Henoch-Schönlein nephritis: a nationwide study.
The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely.


Leishmaniasis vaccines: past, present and future.
No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis.


Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission.
HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.


No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study.
Recent studies using colour-coded Doppler sonography showed that chronic impaired venous drainage from the central nervous system is almost exclusively found in multiple sclerosis (MS) patients. This study aimed to investigate the intracranial and extracranial venous anatomy and the intracerebral venous flow profile in patients with MS and healthy controls using magnetic resonance venography (MRV). Twenty patients with definite MS and 20 age- and gender-matched healthy controls were examined. MR imaging was performed on a whole-body 3T MR system including both 3D phase-contrast and dynamic 3D contrast-enhanced MRV as well as flow quantification of the internal cerebral veins and the straight sinus. Image analysis was performed by two experienced interventional neuroradiologists blinded to clinical data and structural brain imaging. The intracranial and extracranial neck veins were analysed for stenosis/occlusion and alternative venous drainage pattern. A completely normal venous anatomy was observed in 10 MS patients and 12 controls. Anomalies of the venous system (venous stenosis/occlusions) were found in 10 MS patients and eight healthy controls. An anomalous venous system in combination with associated alternative venous drainage was observed in six MS patients and five healthy controls. Flow quantification showed no venous backflow in any MS patient or control. Findings suggestive of anomalies of the cranial venous outflow anatomy were frequently observed in both MS patients and healthy controls. Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions.


Size of canine hepatocellular carcinoma as an adverse prognostic factor for surgery.
Liver neoplasms are problematic among small domestic animals. The etiological cause of hepatocellular carcinomas in domestic animals is still unknown although it is believed that chronic infections and toxic substances can affect the development of this type of tumor. This study aimed to analyze the clinical and morphological characteristics of canine hepatocellular carcinoma. In total, 6,958 cancer operations were performed in the clinic. Liver tumors were detected in 123 dogs in vivo and 375 dogs postmortem. All animals with suspected liver neoplasm were assessed, including history, clinical examination, complete blood count, biochemical blood tests, radiographic examination, and ultrasound with a biopsy for performing cytological and histological analyses. Hepatocellular carcinomas have nonspecific clinical manifestations, also a characteristic aspect of other tumors of the hepatobiliary system. The hematological changes have an impact on the prognosis, and biochemical abnormalities reflect the changes in liver activity. The cytological diagnosis of hepatocellular tumors is difficult because of hepatocyte atypia in highly differentiated carcinomas. Finally, a histological examination was performed in all the dogs diagnosed with hepatocellular carcinoma. Hematological changes in dogs with hepatocellular carcinoma affect their prognosis. Biochemical abnormalities of this pathology reflect the changes in liver activity, not indicating a specific pathology. However, an increase in the activity of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase is an unfavorable prognostic sign. In this study, five of seven dogs with a tumor size of more than 5.0 cm had a life expectancy of 30, 51, and 91 days, suggesting that the size of the tumor is an adverse prognostic factor.


Immune response and neurotrophic factor interactions in peripheral nerve transplants.
Several types of immunocompetent cells of hematopoietic origin are involved in determining the immunological and regenerative fate of peripheral nerve transplants used for neurosurgical repair. The present study compares the immunological fate of nerve isografts and allografts with emphasis on the immunobiological events and neurotrophic interactions leading to graft survival and nerve fiber regeneration through them. The nerve transplantation model is unique as tissue rejection/inflammation is observed along with the nerve regeneration process. Nerve grafts become vascularized within a few days via neovascularization after transplantation. This is followed by progressive invasion of host macrophages and T lymphocytes that recognize the histocompatible antigens and initiate the rejection response. Two main types of donor resident cells are involved in early stages of graft rejection. These are macrophages and Schwann cells. Both of these cells have been found to possess antigen-presenting function and also can produce several cytokines. The most relevant to the peripheral nerves are tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), interferon-gamma (IFN-gamma) and IL-12. TNF-alpha in addition to its capacity to kill cells is involved in activation of macrophages. IL-12 and IFN-gamma have a potential role in modulating and enhancing of the immune response. Finally, IL-1 is of special significance because it promotes the expression of nerve growth factor (NGF) by the Schwann cells of the peripheral nerve and is important for nerve fiber regeneration. NGF in turn has been shown to enhance macrophage function and inflammatory response. Taken together, these findings show that NGF levels and inflammation in injured tissue play an important role in determining the success of transplants and in tissue repair.


Physiology and topography of neurons with multipeaked tuning curves in cat primary auditory cortex.
1. The physiology and topography of single neuron responses along the isofrequency domain of the middle- and high-frequency portions [characteristic frequencies (CFs) greater than 4 kHz] of the primary auditory cortex (AI) were investigated in the barbiturate-anesthetized cat. Single neurons were recorded at several locations along the extent of isofrequency contours, defined from initial multiple-unit mapping. For each neuron a high-resolution excitatory tuning curve was determined, and for some neurons high-resolution two-tone tuning curves were recorded to measure inhibitory/suppressive areas. 2. A physiologically distinct population of neurons was found in the dorsal part of cat AI. These neurons exhibited two or three distinct excitatory frequency ranges, whereas most neurons in AI responded with excitation to a single narrow frequency range. These were called multipeaked neurons because of the shape of their tuning curves. At frequencies between the excitatory regions, the multipeaked neurons were inhibited or unresponsive. 3. Multipeaked neurons exhibited several distinct threshold minima in their frequency tuning curves. Most of the multipeaked neurons (88%) displayed two frequency minima, whereas the rest exhibited three minima. 4. The frequency separation between threshold minima was less than 1 octave in 71% of the double-peaked neurons recorded. Occasionally, the frequency peaks of these neurons closely corresponded to a response to second and third harmonics without a response to the fundamental frequency. 5. Multipeaked neurons exhibited a wide range of total bandwidths (highest excitatory frequency minus lowest excitatory frequency expressed in octaves). Bandwidths of the isolated peaks within the same neuron were also quite variable. 6. Response latencies to tones with frequencies within each peak of a multipeaked neuron could vary considerably. In 71% (17) of the neurons, tones corresponding to the high-frequency peak (CFh) elicited a longer response latency (greater than 4 ms) than those corresponding to the low-frequency peak (CF1). 7. Inhibitory/suppressive bands, as demonstrated with a two-tone paradigm, were often present between the peaks. Typically, neurons with excitatory peaks of similar response latencies showed an inhibitory band located between the peaks. 8. Ninety percent of the topographically localized multipeaked neurons were in the dorsal part of AI (greater than 1 mm dorsal to the maximum in the sharpness-of-tuning map). Although these neurons were restricted to dorsal AI, only 35% of neurons in this region were multipeaked. 9. Multipeaked neurons could show decreased response latencies and thresholds to two-tone combinations.(ABSTRACT TRUNCATED AT 400 WORDS)


Life cycle and suicidal behavior among women.
It is nowadays accepted that, independently of methodological issues, women commit fewer suicides than men but make more frequent attempts. Yet, female suicidal risk varies greatly along the lifetime and is linked to the most significant moments in it. A wide analysis of the existing literature was performed to provide a narrative description on the evolution of female suicidal rates from childhood to old age, considering the milestones in their life history. A detailed analysis of gender differences in suicidal behavior is key to establish preventive measures and priorities. More specific studies are needed to adapt future interventions on female suicide.


The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues.
Copolymers of hydroxyethyl methacrylate and styrene sulfonate complex with isolated gliadin (the toxic fraction of gluten) and prevent damage to the intestinal barrier in HLA-HCD4/DQ8 mice. We studied the activity toward gluten and hordein digestion and biologic effects of poly(hydroxyethyl methacrylate-co-styrene sulfonate (P(HEMA-co-SS)). We also investigated the effect of gliadin complex formation in intestinal biopsy specimens from patients with celiac disease. We studied the ability of P(HEMA-co-SS) to reduce digestion of wheat gluten and barley hordein into immunotoxic peptides using liquid chromatography-mass spectrometry. The biodistribution and pharmacokinetic profile of orally administered P(HEMA-co-SS) was established in rodents using tritium-labeled polymer. We assessed the capacity of P(HEMA-co-SS) to prevent the immunologic and intestinal effects induced by a gluten-food mixture in gluten-sensitized HLA-HCD4/DQ8 mice after short-term and long-term administration. We measured the effects of gliadin complex formation on cytokine release ex vivo using intestinal biopsy specimens from patients with celiac disease. P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein in vitro, thereby decreasing formation of toxic peptides associated with celiac disease. After oral administration to rodents, P(HEMA-co-SS) was predominantly excreted in feces, even in the presence of low-grade mucosal inflammation and increased intestinal permeability. In gluten-sensitized mice, P(HEMA-co-SS) reduced paracellular permeability, normalized anti-gliadin immunoglobulin A in intestinal washes, and modulated the systemic immune response to gluten in a food mixture. Furthermore, incubation of P(HEMA-co-SS) with mucosal biopsy specimens from patients with celiac disease showed that secretion of tumor necrosis factor-α was reduced in the presence of partially digested gliadin. The copolymer P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein and attenuated the immune response to gluten in a food mixture in rodents. It might be developed to prevent or reduce gluten-induced disorders in humans.


