Two-dimensional phase unwrapping using robust derivative estimation and adaptive integration.
The adaptive integration (ADI) method for two-dimensional (2-D) phase unwrapping is presented. The method uses an algorithm for noise robust estimation of partial derivatives, followed by a noise robust adaptive integration process. The ADI method can easily unwrap phase images with moderate noise levels, and the resulting images are congruent modulo 2pi with the observed, wrapped, input images. In a quantitative evaluation, both the ADI and the BLS methods (Strand et al.) were better than the least-squares methods of Ghiglia and Romero (GR), and of Marroquin and Rivera (MRM). In a qualitative evaluation, the ADI, the BLS, and a conjugate gradient version of the MRM method (MRMCG), were all compared using a synthetic image with shear, using 115 magnetic resonance images, and using 22 fiber-optic interferometry images. For the synthetic image and the interferometry images, the ADI method gave consistently visually better results than the other methods. For the MR images, the MRMCG method was best, and the ADI method second best. The ADI method was less sensitive to the mask definition and the block size than the BLS method, and successfully unwrapped images with shears that were not marked in the masks. The computational requirements of the ADI method for images of nonrectangular objects were comparable to only two iterations of many least-squares-based methods (e.g., GR). We believe the ADI method provides a powerful addition to the ensemble of tools available for 2-D phase unwrapping.


Renal pedicle injury in patients with multiple injuries.
In a study of 41 patients seen over 24 years, renal pedicle injuries were associated with life-threatening multiple system injuries and the immediate surgical management of these associated injuries by general surgeons took precedence over that of the renal pedicle injury. The result was the delayed diagnosis of the renal pedicle injury with loss of function of the kidney. In an effort to improve the renal salvage rate aggressive management of renal pedicle injuries with immediate radiologic evaluation and early surgical treatment was instituted in 1969. The records of 41 renal pedicle injuries from 1959 to 1983 were evaluated. Blunt external trauma was the cause in 76%. All 41 patients had multiple system injuries, averaging 3.7 associated injuries per patient, with 35 (85%) having a laparotomy for intra-abdominal injuries and an overall mortality rate of 44%. Conservative management was followed in 13 patients, with injury to the renal artery in nine and a branch of the renal artery in four, with a renal loss/delayed nephrectomy rate of nine of nine (100%) renal artery injuries. Immediate surgical management was performed in 23 patients, with injury to the renal artery in nine, the renal artery and renal vein in four, a branch of the renal artery in two, and the renal vein in eight, with a renal salvage rate of seven of 21 (33%) renal artery and/or vein injuries. Five patients died on admission or on the operating room table. A significant renal salvage rate resulted from immediate radiologic evaluation and early surgical treatment of renal artery/vein injuries compared to zero salvage rate with conservative management.


Recreation for children on social assistance, 4-17 years old, pays for itself the same year.
A randomized control trial completed in the Hamilton-Wentworth and Halton regions of Ontario, Canada, was created to assess the effects and expense of age-appropriate provider-initiated and subsidized versus self-directed and self-financed methods of recreation. Upon completion, this study proved that the annual per-person expenditure for the subsidized, quality recreation paid for itself by children's lower use of healthcare and social services. The children within the subsidized recreation group had lower use of physician, physiotherapy, probation, children's aid society, social work, psychologist and services in comparison with those in the non-subsidized group. The subsidized group also proved to be beneficial for the parents as well. The use of health and social services, by the parents in the subsidized group, was also decreased in comparison with those of the self-financed group. This group also proved to have improvement of the global socioeconomic status, with a 10% greater exit from the social assistance program within 1 year.


[Biological properties of opportunistic microorganisms--agents of acute intestinal infections].
The etiological role of conditionally pathogenic bacteria in acute intestinal infections in the Sumy region has been studied. It is established, that the strains of Klebsiella pneumoniae, Staphylococcus aureus and Enterobacter cloacae isolated from patients with acute intestinal infection were characterized by phenotypic heterogeneity. In 85.0 +/- 5.6% of the studied strains of K. pneumoniae, 30.0 +/- 7.2% of E. cloacae, 20.0 +/- 5.6% S. Aureus the authors have identified pathogenicity factors, which ensure their ability to adhesion and persistence (antiinterferon and anticomplement activity).


