Expression of myosin isoforms in smooth muscle cells in the corpus cavernosum penis.
Corpus cavernosum smooth muscle (CCSM) in the penis is unique in that it exhibits a high resting tone and, on stimulation, the muscle cells relax, allowing cavernous spaces to fill with blood, which results in an erection (tumescence). During detumescence, the muscle cells contract and return to the state of high resting tone. This study was undertaken to determine whether CCSM with these unique properties contains myosin isoforms typical of aorta or bladder smooth muscles, muscles that exhibit tonic and phasic characteristics, respectively. RT-PCR revealed that normal CCSM contains an SM2/SM1 mRNA ratio of 1.2:1 (similar to the rabbit aorta). Approximately 31% of the myosin heavy chain transcripts possess a 21-nt insert (predominant in bladder smooth muscle but not expressed in aorta) that encodes the seven-amino acid insert near the NH2-terminal ATP binding region in the head portion of the myosin molecule found in SMB, with the remaining mRNA being noninserted (SMA). Quantitative competitive RT-PCR revealed that the CCSM possesses approximately 4.5-fold less SMB than the bladder smooth muscle. Western blot analysis using an antibody specific for the seven-amino acid insert reveals that both SM1 and SM2 in the CCSM contain the seven-amino acid insert. Furthermore, SMB containing the seven-amino acid insert was localized in the CCSM by immunofluorescence microscopy using this highly specific antibody. The analysis of the expression of LC17 isoforms a and b in the CCSM revealed that it is similar to that of bladder smooth muscle. Thus the CCSM possesses an overall myosin isoform composition intermediate between aorta and bladder smooth muscles, which generally express tonic- and phasiclike characteristics, respectively. Two-dimensional gel electrophoresis showed a relatively low level (approximately 10%) of Ca2+-dependent light-chain (LC20) phosphorylation at the basal tone, which reaches approximately 23% in response to maximal stimulation. The presence of noninserted and inserted myosin isoforms with low and high levels of actin-activated ATPase activities, respectively, in the CCSM may contribute to the ability of the CCSM to remain in a state of high resting tone and to relax rapidly for normal penile function.


Association of Enterococcus spp. with Severe Combat Extremity Injury, Intensive Care, and Polymicrobial Wound Infection.
Combat-related extremity wound infections can complicate the recovery of injured military personnel. The Enterococcus genus contains both commensal and pathogenic bacteria found in many combat wounds. We describe the patient population susceptible to Enterococcus infection, the characteristics of Enterococcus spp. isolated from combat-related wounds, and the microbiological profile of Enterococcus-positive wounds. Patient and culture data were obtained from the Trauma Infectious Disease Outcomes Study. Subjects were divided into a case group with enterococcal extremity wound infections and a comparator group with wound infections caused by other micro-organisms. Case and comparator subjects had similar patterns of injury and infection. Case subjects had higher Injury Severity Scores (33 vs. 30; p < 0.001), longer hospitalization at U.S. facilities (55 vs. 40 days; p = 0.004), and required more large-volume blood transfusions (>20 units) within 24 h post-injury (53% vs. 30%; p < 0.001). Approximately 60% of case subjects had three or more infections, and 91% had one or more polymicrobial infections, compared with 43% and 50%, respectively, in the comparator group. The thigh was the most common site of Enterococcus spp. isolation, contributing 50% of isolates. Enterococcus faecium was the predominant species isolated from case-group infections overall (66%), as well as in polymicrobial infections (74%). Frequent co-colonizing microbes in polymicrobial wound infections with Enterococcus were other ESKAPE pathogens (64%) (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae [and Escherichia coli], Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and fungi (35%). The specific pathogenicity of Enterococcus relative to other pathogens in polymicrobial wounds is unknown. Identifying strain-specific outcomes and investigating the interactions of Enterococcus strains with other wound pathogens could provide additional tools and strategies for infection mitigation in combat-related wounds.


Epstein-Barr virus encephalitis: findings of MRI, MRS, diffusion and perfusion.
Epstein-Barr virus is an infection that is known as infectious mononucleosis. Even though the central nervous system is not a primary region of involvement of this disease, neurological complications are reported rarely. In this case report, we evaluated a 15-month-old male who presented to the pediatric neurology clinic due to high fever and a neurologic attack. His serological tests and radiological examinations (magnetic resonance imaging (MRI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI) and MR perfusion) were consistent with Epstein-Barr virus encephalitis, which is a very rare complication of infectious mononucleosis. Additionally, we discuss the MRI, MRS, DWI and MR perfusion findings of our case, which were different from other cases reported in the literature.


Immune response and virus population composition: HIV as a case study.
Based on the current understanding of the immune response, we present what we believe to be a new model of intrahost virus dynamics. The model takes into account the relationship between virus replication rate and the level of antigen displayed by infected cells, and shows how the cell-directed immune response controls both virus load and virus replication rate. In contrast to conventional wisdom, it shows that the predominant virus variant does not necessarily have the highest replication rate. A strong immune response produces a selective advantage for latent viruses, whereas a deteriorating immune response invites in viruses of higher replication rates. The model is analysed in light of the well-studied HIV/AIDS disease progression, and shows how a wide range of major, seemingly unrelated issues in the study of HIV may be accounted for in a simple and unified manner.


Sir Hugh Cairns: a pioneering collaborator.
In April 1988, Peter Schurr delivered the twelfth Sir Hugh Cairns Memorial Lecture to the Society of British Neurological Surgeons. In his lecture, The Cairns Tradition, Schurr extolled the personal virtues of Cairns. He encouraged his colleagues to draw inspiration from Cairns' renowned determination, organisation, drive for perfection, compassion, and commitment to the training of those around him. Indeed, Cairns' own personality has come to define the specialty which he established in Britain. Today's neurosurgeons are, whether knowingly or not, formed in his image. But there is a side to Hugh Cairns that has been lost in the telling of his remarkable story, and yet it played a central role in his greatest achievements. This is the side of himself which he turned towards others. Throughout his career, Cairns received an inordinate number of personal accolades. His tutelage under Cushing during a formative trip to America and the impact of his role in caring for T. E. Lawrence are well known to many. But, more than thirty years after Peter Schurr's memorial lecture, and following the eightieth anniversary of the department of neurosurgery founded by Cairns in Oxford, it is his work as a pioneering collaborator which defines his legacy today, and which calls us to learn yet another lesson from his remarkable life. In this legacy article, we review the origins of Cairns' collaborative spirit and uncover the achievements he shared with Charles Hallpike, Howard Florey, Derek Denny-Brown, William Ritchie Russell, Ludwig Guttman, and Peter Medawar, among many others.


Cancer incidence before and after kidney transplantation.
Immune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer and a few virus-associated cancers. Although it is generally accepted that other cancers do not occur at increased rates, there have been few long-term population-based cohort studies performed. To compare the incidence of cancer in patients receiving immune suppression after kidney transplantation with incidence in the same population in 2 periods before receipt of immune suppression: during dialysis and during end-stage kidney disease before renal replacement therapy (RRT). A population-based cohort study of 28,855 patients with end-stage kidney disease who received RRT, with 273,407 person-years of follow-up. Incident cancers (1982-2003) were ascertained by record linkage between the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Cancer Statistics Clearing House. Standardized incidence ratios (SIRs) of cancer, using age-specific, sex-specific, calendar year-specific, and state/territory-specific population cancer incidence rates. The overall incidence of cancer, excluding nonmelanoma skin cancer and those cancers known to frequently cause end-stage kidney disease, was markedly increased after transplantation (n = 1236; SIR, 3.27; 95% confidence interval [CI], 3.09-3.46). In contrast, cancer incidence was only slightly increased during dialysis (n = 870; SIR, 1.35; 95% CI, 1.27-1.45) and before RRT (n = 689; SIR, 1.16; 95% CI, 1.08-1.25). After transplantation, cancer occurred at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18 of these sites. Most of these cancers were of known or suspected viral etiology. Kidney transplantation is associated with a marked increase in cancer risk at a wide variety of sites. Because SIRs for most types of cancer were not increased before transplantation, immune suppression may be responsible for the increased risk. These data suggest a broader than previously appreciated role of the interaction between the immune system and common viral infections in the etiology of cancer.


Double-stranded polynucleotides as interferon inducers.
A discussion of factors considered influential in making a polynucleotide an efficient inducer of interferon was presented. These factors were double-strandedness of the polynucleotides, the sugar moiety of the polynucleotides, thermal stability, resistance to enzymatic degradation, and molecular size of the polynucloetides. Recent developments concerning interferon induction during virus infection were also discussed.


Empathy, better patient care, and how interprofessional education can help.
Interprofessional education (IPE) has been promoted as one way to prepare healthcare students for interprofessional encounters they might experience in the workplace. However, the link between IPE, interprofessional care in the workforce, and better patient outcomes is tenuous, perhaps in part due to the inability of IPE programs to adequately address barriers associated with interprofessional care (e.g., power differentials, role disputes). Empathy, or understanding the experiences of others, has emerged as a critical tool to breaking down barriers inherent to working in teams. Given the evidence connecting empathy to stronger team collaboration and better patient care, researchers significantly revamped programming from a prior training called Interprofessional Education for Complex Neurological Cases (IPE Neuro) to enhance empathy, foster stronger team collaboration, and improve information integration among participants. In this improved three-session program, participants from seven different professions were grouped into teams, assessed a patient volunteer with neurological disorder, and created and presented an integrated, patient-centric treatment plan. Students (N = 31) were asked to report general empathy levels, as well as attitudes, team skills, and readiness toward interprofessional care, before and after the program. We conducted paired samples t-tests and thematic analysis to analyze the data. Results showed that participants reported higher empathy levels, more positive attitudes, and greater team skills pre- to posttest with moderate to large effects. Results bolster IPE Neuro programming as one approach to prepare students for interprofessional care while underscoring the potential implications of IPE to improve empathy levels of healthcare professionals.