Ge12{Fe(CO)3}8(μ-I)4: a germanium-iron cluster with Ge4, Ge2 and Ge units.
The germanium-iron cluster Ge12{Fe(CO)3}8(μ-I)4 was prepared by reacting GeI4 and Fe2(CO)9 in [BMIm]Cl/AlCl3 as ionic liquid (BMIm: 1-butyl-3-methylimidazolium). The cluster contains a Ge12Fe8 metal core consisting of a central Ge4 rectangle, two Ge2 pairs, and four single Ge atoms. These Ge units are interconnected by Fe atoms to a real Ge-Fe cluster. According to DFT calculations, Hund's localization criterion is fulfilled for the whole cluster if we assume three different atomic charges on the Ge4, Ge2, and Ge units.


Critical periodic systemic blood pressure fluctuations during pulmonary valve replacement cardiac surgery in a patient with an incidentally discovered normotensive pheochromocytoma-A case report.
Standard management protocols for patients with pheochromocytoma (PHEO) have been described in current guidelines. However, the standard management approach for cardiac surgical patients with concurrent clinically silent PHEO has not been established yet. The effects of open heart surgery and cardiopulmonary bypass (CPB) on PHEO presentation are poorly documented. Here, we report in detail the anesthetic management and hemodynamic changes in a case of CPB-assisted pulmonary valve replacement surgery with an incidentally discovered normotensive PHEO. A 55-year-old male with normotensive PHEO underwent an open heart pulmonary valve replacement surgery. Blood pressure (BP) fluctuated with an inherent alternation rhythm during the whole process of the surgery with a peak at 230/130 mmHg and nadir at 40/30 mm Hg. Administration of fluids and vasoconstrictor/vasodilator was used for BP optimization. However, the BP changed intractably with delayed responses to the optimization management. The hemodynamic instability observed in this case indicated that the risk of occurrence and severity of the PHEO crisis did not decrease in cases with previously silent PHEO and may be triggered in any clinical scenario, not in tumor removal procedures alone. Careful preoperative evaluation and preparation with multidisciplinary cooperation are of paramount importance for such patients because open chest cardiac surgery and CPB could complicate the situation. In addition, there is little evidence about the benefits of a combined cardiac surgery with PHEO resection in such a clinical scenario, which validates further investigation.


Substrate transport activation is mediated through second periplasmic loop of transmembrane protein MalF in maltose transport complex of Escherichia coli.
In a recent study we described the second periplasmic loop P2 of the transmembrane protein MalF (MalF-P2) of the maltose ATP-binding cassette transporter (MalFGK(2)-E) as an important element in the recognition of substrate by the maltose-binding protein MalE. In this study, we focus on MalE and find that MalE undergoes a structural rearrangement after addition of MalF-P2. Analysis of residual dipolar couplings (RDCs) shows that binding of MalF-P2 induces a semiopen state of MalE in the presence and absence of maltose, whereas maltose is retained in the binding pocket. These data are in agreement with paramagnetic relaxation enhancement experiments. After addition of MalF-P2, an increased solvent accessibility for residues in the vicinity of the maltose-binding site of MalE is observed. MalF-P2 is thus not only responsible for substrate recognition, but also directly involved in activation of substrate transport. The observation that substrate-bound and substrate-free MalE in the presence of MalF-P2 adopts a similar semiopen state hints at the origin of the futile ATP hydrolysis of MalFGK(2)-E.


Higher levels of thymidylate synthase gene expression are observed in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma.
It has been observed previously that the pulmonary metastases of colorectal adenocarcinoma are less responsive to therapy with fluorouracil (FUra) as compared with other sites of metastasis (liver, local). To investigate the basis of this chemoresistance, the levels of thymidylate synthase (TS) mRNA and protein were measured, as TS expression has been shown to be predictive of response to therapy in colorectal cancer. Tumors were obtained from 19 patients with metastatic colorectal cancer (12 hepatic and seven pulmonary). TS expression was measured by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and TS protein levels were measured by Western blotting. The presence of TS amplification was assessed by Southern blotting. Levels of p53 protein were determined using immunohistochemistry. TS mRNA expression was shown to be significantly higher in the pulmonary metastases (mean TS/beta-actin ratio, 19.7; n = 7) as compared with the hepatic metastases (mean TS/beta-actin ratio, 4.7; n = 11) of colorectal cancer. Lower TS expression was observed in patients with hepatic metastases who had received prior FUra versus patients who had not been treated. High levels of TS expression in some samples was associated with low-level (two to three gene copies) increases in TS gene copy numbers and this was observed more frequently in the pulmonary metastatic samples. The increased gene copy numbers occurred both in samples with wild-type p53 and those with mutant p53 tumor-suppressor gene as determined by immunohistochemistry. High levels of TS enzyme may be the basis of the lack of response of pulmonary metastases to FUra treatment.


Individual Differences in Sleep Timing Relate to Melanopsin-Based Phototransduction in Healthy Adolescents and Young Adults.
Individual differences in sleep timing have been widely recognized and are of particular relevance in adolescents and young adults who often show mild to severely delayed sleep. The biological mechanisms underlying the between-subject variance remain to be determined. Recent human genetics studies showed an association between sleep timing and melanopsin gene variation, but support for functional effects on downstream pathways and behavior was not demonstrated before. We therefore investigated the association between the autonomic (i.e., pupil diameter) and behavioral (i.e., sleep timing) readouts of two different downstream brain areas, both affected by the same melanopsin-dependent retinal phototransduction: the olivary pretectal nucleus (OPN) and the suprachiasmatic nucleus (SCN). Our study population included 71 healthy individuals within an age range with known vulnerability to a delayed sleep phase (16.8-35.7 y, 37 males, 34 females). Pupillometry was performed to estimate functionality of the intrinsic melanopsin-signaling circuitry based on the OPN-mediated post-illumination pupil response (PIPR) to blue light. Sleep timing was quantified by estimating the SCN-mediated mid-sleep timing in three different ways in parallel: using a chronotype questionnaire, a sleep diary, and actigraphy. All three measures consistently showed that those individuals with a later mid-sleep timing had a more pronounced PIPR (0.03 < P < 0.05), indicating a stronger blue-light responsiveness of the intrinsic melanopsin-based phototransduction circuitry. Trait-like individual differences in the melanopsin phototransduction circuitry contribute to individual differences in sleep timing. Blue light-sensitive young individuals are more prone to delayed sleep.


Anesthesia for patients with severe chronic obstructive pulmonary disease.
Patients with chronic obstructive lung disease experience an increased risk of perioperative pulmonary complications. This review presents an evidence-based approach to perioperative care designed to optimize management. Recent research has provided guidance regarding intraoperative and postoperative administration of oxygen and the selective use of volatile agents. The significance of preoperative malnutrition and postoperative epidural analgesia on outcomes has also been explored further. The opportunity for anesthesiologists to engage in tobacco interventions and the benefits of addressing smoking cessation have been studied. Optimization for surgery includes preoperative treatment of reversible airway obstruction and respiratory infections, smoking cessation, and possibly nutritional interventions. Meticulous intraoperative monitoring combined with a sound understanding of pathophysiological mechanisms underlying air trapping will help clinicians strike a balance between permissive hypercapnia and adequate ventilation.


Sex therapy for erectile dysfunction: characteristics of couples, treatment outcome, and prognostic factors.
Outcome and prognostic factors were studied in 36 couples who entered sex therapy because of the male partners' erectile dysfunction. Treatment was completed by two thirds. Noncompletion was associated with lower socioeconomic status, the female partner having a history of psychiatric treatment, pretreatment poorer motivation of the male partner, poor communication in the general relationship, and less sexual pleasure experienced by the female. A positive treatment outcome occurred in 69.4%, and was associated with better pretreatment communication and general sexual adjustment, especially the female partner's interest and enjoyment of sex, absence of a positive psychiatric history in the female partner, and a couple's early engagement in homework assignments. Results highlight important aspects of the initial assessment, indicate couples for whom the initial phase of treatment should be prolonged and modified or an alternative approach considered, and have implications for assignment of couples to treatment groups in evaluative studies of therapy.