Self-Employment for People with Psychiatric Disabilities: Advantages and Strategies.
Self-employment is an alternative to wage employment and an opportunity to increase labor force participation by people with psychiatric disabilities. Self-employment refers to individuals who work for themselves, either as an unincorporated sole proprietor or through ownership of a business. Advantages of self-employment for people with psychiatric disabilities, who may have disrupted educational and employment histories, include opportunities for self-care, additional earning, and career choice. Self-employment fits within a recovery paradigm because of the value placed on individual preferences, and the role of resilience and perseverance in business ownership. Self-employment creates many new US jobs, but remains only a small percentage of employment closures for people with psychiatric disabilities, despite vocational rehabilitation and Social Security disability policies that encourage it. This commentary elucidates the positive aspects of self-employment in the context of employment challenges experienced by individuals with psychiatric disabilities and provides recommendations based on larger trends in entrepreneurship.


Cauda equina neurinoma associated with normal pressure hydrocephalus--case report.
A 45-year-old male was hospitalized because of gait disturbance, urinary incontinence, and memory disturbance. A computed tomographic (CT) scan revealed dilatation of the cerebral ventricles, and a metrizamide CT scan showed reflux into all ventricles. Cerebrospinal fluid obtained at the time of metrizamide CT was highly xanthochromic. Myelograms demonstrated a tumor between the inferior portion of the fifth lumbar vertebra and that of the second sacral vertebra. After removal of a spinal tumor involving nerve fibers at the cauda equina, his symptoms disappeared and the spinal fluid protein normalized. Three months after surgery, a CT scan revealed reduction of cerebral ventricular size. There are 10 reported cases of spinal tumors resulting in normal pressure hydrocephalus. All these and present cases involved protein in the spinal fluid, which might have been the cause of the hydrocephalus.


Estimating the causal effect of milk powder supplementation on bone mineral density: a randomized controlled trial with both non-compliance and loss to follow-up.
Although previous studies reported that calcium supplementation can effectively improve bone mineral density in postmenopausal women, some studies showed the reverse conclusion. One of the reasons was that most of the studies did not take into full consideration the information of noncompliers, which seriously influenced the precision of conclusion. The aim of this paper was to investigate the effect of calcium supplementation on bone mineral density with correcting impact of noncompliance using the complier average causal effect (CACE). A randomized controlled trial was designed to investigate the effect of high-calcium milk powder on bone mineral density. One hundred and forty-one postmenopausal women were randomly assigned to either a control group (n=72) or a milk powder supplementation group (n=69). The participants in the intervention group took 50 g of high-calcium milk powder containing 450 mg of elemental calcium and 400 IU vitamin D every morning and evening, respectively. The effects of the intervention on the primary outcome, bone mineral density, were assessed using the CACE model and intention-to-treat (ITT) and per-protocol (PP) analyses. Using the CACE model, the calcium supplementation was found to significantly reduce the bone loss at the lumbar spine compared with the control group at 24 months when adjusting the covariates (effect size 1.170, 95% confidence interval (CI) 0.376~1.964, P=0.0040). At the hip site, there was no significant difference between the calcium group and the control group. Compared with the control group, no significant weight gain was found in the calcium group over 24 months. However, the calcium group had less height loss at 24 months (effect size 1.040, 95% CI 0.012~2.066, P=0.0470) than the control group. High-density lipoprotein was significantly increased in the calcium group at 12 months (effect size 0.120, 95% CI 0.009~0.232, P=0.0340). Serum total cholesterol, triglyceride and low-density lipoprotein were not affected over 24 months. The estimates of complier average causal effect of latent ignorability model with missing data assumption of latent ignorability were consistent with the CACE estimates. Consumption of high-calcium milk powder is effective in reducing the bone loss at the lumbar spine among healthy postmenopausal women. Supplementing with high-calcium milk powder had additional benefits of reducing height loss.


Carcinoma cervicis uteri. Treatment results from the period 1953--1968.
During the course of 16 years, i. e. from 1953 to 1968 inclusively, a total of 2111 patients with carcinoma of the uterine cervix were treated at the Oncological Institute in Brno. Of these, 1829 patients, i. e. 86.6% were irradiated, 282, i. e. 13.4% underwent primarily a radical excision and subsequently were irradiated. During the past years, approximately 95% of all such patients are being given radical irradiation. The mean age is 52.7 years, the sixth decade being numerically the highest in incidence -- 27.4%. The distribution pattern according to the tumor stage: I -- 29.3%, II -- 14.3%, III -- 48.2%, IV -- 8.2%. This distribution remained practically unchanged over the follow-up period of 16 years. The fundamental method treatment of practically 87% of all the patients was actinotherapy consisting in a combined application of radium and X-rays. Of the total number of 2111 patients, 1298, i. e. 61.5% have survived 5 years without any symptoms of the disease, 966 patients, i. e. 59.0% (out of a total of 1671 patients) survived 10 years. The five-year survival symptom-free period for the various stages ia as follows: I -- 82.5%, II -- 77.1%, III -- 52.8% and IV -- 9.8%. A comparison of the results of treatment in patients radically irradiated and those primarily operated upon then subsequently irradiated, i. e. in 619 patients of stage I showed the 5-year recovery to be superior by almost 4% in the former than in the latter group --84.1% as against 80.3%. Over the last 6 years of the follow-up, i. e. 1962--1968, this difference went up to 6.0% in favour of those radically irradiated--85.1% as against 79.2%. An increasing mortality rate due to carcinoma is noted with advancing age.


