Bifidobacterium sp. (3). The above findings indicate the polymicrobial aerobic and anaerobic bacteriology of cholesteatoma.


Hospitalizations Involving an Intensive Care Unit Admission Among Patients Aged 65 Years and Older Within New York City Hospitals During 2000-2014.
To describe hospitalizations involving an intensive care unit (ICU) admission among patients aged 65 years and older within New York City (NYC) hospitals during 2000-2014. Observational study using an all-payer hospital discharge dataset. The setting was in NYC hospitals. Patients aged 65 years and older admitted to an ICU within a NYC hospital during 2000-2014. No interventions were carried out. We calculated the mean annual number of hospitalizations involving an ICU admission. We also examined characteristics of hospitalizations, including the occurrence of in-hospital death and principal diagnosis. There were 5,338,577 hospitalizations of patients aged ≥65 years within NYC hospitals during 2000-2014, of which 765,084 (14.3%) involved an ICU admission. The mean annual number of hospitalizations involving an ICU admission for this age group decreased from 57,938 during 2000-2002 to 45,785 during 2012-2014. The proportion of hospitalizations involving an ICU admission in which in-hospital death occurred decreased from 15.9% during 2000-2002 to 14.5% during 2012-2014. During 2000-2002, 11.6% of hospitalizations involving an ICU admission listed an "infectious" principal diagnosis, increasing to 20.7% during 2012-2014. Listing of a "cardiovascular" principal diagnosis decreased from 46.4% to 33.4% between these time periods. "Infectious" principal diagnoses accounted for 31.0% of all hospitalizations involving an ICU admission in which in-hospital death occurred during the entire study period, while "cardiovascular" principal diagnoses accounted for 21.3%. This investigation provides a clearer understanding of ICU utilization among patients aged 65 years and older in NYC. Ongoing monitoring is warranted given projections that the proportion of New Yorkers aged 65 years and older will increase in coming years. In particular, in light of the observed increase of infectious principal diagnoses during the study period, further investigation is needed into the role of infectious disease in causing critical illness in NYC.


Buteyko Breathing Technique for Exertion-Induced Paradoxical Vocal Fold Motion (EI-PVFM).
The primary purpose of the current study was to determine the usefulness of Buteyko breathing technique (BBT) in reducing dyspnea in patients with one form of Paradoxical Vocal Fold Motion (PVFM), exertion-induced PVFM (EI-PVFM), concomitant with hyperventilation. The secondary purpose was to determine whether BBT had an effect on physiological markers of hyperventilation, as speculated by BBT theory: respiratory tidal minute volume (RTMV), end-tidal carbon dioxide (ETCO2), and resting heart rate (HR). Using a within-subjects, repeated measures group design, 12 participants with EI-PVFM and hyperventilation underwent 12 weeks of BBT, following an initial no-treatment control condition. Outcome measures of PVFM-dyspnea frequency and severity-and of hyperventilation-HR, RTMV, and ETCO2-were acquired pre- and post-treatment. Results showed post-treatment decreases in dyspnea severity, HR, and RTMV, as well as increases in ETCO2. Decreases in dyspnea and RTMV measures remained after correction for alpha inflation. Findings suggest BBT may be useful for some individuals with EI-PVFM and hyperventilation. The high prevalence of hyperventilation in EI-PVFM found in the current study warrants further investigation.


Evaluating the Effects of Ivermectin Treatment on Communities of Gastrointestinal Parasites in Translocated Woylies (Bettongia penicillata).
Wildlife species are often treated with anti-parasitic drugs prior to translocation, despite the effects of this treatment being relatively unknown. Disruption of normal host-parasite relationships is inevitable during translocation, and targeted anti-parasitic drug treatment may exacerbate this phenomenon with inadvertent impacts on both target and non-target parasite species. Here, we investigate the effects of ivermectin treatment on communities of gastrointestinal parasites in translocated woylies (Bettongia penicillata). Faecal samples were collected at three time points (at the time of translocation, and 1 and 3 months post-translocation) and examined for nematode eggs and coccidian oocysts. Parasite prevalence and (for nematodes) abundance were estimated in both treated and untreated hosts. In our study, a single subcutaneous injection of ivermectin significantly reduced Strongyloides-like egg counts 1 month post-translocation. Strongyle egg counts and coccidia prevalence were not reduced by ivermectin treatment, but were strongly influenced by site. Likewise, month of sampling rather than ivermectin treatment positively influenced body condition in woylies post-translocation. Our results demonstrate the efficacy of ivermectin in temporarily reducing Strongyloides-like nematode abundance in woylies. We also highlight the possibility that translocation-induced changes to host density may influence coinfecting parasite abundance and host body condition post-translocation.


Fetal MRI for prediction of neonatal mortality following preterm premature rupture of the fetal membranes.
Lung MRI volumetrics may be valuable for fetal assessment following early preterm premature rupture of the foetal membranes (pPROM). To evaluate the predictive value of MRI lung volumetrics after pPROM. Retrospective cohort study of 40 fetuses after pPROM in a large, tertiary, perinatal referral center. Fetuses underwent MRI lung volumetrics. Estimated lung volume was expressed as percentage of expected lung volume (our own normal references). Primary outcome was neonatal mortality due to respiratory distress before discharge from hospital. Gestational age range was 16-27 weeks. Estimated-to-expected lung volume was 73% in non-survivors and 102% in survivors (P < 0.05). There were no survivors with a lung volume less than 60% of expected. By logistic regression, mortality could be predicted with a sensitivity of 80%, specificity of 86% and accuracy of 85%. Fetal MR lung volumetrics may be useful for predicting mortality due to respiratory distress in children with early gestational pPROM.


Tracheobronchial reconstructions with bronchoplastic closure: an alternative method in treatment of bronchogenic carcinoma involving the carina or tracheobronchial angle.
Our objective was to summarize our experience with tracheobronchial reconstructions using bronchoplastic closure for airway defects after noncircumferential resections of bronchogenic carcinoma involving the carina or tracheobronchial angle. From January 1990 to December 2005, all patients who underwent tracheobronchial reconstructions with bronchoplastic closure for bronchogenic carcinoma involving the carina or tracheobronchial angle were included. The clinical data for patients were collected retrospectively, including demographic characteristics, occurrences of postoperative complications, and survival. A total of 40 patients were eligible, including 23 who had right pneumonectomies, 6 who had right upper lobectomies, and 11 who had left pneumonectomies, associated with lower lateral wall of the trachea resections or with partial carinal resections for centrally localized tumors. The airway defects ranged from 0.5×2 cm to 2×4 cm and involved up to 50% of the airway circumference. Microscopic residual disease was found postoperatively at the bronchial margin in 20% (8/40). Of 40 patients, 2 (5.0%) had pulmonary atelectasis develop, 2 (5.0%) arrhythmia, 2 (5.0%) bronchopleural fistula, and 1 (2.5%) airway stenosis after operation. Thirty-day mortality was 2.5% (1/40). Median survival for 40 patients was 18.5 months with a cumulative survival of 72.2%, 26.6%, and 21.3% at 1, 3, and 5 years, respectively. Tracheobronchial reconstruction using bronchoplastic closure might be a reasonable option for closing massive central airway defects for advanced bronchogenic carcinoma involving the tracheobronchial angle or carina, avoiding tracheal sleeve pneumonectomy with limited excision of the lateral wall of the trachea or carina.