Royal jelly attenuates azathioprine induced toxicity in rats.
In the present study, we investigated the potential protective effects of royal jelly against azathioprine-induced toxicity in rat. Intraperitoneal administration of azathioprine (50 mg/kgB.W.) induced a significant decrease in RBCs count, Hb concentration, PCV%, WBCs count, differential count and platelet count, hepatic antioxidant enzymes (reduced glutathione and glutathione s-transferase) and increase of serum transaminases (alanine aminotransferase and aspartate aminotransferase enzymes) activities, alkaline phosphatase and malondialdehyde formation. Azathioprine induced hepatotoxicity was reflected by marked pathological changes in the liver. Oral administration of royal jelly (200 mg/kgB.W.) was efficient in counteracting azathioprine toxicity whereas it altered the anemic condition, leucopenia and thrombocytopenia induced by azathioprine. Furthermore, royal jelly exerted significant protection against liver damage induced by azathioprine through reduction of the elevated activities of serum hepatic enzymes. Moreover, royal jelly blocked azathioprine-induced lipid peroxidation through decreasing the malondialdehyde formation. In conclusion, royal jelly possesses a capability to attenuate azathioprine-induced toxicity.


Understanding the natural history of focal nodular hyperplasia in the liver with MRI.
To determine the incidence of natural growth or regression of focal nodular hyperplasia (FNH) in the liver. We retrospectively included 120 consecutive patients who were diagnosed to have FNH on MRI. The mean follow-up duration was 19 months (range: 6-64 months). There were 25 men and 95 women (age range: 18-80 years; mean: 45 years). There were 167 FNH lesions in the 120 patients. MRI images were retrospectively reviewed for interval growth or regression of FNH. The maximum size of the lesions was measured on axial arterial-phase images of the initial and the last MRI examinations. An interval increase or decrease in diameter of over 10% of the initial diameter was considered as positive growth or regression, respectively. The use of Oral contraceptives was also documented. Interval growth was seen in 25/167 nodules (15%) over 7-48 months (mean: 21 months), with increase in size of 0.2-1.7 cm (mean: 0.6 cm) and percentage change of 10.5-340% (mean: 64%). Interval regression was seen in 13/167 (8%) of nodules over 7-63 months (mean: 22 months), with decrease in size of 0.2-0.9 cm (mean: 0.5 cm) and percentage change of 10.4-60% (mean: 24%).Five of 17 (29%) female patients with growing FNH and 25/78 (32%) female patients with non-growing FNH had a history of intake of oral contraceptives (P=0.83). Although FNH is benign and of no clinical significance, a substantial percentage of FNH shows interval growth or regression on long-term follow-up with MRI.


Understanding chain looping kinetics in polymer solutions: crowding effects of microviscosity and collapse.
A theoretical framework based on a generalized Langevin equation with fractional Gaussian noise is presented to describe the looping kinetics of chains in polymer solutions. Particular attention is paid to quantitatively revealing crowding effects on the loop formation rate in terms of microviscosity and collapse. By the aid of empirical relations for these two crowding associated physical quantities, we explicitly investigate the relationship between the looping rate and polymer concentration, the degree of polymerization, and system parameters. According to our analysis, the dependence of the looping rate on the crowder volume fraction exhibits three typical regimes: monotonic decreasing, a non-monotonic trend and monotonic increasing. We reveal that these non-trivial behaviors can be attributed to the competition between the two opposing factors of viscosity-associated inhibition and collapse-induced facilitation of loop formation. We apply our theory to analyze the kinetics of single-stranded DNA hairpin base pairing in polyethylene glycol solutions. The theoretical results can reproduce the experimental data on the closing rate of hairpins quantitatively to a certain degree with reasonable fitting parameters. The unexpected increase of the closing rate upon the addition of increasing amounts of polymer is well rationalised. Such good agreements clearly demonstrate the validity of our theory, appropriately addressing the very role of crowding effects in the relevant kinetics.


Determinants of physical activity in active and low-active, sixth grade African-American youth.
This study compared the determinants of physical activity in active and low-active African-American sixth grade students (N = 108, 57 F, 51 M). Objective assessments of physical activity over a seven-day period were obtained using the CSA 7164 accelerometer. Students were classified as active if they exhibited three or more 20-minute bouts of moderate to vigorous physical activity over the seven-day period. Relative to low-actives, active boys reported significantly higher levels of self-efficacy, greater involvement in community physical activity organizations, and were significantly more likely to perceive their mother as active. Relative to low-actives, active girls reported significantly higher levels of physical activity self-efficacy, greater positive beliefs regarding physical activity outcomes, and were significantly less likely to watch television or play video games for > or = 3 hrs/day. These observations provide preliminary guidance as to the design of physical activity interventions targeted at African-American youth.


What range of trait levels can the Autism-Spectrum Quotient (AQ) measure reliably? An item response theory analysis.
It has previously been noted that inventories measuring traits that originated in a psychopathological paradigm can often reliably measure only a very narrow range of trait levels that are near and above clinical cutoffs. Much recent work has, however, suggested that autism spectrum disorder traits are on a continuum of severity that extends well into the nonclinical range. This implies a need for inventories that can capture individual differences in autistic traits from very high levels all the way to the opposite end of the continuum. The Autism-Spectrum Quotient (AQ) was developed based on a closely related rationale, but there has, to date, been no direct test of the range of trait levels that the AQ can reliably measure. To assess this, we fit a bifactor item response theory model to the AQ. Results suggested that AQ measures moderately low to moderately high levels of a general autistic trait with good measurement precision. The reliable range of measurement was significantly improved by scoring the instrument using its 4-point response scale, rather than dichotomizing responses. These results support the use of the AQ in nonclinical samples, but suggest that items measuring very low and very high levels of autistic traits would be beneficial additions to the inventory. (PsycINFO Database Record


Effects of agriculture crop residue burning on children and young on PFTs in North West India.
Variations in pulmonary function tests (PFTs) due to agriculture crop residue burning (ACRB) on children between the age group of 10 to 13 years and the young between 20 to 35 years are studied. The effects of exposure to smoke due to rice-wheat crop residue burning on pulmonary functions like Force Vital Capacity (FVC), Force Expiratory Volume in one second (FEV(1)), Peak Expiratory Flow (PEF) and Force Expiratory Flow in 25 to 75% of FVC (FEF(25-75%)) on 40 healthy subjects of rural/agricultural area of Sidhuwal village of Patiala City were investigated for a period from August 2008 to July 2009. Measurements were taken by spirometry according to the American Thoracic Society standards. High volume sampler (HVS) and Anderson Impactor were used to measure the concentration levels of SPM, PM(10) and PM(2.5) in ambient air of the Sidhuwal village. A significant increase in the concentration levels of SPM, PM(10) and PM(2.5) was observed due to which PFTs of the subjects showed a significant decrease in their values, more prominently in the case of children. PFTs of young subjects recovered up to some extent after the completion of burning period but the PFT values of children remained significantly lower (p<0.001) even after the completion of burning episodes. Small size particulate matter (PM(2.5) and PM(10)) affected the PFTs to a large extent in comparison to the large size particulate matter (SPM). The study indicates that ACRB is a serious environmental health hazard and children are more sensitive to air pollution, as ACRB poses some unrecoverable influence on their PFTs.


Enteral nutritional therapy for induction of remission in Crohn's disease.
Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review. To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness. We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference abstracts. Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review. Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. We performed intention-to-treat and per-protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included abstract publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes. Twenty-seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non-elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non-elemental diets differing in glutamine enrichment. Meta-analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty-four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non-elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per-protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non-elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.Ten trials compared EN to steroid therapy. Meta-analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per-protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per-protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet. Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy.


HIV prevalence and related risk factors among male sex workers in Shenzhen, China: results from a time-location sampling survey.
HIV transmission among men who have sex with men has recently become a major concern in China. Little is known, however, about HIV transmission among male sex workers (MSW). This study aimed to investigate HIV infection prevalence and risk factors among MSW in Shenzhen, China. Following formative research, a cross-sectional study was conducted using time-location sampling among MSW in Shenzhen, from April to July 2008. Behavioural and serological data on HIV and syphilis were collected. The risk factors for HIV infection were analysed using a logistic regression model. In total, 394 MSW were recruited for the survey. The prevalence of HIV and syphilis among these workers was 5.3% and 14.3%, respectively. Only a quarter of the MSW self-identified as homosexual. More than 70% had sex with both men and women. HIV-related knowledge levels were high regardless of HIV serostatus. Consistent condom use was low (37.1%) and varied by type of sexual partner. Factors including more non-commercial male partners, working in small home-based family clubs, being drunk before sexual intercourse, having a history of HIV tests, syphilis infection and a short period of residence in Shenzhen were associated with an increased risk of HIV infection. High-risk sexual practices were common among MSW regardless of their high level of HIV awareness. The working venues were associated with HIV infection and a recent test for HIV was a potential predictor of HIV infection. The time-location sampling method was found to be an appropriate way of recruiting MSW for this study, especially those without fixed working places.