A phase I and pharmacodynamic evaluation of polyethylene glycol-conjugated L-asparaginase in patients with advanced solid tumors.
To evaluate the in vitro activity of polyethylene glycol-conjugated L-asparaginase (PEG-Lasparaginase) against fresh human tumor specimens, using the human tumor clonogenic assay (HTCA), and to perform a phase I dose-escalation clinical trial of PEG-L-asparaginase. The goal of the clinical study was to determine the toxicity and optimum biologic dose of PEG-L-asparaginase based on depletion of serum L-asparagine in patients with advanced solid tumors. A modified method for determination of serum L-asparagine is described. PEG-L-asparaginase was administered by intramuscular injection every 2 weeks to 28 patients with various types of advanced solid tumor malignancies. At least 3 patients were evaluated at each dose level: 250 IU/m2, 500 IU/m2, 1,000 IU/m2, 1,500 IU/m2, 2,000 IU/m2. The in vitro HTCA studies suggested good antitumor activity against malignant melanoma and multiple myeloma. Serum L-asparagine was most consistently and profoundly depleted (up to 4 weeks) in patients treated with 2,000 IU/m2. Patients receiving this dose level also showed more frequent grade 1, grade 2, and occasional grade 3 toxicities of fatigue/weakness, nausea/vomiting, and anorexia/ weight loss. Three patients developed hypersensitivity reactions, but these were not dose related. Two patients developed deep vein thromboses. We saw no episodes of clinical pancreatitis, but there were minor fluctuations of serum amylase and lipase. We saw no partial or complete responses in patients treated in this study, including 11 patients with malignant melanoma. We conclude that PEG-L-asparaginase is generally well tolerated in patients with advanced solid tumors, and a dosage of 2,000 IU/m2 by intramuscular injection every 2 weeks results in significant depletion of serum L-asparagine.


Photodynamic therapy for steroid-associated central serous chorioretinopathy.
To evaluate the short-term efficacy of photodynamic therapy (PDT) for steroid-associated chronic or recurrent central serous chorioretinopathy (CSC). Interventional case series. Retrospective review of nine consecutive cases of steroid-associated CSC treated with PDT using half-fluence for fovea involving treatments (n=4) and full-fluence for extrafoveal treatments (n=5). The main outcome measures included anatomical changes measured on optical coherence tomography (OCT) and changes in best-corrected visual acuity (BCVA) after PDT. All eyes had fovea involving serous retinal detachment on OCT, and six (67%) eyes had a history of three or more recurrences. The mean duration of current episode of CSC prior to PDT was 45 months (range: 3-131 months). The mean follow-up after PDT was 8 months (range: 3-18 months). Serous retinal detachment disappeared in all cases following PDT without any complications. One patient had a recurrence and was re-treated. Compared to the mean BCVA of 20/83 (logMAR 0.62) at baseline, the mean BCVA was 20/40 (logMAR 0.33) at 3 months (p=0.018), and 20/47 (logMAR 0.37) at last follow up (p=0.075). Visual acuity improved by at least two lines in three (33%) eyes. Despite chronicity and recurrences seen in steroid-associated CSC, serous retinal detachment resolved in all cases, and a modest improvement in visual acuity was observed following PDT, at least for the short term. Given the difficulty of managing these cases, PDT as applied in this study may be an effective treatment.