[Significance of an angiogenic factor (in omental lipid) for the vascularization of the cornea].
The existence of an angiogenic factor in the omental lipid was verified by injecting four different test materials in dosages of 50 microliters into the corneas of New Zealand rabbits. The test substances were: 1) phosphate-buffered saline solution; 2) chloroform-methanol solution; 3) phosphate-buffered saline homogenate of the chloroform-methanol extract of the lipid cake from the rabbit omentum. The experimental results show that the modes of neovascularization after injection of lipid and nonlipid materials into rabbit corneas are very similar. For angiogenesis to be stimulated, the noxious substances must be retained in the cornea for several days. One day after injection the phosphate-buffered saline solution is totally resorbed. The other test substances (2-4), are retained within the cornea for days or weeks. Test substance 1 does not induce any corneal vascularization. The injection of test substances 2-4 causes similar corneal neovascularization: the proliferation of vessels always starts from that segment of the limbus closest to the stimulation. Since the extent of vascularization after injection of chloroform-methanol solution alone is similar to that which occurs after injection of an omental lipid extract, the hypothesis of a specific angiogenic factor is not supported. Fluorescein angiography reveals a large outflow of fluid (leakage) out of the neovascularization.


Opisthorchis viverrini and cholangiocarcinoma in Northeast Thailand.
Population-based research is beginning to show clearly the devastating impact that Opisthorchis viverrini infection has on the Laos-descendent population of Northeast Thailand who love to eat uncooked meat and fish, one of which being the parasite's intermediate host: cyprinoid fish. Here, Melissa Haswell-Elkins, Paiboon Sithithaworn and David Elkins discuss the parasite's life cycle and epidemiology, highlighting the close relationship between this infection and bile duct carcinoma, which is a major cause of death among adults in rural Northeast Thailand.


Strain differentiation of Trichophyton rubrum by randomly amplified polymorphic DNA and analysis of rDNA nontranscribed spacer.
Trichophyton rubrum is the most common pathogen causing dermatophytosis. Molecular strain-typing methods have recently been developed to tackle epidemiological questions and the problem of relapse following treatment. A total of 67 strains of T. rubrum were screened for genetic variation by randomly amplified polymorphic DNA (RAPD) analysis, with two primers, 5'-d[GGTGCGGGAA]-3' and 5'-d[CCCGTCAGCA]-3', as well as by subrepeat element analysis of the nontranscribed spacer of rDNA, using the repetitive subelements TRS-1 and TRS-2. A total of 12 individual patterns were recognized with the first primer and 11 with the second. Phylogenetic analysis of the RAPD products showed a high degree of similarity (>90 %) among the epidemiologically related clinical isolates, while the other strains possessed 60 % similarity. Specific amplification of TRS-1 produced three strain-characteristic banding patterns (PCR types); simple patterns representing one copy of TRS-1 and two copies of TRS-2 accounted for around 85 % of all isolates. It is concluded that molecular analysis has important implications for epidemiological studies, and RAPD analysis is especially suitable for molecular typing in T. rubrum.


Cancer therapy and oral mucositis. An appraisal of drug prophylaxis.
Oral mucositis as a consequence of cytotoxic therapy is a major cause of morbidity in cancer patients. Cancer therapy-induced tissue damage leading to mucositis can occur through either direct or indirect stomatotoxicity. Once mucositis has occurred, treatment consists of measures to palliate symptoms. The prevention of cancer therapy-induced oral mucositis is less standardised. Numerous drugs have been used as prophylactic agents to prevent chemo- and radiotherapy-induced mucositis. Controlled trials have shown some degree of prophylactic efficacy for sucralfate, chlorhexidine and benzydamine. Positive but non-placebo-controlled trials requiring more study have been conducted with dinoprostone (prostaglandin E2), silver nitrate, beta-carotene, pentoxifylline and lozenges containing polymixin B, tobramycin and amphotericin B. Current studies have shown a lack of efficacy with allopurinol and granulocyte colony-stimulating factor (G-CSF). Nonpharmacological methods such as oral cryotherapy and helium-neon laser treatments have shown some promise. At the present time no agent has been shown to be uniformly efficacious and can be accepted as standard therapy. Additional studies combining several agents or incorporating nonpharmacological manoeuvres for mucositis prevention are needed.


Malignant fibrous histiocytoma of the gingiva. A clinicopathological study.
A case is reported of malignant fibrous histiocytoma (MFH) of the gingiva. The 65-year-old female presented with a fast-growing mass originating from the left lower gingiva. The tumor measured 15 cm in diameter, occupying the entire oral cavity, protruding outside, and causing a mechanical airway obstruction. It appeared to respond to a 1000 rad single dose of preoperative radiation but recurred soon after composite resection with mandibulectomy, even though surgical margins were reportedly free from microscopic invasion. The patient expired from massive lung metastasis in spite of appreciable local response from treatment. This supports the thesis that MFH is a malignant disease and behaves like any soft-tissue sarcoma, which must be treated aggressively by a combined modality of surgery, radiation, and perhaps chemotherapy.


Distribution of TRPV1 and TRPV2 in the human stellate ganglion and spinal cord.
Immunohistochemistry for the transient receptor potential cation channel subfamily V member 1 (TRPV1) and 2 (TRPV2) was performed on the stellate ganglion and spinal cord in human cadavers. In the stellate ganglion, 25.3% and 16.2% of sympathetic neurons contained TRPV1- and TRPV2-immunoreactivity, respectively. The cell size analysis also demonstrated that proportion of TRPV1- or TRPV2-immunoreactive (-IR) neurons among large (>600 μm(2)) sympathetic neurons (TRPV1, 30.7%; TRPV2, 27.0%) was higher than among small (<600 μm(2)) sympathetic neurons (TRPV1, 22.0%; TRPV2, 13.6%). The present study also demonstrated that 10.0% of sympathetic neurons in the stellate ganglion had pericellular TRPV2-IR nerve fibers. Fourteen percent of large neurons and 7.8% of small neurons were surrounded by TRPV2-IR nerve fibers. TRPV2-immunoreactivity was also detected in about 40% of neuronal cell bodies with pericellular TRPV2-IR nerve fibers. In the lateral horn of the human thoracic spinal cord, TRPV2-immunoreactivity was expressed by some neurons and many varicose fibers surrounding TRPV2-immunonegative neurons. TRPV2-IR pericellular fibers in the stellate ganglion may originate from the lateral horn of the spinal cord. There appears to be TRPV1- or TRPV2-IR sympathetic pathway in the human stellate ganglion and spinal cord.


[Veterinary assistance to dairy farms in the Netherlands: an assessment of the situation by dairy farmers].
A questionnaire-based study was conducted among 466 dairy farmers in the Netherlands. The study investigated the experiences and opinions of dairy farmers about veterinary herd health and production management programmes. The dairy farmers were selected at random, and thus some took part in such programmes whereas others did not. The questionnaire comprised general questions about the farm operation and specific questions about the herd health programme and the practice conducting it, as well as perceived advantages and disadvantages of the veterinary programme. Farmers who did not participate in such programmes were questioned about their reasons for not participating. Both groups were questioned about future perspectives and opportunities. The costs of the programme appeared to be a drawback for participation but not as much as perceived by the practices. According to farmers, programmes focus too much on curative aspects and too little on analysis or prevention, where the needs are. Farm areas not included in the programme are so far not yet covered by other institutions, contrary to the expectations of the veterinarians. In the future, the farmers would be willing to take part in similar or expanded programmes, provided that certain conditions, such as product definition, structure, planning, costs, are properly met.