Stereotactic radiosurgery to the resection cavity for brain metastases: prognostic factors and outcomes.
Adjuvant stereotactic radiosurgery (SRS) alone after surgical resection is increasingly being used to provide excellent local control while avoiding the side effects of whole brain radiation therapy (WBRT). We report our ten year experience using this treatment scheme. To determine the rates and any correlates of local control, distant brain failure, and overall survival using SRS alone to the resection cavity. We performed a retrospective analysis of 509 patients with brain metastasis who underwent Gamma Knife SRS at our institution between 2003 and 2013. Of this group 85 patients were identified that had resection of the metastasis and subsequent SRS to the cavity. Mean dose to the resection cavity was 17.3 Gy (range 14-20) to an average volume of 12cc (range 0.3-83cc). Multiple patient, tumor, and treatment specific factors were collected for analysis (see Table 1). Vital statistics were provided by our institution's tumor registry. The primary endpoint of our analyses was recurrence free survival (RFS); defined as the duration in time between the date of SRS and any local or distant brain tumor recurrence. With a median follow up of 16.4 months, the overall local and distant brain failure at 12 months was 13% (95%CI 5%-21%) and 51% (95%CI 37%-64%) respectively. RPA was class 1 (5%), 2 (75%), and 3 (20%). The median overall survival (OS) was 20 months. The median RFS was 24 months with radiosensitive tumors: non small cell lung cancer (n=12), breast (n=16), gastrointestinal (n=7), small cell lung cancer (n=1), and other (n=9) compared to 5.6 months (p=0.006) in radioresistant tumors: melanoma (n=33), sarcoma (n=1), and renal cell carcinoma (n=6). Median OS for radioresistant and radiosensitive patients was 12 vs 25 months respectively (p=0.11). Additionally, there was a significant improved survival difference seen amongst those who had a gross total resection (GTR, n=46) compared to a sub total resection (n=39) with median OS of 27 vs 16 months (p=0.020) respectively. Radiographic changes suggestive of radiation necrosis were present in 6 patients, 2 of which were determined histiopathologicaly after surgical intervention. Due to the limited number of local recurrence events (n=10), there was insufficient power to analyze prognostic factors for local recurrence. Our results compare favorably with multiple other institution experiences showing excellent local control with SRS to the resection cavity following resection. Radioresistant histologies were associated with a worse RFS. Patients undergoing GTR had a significantly longer OS than those with STR. At our institution we continue to offer patients SRS to the resection cavity for those with good performance status and limited brain metastases.


Comparison of lens thickness measurements using the anterior segment optical coherence tomography and A-scan ultrasonography.
To assess lens thickness (LT) measurements with anterior segment optical coherence tomography (AS-OCT) in comparison with A-scan ultrasonography (A-scan US). Enrolled were 66 eyes of 48 phakic elderly volunteers aged > or = 50 years and 56 eyes of 56 young participants aged 18 to 40 years. LT was measured with the internal manual caliper tools in AS-OCT. The A-scan US measurements were based on an average of 10 consecutive automatic measurements. Reproducibility was assessed by three measurements each with AS-OCT and A-scan US independently obtained by two observers who were masked to one another's results. The failure rates of AS-OCT and A-scan US were 9.1% and 7.6%, respectively, in elderly subjects, but no failure was observed in young subjects. The LT values measured by AS-OCT were significantly greater than A-scan US; the paired difference was 0.135 mm in elderly and 0.101 mm in young subjects (P < 0.001). These differences did not correlate with the nuclear cataract grades (r = 0.078, P = 0.558). Intraobserver agreement on AS-OCT (95% limits of agreement [LoA]: -0.049 to +0.045 mm; ICC: 0.999) was better than A-scan US (95%LoA: -0.194 to +0.218 mm; ICC: 0.974). The 95% LoA of interobserver agreement using AS-OCT and A-scan were -0.084 to +0.073 and -0.278 to +0.239 mm, respectively, and the ICCs were 0.996 and 0.960, respectively. AS-OCT can be used to measure lens thickness in most eyes with clear or opacified lenses. It appears to be an alternative means of measuring lens thickness, particularly when a noncontact method is needed.


High correlation between the Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1, v2.0 and the Abbott m2000 RealTime HIV-1 assays for quantification of viral load in HIV-1 B and non-B subtypes.
HIV-1 viral load assays are critical tools to monitor antiretroviral therapy efficacy in HIV-infected patients. Two assays based on real-time PCR are available, the Abbott Real-Time HIV-1 assay (Abbott assay) and the new Roche COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 test, v. 2.0 (TaqMan(®) test v2.0). We have compared the performance of the two assays in 546 clinical plasma specimens of group M strains from Luxembourg and Rwanda. Our analyses focused on subtype inclusivity and platforms accuracy for 328 low level viremia samples. Strong agreement and linear correlation were observed between the two assays (R(2) = 0.95) over a wide dynamic range. Bland-Altman analysis showed a mean difference of 0.04 log 10 indicating minimal overall viral load quantification differences between both platforms. One subtype C was severely underquantified by TaqMan(®) test v2.0 for which sequence analysis revealed multiple mismatches between the viral sequence and the primer/probe regions. A non significant lower quantification of the Abbott assay was shown for subtype A1 with a mean log 10 difference of 0.24. For specimens under 200 cp/mL, the overall agreement was 90% at the cut-off of 50 cp/mL and 67% at assay's lower limit of detection of 20 and 40 cp/mL. 309 samples were retested by the COBAS(®) AMPLICOR(®) HIV-1 MONITOR Test, v. 1.5 and a lack of agreement between the three assays around their lower limit of quantification was revealed. Both real-time tests were closely comparable in the quantification of viral load specimens of ten HIV-1 subtypes and recombinant forms.


Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death.
Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe thyroidal ER stress and thyroid cell death. Nevertheless, thyroxine was synthesized, and brief treatment of TGrdw/rdw rats with antithyroid drug was lethal to the animals. When untreated, remarkably, thyroxine was synthesized on the mutant thyroglobulin protein, delivered via dead thyrocytes that decompose within the follicle lumen, where they were iodinated and cannibalized by surrounding live thyrocytes. As the animals continued to grow goiters, circulating thyroxine increased. However, when TGrdw/rdw rats age, they cannot sustain goiter growth that provided the dying cells needed for ongoing thyroxine synthesis, resulting in profound hypothyroidism. These results establish a disease mechanism wherein dead thyrocytes support organismal survival.


Ion-Transfer Voltammetry at a Water/1,2-Dichloroethane Interface Using Photoionization by Ultraviolet Irradiation: Detection of Cation Radicals of p-Phenylenediamine Derivatives.
We have attempted to detect electrically neutral substances by ion-transfer voltammetry at an interface between two immiscible electrolyte solutions (ITIES), such as an interface between water and 1,2-dichloroethane (a W/DCE interface), by irradiating the interface with ultraviolet light (200 - 300 nm). In the present work, while considering the facts that p-phenylenediamine derivatives are soluble in DCE, but insoluble in water, and that cation radicals of the derivatives are fairly stable in various media, we photoionized the derivatives in a DCE phase by ultraviolet irradiation, and after that carried out ion-transfer voltammetry at a W/DCE interface. As a result, we could successfully observe ion-transfer waves of cation radicals of the derivatives from the W to DCE phase. Namely, the cation radicals are generated in the DCE phase by ultraviolet irradiation, and subsequently distributed into the W phase. In addition to these ion-transfer waves, we also found that facilitated proton-transfer waves by the derivatives were shifted to a more negative potential region after ultraviolet irradiation, because of hydrogen chloride formed from photodecomposition of DCE by ultraviolet irradiation.


Synthesis and evaluation of tumor-homing peptides for targeting prostate cancer.
High toxicity caused by chemotherapeutic drugs and the acquisition of drug resistance by cancer cells are the major drawbacks in cancer therapy. A promising approach to overcome the posed barriers is conjugating tumor-homing peptides to drugs or nanocarriers. Such high-affinity peptides can specifically target surface markers overexpressed by cancer cells, ensuring a rapid and cancer-specific uptake of the drugs. Since prostate-specific membrane antigen (PSMA) is overexpressed by aggressive prostate cancer cells, targeting this surface protein with peptide conjugates can lead to the development of effective strategies against prostate cancer. In this study, we aimed to determine which PSMA-binding peptide among peptides 563, 562 and 9-mer, show the highest selectivity towards PSMA using 22Rv1 prostate cancer cells, a cell line with moderate PSMA levels. Tumor-homing peptides were synthesized by fluorenylmethoxycarbonyl-based solid-phase peptide synthesis (Fmoc-SPPS) strategy, and evaluated for their prostate cancer cell-specific targeting efficiencies by flow cytometry. Our results showed that the PSMA-binding capacity of peptide 563 was superior to those of 562, 9-mer, and 5-mer; therefore, can be utilized as a potent-targeting agent not only in the treatment of high PSMA positive but also moderate PSMA positive prostate cancer tumors.