Wound healing in nude mice: a study on the regulatory role of lymphocytes in fibroplasia.
In order to understand the role of T cells in postinjury fibroplasia, we have studied wound healing in congenitally athymic nude mice that lack a normally developed T cell system. Healing of incisional wounds, as assessed by wound breaking strength, was significantly stronger in nude mice compared with normal thymus-bearing animals. This was accompanied by a marked increase in the amount of reparative collagen synthesized at the wound site, as assessed by the hydroxyproline content of subcutaneously implanted sponges. Because nude mice have some extrathymic T cell maturation, we used an anti-Thy-1.2 (30H12) monoclonal antibody to selectively deplete T cells in vivo. Although such treatments impaired wound healing in normal mice, they had no effect on any wound healing parameter in nude mice. In a separate experiment, T cell reconstitution of nude mice, sufficient to significantly enhance in vivo delayed hypersensitivity responses, led to a decrease in both wound breaking strength and hydroxyproline deposition in subcutaneously implanted polyvinyl sponges. The data suggest that T cells play a dual role in wound healing: an early stimulatory role on macrophages, endothelial cells, and fibroblasts, and a late counterregulatory role, which may be responsible for the orderly completion of wound repair.


Face gender and emotion expression: are angry women more like men?
Certain features of facial appearance perceptually resemble expressive cues related to facial displays of emotion. We hypothesized that because expressive markers of anger (such as lowered eyebrows) overlap with perceptual markers of male sex, perceivers would identify androgynous angry faces as more likely to be a man than a woman (Study 1) and would be slower to classify an angry woman as a woman than an angry man as a man (Study 2). Conversely, we hypothesized that because perceptual features of fear (raised eyebrows) and happiness (a rounded smiling face) overlap with female sex markers, perceivers would be more likely to identify an androgynous face showing these emotions as a woman than as a man (Study 1) and would be slower to identify happy and fearful men as men than happy and fearful women as women (Study 2). The results of the two studies showed that happiness and fear expressions bias sex discrimination toward the female, whereas anger expressions bias sex perception toward the male.


CASCADE_SCAN: mining signal transduction network from high-throughput data based on steepest descent method.
Signal transduction is an essential biological process involved in cell response to environment changes, by which extracellular signaling initiates intracellular signaling. Many computational methods have been generated in mining signal transduction networks with the increasing of high-throughput genomic and proteomic data. However, more effective means are still needed to understand the complex mechanisms of signaling pathways. We propose a new approach, namely CASCADE_SCAN, for mining signal transduction networks from high-throughput data based on the steepest descent method using indirect protein-protein interactions (PPIs). This method is useful for actual biological application since the given proteins utilized are no longer confined to membrane receptors or transcription factors as in existing methods. The precision and recall values of CASCADE_SCAN are comparable with those of other existing methods. Moreover, functional enrichment analysis of the network components supported the reliability of the results. CASCADE_SCAN is a more suitable method than existing methods for detecting underlying signaling pathways where the membrane receptors or transcription factors are unknown, providing significant insight into the mechanism of cellular signaling in growth, development and cancer. A new tool based on this method is freely available at http://www.genomescience.com.cn/CASCADE_SCAN/.


Adult attachment and preemptive defenses: converging evidence on the role of defensive exclusion at the level of encoding.
The objective of this research was to determine whether the tendency of highly avoidant adults not to recall attachment-related information is best explained through defensive strategies that operate on encoding or retrieval processes. In Study 1 participants listened to an emotionally evocative recording and were given both explicit and implicit tests of their memory for the material. Compared to less avoidant people, highly avoidant people recalled fewer details from the recording and performed worse on an implicit test of their memory for the information. In Study 2 we manipulated people's motivation to retrieve information from memory by offering participants a monetary award for recall. Highly avoidant people recalled less information than less-avoidant people despite the monetary incentive. Taken together, these results suggest that the relative inability of avoidant adults to recall attachment-related information is due to the defensive exclusion of information at the time of encoding rather than the time of retrieval.


Sexual Dimorphism in Small-intestinal Neuroendocrine Tumors: Lower Prevalence of Mesenteric Disease in Premenopausal Women.
Small-intestinal neuroendocrine tumors (SI-NETs) have a modest but significantly higher prevalence and worse prognosis in male patients. This work aims to increase understanding of this sexual dimorphism in SI-NETs. Retrospectively, SI-NET patients treated in a single tertiary center were included and analyzed for disease characteristics. Estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR), and androgen receptor (AR) messenger RNA (mRNA) expression was assessed in primary tumors and healthy intestine. Estrogen receptor alpha (ERα) and AR protein expression were analyzed by immunohistochemistry in primary tumors and mesenteric metastases. Of the 559 patients, 47% were female. Mesenteric metastasis/fibrosis was more prevalent in men (71% / 46%) than women (58% / 37%; P = 0.001 and P = 0.027, respectively). In women, prevalence of mesenteric metastases increased gradually with age from 41.1% in women <50 years to 71.7% in women >70 years. Increased expression of ESR1 and AR mRNA was observed in primary tumors compared to healthy intestine (both P < 0.001). ERα staining was observed in tumor cells and stroma with a strong correlation between tumor cells of primary tumors and mesenteric metastases (rho = 0.831, P = 0.02), but not in stroma (rho = -0.037, P = 0.91). AR expression was only found in stroma. Sexual dimorphism in SI-NETs was most pronounced in mesenteric disease, and the risk of mesenteric metastasis in women increased around menopause. The combination of increased ERα and AR expression in the SI-NET microenvironment suggests a modulating role of sex steroids in the development of the characteristic SI-NET mesenteric metastasis and associated fibrosis.


Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL).
Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 micrograms/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/microliters at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/microliters) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/microliters) in G-CSF-treated patients compared with controls (1880/microliters). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85%) G-CSF patients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.


Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese.
Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10-30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle. To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls. A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4 × 10(-10) (OR = 1.66, 95%CI: 1.43-1.94) for rs738409. Rs738409 also showed the strongest association (p = 3.6 × 10(-6)) with the histological classifications proposed by Matteoni and colleagues based on the degree of inflammation, ballooning degeneration, fibrosis and Mallory-Denk body. In addition, there were marked differences in rs738409 genotype distributions between type4 subgroup corresponding to NASH and the other three subgroups (p = 4.8 × 10(-6), OR = 1.96, 95%CI: 1.47-2.62). Moreover, a subgroup analysis of NAFLD patients against controls showed a significant association of rs738409 with type4 (p = 1.7 × 10(-16), OR = 2.18, 95%CI: 1.81-2.63) whereas no association was obtained for type1 to type3 (p = 0.41). Rs738409 also showed strong associations with three clinical traits related to the prognosis of NAFLD, namely, levels of hyaluronic acid (p = 4.6 × 10(-4)), HbA1c (p = 0.0011) and iron deposition in the liver (p = 5.6 × 10(-4)). With these results we clearly demonstrated that Matteoni type4 NAFLD is both a genetically and clinically different subset from the other spectrums of the disease and that the PNPLA3 gene is strongly associated with the progression of NASH in Japanese population.


A randomised controlled clinical trial and gait analysis of fixed- and mobile-bearing total knee replacements with a five-year follow-up.
This study compared the outcome of total knee replacement (TKR) in adult patients with fixed- and mobile-bearing prostheses during the first post-operative year and at five years' follow-up, using gait parameters as a new objective measure. This double-blind randomised controlled clinical trial included 55 patients with mobile-bearing (n = 26) and fixed-bearing (n = 29) prostheses of the same design, evaluated pre-operatively and post-operatively at six weeks, three months, six months, one year and five years. Each participant undertook two walking trials of 30 m and completed the EuroQol questionnaire, Western Ontario and McMaster Universities osteoarthritis index, Knee Society score, and visual analogue scales for pain and stiffness. Gait analysis was performed using five miniature angular rate sensors mounted on the trunk (sacrum), each thigh and calf. The study population was divided into two groups according to age (≤ 70 years versus > 70 years). Improvements in most gait parameters at five years' follow-up were greater for fixed-bearing TKRs in older patients (> 70 years), and greater for mobile-bearing TKRs in younger patients (≤ 70 years). These findings should be confirmed by an extended age controlled study, as the ideal choice of prosthesis might depend on the age of the patient at the time of surgery.


Tooth mineralisation relative to somatic growth retardation in the rat.
The morphology and sequence of mineral deposition on the crowns of rat molar teeth have been investigated by means of contact radiography relative to their postnatal development following a period of somatic retardation induced by nutritional suppression. Differences in deposition appeared 3 days after birth in the first molar crown and continued until day 7. Second molar differences manifested between day 4 and 5 reaching a comparable level by day 10. Third molar mineralisation appeared identical in both control and experimental specimens indicating that they were not sensitive to the influence of direct maternal control since lactation at the time of mineralisation was being superceded by general food sources. The slowing of molar crown growth is not regarded as a mineral deficit but basically related to the organic matrix and protein and energy deficiency.


Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns.
Because visceral obesity predicts insulin resistance, we studied whether alterations in the gene encoding for the beta 3-adrenergic receptor in visceral fat are associated with insulin resistance. We studied the frequency of a cytosine-to-thymidine mutation that results in the replacement of tryptophan by arginine at position 64 (Trp64Arg) of the beta 3-adrenergic receptor by restriction-enzyme digestion with BstOl in 335 subjects from western Finland, 207 of whom were nondiabetic and 128 of whom had non-insulin-dependent diabetes mellitus (NIDDM). We also determined the frequency of the mutation in 156 subjects from southern Finland. Sensitivity to insulin was measured by the hyperinsulinemic-euglycemic clamp technique in 66 randomly selected nondiabetic subjects. In the subjects from western Finland, the frequency of the mutated allele was similar in the nondiabetic subjects and the subjects with NIDDM (12 vs. 11 percent). The mean age of the subjects at the onset of diabetes was lower among those with the mutation than those without it (56 vs. 61 years, P = 0.04). Among the nondiabetic subjects, those with the mutation had a higher ratio of waist to hip circumference (P = 0.02), a greater increase in the serum insulin response after the oral administration of glucose (P = 0.05), a higher diastolic blood pressure (82 vs. 78 mm Hg, P = 0.01), and a lower rate of glucose disposal during the clamp study (5.3 vs. 6.5 mg [29 vs. 36 mumol] per kilogram of body weight per minute; P = 0.04) than the subjects without the mutated allele. In an analysis of sibling pairs, the siblings with the mutation generally had higher waist:hip ratios (P = 0.05) and higher responses of blood glucose and serum insulin after the oral administration of glucose than their siblings without the mutation (P = 0.02 and P = 0.005, respectively). The Trp64Arg allele of the beta 3-adrenergic receptor is associated with abdominal obesity and resistance to insulin and may contribute to the early onset of NIDDM:


Lovastatin modulates in vivo and in vitro the plasminogen activator/plasmin system of rat proximal tubular cells: role of geranylgeranylation and Rho proteins.
Interstitial fibrosis is one of the most deleterious events during the progression of renal deterioration after renal mass reduction. In vivo, hydroxymethylglutaryl CoA reductase inhibitors (HRI) were shown to reduce progression of glomerulosclerosis, but the mechanisms are still unclear. The present study investigates, in vivo, whether lovastatin, a potent HRI, was able to modulate the plasminogen-plasmin pathway, one of the most efficient systems involved in extracellular matrix remodeling, and characterizes in vitro the cellular mechanisms of these effects. Proximal tubules freshly isolated from rats treated for 2 d with lovastatin (4 mg/kg per d) showed increased tissue-type plasminogen activator (tPA) and urokinase (uPA) activities and antigens. Incubation with lovastatin (5 microM) of proximal tubules isolated from untreated rats induced an increase in tPA and uPA and a decrease in plasminogen activator inhibitor-1 (PAI-1) activities. In vitro, supernatants, cytosols, and membranes of renal proximal tubular cells in primary cultures had no detectable uPA activity, and lovastatin (0.1 to 10 microM) induced an increase in tPA and a decrease in PAI-1 activities and antigens. These effects were reversed by mevalonate and geranylgeranyl-pyrophosphate (GGPP) but not by farnesyl-pyrophosphate or LDL cholesterol. C3 exoenzyme, an inhibitor of the geranylgeranylated-activated Rho protein, reproduced the effect of lovastatin on tPA and PAI- activity and blocked its reversion by GGPP. The effect of lovastatin was associated with a disruption of cellular actin stress fibers, which was reversed by GGPP and reproduced by C3 exoenzyme. In conclusion, HRI can modify the fibrinolytic potential of proximal tubules, most likely via inhibition of geranylgeranylated Rho protein and disruption of the cytoskeleton. The resulting increase of proteolytic activity of tubular cells may serve to prevent extracellular matrix deposition and renal interstitial fibrosis.


Overweight and Obesity Among School-aged Children and Maternal Preventive Practices against Childhood Obesity in Select Local Government Areas of Lagos, Southwest, Nigeria.
Childhood obesity is an emerging epidemic in the developing countries, particularly in the urban settings. This study examines the prevalence of overweight and obesity among school-aged children and the maternal preventive practices against childhood obesity. This is a cross-sectional study of school-aged children aged 6-13 years and mothers from two Local Government Areas of Lagos State, Southwest Nigeria. Multi-stage sampling technique was used to select study areas and participants, while data were collected using an interviewer administered questionnaire. The Body Mass Index (BMI) of children were determined using the World Health Organisation (WHO) 2007 reference charts. Chi-square test was used to analyze categorical variables and logistic regression analyses were conducted to determine the factors associated with the nutritional status and maternal childhood obesity preventive practices. All analyses were conducted using the Statistical Package for Social Sciences (SPSS) 21. In all, 440 children comprising of 232 boys (52.7%) and 208 girls (42.3%) were studied. Of these, 29 of the participants (6.6%) were overweight, while 39 of them (8.9%) were obese. Most of the children (71.2%) consumed root/tubers and processed cereals while 9 (0.02%) and (17) 0.04% consumed fruits and vegetables. BMI was only significantly related to child age and sex. In all, 243 mothers (55.2%) had good practices against childhood obesity. Levels of maternal preventive practices were not significantly associated with child BMI. Overweight/obesity among school-aged children in Lagos is high. Only half of the mothers were involved in preventive practices against childhood obesity. There is need for continuous education and advocacy concerning healthy diet and other preventive strategies against childhood obesity in Lagos, and potentially other parts of the developing world.


HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients.
Breast cancer is a highly heterogeneous malignancy. The triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer subtypes are highly aggressive and are associated with a poor prognosis. The therapeutic targets for TNBC remain undefined, and many patients with the HER2 subtype acquire resistance to therapy after prolonged treatment. The objective of this study was to evaluate the prognostic significance of HER3 expression in invasive breast carcinoma. We established matched tissue microarray (TMA) blocks and clinical data from 950 cases of invasive breast carcinoma with long-term clinical follow-up data (median 109.7 months). Using the TMAs, we characterized the expression of ER, PR, HER2, EGFR, and HER3 by immunohistochemistry. Each case was classified as one of four IHC-based subtypes based on the expression of hormonal receptor (HR) and HER2. The clinicopathological characteristics and survival of 950 patients were analyzed by subtype. In the TNBC subtype, the HER3(+) group showed poorer disease-free survival (DFS, P = 0.010) and overall survival (OS, P = 0.015) than the HER3(-) group. In the HER2 subtype, the HER3(+) group also showed poorer DFS (P = 0.022) and OS (P = 0.077) than the HER3(-) group. However, there was no difference in patients with HR-positive breast cancer. HER3 expression was associated with poor DFS in both the TNBC and HER2 subtypes and poor OS in the TNBC subtype. HER3 overexpression is an important prognostic marker in hormone receptor-negative breast cancer, and further study is needed to clarify the role of HER-3 targeted treatment.


SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study.
We conducted a case-control study on asbestos exposure and presence of SV40 in tumor samples of malignant mesotheliomas (MMs) and bladder urotheliomas (BUs). PCR analysis revealed the presence of SV40 DNA (SV40+) in eight (42.1%) MMs and 6 (33.3%) BUs. The odds ratio for MM Asb- and SV40+ was 0.4 [95% confidence interval (95% CI), 0.03-4.0], for Asb+ and SV40- was 3.6 (95% CI, 0.6-21.0), and for Asb+ and SV40+ was 12.6 (95% CI, 1.2-133.9). Our results suggest that SV40 increases the risk of MM among individuals exposed to asbestos.


Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study.
Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016. This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. We obtained data from MSIS and from a standardized form that was sent to health care providers at the time of patient notification to MSIS. We determined completion rates. Pearson's chi squared test was used to study associations between pairs of categorical variables and separate crude and multivariable logistic regression models were used to identify factors associated with treatment completion and adverse drug effects. We obtained information on treatment completion from 719 of the 726 individuals notified for LTBI treatment in 2016. Overall, 91% completed treatment. Treatment completion was highest in the foreign-born group [foreign-born, n = 562 (92%) vs Norwegian-born, n = 115 (85%), p = 0.007]. Treatment completion did not differ significantly between prescribed regimens (p = 0.124). Adverse events were the most common reason for incomplete treatment. We found no significant differences in adverse events when comparing weekly rifapentine (3RPH) with three months daily isoniazid and rifampicin (3RH). However, there were significantly fewer adverse events with 3RPH compared to other regimens (p = 0.037). Age over 35 years was significantly associated with adverse events irrespective of regimen (p = 0.024), whereas immunosuppression was not significantly associated with adverse events after adjusting for other variables (p = 0.306). Treatment under direct observation had a significant effect on treatment completion for foreign-born (multivariate Wald p-value = 0.017), but not for Norwegian-born (multivariate Wald p-value = 0.408) individuals. We report a very high treatment completion rate, especially among individuals from countries with high TB incidence. The follow-up from tuberculosis-coordinators and the frequent use of directly observed treatment probably contributes to this. Few severe adverse events were reported, even with increased age and in individuals that are more susceptible. While these results are promising, issues of cost-effectiveness and targeting treatment to individuals at highest risk of TB are important components of public health impact.


XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent.
We have reported that the radical scavenger XJB-5-131 attenuates or reverses progression of the disease phenotype in the HdhQ(150/150) mouse, a slow onset model of HD. Here, we tested whether XJB-5-131 has beneficial effects in R6/2 mice, a severe early onset model of HD. We found that XJB-5-131 has beneficial effects in R6/2 mice, by delaying features of the motor and histological phenotype. The impact was sex-dependent, with a stronger effect in male mice. XJB-5-131 treatment improved some locomotor deficits in female R6/2 mice, but the effects were, in general, greater in male mice. Chronic treatment of male R6/2 mice with XJB-5-1-131 reduced weight loss, and improved the motor and temperature regulation deficits, especially in male mice. Treatment with XJB-5-131 had no effect on the lifespan of R6/2 mice. Nevertheless, it significantly slowed somatic expansion at 90 days, and reduced the density of inclusions. Our data show that while treatment with XJB-5-131 had complex effects on the phenotype of R6/2 mice, it produced a number of significant improvements in this severe model of HD.