Positive and negative regulation in the promoter of the ORF46 gene of Kaposi's sarcoma-associated herpesvirus.
The ORF46 gene of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes uracil DNA glycosylase, an enzyme involved in DNA repair. In this study, we show that the transcriptional start site of the ORF46 gene is located at nucleotide 69,425 of the viral genome and ORF50 protein, a latent-lytic switch transactivator, activates the ORF46 promoter via RBP-Jκ protein. Three consensus RBP-Jκ-binding sites found in the ORF46 promoter are critical for the binding of RBP-Jκ protein and conferring the ORF50 responsiveness. In addition, a negative regulatory region has been determined in the ORF46 promoter, which mediates the suppression of the ORF50 responsiveness. The functional negative region of the ORF46 promoter is mainly composed of the Sp1-binding sites. Like the negative region of the ORF46 promoter, addition of Sp1-binding sequences alone in an ORF50-responsive promoter efficiently confers the suppression of the ORF50 responsiveness. Furthermore, sodium butyrate, a pleiotropic inducing agent for the KSHV lytic cycle, is able to relieve the negative regulation of the ORF46 promoter in the latently KSHV-infected cells. The identification of multiple positive and negative cis-acting regulatory elements in the viral promoters emphasizes the elaborate controls in the KSHV lytic cycle, which ensure the adequate expression of each viral lytic gene.


Personal and social contextual correlates of adolescent dating violence.
To examine the association of dating violence with personal and social contextual factors among a sample of 12- to 17-year-olds enrolled in managed care health plans. A sample of 444 youth (45% male; 80% African-American; 38% aged 12-13 years) agreed to participate in an alcohol risk-prevention randomized controlled trial, and completed a survey. Cross-tabulations and calculation of odds ratios were performed to assess associations between dating violence and sociodemographics, religious service attendance, personal alcohol use, peer-drinking exposures and parental monitoring. Logistic regression modeling was used to identify the significant predictors of dating violence. Seven percent of youth reported recent dating violence. In a logistic regression model, peer-drinking exposures was associated with dating victimization (OR = 3.24; CI = 1.04-10.15). Religious service attendance (OR =0.40; CI = 0.17-0.91) and parental monitoring (OR = 0.41; CI = 0.17-0.99) were protective against dating violence. Religious service attendance and frequent parental monitoring were associated with a lower prevalence of recent dating violence. Conversely, being in places where one's friends are drinking alcohol was associated with an increased risk of victimization. It may be that dating violence is, in part, mediated by adolescents' important social contacts.


A linear-scaling self-consistent generalization of the multistate empirical valence bond method for multiple excess protons in aqueous systems.
An extension to the multistate empirical valence bond (MS-EVB) method is presented in this paper that is capable of treating multiple excess protons within the context of molecular-dynamics simulation. The computational cost of the method scales linearly with respect to the number of excess protons. Calculations for a 0.44 M HCl systems are carried out to illustrate the multiproton extension of the MS-EVB method. A significant decrease in the Eigen-type H(9)O(4)(+) cation is observed in the contact ion-pair configuration formed between Cl(-) and hydronium ions.


p62/SQSTM1 - steering the cell through health and disease.
SQSTM1 (also known as p62) is a multifunctional stress-inducible scaffold protein involved in diverse cellular processes. Its functions are tightly regulated through an extensive pattern of post-translational modifications, and include the isolation of cargos degraded by autophagy, induction of the antioxidant response by the Keap1-Nrf2 system, as well as the regulation of endosomal trafficking, apoptosis and inflammation. Accordingly, malfunction of SQSTM1 is associated with a wide range of diseases, including bone and muscle disorders, neurodegenerative and metabolic diseases, and multiple forms of cancer. In this Review, we summarize current knowledge regarding regulation, post-translational modifications and functions of SQSTM1, as well as how they are dysregulated in various pathogenic contexts.


A technical modification to improve experimental production of hepatogenic ascites.
Constriction of the thoracic inferior vena cava is a useful experimental maneuver to reproduce massive ascites. Unfortunately, the margin of safety of this technique is narrow in that too much constriction overly restricts venous return with subsequent shock and death, and lesser constriction is often associated with extensive venous collateralization via the azygos system and failure to sustain hepatic congestion. By combining azygos vein ligation with 50% constriction of the supradiaphragmatic inferior vena caval circumference at the time of the initial thoracotomy, we have found that intense hepatic congestion is sustained and that dogs consistently develop massive ascites within 2-3 weeks.


The localisation of enzymes of nitrogen assimilation in maize leaves and their activities during greening.
The activities of nitrate reductase (EC1.6.6.1), nitrite reductase (EC 1.6.6.4), glutamine synthetase (EC6.3.1.2), glutamate synthase (EC1.4.7.1) and NAD(P)H-dependent glutamate dehydrogenase (EC 1.4.1.3) were investigated in mesophyll and bundle sheath cells of maize leaves (Zea mays L.). Whereas nitrate and nitrite reductase appear to be restricted to the mesophyll and GDH to the bundle sheath, glutamine synthetase and glutamate synthase are active in both tissues.During the greening process, the activities of nitrate and nitrite reductase increased markedly, but glutamine synthetase, glutamate synthase and glutamate dehydrogenase changed little.


Examination of the newborn: the key skills. Part 3: the hips.
Midwives are increasingly performing the examination of the newborn. his article considers the importance of the examination of the hips in the screening process. The significance of history taking, knowledge of risk factors and the hip examination will be explored. The necessity for early detection and treatment of hip abnormalities, along with referral pathways that the National Screening Committee quires will be highlighted. The impact of late detection of developmental dysplasia of the hip (DDH) on the lives of families and children will also be considered.


Extremely low frequency (ELF) electric and magnetic field exposure limits: rationale for basic restrictions used in the development of an Australian standard.
There are large disparities between basic restrictions for exposure to extremely low-frequency (0-3 kHz) Electric and Magnetic Fields set by two major international bodies. Both bodies agree that these basic restrictions should prevent neuro-stimulatory effects: the retinal phosphene at frequencies up to a few hundred Hertz and peripheral nervous stimulation (PNS) at higher frequencies. The disparity arises from differences in estimated thresholds and frequency dependence, and whether restrictions should be of tissue induced current density or electric field. This paper argues that the latter metric more directly relates to neurostimulatory processes. By analysing available literature, a threshold for retinal phosphenes occurrence is found to be 56 mV/m (95% Confidence Interval 2-1330 mV/m), with a characteristic frequency of 20 Hz. Similarly, the smallest PNS sensation threshold is identified at 2 V/m (characteristic frequency above 3 kHz). In the case of the former, the large range of uncertainty suggests a 'power of ten' value of 100 mV/m. For the latter, because of the small margin between sensation and pain threshold, and because of the large individual variation, the smallest estimate of sensation threshold (2 V/m) represents a basic restriction with precaution incorporated.