-Characterization of pyruvate kinase from the anoxia tolerant turtle, Trachemys scripta elegans: a potential role for enzyme methylation during metabolic rate depression.
Pyruvate kinase (PK) is responsible for the final reaction in glycolysis. As PK is a glycolytic control point, the analysis of PK posttranslational modifications (PTM) and kinetic changes reveals a key piece of the reorganization of energy metabolism in an anoxia tolerant vertebrate. To explore PK regulation, the enzyme was isolated from red skeletal muscle and liver of aerobic and 20-hr anoxia-exposed red eared-slider turtles (Trachemys scripta elegans). Kinetic analysis and immunoblotting were used to assess enzyme function and the corresponding covalent modifications to the enzymes structure during anoxia. Both muscle and liver isoforms showed decreased affinity for phosphoenolpyruvate substrate during anoxia, and muscle PK also had a lower affinity for ADP. I50 values for the inhibitors ATP and lactate were lower for PK from both tissues after anoxic exposure while I50 L-alanine was only reduced in the liver. Both isozymes showed significant increases in threonine phosphorylation (by 42% in muscle and 60% in liver) and lysine methylation (by 43% in muscle and 70% in liver) during anoxia which have been linked to suppression of PK activity in other organisms. Liver PK also showed a 26% decrease in tyrosine phosphorylation under anoxia. Anoxia responsive changes in turtle muscle and liver PK coordinate with an overall reduced activity state. This reduced affinity for the forward glycolytic reaction is likely a key component of the overall metabolic rate depression that supports long term survival in anoxia tolerant turtles. The coinciding methyl- and phospho- PTM alterations present the mechanism for tissue specific enzyme modification during anoxia.


Who's buying lunch: are gifts to surgeons from industry bad for patients?
Why does gifting exist in the medical marketplace? It provides a sales advantage in a competitive marketplace by establishing crucial relationships with the patients' fiduciary: the physician and surgeon. Do gifts to physicians from industry harm patients? One can cite mountains of indirect evidence that they do, and maybe in the case of recalled devices and drugs there are actual corpses, but these examples are retrospective and it is impossible to prove that removing detailing eliminates the harm. Banning gifts to surgeons would not completely fix the ethical problem of pharmaceutical and device marketing. Gifts are important because they buy access and foster relationships, but inherent bias in research and the medical literature makes it very difficult to remain objective. It is a race, and education has not kept pace with advertising; only 10% of 575 internal medicine physicians thought they had had sufficient training during medical school and residency regarding professional interaction with sales representatives. Would banning gifts help at all? Would enforcing an unpopular ethical code protect patients? There might be a small improvement, but not as significant as eliminating representatives and product samples altogether. This is not likely to happen without an enormous fight against the wealthiest industry in America. The solution is education. To borrow industry's argument, physicians and surgeons are ethical creatures with capacity for judgment and integrity. They need to understand and believe the magnitude of the problem. Detailing exists because there is a market for it, empowering surgeons with ethical training reduces the demand for goodies, and at some point the popular choice will be to buy their own lunch. Business ethics are not medical ethics. Industry is behaving exactly as it must to maximize profits. Although it is painful for some surgeons, surgical residencies, and professional organizations to envision a future with diminished corporate gifts, it is every surgeon's responsibility to consider whether their dealings with the pharmaceutical and medical equipment industries withstand the harsh light of realities presented herein.


Cholesterol-dependent cytolysins.
The cholesterol-dependent cytolysins (CDCs) are part of a large family of pore-forming proteins that include the human proteins perforin and the complement membrane attack complex. The activity of all family members is focused on membranes, but the proteins are themselves involved in a diverse range of phenomena. An overview of some of these phenomena is provided here, along with an historical perspective of CDCs themselves and how our understanding of their mechanism of action has developed over the years. The way in which pore formation depends on specific characteristics of the membrane under attack as well as of the protein doing the attacking is emphasised. The cholesterol-dependent cytolysins (CDCs) have been the focus of a renewed keen research interest for over ten years now. Their importance has been even further enhanced by the homology now identified between them and the membrane attack complex/perforin (MACPF) family of proteins, which includes several components of the complement cascade as well as perforin itself. In this chapter I aim to provide an overview of our understanding of the interaction between CDCs and other members of what is now called the MACPF/CDC superfamily, with their target membranes. CDCs (also in the past known as thiol-activated toxins or cholesterol-binding toxins) were originally identified from four Gram-positive bacterial genera (Clostridium, Listeria, Bacillus and Streptococcus). Well-known examples include listeriolysin, perfringolysin, streptolysin and pneumoysin. Listeriolysin from L. monocytogenes is responsible for the escape of bacteria from the phagosome to colonise the cytoplasm and has been applied as a protein adjuvant in the development of vaccines against cancer and tuberculosis, for example. Perfringolysin from C. perfringens (Fig. 1A) has become perhaps the most studied CDC4 and has an important role in pathology associated with infection (gangrene). Streptolysin from S. pyogenes is another intensely studied CDC and has been applied widely in experimental permeabilisation of biological membranes. Pneumolysin is a major virulence determinant for S. pneumoniae, allowing bacterial invasion of tissues and mediating inflammation and the activation of the complement cascade. However, CDCs have now, for example, been identified in the bacteria Arcanobacterium pyogenes and Gardnerella vaginalis and there also appear to be homologues outside prokaryotes such as the sea anemone Metridium senile pore-forming toxin metridiolysin. The homology with the MACPF family was unknown until the first structures of the canonical fold of that family were solved, revealing the now characteristic MACPF/CDC fold of a twisted 3-sheet around which helices are clustered (Fig. 1A and D). Without any significant other sequence homology, the fold of this superfamily of pore-forming and membrane-binding proteins has been conserved by compensatory mutation around a handful of key conserved glycines. The glycines presumably act as critical hinges during the dramatic refolding that CDCs are known to undergo and which is presumably the selective advantage of this specific structure that has caused it to be conserved over such a vast evolutionary timescale. While not all MACPF domains are involved in pore formation-for example, C6 and C8beta--they are all apparently involved in action on membranes. The dramatic refolding undergone by CDCs is tightly coupled to their oligomerisation and results in the conversion of the helices hemming the core 3-sheet of the MACPF/CDC domain into a pair of beta-hairpins which in tandem and alongside those from other subunits within the oligomer insert into the membrane to create a pore (Fig. 1A-C). It is obviously the basic assumption that where nonCDC members of the superfamily-such as complement proteins and perforin-act on membranes they do so by a mechanism involving similar refolding.58 Even where a member of the MACPF/CDC superfamily is not known to form a pore, or has been shown not to-at least alone-the same conformational change could have other adaptive functions during activity on or at membranes. However, the bicomponent nature of some pore-forming toxins alerts us that showing an absence of activity for one pure protein does not mean that they do not contribute to pore formation quite directly, since that may require the presence of another MACPF/CDC family member or members from the same specific system. Complement acts by a combination of the C5b-8 complex of proteins preassembled on a target membrane recruiting C9 to form a lesion, which may be a complete ring of C9 associated with the C5b-8 or an arc-electron microscopy images show both possibilities.Perforin acts in concert with granzymes, to trigger apoptosis when delivered by cytotoxic cells at their targets (damaged, transformed and infected host cells). Incomplete rings are visible for perforin also and there are many unresolved issues concerning its mechanism and the dependence ofgranzymes on it for their delivery.


Omega-3 Fatty Acids in the Management of Epilepsy.
Omega-3 and omega-6 fatty acids are polyunsaturated fatty acids (PUFAs) with multiple double bonds. Linolenic and alpha-linolenic acids are omega-6 and omega-3 PUFAs, precursors for the synthesis of long-chain PUFAs (LC-PUFAs), such as arachidonic acid (omega-6 PUFA), and eicosapentaenoic and docosahexaenoic acids (omega-3 PUFAs). The three most important omega-3 fatty acids are alpha-linolenic, eicosapentaenoic and docosahexaenoic acids, which cannot be synthesized in enough amounts by the body, and therefore they must be supplied by the diet. Omega-3 fatty acids are essential for the correct functioning of the organism and participate in many physiological processes in the brain. Epilepsy is a common and heterogeneous chronic brain disorder characterized by recurrent epileptic seizures leading to neuropsychiatric disabilities. The prevalence of epilepsy is high achieving about 1% of the general population. There is evidence suggesting that omega-3 fatty acids may have neuroprotective and anticonvulsant effects and, accordingly, may have a potential use in the treatment of epilepsy. In the present review, the potential use of omega-3 fatty acids in the treatment of epilepsy, and the possible proposed mechanisms of action are discussed. The present article summarizes the recent knowledge of the potential protective role of dietary omega-3 fatty acids in epilepsy.