Comprehensive evaluation of disease coding quality in gastroenterology and its impact on the diagnosis-related group system: a cross-sectional study.
According to the diagnosis-related group (DRG) requirement, issues of diagnosis and procedure coding in the gastroenterology department of our hospital were analyzed and improvement plans were proposed to lay the foundation for effective implementation of DRGs. The title page of case-history of 1600 patients admitted to the Department of Gastroenterology of this hospital from January 1, 2021 to December 31, 2021 was sampled as a data source, and the primary and other diagnostic codes, operation or procedure codes involved in the title page of case-history were categorized and statistically analyzed. Of the 531 cases treated with gastrointestinal endoscopy in our hospital in 2021, coding errors were identified in 66 cases and unsuccessful DRG enrollment in 35 cases, including 14 cases with incorrect coding of the primary diagnosis (8 cases with unsuccessful DRG enrollment), 37 cases with incorrect coding of the primary operation (23 cases with unsuccessful DRG enrollment), and 8 cases with incorrect coding of both the primary diagnosis and the primary operation (4 cases with unsuccessful DRG enrollment). Analysis of 66 inpatient cases with coding problems showed a total of 167 deficiencies, including 36 deficiencies in major diagnoses, 84 deficiencies in other diagnoses, and 47 deficiencies in surgery or operation coding. The accuracy of coding of disease diagnosis and surgical operation is the basis for the smooth implementation of DRGs. The medical staff of this hospital has poor cognition of DRGs coding and fails to recognize the important role of the title page of case-history quality to DRGs system, and their attention to DRGs and knowledge base of disease classification coding should be improved. In addition, the high incidence of coding errors, especially the omission of disease diagnosis, requires increased training of physicians and nurses on clinical knowledge and requirements for DRGs medical records, thereby improving the quality of medical cases and ensuring the accuracy of DRGs information.


Estimation of Tacrolimus Clearance in Saudi Adult Kidney Transplant Recipients.
Tacrolimus is commonly used in adult kidney transplant patients. Only few studies have so far described the pharmacokinetics of tacrolimus in the Saudi population. Thus, the goal of this study is to determine the population pharmacokinetics of tacrolimus in Saudi adult kidney transplant recipients and to identify the factors that explain variability. We performed a retrospective chart review of adult patients who received oral tacrolimus at two centers. We developed the population pharmacokinetic models using Monolix 4.4. The factors screened for influence on these parameters were weight, age, gender, liver function tests, and creatinine clearance. The analysis included a total of 149 tacrolimus plasma concentrations from 139 patients. A one-compartment open model with linear absorption and elimination adequately described the data. The average parameter estimates for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 9.1 L/h and 912 L, respectively. The interindividual variabilities (coefficients of variation) in CL/F and V/F were 20% and 18%, respectively. Aspartate aminotransferase was identified to be the main covariate that influences tacrolimus CL/F. In conclusion, the population pharmacokinetic model of tacrolimus was established and a significant covariate of the model was identified. These findings offer a rationale for the personalization of tacrolimus dosing regimens. Further studies are required to understand the factors that may influence the pharmacokinetics of tacrolimus and assist in drug dosage decisions.


Value of the TTM risk score for early prognostication of comatose patients after out-of-hospital cardiac arrest in a Swiss university hospital.
Comatose patients admitted to the intensive care unit (ICU) after out-of-hospital cardiac arrest frequently die after withdrawal of life support. Guidelines recommend scheduling prognostication no sooner than 96 hours after cardiac arrest, and strict withdrawal criteria leave many patients waiting for improvement for days without ever reaching a favourable outcome. In clinical practice, physicians are frequently confronted with vague living wills expressed by next of kin or an imprecise advance care directive soon after cardiac arrest. Often a decision to admit a patient to an ICU or limiting ICU treatment in terms of time or intensity is made early, based on the patient's preferences. The Target Temperature Management (TTM) risk score is an imperfect measure that predicts outcome early, at the time of ICU admission. It was developed on a data set of 939 patients included in the TTM Trial, a study in which unconscious patients after cardiac arrest were randomised into two temperature management arms. Patient selection in that trial might impede generalisability. We aimed to validate the TTM risk score with 100 consecutive patients treated in our ICU. Although we had different survival rates, reflecting a different patient population, we were able to confirm the score's albeit imperfect ability to predict outcome early after cardiac arrest. The suggested cut-off values of 10 and 16 can be used as a basis for discussion with the family; in particular, a risk score value below 10 predicts a favourable outcome and might guide early discussion. As in the original study, the outcome of an individual patient cannot be predicted. (ClinicalTrials.gov Identifier: NCT02722460).


Stimulus features relevant to the perception of sharpness and mechanically evoked cutaneous pain.
Mechanical probes of various sizes and shapes were used to determine thresholds for the perception of pressure, sharpness, and pain on the human finger. As force increased, perception changed from dull pressure to sharp pressure to sharp pain. With the smallest probe (0.01 mm2), sharpness threshold was very close to pressure threshold. As probe size increased, sharpness and pain threshold expressed in terms of force) increased in proportion to probe circumference (not probe area), whereas pressure threshold increased relatively little. Pain and sharpness thresholds also increased as probe angle became obtuse. There was a statistically significant increase in both thresholds with a probe angle change of 15 degrees. Thus, both size and shape are necessary to describe a mechanical stimulus adequately, and pressure (force/area) is not a sufficient metric for pain studies. Thresholds varied at different skin sites on the finger. The dorsal surface had lower thresholds than the volar surface, but the difference between the two areas was not always statistically significant. The compliance of the skin (e.g., the amount of indentation produced by a given force) exhibited no relation to sharpness or pain threshold, whether considered within subjects at various skin sites, or across subjects at the same skin site. Comparison of the perceptual thresholds with the thresholds for nociceptors determined in electrophysiological studies indicates that the sensation of nonpainful sharpness is likely to be mediated by nociceptors. Furthermore, considerably more than threshold activation of nociceptors is necessary for normal pain perception.


Mass Measurements of Focal Adhesions in Single Cells Using High Resolution Surface Plasmon Resonance Microscopy.
Surface plasmon resonance microscopy (SPRM) is a powerful label-free imaging technique with spatial resolution approaching the optical diffraction limit. The high sensitivity of SPRM to small changes in index of refraction at an interface allows imaging of dynamic protein structures within a cell. Visualization of subcellular features, such as focal adhesions (FAs), can be performed on live cells using a high numerical aperture objective lens with a digital light projector to precisely position the incident angle of the excitation light. Within the cell-substrate region of the SPRM image, punctate regions of high contrast are putatively identified as the cellular FAs. Optical parameter analysis is achieved by application of the Fresnel model to the SPRM data and resulting refractive index measurements are used to calculate protein density and mass. FAs are known to be regions of high protein density that reside at the cell-substratum interface. Comparing SPRM with fluorescence images of antibody stained for vinculin, a component in FAs, reveals similar measurements of FA size. In addition, a positive correlation between FA size and protein density is revealed by SPRM. Comparing SPRM images for two cell types reveals a distinct difference in the protein density and mass of their respective FAs. Application of SPRM to quantify mass can greatly aid monitoring basic processes that control FA mass and growth and contribute to accurate models that describe cell-extracellular interactions.


Fibrin as a cell carrier in cardiovascular tissue engineering applications.
In cardiovascular tissue engineering approaches, efficient seeding methods are essential. To achieve this and to save time, cells can be encapsulated in gels. Combining the advantages of a gel as a cell carrier with the advantages of a fiber-based scaffold, providing structural integrity to the developing tissue, might offer several advantages. In this study, seeding by using fibrin as a cell carrier is compared to the conventional static seeding method with regard to tissue development. Seeding with fibrin resulted in less loss of soluble collagen into the medium and a more mature extracellular matrix in a shorter period of time. The use of fibrin degradation inhibitors was shown to inhibit extracellular matrix formation, although it did not hamper cell proliferation. The use of fibrin as a cell carrier to seed cells into a fiber-based scaffold may represent a promising, timesaving approach in cardiovascular tissue engineering applications.


Does actin bind to the ends of thin filaments in skeletal muscle?
We examined whether or not purified actin binds to the ends of thin filaments in rabbit skeletal myofibrils. Phase-contrast, fluorescence, and electron microscopic observations revealed that actin does not bind to the ends of thin filaments of intact myofibrils. However, in I-Z-I brushes prepared by dissolving thick filaments at high ionic strength, marked binding of actin to the free ends, i.e., the pointed ends, of thin filaments was observed when actin was added at an early phase of polymerization. As the polymerization of actin proceeded, the binding efficiency decreased. The critical actin concentration for this binding was higher than that for polymerization in solution. The binding of G-actin was not observed at low ionic strength. On the basis of these results, we suggest that a particular structure suppressing the binding of actin is present at the free ends of thin filaments in intact myofibrils and that a part of the end structure population is eliminated or modified at high ionic strength so that further binding of actin becomes possible. The myofibril and I-Z-I brush appear to be useful systems for studies aimed at elucidating the organizational mechanisms of actin filaments in vivo.