Nucleotide-induced movements in the myosin head near the converter region.
Structural changes in subfragment 1 of skeletal muscle myosin were investigated by cross-linking trypsin-cleaved S1 with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. In the absence of nucleotide the alkali light chains are cross-linked to the 27 kDa heavy chain fragment; the presence of MgATP reduces the efficiency of this reaction. On the other hand, MgATP promotes the cross-link formation between the N-terminal 27 kDa and C-terminal 20 kDa fragments of the heavy chain. The chemical cleavage of the cross-linked heavy chains fragments with N-chlorosuccinimide and hydroxylamine indicates that the cross-links are formed between the regions spanning residues 131-204 and 699-809. These results indicate that the two regions of the heavy chain that are relatively distant in nucleotide-free skeletal S1 [Rayment et al. (1993) Science 261, 50-58] can potentially interact upon addition of nucleotide.


Intraoperative test stimulation with a modified implantable pulse generator in deep brain stimulation.
A modified implantable pulse generator (MIPG) for intraoperative test stimulation in chronic deep brain stimulation is described. The MIPG can be used for bipolar stimulation with quadripolar electrodes. The device is programmed and controlled with a standard console programmer. It can also be used for postoperative test stimulation with externalized electrodes. In our experience, the MIPG has several advantages as compared to the screener that is usually used.


Effect of induced hypercalcemia on ultimobranchial gland of the lizard, Calotes versicolor.
The ultimobranchial of the lizard Calotes consists of parenchymal patches and several follicles. After induced hypercalcemia, the gland became more active suggesting the hypocalcemic secretion from the gland.


The binding of palmitoyl-CoA to bovine serum albumin.
Bovine serum albumin (BSA) is routinely utilized in vitro to prevent the adverse detergent effects of long-chain acyl-CoA esters (i.e., palmitoyl-CoA) in enzyme assays. Determination of substrate saturation kinetics in the presence of albumin would only be valid if the relationship between bound and free substrate concentrations was known. To elucidate the relationship between bound and free palmitoyl-CoA concentrations in the presence of BSA, several different techniques including equilibrium dialysis, equilibrium partitioning, fluorescence polarization and direct fluorescence enhancement were investigated. Direct fluorescence enhancement using a custom synthesized fluorescent probe, 16-(9-anthroyloxy)palmitoyl-CoA (AP-CoA), was the best approach to this question. Measurement of the relationship between mol of palmitoyl-CoA bound per mol of BSA (nu) versus -log[free palmitoyl-CoA] revealed that the binding of palmitoyl-CoA to BSA, like palmitate was nonlinear, suggesting the presence of more than one class of acyl-CoA binding sites. Computer analyses of the binding data gave a best fit to the 2,4 two-class Scatchard model, suggesting the presence of two high-affinity primary binding sites (k1 = (1.55 +/- 0.46) x 10(-6) M-1) and four lower affinity secondary binding sites (k2 = (1.90 +/- 0.09) x 10(-8) M-1). Further analyses using the six parameter stoichiometric (stepwise) ligand binding model supports the existence of six binding sites with the higher affinities associated with the binding of the first mole of palmitoyl-CoA and weaker binding occurring after the first two sites are occupied. The association constants from this model of multiple binding diminish sequentially (i.e., K1 greater than K2 greater than K3 greater than...greater than or equal to K6), suggesting that each mol of long-chain acyl-CoA binds to BSA with decreasing affinities.


Melatonin potentiates the vasoconstrictive effect of noradrenaline in renal artery from newborn hooded seals (Cystophora cristata) and harp seals (Phoca groenlandica).
Isometric tension was recorded by force displacement transducers in ring segments of the inferior branch of the renal artery from newborn hooded seals (Cystophora cristata, n=6), harp seals (Phoca groenlandica, n=3) and domestic pigs (Sus scrofa f. domestica, n=5). Arterial segments were mounted in heated organ baths and exposed to graded concentrations of noradrenaline (NA) and adrenaline (A), alone or together with melatonin. The melatonin concentration in the bath was similar to the plasma concentration normally found in each experimental animal. Melatonin alone did not affect the tension in any of the species, but melatonin potentiated the contraction induced by NA in hooded and harp seal arteries to a maximum of about 25% above the resting, pre-stretch level. The selective melatonin receptor antagonist luzindole reduced this potentiation by 80%. Species-specific concentrations of melatonin did not potentiate the NA-effect in the domestic pig or the A-induced contraction in any of the species. The results indicate that melatonin specifically increases the NA-sensitivity of smooth muscles in renal arteries from newborn seals. It is presumed that similar effects may operate in foetal and maternal seals and may influence their circulation during maternal diving.


[Clinical value of pegylated interferon-α plus ribavirin-based therapy in antiviral treatment of chronic hepatitis C in China].
Chronic hepatitis C virus (HCV) infection is one of the most common causes of liver cirrhosis and hepatocellular carcinoma in China. The older standard treatment regimen for chronic hepatitis C was the pegylated interferon-alfa plus ribavirin(PR). Now newer oral medications called direct antiviral agents (DAAs) has been gradually changed to PR-based DAAs and interferon-free, oral DAAs; making chronic hepatitis C a curable disease. This article intends to expound the advantages and disadvantages of PR-based therapy and provide reference for the treatment of chronic hepatitis C.


Myelodysplastic syndrome with a t(2;11)(p21;q23-24) and translocation breakpoint close to miR-125b-1.
The upregulation of oncogenes and the formation of fusion genes are commonly observed in hematological malignancies with recurring balanced translocations. However, in some malignancies exhibiting balanced chromosomal rearrangements, neither oncogene deregulation nor generation of fusion genes appears to be involved, suggesting that other mechanisms are at play. In the rare myelodysplastic syndrome (MDS) containing a t(2;11)(p21;q23-24) translocation, breakpoints near a microRNA locus, miR-125b-1, in 11q24 have been suggested to be pathogenetically involved. Here we report the detailed mapping and sequencing of the breakpoint located only 2 kilobases from miR-125b-1 in an MDS patient with a t(2;11)(p21;q23-24).


Patients' journeys to a narcolepsy diagnosis: a physician survey and retrospective chart review.
Narcolepsy is a lifelong disorder with potentially debilitating symptoms. Obtaining an accurate diagnosis often requires multiple tests and physician visits. This report describes results from an online, quantitative, company-sponsored survey in which physicians provided information from the charts of their patients with narcolepsy. Neurologists, pulmonologists, psychiatrists, and other specialists who were board certified in sleep medicine; had 2 to 30 years of clinical experience; and treated ≥ 5 narcolepsy patients per month were invited to complete ≤ 6 surveys using charts of patients who were treated for narcolepsy in the last 6 months. Data from 252 patients were collected from 77 physicians. Patients were predominantly male (55%), white (67%), and had a median age of 38 years (range: 12-83 years). Referral to the respondent physician was common, mainly from primary care physicians. The most common initial symptoms were excessive daytime sleepiness (91%), trouble staying awake during the day (44%), and trouble concentrating/functioning during the day (43%). Overall, initial symptoms were of at least moderate severity in 85% of patients. Most patients completed overnight polysomnography (83%), a Multiple Sleep Latency Test (76%), and/or the Epworth Sleepiness Scale (62%). The median time from patient-reported symptom onset to diagnosis was 22 months (range: 0-126 months); at least half saw ≥ 2 providers before being diagnosed; and 60% of patients had previously been misdiagnosed with other disorders, including depression (31%), insomnia (18%), and/or obstructive sleep apnea (13%). In this study, the journey to a narcolepsy diagnosis required evaluation by multiple physicians and took nearly 2 years in 50% of patients, and > 5 years in 18%. These data highlight the need for increased awareness of the signs and symptoms of narcolepsy.