Elimination of HIV transmission through novel and established prevention strategies among people who inject drugs.
Despite the effectiveness of existing HIV prevention strategies for people who inject drugs (PWID), uncontrolled outbreaks of HIV among this group are common and occur around the world. In this Review, we summarise recent evidence for novel and established HIV prevention approaches to eliminate HIV transmission among PWID. Effective HIV prevention strategies include mobile needle and syringe programmes, pre-exposure prophylaxis, supervised injection facilities, and, to a lesser extent, some behavioural interventions. Studies have also shown the cost-effectiveness of long-standing HIV prevention strategies including needle and syringe programmes, opioid agonist therapy, and antiretroviral therapy for prevention. Although each individual intervention can reduce the risk of HIV acquisition among PWID, there is a consensus that a combination of approaches is required to achieve substantial and durable reductions in HIV transmission. Unfortunately, in many settings, the implementation of these interventions is often limited by public and political opposition that manifests as structural barriers to HIV prevention, such as the criminalisation of drug use. Given that there is ample evidence showing the effectiveness of several HIV prevention methods, social and political advocacy will be needed to overcome these barriers and integrate innovative HIV prevention approaches with addiction science to create effective drug policies.


African American women in the workplace: relationships between job conditions, racial bias at work, and perceived job quality.
Although studies have described work processes among employed African American women, few have examined the influence of these processes on job outcomes. This study examined relationships between African American women's exposure to a range of occupational stressors, including two types of racial bias--institutional discrimination and interpersonal prejudice--and their evaluations of job quality. Findings indicated that institutional discrimination and interpersonal prejudice were more important predictors of job quality among these women than were other occupational stressors such as low task variety and decision authority, heavy workloads, and poor supervision. Racial bias in the workplace was most likely to be reported by workers in predominantly white work settings. In addition, Black women who worked in service, semiskilled, and unskilled occupations reported significantly more institutional discrimination, but not more interpersonal prejudice, than did women in professional, managerial, and technical occupations or those in sales and clerical occupations.


Energy cost and muscular activity required for leg swing during walking.
To investigate the metabolic cost and muscular actions required for the initiation and propagation of leg swing, we applied a novel combination of external forces to subjects walking on a treadmill. We applied a forward pulling force at each foot to assist leg swing, a constant forward pulling force at the waist to provide center of mass propulsion, and a combination of these foot and waist forces to evaluate leg swing. When the metabolic cost and muscle actions were at a minimum, the condition was considered optimal. We reasoned that the difference in energy consumption between the optimal combined waist and foot force trial and the optimal waist force-only trial would reflect the metabolic cost of initiating and propagating leg swing during normal walking. We also reasoned that a lower muscle activity with these assisting forces would indicate which muscles are normally responsible for initiating and propagating leg swing. With a propulsive force at the waist of 10% body weight (BW), the net metabolic cost of walking decreased to 58% of normal walking. With the optimal combination, a propulsive force at the waist of 10% BW plus a pulling force at the feet of 3% BW the net metabolic cost of walking further decreased to 48% of normal walking. With the same combination, the muscle activity of the iliopsoas and rectus femoris muscles during the swing phase was 27 and 60% lower, respectively, but the activity of the medial gastrocnemius and soleus before swing did not change. Thus our data indicate that approximately 10% of the net metabolic cost of walking is required to initiate and propagate leg swing. Additionally, the hip flexor muscles contribute to the initiation and propagation leg swing.


Ocean warming and acidification degrade shoaling performance and lateralization of novel tropical-temperate fish shoals.
Gregarious behaviours are common in animals and provide various benefits such as food acquisition and protection against predators. Many gregarious tropical species are shifting poleward under current ocean warming, creating novel species and social interactions with local temperate taxa. However, how the dynamics of these novel shoals might be altered by future ocean warming and acidification remains untested. Here we evaluate how novel species interactions, ocean acidification and warming affect shoaling dynamics, motor lateralization and boldness of range-extending tropical and co-shoaling temperate fishes under controlled laboratory conditions. Fishes were exposed to 1 of 12 treatments (combinations of three temperature levels, two pCO2 levels and two shoal type levels: mixed species or temperate only) for 38 days. Lateralization (a measure of asymmetric expression of cognitive function in group coordination and predator escape) of tropical and temperate species was right-side biased under present-day conditions, but side bias significantly diminished in tropical and temperate fishes under ocean acidification. Ocean acidification also decreased shoal cohesion irrespective of shoaling type, with mixed-species shoals showing significantly lower cohesion than temperate-only shoals irrespective of climate stressors. Tropical fish became bolder under ocean acidification (after 4 weeks), and temperate fish became bolder with increasing temperature, while ocean acidification dampened temperate fish boldness. Our findings highlight the direct effect of climate stressors on fish behaviour and the interplay with the indirect effects of novel species interactions. Because strong shoal cohesion and lateralization are key determinants of species fitness, their degradation under ocean warming and acidification could adversely affect species performance in novel assemblages in a future ocean, and might slow down tropical species range extensions.