The Use and Abuse of Growth Hormone in Sports.
GH is banned by the World Anti-Doping Agency as a performance-enhancing anabolic agent. Doping with GH likely began in the early 1980s and became more prevalent with the advent of recombinant technology well before any scientific evidence of benefit. The expectation that GH improves physical function stems from its anabolic and lipolytic properties. Athletic performance depends on muscle strength and the energy required to power muscle function. In recreational athletes, GH selectively improves anaerobic sprint capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH is secreted as a family of isoform peptides in a pulsatile manner reflecting intermittent secretion and rapid clearance. Its anabolic actions are largely mediated by IGF-I, which stimulates whole-body protein synthesis, including skeletal muscle and collagen proteins. Two methods have been validated for detecting GH abuse in athletes. The first (the isoform method) is based on distinguishing pure recombinant 22-kDa GH from the heterogeneous isoforms secreted from the pituitary. The second (the marker method) is based on measuring blood levels of GH-responsive proteins, specifically IGF-I and the N-terminal propeptide of type III collagen (P-III-NP). Only a handful of athletes have been caught since the implementation of GH doping tests in 2004. The low rate likely reflects the limitation of in-competition testing using current methods. Improved detection rates may be achieved by more out-of-competition testing, introducing athletes' biological passports, and the development of novel methods. Governance, operational, technical, and political factors influence the effectiveness of an anti-doping program.


Blood pressure in healthy pregnancy and factors associated with no mid-trimester blood pressure drop: a prospective cohort study.
The well-known mid-trimester drop in blood pressure (BP) during normal pregnancy was recently questioned. To describe longitudinal changes in BP during healthy pregnancies and to investigate factors associated with no mid-trimester drop in BP. A prospective cohort with 158 healthy pregnant women was followed up in a public health care center in Rio de Janeiro, Brazil. We used linear mixed-effects models to estimate longitudinal changes in systolic BP (SBP) and diastolic BP (DBP) during pregnancy. Poisson regression models were performed to identify factors associated with no mid-trimester drop in BP. Significant mid-trimester increase in SBP (5.6 mm Hg; 95% confidence interval (CI) = 4.6-6.7) and DBP (4.4 mm Hg; 95% CI = 3.4-5.3) was observed in 44.3% and 39.9% of the sample, respectively. Women (37.1%) who had not a mid-trimester SBP drop still had a DBP drop. White skin color (incidence ratio (IR): 1.71; 95% CI = 1.22-2.39), family history of hypertension (IR: 1.93; 95% CI = 1.29-2.89), early pregnancy obesity (IR: 2.29; 95% CI = 1.27-4.11), outside temperature variation (IR: 1.45; 95% CI = 1.00-2.10), and gestational weight gain from the first to second trimester (IR: 1.71; 95% CI = 1.01-2.88 and IR: 2.32; 95% CI = 1.39-3.89 for second and third tertiles) were characteristics associated with no mid-trimester drop in SBP. The same characteristics were associated with no mid-trimester drop in DBP, except family history of hypertension and outside temperature variation. Some women without a mid-trimester SBP drop still present a DBP drop. The different patterns of mid-trimester change in BP seem to be determined by preexisting and pregnancy-related factors.


Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes.
Inflammation in response to oxidized lipoproteins is thought to play a key role in acute coronary syndromes (ACS), but the pattern of immune activation has not been fully characterized. We sought to perform detailed phenotypic and functional analysis of CD8 T lymphocytes from patients presenting with ACS to determine activation patterns and potential immunologic correlates of ACS. We used polychromatic flow cytometry to analyze the cytokine production profiles of naïve, effector, and memory CD8 T cells in patients with ACS compared with control subjects with stable coronary artery disease. ACS was associated with an altered distribution of circulating CD8(+) T-cell maturation subsets with reduced proportions of naïve cells and expansion of effector memory cells. ACS was also accompanied by impaired interleukin-2 production by phenotypically naïve CD8 T cells. These results were validated in a second replication cohort. Naïve CD8 cells from patients with ACS also had increased expression of programmed cell death-1, which correlated with interleukin-2 hypoproduction. In vitro, stimulation of CD8 T cells with oxidized low-density lipoprotein was sufficient to cause programmed cell death-1 upregulation and diminished interleukin-2 production by naïve CD8 T cells. In this exploratory analysis, naïve CD8(+) T cells from patients with ACS show phenotypic and functional characteristics of immune exhaustion: impaired interleukin-2 production and programmed cell death-1 upregulation. Exposure to oxidized low-density lipoprotein recapitulates these features in vitro. These data provide evidence that oxidized low-density lipoprotein could play a role in immune exhaustion, and this immunophenotype may be a biomarker for ACS.


A Framework for Systematic Evaluation and Quantitative Integration of Mechanistic Data in Assessments of Potential Human Carcinogens.
Recently, the key characteristics of carcinogens (KCC) have been proposed as an organizational approach for the evaluation of mechanistic data related to carcinogenicity. Our objective was to develop a framework to systematically and quantitatively integrate KCC data using elements that are important to risk assessment. Methods for developing the framework included: defining objectives, identifying and accommodating key considerations for components, input, and output of the framework, and operational development via iterative testing by a multidisciplinary team. The proposed framework involves 3 steps: (1) a structured, yet flexible, appraisal of individual studies and endpoints, (2) a structured and transparent evaluation of the body of evidence for each key characteristic, and (3) an evaluation of all of the KCC-relevant data relative to tumors and/or cancer types. In step 1, data are assessed and scored for reliability, strength, and activity. In step 2, a mathematical algorithm is used to integrate (and weight) the quality, relevance, and activity for each of the KCCs. These scores facilitate subsequent evaluations related to the overall body of evidence in step 3 in which KCCs can be linked, assessing potential adverse outcome pathways or networks, and finally, considered in the context of observed carcinogenic responses in animals and/or humans. The output is an overall conclusion regarding KCC activity as it relates to carcinogenic responses. The proposed framework provides a flexible solution to quantitatively integrate KCC data in a systematic and transparent manner that provides weighting of data most well-suited for the assessment of potential human carcinogenicity.


'They can't solve the problem without us': a qualitative study of stakeholder perspectives on user involvement in drug treatment services in England.
Providers of public health care are under pressure to involve service-users in service development. This pressure emanates from legislators and the public who promote user involvement (UI), as a 'means to an end' and/or 'an end in itself'. Case studies in six English commissioning areas explored the process and purpose of UI in drug treatment services. In-depth interviews with 139 respondents who commission, manage, deliver or use services were conducted. We identified 'non-', 'passive-' and 'active participant' users. Active users were commonly motivated by a desire for social justice, a social conscience and personal development. UI was evidently influenced by multiple social organizational and personal factors. Some 'generic' factors have been reported in other settings. However, the illegality of drug use powerfully affects all stakeholders creating a context unique to drug treatment settings. Stigma and power imbalances were pervasive, and strong tensions concerning the goal and purpose of UI were apparent. Within the UK context, we identified five organizational approaches to UI. Based on rationale and objectives of UI, and the scope of influence accorded users, organizations could be characterised as protagonists, pragmatists, sceptics, abstainers or avoiders. We conclude that many tensions apparent in local level UI have roots in UI policy, which is ambiguous about: (1) benefit and rights, and (2) the promotion of healthcare objectives within a UK drug strategy driven by a crime reduction agenda. This duality must be resolved for UI to flourish at local level.


Does Improved Attention Induced by Caffeine Intake Affect Olfactory Function?
Past several studies have proven that caffeine facilitates attentional enhancement by acting as an adenosine antagonist once it is absorbed by the body, resulting in improved psycho-behavioral function. Modern clinical olfactory function tests are usually assessed by psychophysical tests but due to a paucity of data, the influence of enhanced attention by caffeine on olfactory function still remains unclear. The objective of this study was to compare results of cognitive function (attention) and olfactory function before and after caffeine administration in order to analyze effects of caffeine on olfactory function in normosmic subjects. This study enrolled 49 participants of Konkuk University Hospital with a mean age of 27.7 years who had patent olfactory clefts and no olfactory dysfunction from May 2015 to February 2016. Subjects were restrained from caffeine 10 hours before the test. On day 1, participant's subjective olfactory function was evaluated before and after uptake of either caffeinated or decaffeinated coffee using visual analog scale (VAS) score, minimum cross-sectional area (MCA) measured by acoustic rhinometry, and the Korean version of Sniffin' Stick II (KVSS II). Evaluation of participant's attentional degree was measured by d2 test. On day 2, the same procedure was carried out with counterpart substance. The type of coffee initially administrated was randomly selected. After administration, caffeinated coffee resulted in significant attentional enhancement than decaffeinated coffee. Results of d2 test showed statistically significant differences in the parameters of total number of errors and omission errors. In both the caffeinated and decaffeinated groups, the patients showed slight increase in VAS score and nasal cavity area; however, the difference was not statistically significant. Also, caffeinated coffee intake compared to decaffeinated coffee intake showed no significant relevance to olfactory function. Caffeine may significantly improve attentional congnitive function, while not have acute effects on olfactory function.