[Effect of hemodialysis on digoxin pharmacokinetics in heart failure in patients with chronic kidney failure].
The authors have estimated the effect of hemodialysis on the pharmacokinetics of digoxin instilled intravenously to patients with the terminal stage of chronic renal insufficiency. It has been shown that dialysis was associated with an almost double increase in the clearance constant of digoxin due to its additional elimination through the membrane of the dialyzer. Over five h of dialysis the body excretes 12.5% of the administered dose of digoxin which is only 3.8% more (by 19 micrograms) than the average amount eliminated without dialysis. The contribution of dialysis to the elimination of digoxin is insignificant and, therefore, the regimen of its administration on days when dialysis is performed should be left unchanged.


Neural Plasticity of Mild Tinnitus: An fMRI Investigation Comparing Those Recently Diagnosed with Tinnitus to Those That Had Tinnitus for a Long Period of Time.
Objectives. The aim of the study was to compare differences in neural correlates of tinnitus in adults with recent onset and others who had the disorder for longer than a year. Design. A total of 25 individuals with tinnitus were divided into groups based on the amount of time for which they had experienced tinnitus: <1 year (RTIN) or >1 year (LTIN). Subjects underwent an fMRI scan while listening to affective sounds from the International Affective Digital Sounds database. Resting state functional connectivity data were also collected. Results. The RTIN group recruited the posterior cingulate and insula to a greater extent than the LTIN group when processing affective sounds. In addition, we found that the LTIN group engaged more frontal regions when listening to the stimuli compared to the RTIN group. Lastly, we found increased correlations between the default mode network and the precuneus in RTIN patients compared to LTIN at rest. Conclusion. Our results suggest that the posterior cingulate and insula may be associated with an early emotional reaction to tinnitus in both task and resting states. Over time, tinnitus patients may recruit more frontal regions to better control their emotional response and exhibit altered connectivity in the default mode network.


Rehabilitation psychology: meeting the needs of individuals with acquired disabilities in Ireland.
The current articles reviews the epidemiology of disability in Ireland, discusses the political and social factors which have increased focus on disability issues and offers training guidelines for rehabilitation psychology based on those of the APA's Rehabilitation Psychology Division. With the growing number of individuals with acquired (vs developmental) disabilities in Ireland, there is increased recognition of the need to train psychologists to assist persons with acquired disabilities (e.g. spinal cord injury, acquired brain injury, stroke, etc.) in adjusting to their impairments, reintegrating back into their communities and reducing the long-term financial costs associated with disability. Social and political factors suggest that the time is right to develop rehabilitation psychology as a specialty in Ireland given the increased focus on disability in Ireland, including recently passed disability legislation (i.e. 2005 Disability Bill), international events (e.g. 2003 Dublin World Special Olympics) and increases in rehabilitation training programmes (i.e. medicine; physio, occupational and speech therapy).


Chronic streptococcal and non-streptococcal pharyngitis.
Pharyngitis is a common medical problem in the outpatient medical setting, resulting in more than seven million pediatric visits each year. Most types of pharyngitis are caused by infectious etiologies. The most common cause of pharyngitis is viral infection; however, some of the more serious types of pharyngitis are attributed to bacterial etiologies, such as group A β-hemolytic Streptococcus pyogenes (GAS). Complications from GAS pharyngitis include rheumatic fever, deep space abscesses, and toxic shock. Although most episodes of pharyngitis are acute in nature, a small percentage becomes recurrent or chronic. With regards to chronic pharyngitis, non-infectious etiologies, such as laryngopharyngeal reflux and periodic fever, aphthous ulcers, pharyngitis, and adenitis syndrome also need to be considered. Both medical and surgical therapies are effective in managing pharyngitis. First-line medical therapy includes antibiotic therapy. For certain indications, surgical management via adenotonsillectomy is recommended. Adenotonsillectomy has been shown to be effective in reducing disease burden and improving disease-specific and global quality of life. Several techniques for adenotonsillectomy exist, including traditional and intracapsular tonsillectomies.


Early detection of skeletal muscle bioenergetic deficit by magnetic resonance spectroscopy in cigarette smoke-exposed mice.
Skeletal muscle dysfunction is a common complication and an important prognostic factor in patients with chronic obstructive pulmonary disease (COPD). It is associated with intrinsic muscular abnormalities of the lower extremities, but it is not known whether there is an easy way to predict its presence. Using a mouse model of chronic cigarette smoke exposure, we tested the hypothesis that magnetic resonance spectroscopy allows us to detect muscle bioenergetic deficit in early stages of lung disease. We employed this technique to evaluate the synthesis rate of adenosine triphosphate (ATP) and characterize concomitant mitochondrial dynamics patterns in the gastrocnemius muscle of emphysematous mice. The fibers type composition and citrate synthase (CtS) and cytochrome c oxidase subunit IV (COX4) enzymatic activities were evaluated. We found that the rate of ATP synthesis was reduced in the distal skeletal muscle of mice exposed to cigarette smoke. Emphysematous mice showed a significant reduction in body weight gain, in the cross-sectional area of the total fiber and in the COX4 to CtS activity ratio, due to a significant increase in CtS activity of the gastrocnemius muscle. Taken together, these data support the hypothesis that in the early stage of lung disease, we can detect a decrease in ATP synthesis in skeletal muscle, partly caused by high oxidative mitochondrial enzyme activity. These findings may be relevant to predict the presence of skeletal bioenergetic deficit in the early stage of lung disease besides placing the mitochondria as a potential therapeutic target for the treatment of COPD comorbidities.


Enhanced emotion regulation capacity and its neural substrates in those exposed to moderate childhood adversity.
Individuals exposed to childhood adversities (CA) present with emotion regulation (ER) difficulties in later life, which have been identified as risk and maintenance factors for psychopathologies. However, it is unclear if CA negatively impacts on ER capacity per se or whether observed regulation difficulties are a function of the challenging circumstances in which ER is being deployed. In this longitudinal study, we aimed to clarify this association by investigating the behavioral and neural effects of exposure to common moderate CA (mCA) on a laboratory measure of ER capacity in late adolescence/young adulthood. Our population-derived samples of adolescents/young adults (N = 53) were administered a film-based ER-task during functional magnetic resonance imaging that allowed evaluation of ER across mCA-exposure. mCA-exposure was associated with enhanced ER capacity over both positive and negative affect. At the neural level, the better ER of negative material in those exposed to mCA was associated with reduced recruitment of ER-related brain regions, including the prefrontal cortex and temporal gyrus. In addition mCA-exposure was associated with a greater down-regulation of the amygdala during ER of negative material. The implications of these findings for our understanding of the effects of mCA on the emergence of resilience in adolescence are discussed.


Ratio of controller to total asthma medications: determinants of the measure.
To investigate differences in demographics, physician specialty, and medication use between patients who achieve high versus low ratios of controller to total asthma medications. Cohort analysis. We used a Health Insurance Portability and Accountability Act-compliant claims database to identify patients aged 5 to 56 years with persistent asthma during a premeasurement year and a measurement year. Based on values in the measurement year, the ratio of controller to total asthma medications ratio was defined using the following formula: (Units of Controllers) / (Units of Controllers + Relievers). Descriptive analysis and multivariate logistic regression models were used to examine patients with high and low ratios. The final study group comprised 38,538 patients with persistent asthma; 28,496 (73.9%) had high ratios. Specialty of usual-care physician differed (P <.001), with more high-ratio patients than low-ratio patients having an allergist or pulmonologist. Patients who received combination inhaled corticosteroid-long-acting beta-agonist therapy (odds ratio [OR], 2.4) or leukotriene receptor antagonist therapy (OR, 3.5) were more likely to be in the high-ratio group compared with those dispensed a single inhaled corticosteroid. High-group and low-group assignment could be calculated by partial-year data: assignment based on 1 quarter of data was concordant with assignment based on full-year ratio in 91% of cases (Pearson product moment correlation coefficient, 0.864; kappa statistic, 0.761), and assignment based on 2 quarters of data was concordant with full-year results in 94% of cases (Pearson product moment correlation coefficient, 0.928; kappa statistic, 0.843). A high ratio of controller to total asthma medications is associated with greater controller adherence and with more controller fills. The ratio can be calculated using 1 or 2 quarters of pharmacy claims data, at a time when intervention may reduce asthma-related exacerbations. Interventions that may improve the ratio include changing from single inhaled corticosteroid therapy and from asthma specialist care.


Evolutionary analysis of the two-component systems in Pseudomonas aeruginosa PAO1.
Gene organization and functional motif analyses of the 123 two-component system (2CS) genes in Pseudomonas aeruginosa PAO1 were carried out. In addition, NJ and ML trees for the sensor kinases and the response regulators were constructed, and the distances measured and comparatively analyzed. It was apparent that more than half of the sensor-regulator gene pairs, especially the 2CSs with OmpR-like regulators, are derivatives of a common ancestor and have most likely co-evolved through gene pair duplication. Several of the 2CS pairs, especially those with NarL-like regulators, however, appeared to be relatively divergent. This is supportive of the recruitment model, in which a sensor gene and regulator gene with different phylogenetic history are assembled to form a 2CS. Correlation of the classification of sensor kinases and response regulators provides further support for these models. Upon comparison of the phylogenetic trees comprised of sensors and regulators, we have identified six congruent clades, which represent the group of the most recently duplicated 2CS gene pairs. Analyses of the congruent 2CS pairs of each of the clades revealed that certain paralogous 2CS pairs may carry a redundant function even after a gene duplication event. Nevertheless, comparative analysis of the putative promoter regions of the paralogs suggested that functional redundancy could be prevented by a differential control. Both codon usage and G+C content of these 2CS genes were found to be comparable with those of the P. aeruginosa genome, suggesting that they are not newly acquired genes.