The epidemiology of reoperation after flexor tendon repair.
To describe the incidence of reoperation and the demographic factors that may be associated with reoperation after flexor tendon repair. Using a New York statewide hospital administrative database covering an 8-year period, we examined unique patient discharges with an index procedure of flexor tendon repair for reoperation (re-repair or tenolysis). We compared the age, sex, race, and insurance type by reoperation status using standard univariate statistics and multivariate regression analysis. We performed trend analysis using the Cochran-Armitage trend test. From 1998 to 2005, there were 5,229 flexor tendon repairs with a frequency of reoperation of 6%; of these, 91% were in the first year after the primary procedure. Those who underwent reoperation were significantly older than those who did not undergo reoperation. Patients with workers' compensation were 63% more likely to undergo reoperation than those with other forms of insurance. Patients who had concomitant nerve repair during the index procedure were 26% less likely to undergo reoperation. The rate of reoperation did not change during the study period. These results may be useful in shaping research agendas to evaluate sociodemographic factors contributing to reoperations. Prognostic II.


Fatty acid composition of aquatic insect larvae Stictochironomus pictulus (Diptera: Chironomidae): evidence of feeding upon methanotrophic bacteria.
Larvae of the chironomid Stictochironomus pictulus were collected from Lake Biwa, central Japan. Both the fatty acid composition of the total lipid fraction and the carbon stable isotope ratios of whole larvae were determined. Larvae showed delta(13)C values of -57.4 per thousand to -62.4 per thousand, similar to the values of methane recorded from the lake sediments. A high level of monounsaturated fatty acids (MUFAs; approximately 50% of total fatty acids) and an extremely low level of n-3 series polyunsaturated fatty acids (PUFAs) in the total lipids of S. pictulus indicated a predominantly bacterial nutrition for this species. Moreover, chironomid tissues contained large amounts of the Type I methanotroph group-specific fatty acid, 16:1(n-8) (approximately 8% of total fatty acids). This is the first time such a fatty acid biomarker has been described from freshwater invertebrates. The data suggest that S. pictulus larvae directly feed upon methanotrophic bacteria.


Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.
Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms. This modulation may involve specific and differentiated pathways in different tissues that also may cause a differential sensitivity related to differential induction of some enzymes.


New pentacyclic triterpenes from Gypsophila oldhamiana and their biological evaluation as glycogen phosphorylase inhibitors.
The three new pentacyclic triterpenes 1-3 were isolated and elucidated from the roots of Gypsophila oldhamiana, together with seven known triterpenes (4-10). These triterpenes were evaluated for their glycogen phosphorylase inhibitory activity and preliminary structure-activity trends are suggested.


The VITA Project: heritability of resistance to activated protein C. Vincenza Thrombophilia and Arteriosclerosis.
Resistance to activated protein C (APC) is a risk factor for venous thromboembolism also in absence of the FV Leiden mutation. To evaluate the influence of genetic factors on APC resistance, we evaluated the heritability of the APC resistance phenotype in 1,519 sib-parent pairs randomly selected from the VITA Project. After adjustment for known influencing factors, a high heritability coefficient (0.58) was observed and parental response to APC was the single most important factor in predicting the corresponding phenotype in sibs. In 32 parent-sib pairs in which phenotypic resistance to APC unrelated to FV Leiden was present in both parents and sibs, no additional mutation on the 306-aminoacid residue of FV (FV Cambridge and FV Hong Kong) was found. In these 32 parent-sib pairs, FVIII:C and vWf:Ag levels were not significantly increased and there was no excess prevalence of the R2 allele of exon 13 of FV gene. This study suggests that the response to APC is significantly influenced by genetic factors also at a population level, but the responsible mechanisms are still undefined.


Occupational airborne contact dermatitis caused by thyme dust.
The aim of the study was to assess occupational hazards to the farmer's skin associated with processing thyme (Thymus vulgaris L.). 46 farmers were studied during the threshing of dried thyme. They were questioned about work-related skin problems and examined before and after work. In all persons, serum thyme-specific IgE was measured. Skin prick tests, the Ouchterlony test and the migration inhibition test were carried out with allergens of airborne bacteria and fungi present in the working environment. Of the 46 farmers studied, 4 showed skin symptoms after 5-30 min of exposure to thyme dust. Thyme-specific IgE was found in 1 person with work-related symptoms, but also in 2 asymptomatic farmers. Therefore, the importance of IgE seems to be questionable in eczema related to thyme dust. Skin and blood tests with microbial allergens also showed no significant differences between the symptomatic and asymptomatic farmers. To our knowledge, this is the 1st description of occupational airborne contact dermatitis caused by thyme dust. The etiology of thyme-related skin symptoms remains obscure, although an irritant mechanism seems probable.


Ouabain induces secretion of proatrial natriuretic factor by rat atrial cardiocytes.
Neonatal rat atrial and ventricular cardiocytes in primary culture secrete proatrial natriuretic factor (proANF), the 126-amino acid precursor of atrial natriuretic factor (ANF). The cellular mechanisms of proANF secretion differ in the two cell types: atrial cardiocytes store proANF in abundant secretory granules before secretion, whereas ventricular cardiocytes secrete the precursor rapidly after synthesis. In this study, we used the Na+-K+-adenosinetriphosphatase (ATPase) inhibitor ouabain to investigate the functional significance of these differing secretory mechanisms. Ouabain increased immunoreactive ANF (iANF) secretion by atrial cardiocytes 1.5- to 2.4-fold. Metabolic labeling studies demonstrated that proANF was the form of iANF released in response to ouabain. Ventricular secretion of iANF was unaffected by the Na+-K+-ATPase inhibitor. These observations are consistent with a model in which atrial cardiocytes are able to release proANF via a regulated secretory pathway, whereas ventricular cardiocytes utilize a constitutive secretory pathway. The ability of ouabain to stimulate proANF secretion suggests that an increase in intracellular calcium concentration may promote fusion of secretory granules with atrial cell membranes thereby mediating exocytosis of stored proANF.


Effect of dexmedetomidine on the minimum alveolar concentration of isoflurane in cats.
This study reports the effects of dexmedetomidine on the minimum alveolar concentration of isoflurane (MAC(iso) ) in cats. Six healthy adult female cats were used. MAC(iso) and dexmedetomidine pharmacokinetics had previously been determined in each individual. Cats were anesthetized with isoflurane in oxygen. Dexmedetomidine was administered intravenously using target-controlled infusions to maintain plasma concentrations of 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, and 20 ng/mL. MAC(iso) was determined in triplicate at each target plasma dexmedetomidine concentration. Blood samples were collected and analyzed for dexmedetomidine concentration. The following model was fitted to the concentration-effect data: [Formula in text] where MAC(iso.c) is MAC(iso) at plasma dexmedetomidine concentration C, MAC(iso.0) is MAC(iso) in the absence of dexmedetomidine, I(max) is the maximum possible reduction in MAC(iso), and IC(50) is the plasma dexmedetomidine concentration producing 50% of I(max). Mean ± SE MAC(iso.0), determined in a previous study conducted under conditions identical to those in this study, was 2.07 ± 0.04. Weighted mean ± SE I(max), and IC(50) estimated by the model were 1.76 ± 0.07%, and 1.05 ± 0.08 ng/mL, respectively. Dexmedetomidine decreased MAC(iso) in a concentration-dependent manner. The lowest MAC(iso) predicted by the model was 0.38 ± 0.08%, illustrating that dexmedetomidine alone is not expected to result in immobility in response to noxious stimulation in cats at any plasma concentration.