Large thymic carcinoma presenting with right ventricular failure: a case report.
Thymic carcinoma is an overall rare tumour with variable clinical manifestations. Right ventricular failure remains an uncommon occurrence and has not been reported in literature so far. A 40-year-old lady presented with the complaints of progressively worsening retrosternal chest pain, shortness of breath, easy fatigability and cough since 1 year. Computed tomography scan of the thorax revealed a mass measuring 12 x 10 cm in the anterior mediastinum. This mass appeared to be adherent to both lungs and pericardium and was impinging on the right atrium and right ventricle. It appeared to be infiltrating the ascending aorta, pulmonary arteries and superior vena cava. Ultrasound of the abdomen showed hepatomegaly and moderate ascites. Echocardiography showed evidence of right ventricular dysfunction as well as elevated right ventricular systolic pressures secondary to extrinsic compression. Percutaneous biopsy of the thymus was performed showing a malignant thymoma. Radical thymectomy with resection of pericardium was planned. Intra-operatively, the tumour was separated from the right and left lungs, pulmonary artery and aortic arch. Morphologically, immunochemically and clinically, the features were consistent with those seen in Masoka stage III thymic carcinoma. She also received six cycles of chemotherapy (PAC regimen) including cisplatin (50 mg/m2), doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2). Radiation therapy in the adjuvant setting was planned but the patient was lost to follow-up after 4 months. Although right ventricular failure is a very rare presentation of thymic carcinoma, clinicians should be aware of this presentation to appreciate the complete clinical spectrum of presentation of this neoplasm.


Call for a global ban policy on and scientific management of asbestos to eliminate asbestos-related diseases.
Asbestos is a primary cause of cancer worldwide. Global estimates indicate workplace exposure of 125 million people and about 255,000 deaths each year. Of the approximately 300 million metric tonnes of asbestos ever produced worldwide, most will become waste and disposed of in landfills. The recycling and transforming asbestos fibre into a non-harmful product offer a sustainable solution, but a global commitment remains elusive. Urgent action is needed. Sixty-seven countries have banned the use of asbestos-containing material, however, repeated calls to stop the use of asbestos globally have gone unheeded. We call for more stringent uniform global legislation and policies, backed up by funds to induce action along with research and education required to eliminate use of asbestos. Only by doing this, will we prevent deaths due to asbestos and help protect the environment.


Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.
Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.


Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice.
Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.


Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway.
TEA domain (TEAD) transcription factors bind to the coactivators YAP and TAZ and regulate the transcriptional output of the Hippo pathway, playing critical roles in organ size control and tumorigenesis. Protein S-palmitoylation attaches a fatty acid, palmitate, to cysteine residues and regulates protein trafficking, membrane localization and signaling activities. Using activity-based chemical probes, we discovered that human TEADs possess intrinsic palmitoylating enzyme-like activities and undergo autopalmitoylation at evolutionarily conserved cysteine residues under physiological conditions. We determined the crystal structures of lipid-bound TEADs and found that the lipid chain of palmitate inserts into a conserved deep hydrophobic pocket. Strikingly, palmitoylation did not alter TEAD's localization, but it was required for TEAD's binding to YAP and TAZ and was dispensable for its binding to the Vgll4 tumor suppressor. Moreover, palmitoylation-deficient TEAD mutants impaired TAZ-mediated muscle differentiation in vitro and tissue overgrowth mediated by the Drosophila YAP homolog Yorkie in vivo. Our study directly links autopalmitoylation to the transcriptional regulation of the Hippo pathway.


Recruitment of PfSET2 by RNA polymerase II to variant antigen encoding loci contributes to antigenic variation in P. falciparum.
Histone modifications are important regulators of gene expression in all eukaryotes. In Plasmodium falciparum, these epigenetic marks regulate expression of genes involved in several aspects of host-parasite interactions, including antigenic variation. While the identities and genomic positions of many histone modifications have now been cataloged, how they are targeted to defined genomic regions remains poorly understood. For example, how variant antigen encoding loci (var) are targeted for deposition of unique histone marks is a mystery that continues to perplex the field. Here we describe the recruitment of an ortholog of the histone modifier SET2 to var genes through direct interactions with the C-terminal domain (CTD) of RNA polymerase II. In higher eukaryotes, SET2 is a histone methyltransferase recruited by RNA pol II during mRNA transcription; however, the ortholog in P. falciparum (PfSET2) has an atypical architecture and its role in regulating transcription is unknown. Here we show that PfSET2 binds to the unphosphorylated form of the CTD, a property inconsistent with its recruitment during mRNA synthesis. Further, we show that H3K36me3, the epigenetic mark deposited by PfSET2, is enriched at both active and silent var gene loci, providing additional evidence that its recruitment is not associated with mRNA production. Over-expression of a dominant negative form of PfSET2 designed to disrupt binding to RNA pol II induced rapid var gene expression switching, confirming both the importance of PfSET2 in var gene regulation and a role for RNA pol II in its recruitment. RNA pol II is known to transcribe non-coding RNAs from both active and silent var genes, providing a possible mechanism by which it could recruit PfSET2 to var loci. This work unifies previous reports of histone modifications, the production of ncRNAs, and the promoter activity of var introns into a mechanism that contributes to antigenic variation by malaria parasites.


Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake.
The importance of membrane transporters for drug pharmacokinetics has been increasingly recognized during the last decade. Organic anion transporting polypeptide 1B1 (OATP1B1) is a genetically polymorphic influx transporter expressed on the sinusoidal membrane of human hepatocytes, and it mediates the hepatic uptake of many endogenous compounds and xenobiotics. Recent studies have demonstrated that OATP1B1 plays a major, clinically important role in the hepatic uptake of many drugs. A common single-nucleotide variation (coding DNA c.521T>C, protein p.V174A, rs4149056) in the SLCO1B1 gene encoding OATP1B1 decreases the transporting activity of OATP1B1, resulting in markedly increased plasma concentrations of, for example, many statins, particularly of active simvastatin acid. The variant thereby enhances the risk of statin-induced myopathy and decreases the therapeutic indexes of statins. However, the effect of the SLCO1B1 c.521T>C variant is different on different statins. The same variant also markedly affects the pharmacokinetics of several other drugs. Furthermore, certain SLCO1B1 variants associated with an enhanced clearance of methotrexate increase the risk of gastrointestinal toxicity by methotrexate in the treatment of children with acute lymphoblastic leukemia. Certain drugs (e.g., cyclosporine) potently inhibit OATP1B1, causing clinically significant drug interactions. Thus, OATP1B1 plays a major role in the hepatic uptake of drugs, and genetic variants and drug interactions affecting OATP1B1 activity are important determinants of individual drug responses. In this article, we review the current knowledge about the expression, function, substrate characteristics, and pharmacogenetics of OATP1B1 as well as its role in drug interactions, in parts comparing with those of other hepatocyte-expressed organic anion transporting polypeptides, OATP1B3 and OATP2B1.


A checklist of the helminth parasites of marine mammals from Argentina.
Based on published records and new data accumulated by the authors, we generated a list of the helminth parasites of marine mammals from off the coast of Argentina. We found 49 reports of helminths parasitizing cetaceans and pinnipeds from Argentina from 1952 to 2015. The list includes 54 taxa of helminths (8 acanthocephalans, 24 nematodes, 11 cestodes and 11 trematodes) associated with 18 species of cetaceans and 5 species of pinnipeds. Most of the records represent adults (5 acanthocephalans, 16 nematodes, 6 cestodes and 11 trematodes), followed by larvae (10 nematodes and 3 metacestodes) and juveniles (4 acanthocephalans and 2 cestodes). The checklist contains 24 named species (5 acanthocephalans, 8 nematodes, 4 cestodes and 7 trematodes) and 30 undetermined helminth taxa (3 acanthocephalans, 16 nematodes, 7 cestodes and 4 trematodes). The present account contains a parasite/host lists and information on the habitat, developmental stage and distribution of the parasites listed, repositories of their type and voucher specimens and references. A host-parasite list is also presented. The data compiled on the helminth of marine mammals from Argentina in the present study revealed gaps in the knowledge of their taxonomic identification, composition, distribution, host specificity and life cycles. These gaps are also briefly discussed in order to provide an outline for future research.


Hospitals by day, dispensaries by night: Hourly fluctuations of maternal mortality within Mexican health institutions, 2010-2014.
Quality of obstetric care may not be constant within clinics and hospitals. Night shifts and weekends experience understaffing and other organizational hurdles in comparison with the weekday morning shifts, and this may influence the risk of maternal deaths. To analyze the hourly variation of maternal mortality within Mexican health institutions. We performed a cross-sectional multivariate analysis of 3,908 maternal deaths and 10,589,444 births that occurred within health facilities in Mexico during the 2010-2014 period, using data from the Health Information Systems of the Mexican Ministry of Health. We fitted negative binomial regression models with covariate adjustment to all data, as well as similar models by basic cause of death and by weekdays/weekends. The outcome was the Maternal Mortality Ratio (MMR), defined as the number of deaths occurred per 100,000 live births. Hour of day was the main predictor; covariates were day of the week, c-section, marginalization, age, education, and number of pregnancies. Risk rises during early morning, reaching 52.5 deaths per 100,000 live births at 6:00 (95% UI: 46.3, 62.2). This is almost twice the lowest risk, which occurred at noon (27.1 deaths per 100,000 live births [95% U.I.: 23.0, 32.0]). Risk shows peaks coinciding with shift changes, at 07:00, and 14:00 and was significantly higher on weekends and holidays. Evidence suggests strong hourly fluctuations in the risk of maternal death with during early morning hours and around the afternoon shift change. These results may reflect institutional management problems that cause an uneven quality of obstetric care.