Applications of functional data analysis: A systematic review.
Functional data analysis (FDA) is increasingly being used to better analyze, model and predict time series data. Key aspects of FDA include the choice of smoothing technique, data reduction, adjustment for clustering, functional linear modeling and forecasting methods. A systematic review using 11 electronic databases was conducted to identify FDA application studies published in the peer-review literature during 1995-2010. Papers reporting methodological considerations only were excluded, as were non-English articles. In total, 84 FDA application articles were identified; 75.0% of the reviewed articles have been published since 2005. Application of FDA has appeared in a large number of publications across various fields of sciences; the majority is related to biomedicine applications (21.4%). Overall, 72 studies (85.7%) provided information about the type of smoothing techniques used, with B-spline smoothing (29.8%) being the most popular. Functional principal component analysis (FPCA) for extracting information from functional data was reported in 51 (60.7%) studies. One-quarter (25.0%) of the published studies used functional linear models to describe relationships between explanatory and outcome variables and only 8.3% used FDA for forecasting time series data. Despite its clear benefits for analyzing time series data, full appreciation of the key features and value of FDA have been limited to date, though the applications show its relevance to many public health and biomedical problems. Wider application of FDA to all studies involving correlated measurements should allow better modeling of, and predictions from, such data in the future especially as FDA makes no a priori age and time effects assumptions.


[Information aspects of neuromicrovascular communications in traumatic neuropathies].
Based on the examination of 57 patients with nerve injuries and after the sympathectomy and 30 controls, the possibility of studying information processes in microvascular nets by the wavelet analysis of oscillatory blood flow structures has been shown for the first time. The general quantity of information, its valuable and semantic features, the influence of discrete information channels and information regime (multichanneled or by resonance) have been evaluated in microvascular nets. The deficit of both the general quantity of information and its semantic signs was characteristic of the denervation syndrome. Changes in the semantic information signs occurred mainly after the sympathectomy. The changes in the information processes reflect the functional significance of microcirculation during the nerve regeneration and skin reinnervation. The increment of the information quantity, with mainly trophic signs, occurred during the pre-impulse period of regeneration, while the semantic content of information was mainly modulated at the impulse stage. The main features of the transitional period (from pre-impulse to impulse stage) were determined as follows: the decrease of sporadic processes, the increase of determinism in the system control, the predomination of trophic information assimilation with the increment of own myogenic activity, the possibility of multichanneled regime or resonance.


Further studies on the classification of fowl adenoviruses.
In addition to the 8 fowl adenovirus serotypes described previously, 3 new serotypes were recognized. Two, A-2 and C2-B, were isolated in the U.S.A., and one, 380, in Northern Ireland. In addition another isolate, X-11, has a broader antigenicity than YR-36 and therefore should be used instead of YR-36 as prototype strain. It is concluded that there are at least 11 distinct fowl adenovirus serotypes on the basis of the serum-neutralization test.


LFACon: Introducing Anglewise Attention to No-Reference Quality Assessment in Light Field Space.
Light field imaging can capture both the intensity information and the direction information of light rays. It naturally enables a six-degrees-of-freedom viewing experience and deep user engagement in virtual reality. Compared to 2D image assessment, light field image quality assessment (LFIQA) needs to consider not only the image quality in the spatial domain but also the quality consistency in the angular domain. However, there is a lack of metrics to effectively reflect the angular consistency and thus the angular quality of a light field image (LFI). Furthermore, the existing LFIQA metrics suffer from high computational costs due to the excessive data volume of LFIs. In this paper, we propose a novel concept of "anglewise attention" by introducing a multihead self-attention mechanism to the angular domain of an LFI. This mechanism better reflects the LFI quality. In particular, we propose three new attention kernels, including anglewise self-attention, anglewise grid attention, and anglewise central attention. These attention kernels can realize angular self-attention, extract multiangled features globally or selectively, and reduce the computational cost of feature extraction. By effectively incorporating the proposed kernels, we further propose our light field attentional convolutional neural network (LFACon) as an LFIQA metric. Our experimental results show that the proposed LFACon metric significantly outperforms the state-of-the-art LFIQA metrics. For the majority of distortion types, LFACon attains the best performance with lower complexity and less computational time.


Evidence of serial connection between the plasma volume and two interstitial fluid compartments.
Kinetic analysis of fluid volume shifts can identify two interstitial fluid compartments with different turnover rates, but how they are connected to the bloodstream is unknown. Retrospective data were retrieved from 217 experiments where 1.5 L of Ringer's solution (mean) had been administered by intravenous infusion over 30 min to awake and anesthetized humans (mean age 40 years). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed models software. Possible modes of connection between the two interstitial fluid compartments and the bloodstream were judged by covariance analysis between kinetic rate constants, physiological variables, and time factors. The return flow of already distributed fluid to the plasma via a fast-exchange interstitial compartment was inhibited ongoing infusion of fluid (-38 %), which was probably due to increase of the venous pressure during volume loading. Ongoing infusion also greatly retarded the entrance of fluid to the slow-exchange compartment (-85 %), which suggests that infused Ringer's first had to enter the fast-exchange compartment. A high mean arterial pressure markedly increased the urine output and, to a lesser degree, also the rate of entrance of fluid to the fast-exchange compartment. Moreover, a high blood hemoglobin concentration retarded the rate of entrance of fluid to the fast-exchange compartment. The fast-exchange but not the slow-exchange interstitial fluid compartment was affected by intravascular events, which suggests that only the fast-exchange compartment is directly connected to the circulating blood.


Development of the Synarcual in the Elephant Sharks (Holocephali; Chondrichthyes): Implications for Vertebral Formation and Fusion.
The synarcual is a structure incorporating multiple elements of two or more anterior vertebrae of the axial skeleton, forming immediately posterior to the cranium. It has been convergently acquired in the fossil group 'Placodermi', in Chondrichthyes (Holocephali, Batoidea), within the teleost group Syngnathiformes, and to varying degrees in a range of mammalian taxa. In addition, cervical vertebral fusion presents as an abnormal pathology in a variety of human disorders. Vertebrae develop from axially arranged somites, so that fusion could result from a failure of somite segmentation early in development, or from later heterotopic development of intervertebral bone or cartilage. Examination of early developmental stages indicates that in the Batoidea and the 'Placodermi', individual vertebrae developed normally and only later become incorporated into the synarcual, implying regular somite segmentation and vertebral development. Here we show that in the holocephalan Callorhinchus milii, uniform and regular vertebral segmentation also occurs, with anterior individual vertebra developing separately with subsequent fusion into a synarcual. Vertebral elements forming directly behind the synarcual continue to be incorporated into the synarcual through growth. This appears to be a common pattern through the Vertebrata. Research into human disorders, presenting as cervical fusion at birth, focuses on gene misexpression studies in humans and other mammals such as the mouse. However, in chondrichthyans, vertebral fusion represents the normal morphology, moreover, taxa such Leucoraja (Batoidea) and Callorhinchus (Holocephali) are increasingly used as laboratory animals, and the Callorhinchus genome has been sequenced and is available for study. Our observations on synarcual development in three major groups of early jawed vertebrates indicate that fusion involves heterotopic cartilage and perichondral bone/mineralised cartilage developing outside the regular skeleton. We suggest that chondrichthyans have potential as ideal extant models for identifying the genes involved in these processes, for application to human skeletal heterotopic disorders.


[Decreased intraepithelial lymphocytes in the intestinal mucosa in children with malnutrition and parasitic infections].
In Gabon, 15 children aged 13 to 36 months admitted for malnutrition with chronic diarrhea underwent a small bowel biopsy for detection of parasites in the duodenal contents and histologic evaluation of the intestinal mucosa. In every case, intraepithelial lymphocyte counts (IELC) were under the lower limit of normal for children and adults, regardless of whether or not parasites were found. Partial villous atrophy was a consistent finding. Proportion of lymphocytes among intraepithelial cells was 7.4% in the 6 children with no parasitic infection, 7.9% in the children with giardiasis, and 8.1% in the children with strongyloidiasis. Appropriate treatment of the parasitic infections was quickly followed by resolution of the diarrhea in the nine patients with demonstrable intestinal parasites. These data should be compared with the well documented lymphocyte function anomalies associated with protein-calory malnutrition. The fall in IELC and lack of response to local anigenic stimulations are features of malnutrition.


A multicenter analysis of factors associated with change in height after adolescent idiopathic scoliosis deformity surgery in 447 patients.
In the surgical management of adolescent idiopathic scoliosis (AIS), patients are often preoperatively informed that they will gain height as a result of their surgery. However, current estimations conflict significantly and do not have any clinical correlation. The authors developed a formula that would predict postoperative gains in height after deformity correction in AIS. A large, multicenter, prospective database was retrospectively queried for AIS patients with Lenke Type 1, 2, or 3 curves having undergone posterior spinal fusion alone. A univariate and multivariate analysis was performed to identify which factors contributed significantly to changes in height. Four hundred forty-seven patients were included in the series. Factors correlating with changes in postoperative height included: upper thoracic curve magnitude, main thoracic curve magnitude, lumbar curve magnitude, T2-12 kyphosis, T5-12 kyphosis, curve flexibility, number of levels fused, presence of Ponte osteotomies, total preoperative coronal Cobb angle, change in coronal curve magnitude, total preoperative sagittal curvature, change in sagittal curvature, and thoracic curve correction. When combined in a multivariate regression analysis the following variables remained significant: thoracic curve magnitude (p < 0.01), number of levels fused (p < 0.01), change in total sagittal curvature (p < 0.01), and the presence of osteotomies (p = 0.03). The contribution from the thoracic curve magnitude was significantly greater than any of the other parameters identified (R2 = 0.140). Change in height (in cm) = ([thoracic curve magnitude × 0.039] + [number of levels fused × 0.193] - [change in sagittal curvature × 0.033] + [x × 0.375]) - 1.858, where x = 1 if 1 or more osteotomies were performed and x = 0 if no osteotomy was performed. The authors' results suggest that changes in the coronal plane contribute more significantly to height changes than those in the sagittal plane and approximately 0.39 cm of height gain can be expected for each 10° of coronal curve preoperatively. Unfortunately, a significant fraction of the postoperative height changes cannot be predicted by currently measured parameters.