Rhinomanometric and olfactometric variations throughout the menstrual cycle.
A prospective study was performed to evaluate the rhinomanometric values and the changes in the olfactory threshold that occur in women throughout the menstrual cycle. The subjects were 60 healthy volunteer premenopausal women 18 to 40 years of age. We performed rhinomanometric and olfactometric measurements during the follicular, periovular, and luteal phases of the menstrual cycle. Rhinomanometry showed a higher (not statistically significant) airflow during the periovular phase than during the follicular and luteal phases. Olfactometry showed a higher sensitivity during the follicular phase (p < .05) and the periovular phase (p < .001) than during the luteal phase. We conclude that airflow and transnasal pressure during spontaneous respiration, as well as the olfactory threshold to odors, seem to depend on the variations of the ovarian steroids that occur during the menstrual cycle.


Studying radiolytic ageing of nuclear power plant electric cables with FTIR spectroscopy.
Due to the willingness to extend the nuclear power plants length of life, it is of prime importance to understand long term ageing effect on all constitutive materials. For this purpose gamma-irradiation effects on insulation of instrumentation and control cables are studied. Mid-infrared spectroscopy and principal components analysis (PCA) were used to highlight molecular modifications induced by gamma-irradiation under oxidizing conditions. In order to be closer to real world conditions, a low dose rate of 11Gyh-1 was used to irradiate insulations in full cable or alone with a dose up to 58 kGy. Spectral differences according to irradiation dose were extracted using PCA. It was then possible to observe different behaviors of the insulation constitutive compounds i.e. ethylene vinyl acetate (EVA), ethylene propylene diene monomer (EPDM) and aluminium trihydrate (ATH). Irradiation of insulations led to the oxidation of their constitutive polymers and a modification of filler-polymer ratio. Moreover all these modifications were observed for insulations alone or in full cable indicating that oxygen easily diffuses into the material. Spectral contributions were discussed considering different degradation mechanisms.


Extended-release tacrolimus: a review of its use in de novo kidney transplantation.
Extended-release tacrolimus (tacrolimus ER) [Advagraf(®); Astagraf XL(®); Graceptor(®); Prograf XL(®)] is a once-daily formulation of the immunosuppressive calcineurin inhibitor, which is approved in many countries worldwide for the prophylaxis of transplant rejection in adult de novo kidney transplant recipients. It is absorbed more slowly than the conventional, twice-daily, immediate-release formulation, initially producing lower exposure when administered at the same daily dosage, but providing equivalent exposure upon repeat administration with therapeutic drug monitoring. In randomized, controlled, phase III/IV trials, with extended follow-up to 4 years, the efficacy of tacrolimus ER was similar to that of twice-daily tacrolimus with regard to the prevention of acute rejection or graft dysfunction in adult de novo kidney transplant recipients. Renal function was significantly better with tacrolimus ER, but not tacrolimus, than with ciclosporin. The tolerability profile of tacrolimus ER was descriptively similar to that of the original twice-daily formulation, with no notable differences. Therefore, tacrolimus ER retains the immunosuppressive activity of the original formulation in the prophylaxis of transplant rejection in adult de novo kidney transplant recipients and offers the benefits of once-daily administration.


Crystallographic identification of an unusual homoleptic palladium citrate [Na(OH2)6]·{[Na3(OH2)8]3[NaPd3(C6H4O7)3]2}·(H2O) stabilised by intermetallic aggregation with sodium and heavy hydration.
A rare precious metal binary citrate represented by palladium in the form of a water-rich Na–Pd intermetallic aggregate has been isolated and crystallographically characterised. It shows a penta-anionic [NaPd3(citrate)3]5− core balanced by [Na3]3+ and Na+ hydrates in a 3-D coordination network stabilised exclusively by citrate bridges and fortified by extensive H-bonding.


Recognizing endometriosis as a social disease: the European Union-encouraged Italian Senate approach.
Started at the grassroot level, increased awareness and investment in research has resulted in unprecedented recognition of endometriosis by the European Parliament, taken up by the Italian Senate in a 5-year action plan. This offers welcome assurance to the scientific community.


Splenectomy and infection in Hodgkin's disease.
The incidence of infection in 56 patients with Hodgkin's disease who had undergone staging laparotomy with splenectomy was compared with that of 28 non-splenectomized patients with Hodgkin's disease treated concurrently. The results suggest that splenectomy does not result in a major change in the incidence of infection experienced by such patients with stage II or stage III disease. Aggressive therapy may be of greater importance in increasing the susceptibility to infection in Hodgkin's disease.


Intermediate lymphocytic lymphoma: an immunohistologic study with comparison to other lymphocytic lymphomas.
In an immunohistologic analysis of 13 cases of intermediate lymphocytic lymphoma (ILL), the immunophenotype of ILL was compared to the immunophenotypes of other B-lymphocytic lymphomas and the normal lymphoid follicle to determine the normal cell in the scheme of B-cell differentiation that corresponds to ILL. The characteristic immunophenotype of ILL was surface IgM +/- D+, cytoplasmic immunoglobulin -, B1+, BA1+, B2-, BA2-, B4+, Leu 14+, HLA-DR+, Leu 1+, and common acute lymphoblastic leukemia associated (CALLA) antigen -. The immunophenotype of ILL was similar to that of lymphocytes in normal primary follicles and the mantle zones of secondary follicles. The "immature" phenotype of ILL was identical to that of small lymphocytic lymphoma, which strongly supports their close lineage relationship. In contrast, the "mature" phenotypes of the follicular center cell and lymphoplasmacytoid lymphomas suggest that they correspond to normal cells at later stages of differentiation. Our findings indicate that B-lymphocytic lymphomas recapitulate the normal stages of B-cell differentiation. The cell of ILL appears to be an immature B cell that homes to, and resides in, primary follicles and the mantle zones of secondary follicles. The cytologic, architectural, immunologic, and clinical features of ILL indicate that it should be included as a separate category in the International Working Formulation.


Computer-aided design of a PDZ domain to recognize new target sequences.
PDZ domains are small globular domains that recognize the last 4-7 amino acids at the C-terminus of target proteins. The specificity of the PDZ-ligand recognition is due to side chain-side chain interactions, as well as the positioning of an alpha-helix involved in ligand binding. We have used computer-aided protein design to produce mutant versions of a Class I PDZ domain that bind to novel Class I and Class II target sequences both in vitro and in vivo, thus providing an alternative to primary antibodies in western blotting, affinity chromatography and pull-down experiments. Our results suggest that by combining different backbone templates with computer-aided protein design, PDZ domains could be engineered to specifically recognize a large number of proteins.