Multiple signal classification technique for phase estimation from a fringe pattern.
The paper introduces a multiple signal classification technique based method for fringe analysis. In the proposed method, the phase of a fringe pattern is locally approximated as a polynomial. The polynomial phase signal is then transformed to obtain signals comprising of only even- or odd-order polynomial coefficients. Subsequently, covariance matrix formulation is applied, and the two sets of coefficients are jointly estimated from the noise subspace of the covariance matrix using the multiple signal classification technique. The method allows simultaneous estimation of multiple coefficients and provides phase without the requirement of complex unwrapping algorithms. The effectiveness of the proposed method is validated through numerical simulation.


Native predators do not influence invasion success of pacific lionfish on Caribbean reefs.
Biotic resistance, the process by which new colonists are excluded from a community by predation from and/or competition with resident species, can prevent or limit species invasions. We examined whether biotic resistance by native predators on Caribbean coral reefs has influenced the invasion success of red lionfishes (Pterois volitans and Pterois miles), piscivores from the Indo-Pacific. Specifically, we surveyed the abundance (density and biomass) of lionfish and native predatory fishes that could interact with lionfish (either through predation or competition) on 71 reefs in three biogeographic regions of the Caribbean. We recorded protection status of the reefs, and abiotic variables including depth, habitat type, and wind/wave exposure at each site. We found no relationship between the density or biomass of lionfish and that of native predators. However, lionfish densities were significantly lower on windward sites, potentially because of habitat preferences, and in marine protected areas, most likely because of ongoing removal efforts by reserve managers. Our results suggest that interactions with native predators do not influence the colonization or post-establishment population density of invasive lionfish on Caribbean reefs.


Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland).
Environmental, cultural and health care differences may account for variation among countries in the prevalence of asthma and respiratory symptoms in teenagers. To examine the prevalence of respiratory symptoms and the level of diagnosis, and to compare determinants of asthma and severe wheeze in two countries. Self-completion questionnaires based on the International Study of Asthma and Allergies in Childhood (ISAAC) protocol were provided to school children in Ireland (Republic and Northern Ireland). In the Republic of Ireland, all children in classes largely aged 13-14 years from 30 post-primary schools were selected by random sampling stratified by school size, composition and Health Board in Spring 1995. In Northern Ireland, all children largely aged 13-14 years of age from 26 post-primary schools were selected by random sampling stratified by school type, composition and Education and Library Board in Spring 1996. Questionnaires were completed by 2,364 children from Northern Ireland and 2,671 from the Republic, about 90% of those eligible to participate. The prevalences of wheeze at various levels of severity, of diagnosed asthma and of treated wheeze were very similar in Northern Ireland and the Republic of Ireland. A significant proportion of those reporting more severe symptomatology (four or more attacks of wheeze in the past 12 months and/or one or more nights disturbed and/or moderate or greater disruption of daily activities and/or speech restriction due to wheeze) had been neither diagnosed nor treated for asthma (20-37%). To investigate the determinants of the more severe symptomatology of asthma or treated wheeze a series of stepwise multiple regression analyses was performed. A history of atopy, cigarette smoking, the possession of a furry pet other than a dog or cat and age were each independently associated with severe wheeze, whilst atopy, a furry pet (as above) and gender were each independently associated with asthma or treated wheeze. Cigarette smoking is closely associated with the reporting of significant respiratory symptoms together with atopy and exposure to furry pets. Some 20-37% of severe symptoms were neither diagnosed nor treated as asthma.


Ecological aspects of phebotomine (Diptera, Psychodidae) in an endemic area of tegumentary leishmaniasis in the northeastern Argentina, 1993-1998.
The first epidemic tegumentary leishmaniasiś outbreak in the province of Misiones was recorded in 1998, in the locality of Puerto Esperanza. Phlebotominae collected in the region, previously or simultaneously to the outbreak (September 1993-December 1998) showed that the species Lutzomyia intermedia s. l. was prevalent (94%, n 6,150) at all the sites sampled with miniature light trap (10) and Shannon trap (3). L. pessoai, L. whitmani, L. migonei, L. shannoni, L. fischeri, L. misionensis, Brumptomyia avellari and B. guimaraesi were also captured. Sand fly distribution in time and space suggests that in the province of Misiones (1) the species already present before 1990 could give rise to the epidemic by the density/dispersion fluctuation of their local populations; (2) the abundance of L. intermedia s. l. was associated with environments with ecotones of primary-secondary vegetation, close to water bodies and with moderate human disturbance; (3) this species showed, towards the end of 1997, peaks of exceptional abundance, subsequent to rainfall peaks in 1996. This increase in abundance of potential vector sand fly populations close to houses with colonizable surroundings could have generated the 1998 epidemic outbreak.


Derivation and implications of MMPI cluster groups in clinically depressed inpatient females.
The purpose of this study was to subclassify clinically depressed patients based on a cluster-analytic examination of the MMPI. Subjects were 79 female inpatients with major depression. A cluster analysis of the MMPI validity and clinical scales resulted in three clusters labeled psychotic (287 MMPI profile), hostile (24 MMPI profile), and histrionic (32 MMPI profile) depression. The psychotic group exhibited the greatest depression as measured by the Beck Depression Inventory (BDI). The psychotic and hostile groups, however, did not differ on other associated aspects of depression, such as negative cognitions, nonassertiveness, or personality style. The hostile group reported the fewest physical difficulties and the most excessive alcohol use. The groups, however, did not differ on other aspects of depression history or presentation such as family history of depression or previous hospitalizations. A repeated measures ANOVA for the three cluster groups on the BDI at admission, discharge, and 6 months after discharge indicated that all groups showed improvement at discharge but that only the hostile depressive group continued to show improvement at the 6-month follow-up.


The role of laparoscopy in non-palpable undescended testicle: Analysis and review of the experience from two cities in Sudan.
It is estimated that 1%-2% of male infants have undescended testicles. The reliability of ultrasound (US) to identify the non-palpable undescended testicles (NPUDT) is controversial. Laparoscopy remains the gold standard to diagnose and manage NPUDT. The objective is to highlight the role of laparoscopy in the management of NPUDT in 2 cities from Sudan over the past decade. Patients presented to Gadarif Teaching Hospital and Almak Nimir University Hospital with NPUDT were assessed by clinical examination and US. The testis, when found during laparoscopy, was either brought down to the scrotum in a single or two-stage or removed depending on the findings. Data were collected and analysed. Patients covered the age range between 18 months and 65 years. The average was 12.4. The majority, 94 (67.2%) patients were older than 5 years. The main presenting symptom was either bilateral or unilateral empty scrotum. In 12 (8.4%) patients, the main presenting symptom was primary infertility. US was done in 120 (86.6%) of the patients and failed to see the testis in more than half of them. A single-stage procedure in the form of laparoscopic search assisted with orchidopexy was achieved in 90 (62.9%) patients and orchiectomy in 13 (9.1%) patients, while in 12 (8.4%) patients the testis was not found. Other procedures were applied on the 28 (19.6%) patients who needed staged operation in the form of Fowler Stephen's, in bilateral cases, in 6 (4.2%) patients. Shehata's operation in nine patients (64%) and open orchidopexy for 8 (5.6%) patients. The post-operative complication was encountered in 14 (9.8%) of the patients in this group in the form of bleeding, vassal injury and testicular atrophy. Laparoscopy provides the most accurate interventional option for managing patients with NPUDT. Laparoscopic orchidopexy, whether single stage for low or 2-stages for high intra-abdominal testis, is a proven and effective extension of lap-search with minimal complications.


Geographic variations in breast cancer survival among older women: implications for quality of breast cancer care.
Breast cancer care, such as utilization of screening procedures and types of treatment received, varies substantially by geographic region of the United States. However, little is known about variations in survival with breast cancer. We examined breast cancer incidence, survival, and mortality in the 66 health service areas covered by the Surveillance, Epidemiology, and End Results (SEER) program for women aged 65 and older at diagnosis. Incidence and survival data were derived from SEER, while breast cancer mortality data were from Vital Statistics data. There was considerable variation in breast cancer survival among the 66 health service areas (chi2 = 202.7, p <.0001). There was also significant variation in incidence and mortality from breast cancer. In a partial correlation weighted for the size of the health service area, both incidence (r =.812) and percent 5-year survival (r = -.587) correlate with mortality. In a Poisson regression analysis, the combination of variation in incidence and variation in survival explains 90.9% of the variation in mortality. There is considerable geographic variation in survival from breast cancer among older women, and this contributes to variation in breast cancer mortality. Geographic variations in breast cancer mortality should diminish as the quality of breast cancer care becomes more standardized.