Surgical palliation at a cancer center: incidence and outcomes.
Surgical intervention in palliative care is common; however, the indications, risks, and outcomes are not well described. Retrospective review of surgical cases during a 1-year period with a minimum 1-year survival update. A National Cancer Institute-designated comprehensive cancer center. Patients with a cancer diagnosis undergoing operative procedures. Number of palliative surgeries and analysis of length of stay, morbidity, and mortality. Palliative surgeries comprised 240 (12.5%) of 1915 surgical procedures. There were 170 major and 70 minor procedures. Neurosurgical (46.0%), orthopedic (31.3%), and thoracic (21.5%) surgical procedures were frequently palliative. The most common primary diagnoses were lung, colorectal, breast, and prostate cancers. Length of hospital stay was 12.4 days (range, 0-99 days), with 21.3% of procedures performed on an outpatient basis. The 30-day mortality was 12.2%, with 5 patients dying within 5 days of their procedure. The overall mortality was 23.3% (56/240). Mortality for surgical procedures classified as major was 21.9% (44/170) and 10.0% (7/70) for those classified as minor (Fisher exact test, P<.01). Significant numbers of palliative procedures are performed at our cancer center. Overall morbidity and mortality were high; however, a significant number of patients had short hospital stays and low morbidity. Palliative surgery should remain an important part of end-of-life care. Patients and their families must be aware of the high risks and understand the clear objectives of these procedures.


Utilization of Interspinous Devices Throughout the United States Over a Recent Decade: An Analysis of the Nationwide Inpatient Sample.
Retrospective database study. Analysis of economic and demographic data concerning interspinous device (ID) placement throughout the United States to improve value-based care and health care utilization. The National Inpatient Sample (NIS) database was queried for patients who underwent insertion of an interspinous process spinal stabilization device (ICD-9-CM 84.80) between 2008 and 2014 across 44 states. Demographic and economic data were obtained which included the annual number of surgeries, age, sex, insurance type, location, and frequency of routine discharge. The NIS database represents a 20% sample of discharges from US hospitals, which is weighted to provide national estimates. There was a 73% decrease in ID implanted from 2008 to 2014. The mean cost associated with insertion of the device increased 28% from $13 653 in 2008 to $17 515 in 2014. The mean length of stay (LOS) increased from 1.8 to 2.4 days. Patients aged 45 to 64 years increased from 14.1% to 34.3% while patients aged 65 to 84 years decreased from 74.4% to 60.6%. By region, 34% of ID placement occurred in the South followed by 19.7% that occured in the Northeast. When stratifying by median income for patient zip code, the procedure was performed more in cities designated as higher rather than lower income areas (74.2% and 19.5%, respectively). Throughout the United States, there was a progressive decline in the insertion of interspinous spacers by 73% over the study period. The total costs for the procedure increased by 28% while the aggregate national charges decreased by 55.6% between 2008 and 2014.


The application of C12 biochip in the diagnosis and monitoring of colorectal cancer: systematic evaluation and suggestion for improvement.
The 12 tumor markers' (TMs) biochip diagnostic (C12) system has been proven useful in some previous studies but its value for colorectal cancer (CRC) only was not systematically investigated. To evaluate the value of C12 system for CRC. The associations between TMs and clinicopathological characteristics were evaluated. The most relevant TMs, the most useful combinations, and the correlations between TM levels were assessed. The TMs detected by the C12 system in the sera of 170 pathologically confirmed CRC patients were analyzed. One or more TMs higher than or equal to reference value were defined as positive. Chi-square test, Spearman rank correlation test and Receiver-operating characteristic (ROC) curves were used for the analysis. The overall positive rate was 41.76%, and was low in stage 0-I (12.90%). Carcinoembryonic cantigen (CEA) had the highest positive rate of 36.47%. The positive rates were significantly correlated to clinical stages and lymph node status, but not to age, sex, tumor location and pathological types. Any combinations of the five highest positive TMs did not have significantly improvements. The levels of three most related TMs (CEA, CA19-9, CA242) of CRC had positive correlation with each other. CA242 and beta-HCG levels were associated with lymph node metastasis. C12 system has some value in advanced CRC, but not in early CRC.


Characterization of monoclonal antibodies against human low density lipoprotein.
Seven monoclonal antibodies against human low density lipoprotein (LDL) have been characterized as to their specificity and ability to interfere with the LDL pathway in cultured human fibroblasts. The immunoreactivity with LDL of two of the antibodies (2D8 and 4G3) was particularly sensitive to modification of lysine and arginine residues in LDL. Cotitration experiments indicated that the antibodies 3A8 and 3A10 may react with the same determinant and that five antibodies (5E11, 3A8, 3A10, 4G3 and 3F5) recognized determinants that were grouped in the same region of the molecule. The two other antibodies (1D1 and 2D8) reacted with determinants distant from this region. When tested in molar excess relative to LDL, Fab fragments of 5E11, 3A8, 3A10, 4G3 and 3F5 (but not 1D1 or 2D8) were capable of blocking the binding of 125I-LDL to the LDL receptor and interfering with LDL suppression of cholesterol synthesis in cultured fibroblasts. Increasing the concentration 10-fold did not change the results significantly. Based on these results we have proposed a map of the determinants as they would appear in LDL.


Low 25 Hydroxyvitamin D Levels are Independently Associated with Autoimmune Thyroiditis in a Cohort of Apparently Healthy Overweight and Obese Subjects.
Low vitamin D levels have been associated with autoimmune disorders and, then, with the Hashimoto's autoimmune thyroiditis (AT), the most common autoimmune disease. Obesity is characterized by lower vitamin D levels and higher risk to develop autoimmune diseases. The aim of the study was to examine the possibility of an association between AT and decreased 25(OH) vitamin D (25(OH)D) levels in a cohort of otherwise healthy overweight and obese subjects. Two hundred sixty one overweight subjects (mean age: 40.9 + 15.6 years, 200 women and 61 men) were enrolled for this study. All of them did not show any clinically evident metabolic or chronic diseases (i.e. hypertension, diabetes mellitus, renal failure, etc.) and did not use any kind of drug. Serum fasting levels of 25(OH)D, anti-thyroid peroxidase (TPO-Ab) and antithyroglobulin (TG-Ab) antibodies, free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), glucose, uric acid and lipids (triglycerides, total, HDL and LDL cholesterol) were measured. Demographic, anthropometric and clinical parameters (age, body mass index (BMI), waist circumference, blood pressure) were also assessed. Fifty five percent of all subjects (144/261) showed vitamin D deficiency (≤ 20 ng/ml), and 17% of all individuals had AT (45/261). The percentage of subjects having vitamin D deficiency was significantly higher among those with AT (31 of 45, 69%) than in those without AT (113 of 216, 52%) (χ2= 4.1, p = 0.042). TSH levels were significantly higher in subjects with AT as compared to those without AT (M-W = 7715.5, p < 0.0001). The final logistic model of a multivariate analysis, performed with AT as the dependent variable and sex, age, BMI category, 25(OH)D category, and HDLcholesterol and TSH levels as the independent ones, showed that patients with AT were more likely to have deficiency of 25(OH)D (p = 0.031) and higher TSH (p < 0.005) levels. Seventy six percent of patients with vitamin D deficiency (110 of 144) were obese whereas 59% of patients without vitamin D deficiency were obese (69 of 117) (p=0.003). Waist circumference was different between subjects with deficiency or normal 25 (OH) D levels (p=0.016). This study clearly shows that vitamin D deficiency is significantly associated to AT in overweight and obese subjects and confirms that obesity is associated to lower vitamin D circulating levels. We suggest that screening for AT should be suggested in all obese subjects with vitamin D deficiency and that vitamin D deficiency should be researched in all obese subjects with AT.


The Dapsone hypersensitivity syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations.
4,4'-Diaminodiphenylsulphone (Dapsone) is widely used for a variety of infectious, immune and hypersensitivity disorders, with indications ranging from Hansen's disease, inflammatory disease and insect bites, all of which may be seen as manifestations in certain occupational diseases. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma. Methemoglobinemia with resultant cyanosis, bone marrow aplasia and/or hemolytic anemia, peripheral neuropathy and the potentially fatal dapsone hypersensitivity syndrome (DHS), the focus of this review, may all occur individually or in combination. DHS typically presents with a triad of fever, skin eruption, and internal organ (lung, liver, neurological and other systems) involvement, occurring several weeks to as late as 6 months after the initial administration of the drug. In this sense, it may resemble a DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms). DHS must be promptly identified, as untreated, the disorder could be fatal. Moreover, the pulmonary/systemic manifestations may be mistaken for other disorders. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy. Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management.


[Omega-3-fatty acids, Mediterranean cooking, low-fat diet. What really prevents myocardial infarct?].
The strength of evidence in support of dietary measures in the secondary prevention of coronary artery disease is variable (Table 1). The most impressive data available concern the impact of omega-3 fatty acids found in sea-fish at an intake of about 1.0 g/day, but the data underscoring the value of a Mediterranean diet are also convincing. No comparable data are available for low-fat and fat-modified diets. For diabetics, an HbA1c of < 7% should be achieved. There is indirect evidence that a body mass index of between 18.5 and 23.9 kg is optimal, and can be achieved by physical exercise and weight control. Weight reduction also lowers blood pressure, a goal that can equally be reached by a low-salt diet rich in fruit and vegetables, and the practice of endurance sports. The results of ongoing studies on the use of vitamin supplements are as yet unavailable.


Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR.
Little is known about what roles the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play in drug metabolism in high-altitude hypoxia. Likewise, the potential interaction of nuclear receptors and drug metabolism enzymes during drug metabolism of high-altitude hypoxia is not fully understood. In this work, we investigated the effects of high-altitude hypoxia on transcriptional regulation of cytochrome P450 (CYP450) and UDP-glucuronosyltransferase 1A1 (UGT1A1) genes mediated by PXR and CAR proteins. The protein and mRNA expressions of CYP450, UGT1A1, PXR, and CAR were determined by enzyme-linked immunosorbent assay and qPCR in rats and HepG2 cell lines under hypoxia. Hypoxia potently inhibited the CYP450 isoforms, UGT1A1, PXR, and CAR protein and mRNA expression. To clarify whether PXR and CAR regulate various genes involved in drug metabolism of high-altitude hypoxia, we investigated the expression of CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 using a dual-luciferase reporter assay after treatment with Ketoconazole (KCZ) and Retinoic acid (RA), or silenced PXR and CAR gene expression. In HepG2 cells, hypoxia, KCZ, and RA inhibited CYP450 isoforms and UGT1A1 expression. Activation of PXR and CAR in cells treated with 6-(4-chlorophenyl)-imidazo (2,1-b) thiazole-5-carbaldehyde (CITCO) and rifampicin (Rif) resulted in the enhancement of CYP450 isoforms, UGT1A1, PXR, and CAR. In contrast, this effect was not observed under hypoxia. Taken together, our results suggest that hypoxia inhibits CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 expression via the PXR and CAR regulatory pathway.


Does reproduction protect against oxidative stress?
A central principle of life-history theory is that parents trade investment in reproduction against that in body maintenance. One physiological cost thought to be important as a modulator of such trade-off is oxidative stress. Experimental support for this hypothesis has, however, proved to be contradictory. In this study, we manipulated the nestling rearing effort of captive canaries (Serinus canaria) soon after the hatching of their nestlings using a brood-size manipulation to test whether an increase in nestling rearing effort translates into an increase in oxidative damage, an increase in ceruloplasmin (which is upregulated in response to oxidative damage) and a decrease in thiol antioxidants. We also compared the blood oxidative stress level of reproducing birds with that of non-reproducing birds, a crucial aspect that most studies have invariably failed to include in tests of the oxidative cost of reproduction. Compared with non-breeding canaries and pre-manipulation values, plasma oxidative damage (reactive oxygen metabolites and protein carbonyls) decreased in breeding canaries irrespective of sex and brood size. In contrast, oxidative damage did not change in non-breeding birds over the experiment. Ceruloplasmin activity in plasma and both non-protein and protein thiols in red blood cells did not change throughout the experiment in both treatment groups. Our results suggest that reproduction may result in decreased rather than increased blood oxidative stress. Our results may explain some of the inconsistencies that have so far been reported in experimental tests of the oxidative cost of reproduction hypothesis.


Significance of eosinophiluria in urinary schistosomiasis. A study using Hansel's stain and electron microscopy.
Urine deposit smears of 58 patients with urinary schistosomiasis, 20 with acute glomerulonephritis, and 14 with urinary stones were stained with Hansel's stain. Eosinophiluria was seen in all cases of urinary schistosomiasis (median 0.73 [73%] of urinary white blood cells [WBCs]); 13 (65%) of those with acute glomerulonephritis (median 0.03 [3%] of urinary WBCs); and 2 (14%) patients with urinary stones (0.01 [1%] and 0.05 [5%] of urinary WBCs). Other features included the presence of ova and activated macrophages and giant cells in urinary schistosomiasis, an increased number of mononuclear cells and stained cellular casts in acute glomerulonephritis, and an increased number of neutrophils in urinary stones. In schistosomiasis, urine differential leukocyte counts were unrelated to those of the blood. Moreover, urine eosinophil percentages were always higher than those in the blood. Thus, in urinary schistosomiasis, eosinophiluria could be explained by exudation, sloughing of granulomata, as well as bleeding from the urinary tract surface. Electron microscopic examination confirmed that most of the leukocytes were eosinophils. Some of these were adherent and degranulating over ova with variable miracidial damage. Urine eosinophil and egg counts were not correlated to each other. Staining urine deposit smears, with the use of Hansel's stain, is useful in the investigation of hematuria. Heavy eosinophiluria and few mononuclear cells favor the diagnosis of urinary schistosomiasis rather than acute glomerulonephritis or urinary stones. These results diminish the value of eosinophiluria as corroborative evidence of drug-induced interstitial nephritis in areas of endemic urinary schistosomiasis.


Time Frame Affects Vantage Point in Episodic and Semantic Autobiographical Memory: Evidence from Response Latencies.
Previous research suggests that, with the passage of time, representations of self in episodic memory become less dependent on their initial (internal) vantage point and shift toward an external perspective that is normally characteristic of how other people are represented. The present experiment examined this phenomenon in both episodic and semantic autobiographical memory using latency of self-judgments as a measure of accessibility of the internal vs. the external perspective. Results confirmed that in the case of representations of the self retrieved from recent autobiographical memories, trait-judgments regarding unobservable self-aspects (internal perspective) were faster than trait judgments regarding observable self-aspects (external perspective). Yet, in the case of self-representations retrieved from memories of a more distant past, judgments regarding observable self-aspects were faster. Those results occurred for both self-representations retrieved from episodic memory and for representations retrieved from the semantic memory. In addition, regardless of the effect of time, greater accessibility of unobservable (vs. observable) self-aspects was associated with the episodic rather than semantic autobiographical memory. Those results were modified by neither declared trait's self-descriptiveness (yes vs. no responses) nor by its desirability (highly desirable vs. moderately desirable traits). Implications for compatibility between how self and others are represented and for the role of self in social perception are discussed.


Repolarization changes induced by air pollution in ischemic heart disease patients.
Epidemiologic studies report associations between particulate air pollution and cardiovascular morbidity and mortality, but the underlying pathophysiologic mechanisms are still unclear. We tested the hypothesis that patients with preexisting coronary heart disease experience changes in the repolarization parameters in association with rising concentrations of air pollution. A prospective panel study was conducted in Erfurt, East Germany, with 12 repeated electrocardiogram (ECG) recordings in 56 males with ischemic heart disease. Hourly particulate and gaseous air pollution and meteorologic data were acquired. The following ECG parameters reflecting myocardial substrate and vulnerability were measured: QT duration, T-wave amplitude, T-wave complexity, and variability of T-wave complexity. Fixed effect regression analysis was used adjusting for subject, trend, weekday, and meteorology. The analysis showed a significant increase in QT duration in response to exposure to organic carbon; a significant decrease in T-wave amplitude with exposure to ultrafine, accumulation mode, and PM2.5 particles (particles < 2.5 microm in aerodynamic diameter); and a corresponding significant increase of T-wave complexity in association with PM2.5 particles for the 24 hr before ECG recordings. Variability of T-wave complexity showed a significant increase with organic and elemental carbon in the same time interval. This study provides evidence suggesting an immediate effect of air pollution on repolarization duration, morphology, and variability representing myocardial substrate and vulnerability, key factors in the mechanisms of cardiac death.


H1-receptor antagonists: effects on leukocytes, myth or reality?
H1-receptor antagonists of the first and second generation have been used for many years to relieve symptoms arising from the action of histamine on the H1 receptor. However, allergic inflammation is more than histamine release and action. Leukocyte infiltration during late allergic manifestations was demonstrated as being a hallmark of allergic inflammation. Second-generation H1-receptor antagonists were studied in models of mast cell degranulation in vitro and of leukocyte infiltration in vivo. Analysis of the literature showed that a drug which is no more metabolized than cetirizine and fexofenadine allows a better relevance of in vitro models. Up to now, cetirizine was the only product in vivo able to reduce eosinphil infiltration in skin, nose, eyes and lungs during experimental allergenic challenges and late allergic inflammatory manifestations. Today, relevance of these properties can be seen in the recently published clinical results showing that cetirizine prevents the development of asthma in specifically sensitized infants with atopic dermatitis.


Cost-effectiveness modelling of IVF in couples with unexplained infertility.
Does delaying IVF for 6 months in couples with unexplained infertility, compared with immediate IVF treatment, decrease the cost of IVF without compromising success rates? Decision modelling was used to evaluate the cost and outcomes of immediate IVF versus delayed IVF for a cohort of women aged <40 years suffering unexplained infertility. Australian data and costs were used in the analysis. For different age groups, three scenarios were tested where 10%, 50% and 90% of couples with unexplained infertility delayed IVF for 6 months if they had a good prognosis for natural conception. The study included a total of 8781 couples aged <40 years, diagnosed with unexplained infertility and who had IVF in 2013. The studied couples underwent 27,648 fresh and frozen embryo transfers, for an estimated total cost of $141 million. Potential out-of-pocket cost savings if 90% of couples delayed IVF ranged from $4.7 to $12.2 million, with Medicare cost savings of up to $15.1 million. The impact on the total pregnancy and live birth rates after 18 months was minimal. In couples with unexplained infertility and a good prognosis for natural conception, delaying IVF for 6 months could substantially decrease out-of-pocket costs without compromising pregnancy and live birth rates over an 18-month period.