Paired-ion chromatographic analysis of tamoxifen and two major metabolites in plasma.
A method is described for the clinical analysis of the non-steroidal anti-estrogenic, antineoplastic agent, tamoxifen and its 4-hydroxy and N-desmethyl metabolites in human plasma. The analytes are extracted from biological fluid with diethyl ether and subsequently converted to fluorescent phenanthrene derivatives by irradiation with UV light. The fluorophores are separated by paired-ion chromatography on a reversed-phase (C18) column. Spectrofluorometric monitoring of the column eluent allows quantitation of analytes as their phenanthrene derivatives to levels of 100 pg/ml of plasma.


Immunohistochemical localization of vitronectin, its receptor and beta-3 integrin in Alzheimer brain tissue.
The vitronectin receptor (VNR) is an integrin which consists of an alpha-subunit which can associate with multiple beta-subunits. A polyclonal antibody to this integrin weakly stained resting microglia in white matter of control brain and strongly stained reactive microglia in both gray and white matter of Alzheimer brain. This antibody, as well as a monoclonal antibody to beta 3, stained some platelets in capillaries of both control and Alzheimer tissue. When the antiserum was immunoabsorbed with a preparation enriched in the alpha-chain of the vitronectin receptor, it failed to stain microglial cells, but continued to stain platelets. When it was immunoabsorbed with a peripheral blood platelet preparation, all immunostaining was abolished. These results indicate that the vitronectin receptor of microglia is associated with a beta-chain different from beta 3, but that beta 3 is expressed by some platelets in brain capillaries. An antibody to vitronectin itself stained senile plaques and neurofibrillary tangles in Alzheimer entorhinal cortex, but only residual plasma in control tissue. Senile plaques positive for vitronectin had microglial cores strongly positive for the vitronectin receptor. The high levels of vitronectin receptor on reactive microglia in areas containing extracellular vitronectin suggest the possibility that vitronectin is serving an opsonizing function for microglial phagocytosis.


Lipopolysaccharide increases the incidence of collagen-induced arthritis in mice through induction of protease HTRA-1 expression.
The protease HTRA-1 is closely associated with rheumatoid arthritis (RA). The molecular mechanisms that control HTRA-1 expression are currently unknown. This study was undertaken to determine the regulatory role of Toll-like receptors (TLRs) on HTRA-1 expression in mice with collagen-induced arthritis (CIA) and in synovial cells from RA patients. HTRA-1 messenger RNA and protein production in mouse fibroblasts, mouse macrophages, and freshly isolated RA patient synovial cells treated with TLR ligands were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Arthritis incidence and severity were determined using clinical scores and histopathologic analysis. Involvement of HTRA-1 in lipopolysaccharide (LPS)-increased arthritis incidence and severity in mice was determined using anti-HTRA-1 monoclonal antibody. The signal pathways involved in HTRA-1 expression were accessed by specific inhibitors, RNA interference, dual-luciferase reporter, and chromatin immunoprecipitation methods. LPS and tenascin-C, but not the other TLR ligands tested, strongly induced HTRA-1 expression. LPS significantly increased HTRA-1 expression in the joint tissue as well as arthritis incidence and severity in mice with CIA. Blocking HTRA-1 by antibody significantly decreased LPS-promoted CIA severity. Inhibiting NF-κB significantly decreased LPS-induced HTRA-1 expression in mouse and human cells. Dual-luciferase reporter assay and ChIP analysis showed that p65 directly binds to HTRA-1 promoter (amino acid 347). Our findings indicate that TLR-4 activation increases HTRA-1 expression through the NF-κB pathway in fibroblasts and macrophages. HTRA-1 expression is involved in the enhancing effects of LPS on CIA. This study offers new insights into the regulation of HTRA-1 expression via LPS/TLR-4 and the role of HTRA-1 in RA pathogenesis.


Skin alterations of intact skin and risk factors associated with pressure ulcer development in surgical patients: a cohort study.
The pathology literature suggests three types of pressure ulcer with six possible mechanisms leading to tissue breakdown. A limitation of current evidence is the difficulty in replicating the clinical situation and in determining the point at which a tissue assault becomes irreversible and results in tissue breakdown. In particular clinical observations of alteration in darkly pigmented skin, blanching erythema, non-blanching erythema and non-blanching erythema with other skin changes including induration, oedema, pain, warmth or discolouration have not been assessed in relation to subsequent skin/tissue loss and their pathophysiological and aetiological importance is not fully understood. To assess the validity of clinical signs of erythema as predictors of pressure ulcer development and identify variables which independently are predictive of Grade 2 pressure ulcer development. Prospective cohort study. 109 general, vascular and orthopaedic hospital patients, aged over 55 years with an expected length of stay of 5 days were recruited. Of these 97 were pressure ulcer free at baseline and/or had complete follow-up including 59 women and 38 men with a median age of 75 years (range 55-95). Single centre large acute UK NHS hospital. To identify clinical signs of erythema predictive of skin loss, the odds of pressure ulcer development were examined using logistic regression. To identify variables independently predictive of Grade 2 pressure ulcer development logistic regression modeling was undertaken. There was significantly increased odds of pressure ulcer development associated with non-blanching erythema (7.98, p=0.002) and non-blanching erythema with other skin changes (9.17, p=0.035). Logistic regression modeling identified non-blanching erythema, pre-operative albumin, weight loss, and intra-operative minimum diastolic blood pressure, as independent predictors of Grade > or =2 pressure ulcer development. Non-blanching erythema with or without other skin changes is distinct from normal skin/blanching erythema and is associated with subsequent pressure ulcer development.


Fluorescence from diffusing single molecules illuminates biomolecular structure and dynamics.
This review provides an account of single-molecule fluorescence methodologies for freely diffusing molecules applied to a diverse array of biological problems pertaining to biomolecular folding and assembly. We describe the principles of confocal fluorescence microscopy to detect and analyze fluorescence bursts from diffusing single molecules. These methods including single-molecule fluorescence resonance energy transfer, coincidence, correlations and polarization offer a powerful means to uncover hidden information about conformational sub-populations and interconversion dynamics of biomolecular systems in a wide range of timescales. We offer several key examples to illustrate how these methodologies have been extremely useful in teasing out structural and dynamical aspects of many important biomolecular systems.


Significance of respiratory isolates of Mycobacterium avium complex in HIV-positive and HIV-negative patients.
Mycobacterium avium complex (MAC) is isolated with increasing frequency from respiratory specimens. This study was an attempt to determine the significance of this in human immunodeficiency virus (HIV)-positive and HIV-negative patients. A retrospective cohort study was conducted at Bellevue Hospital, a large municipal hospital in New York City, including all patients with two or more respiratory tract specimens positive for MAC during the period January 1996 to October 1996. Eighty patients met inclusion criteria. Forty-six were HIV-positive, and 34 were HIV-negative. Age, gender distribution, and race were comparable. Cough was a common complaint in all patients, whereas HIV-positive patients were significantly more likely to have fever (19 vs. 2, P < 0.0001). Abnormal chest radiographs were common in both groups (P > 0.8), although HIV-positive patients were more likely to have diffuse abnormalities (P < 0.0001). Focal radiographic findings were similar for both groups; however, there was a trend toward more lymphadenopathy in the HIV-positive group, though this did not reach statistical significance (P = 0.17). Notably, patients in both groups frequently had an established concurrent pulmonary diagnosis or evidence of disseminated MAC infection. Patients who were HIV-positive had Pneumocystis carinii pneumonia (n = 10), pneumonia (n = 10), and disseminated MAC disease (n = 12); whereas the concurrent disease in HIV-negative patients predominantly was active tuberculosis (n = 13). According to the recent American Thoracic Society-recommended criteria for the diagnosis of pulmonary disease caused by nontuberculous mycobacteria only 7 of 46 HIV-positive patients and 1 of 34 HIV-negative patients met clinical, bacteriologic, and radiographic criteria for pulmonary disease caused by MAC (P = 0.052). Mycobacterium avium complex often is cultured from patients with other lung diseases, and its presence in sputum infrequently signifies true disease, though it is more likely to do so in HIV-positive patients.


Surgery for pulmonary metastasis: a 20-year experience.
During a recent 20-year period, 556 patients underwent operation for pulmonary metastasis at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. The surgical mortality was 1.5% for 772 resections. A selection of 443 patients was made to evaluate the contribution of operative intervention as a primary treatment, with selective adjunctive therapy when applicable. The success of a surgical approach is dependent primarily on adherence to selection criteria; it is important that only patients in whom all known disease can be completely removed with the planned resection and who have full control of the primary site are treated. The overall survival for the group was 35%. For patients with carcinoma, survival ranged from 24% for those with primary uterine cervix tumors to approximately 54% for urinary tract, male genital tract, and corpus of uterus primary tumors. In the group with sarcoma, patients with skeletal tumors had a 46.4% survival rate (50.7% for those with osteogenic sarcoma), and 33% of the patients with soft tissue tumors had long-term survival. The outcome for patients with melanoma was poor; only 12.1% survived 5 years. If the original criteria apply, multiple and bilateral lesions can be successfully managed. Patients undergoing planned adjuvant treatment had a superior outcome compared with those not so treated. However, a significant survival advantage was shown only for patients with sarcoma. The failure to control all disease in patients in whom pulmonary metastasis is controlled surgically can only be improved on through the use of systemically active adjuvant treatment.


Subependymomas of the lateral ventricle: tumor recurrence correlated with increased Ki-67 labeling index.
Subependymomas of the lateral ventricles are rare tumors. We present two patients with subependymomas of the lateral ventricle, who underwent gross total resection of the tumor via transcallosal approach. The patient, with increased Ki-67 labeling index had recurrence of tumor two years after the initial operation. We emphasize at the risk of recurrence which is probably correlated with Ki-67 labeling index.


EOG as a monitor of desferrioxamine retinal toxicity.
Iron overload caused by blood transfusion-dependent anaemia usually results in lethal cardiac toxicity unless treated by iron-chelation therapy. Chelation therapy with desferrioxamine (DFO) is well established and widely used to remove excess iron. Unfortunately, visual disorders have been recorded after DFO infusion. In this investigation, a 61-year-old Caucasian female received DFO for her autoimmune haemolytic anaemia. Prior to starting with the DFO treatment, her baseline ophthalmic screening and electrooculogram (EOG) were completely normal. Two years later she noticed a grey scotoma in her right eye. Visual acuity in this eye was reduced from 6/5 to 6/9 and funduscopy revealed evidence of non-specific mottling of the retinal pigment epithelium of both retinae. The EOG was flat (106%) in the right eye and subnormal in the left (155%). The lower limit of our EOG Arden Ratio for normal subjects is 180%. After her DFO treatment was stopped, her right visual acuity returned to 6/5, her field tests showed progressive improvement bilaterally and the EOG went back to the normal range. While waiting for splenectomy, the patient was restarted on a lower dose of DFO and EOG measurements were carried out every two (or three) weeks to monitor for DFO toxicity. The EOG varied during this period indicating some deterioration of function in the retinal pigment epithelium. However, normalisation of the EOG values (right = 217%, left = 217%) occurred after splenectomy and cessation of DFO therapy. Her visual function was normal and her visual acuity 6/4 bilateral when she was discharged from our outpatient clinic. On reviewing her history it was apparent that the EOG was the most sensitive indicator of DFO toxicity.


[Chemical study on ethyl acetate portion of Ehretia thyrsiflora, boraginaceae species of Kudingcha].
To investigate the chemical constituents of Ehretia thyrsiflora. Compounds were isolated by using silica gel, Sephadex LH-20 and RP-C18 chromatography; their structures were elucidated by means of spectral data analysis. Seven compounds were isolated and identified as methyl rosmarinate (1), caffeic acid (2), quercetin (3), kampferol (4), kaempferol 3-O-alpha-D-arabinoside (5), quercetin 3-O-alpha-D-arabinoside (6), and p-hydroxy benzoic acid (7). All these compounds were isolated from E. thyrsiflora for the first time. Compounds 2-7 were isolated from genus Ehretia for the first time.


Kagome Chiral Spin Liquid as a Gauged U(1) Symmetry Protected Topological Phase.
While the existence of a chiral spin liquid (CSL) on a class of spin-1/2 kagome antiferromagnets is by now well established numerically, a controlled theoretical path from the lattice model leading to a low-energy topological field theory is still lacking. This we provide via an explicit construction starting from reformulating a microscopic model for a CSL as a lattice gauge theory and deriving the low-energy form of its continuum limit. A crucial ingredient is the realization that the bosonic spinons of the gauge theory exhibit a U(1) symmetry protected topological (SPT) phase, which upon promoting its U(1) global symmetry to a local gauge structure ("gauging"), yields the CSL. We suggest that such an explicit lattice-based construction involving gauging of a SPT phase can be applied more generally to understand topological spin liquids.


Phloridzin docosahexaenoate, a novel fatty acid ester of a plant polyphenol, inhibits mammary carcinoma cell metastasis.
Triple-negative breast cancer (TNBC) tends to recur and metastasize following initial chemotherapy, which presents a treatment challenge. Here, we detail the anti-metastatic activity of phloridzin docosahexaenoate (PZ-DHA), synthesized from the natural polyphenol, phloridzin, and the ω-3 fatty acid, docosahexaenoic acid. Sub-cytotoxic PZ-DHA suppressed the migration of MDA-MB-231, SUM149, and 4T1 cells, as well as invasion by MDA-MB-231 and 4T1 cells. Sub-cytotoxic PZ-DHA also inhibited MDA-MB-231 expression of matrix metalloproteinase 2, and expression of epithelial-to-mesenchymal transition-associated transcription factors by MDA-MB-231 and SUM149 cells. Transforming growth factor-β-induced Rho GTPase signaling in MDA-MB-231 cells and non-malignant MCF-10A mammary epithelial cells was suppressed by sub-cytotoxic PZ-DHA, which also inhibited Akt/phosphoinositide 3-kinase and extracellular signal-regulated kinase 1 and 2 signaling in MDA-MB-231 cells. Finally, intraperitoneal administration of PZ-DHA suppressed the metastasis of 4T1 and GFP-transfected MDA-MB-231 cells from the mammary fat pad to the lungs of BALB/c and NOD-SCID female mice, respectively, which was unrelated to any inhibition of primary tumor growth. There was no evidence of toxicity as PZ-DHA treatment did not affect liver or kidney function. We conclude that PZ-DHA might prevent or inhibit the progression of TNBC.