Arabidopsis MAPKs: a complex signalling network involved in multiple biological processes.
Many changes in environmental conditions and hormones are mediated by MAPK (mitogen-activated protein kinase) cascades in all eukaryotes, including plants. Studies of MAPK pathways in genetic model organisms are especially informative in revealing the molecular mechanisms by means of which MAPK cascades are controlled and modulate cellular processes. The present review highlights recent insights into MAPK-based signalling in Arabidopsis thaliana (thale cress), revealing the complexity and future challenges to understanding signal-transduction networks on a global scale.


Viewpoint: the ENIGMAS trial - when should we treat patients with moderate aortic stenosis?
Aortic stenosis (AS) is the most frequent valvular heart disease encountered in our daily practice. Although there are clear guidelines for severe AS management, cardiologists often have few treatment options for patients with moderate AS; however, there is higher mortality in this patient subgroup versus an age-matched population. The authors reviewed all of the studies on moderate AS, summarized the factors that increase disease progression and discussed an ideal trial design to prospectively evaluate AS progression factors using modern cardiology tools such as strain and magnetic resonance imaging.


Expression and alternative splicing of the mouse autoimmune regulator gene (Aire).
AIRE, the gene responsible for the autoimmune polyglandular syndrome type 1 (APS1) or APECED, may act as a transcription factor according to its predicated protein structure. Here we demonstrate the low expression level of the mouse Aire gene as it is undetectable by Northern blot analyses. However, RT-PCR analyses revealed expression of Aire in mouse thymus, ovary, lung, testis, kidney and adrenal gland. Barely detectable level of RT-PCR product was also found in thyroid gland and heart but no amplification was detected in pancreas, spleen and liver. Competitive RT-PCR assays demonstrated highest expression level of Aire mRNA in thymus. In addition to the complete cDNA (Aire or Aire-1a), we identified 11 alternative splicing forms (designated as Aire-1b, Aire-1c, Aire-1d, Aire-2a, Aire-2b, Aire-2c, Aire-2d, Aire-3a, Aire-3b, Aire-3c and Aire-3d). These forms result from combinations of four alternative splicing units (exon 10, exon 11, 12 bp in exon 6 and 3 bp in exon 8). The relative abundance of these splicing forms was also determined.


Determinants of physical activity initiation and maintenance among community-dwelling older persons.
Understanding determinants of initiation and maintenance of an active lifestyle among older individuals is of great concern to public health because of the increasing evidence that lifestyle may alter the course of frequently occurring chronic diseases. Two thousand five hundred seven community-dwelling Medicare beneficiaries age 65 and over were interviewed at three points over 4 years regarding their physical activity, defined as a self-report of walking briskly, gardening, or heavy housework at least three times a week. Extensive data were also collected on health status, health services use, sociodemographics, and, at the final interview, self-mastery, importance of various factors in the decision to be physically active, and interaction with their physician regarding physical activity. Determinants of initiation and maintenance of physical activity were identified using logistic regressions. Forty-one percent maintained an active lifestyle; 12% initiated an active lifestyle; 22% declined to become sedentary; 25% were sedentary at all observation. Predictors of both initiation and maintenance of physical activity were younger age, moderate to excellent health, and the patient's belief that physical activity was important to his/her health. Among the 301 patients who initiated activity, 40% said their physician was a very important influence. Strengthening the belief of older individuals in the benefits to their health of physical activity holds promise for increasing the proportion of community-dwelling older persons who move from a sedentary lifestyle to a more physically active lifestyle and for maintaining such activity.


Insights into immune-response gene function using an Ia mutant mouse strain.
The class II genes of the major histocompatibility complex (MHC) encode the immune response-associated or Ia antigens. These highly polymorphic glycoprotein heterodimers have been shown to play a pivotal role in diverse immunological functions. Although the precise molecular and cellular interactions have yet to be elucidated, structural determinations on Ia molecules are known to control the immune response to foreign antigens. Several recent advances into our understanding of how Ia molecules function were made possible by the discovery of the B6,C-H-2bm12 (bm12) mouse strain. The bm12 strain carries a mutation that occurred spontaneously in one of its genes encoding an Ia polypeptide chain. Information from studies using bm12 include (1) insights into the evolution of class II genes and its functional significance; (2) the definition of multiple functional sites on Ia and their relative importance; and (3) the demonstration that Ia conformation is important in determining its functional capacity. These findings using the bm12 mutant are reviewed in the context of other recent studies of Ia recognition.


A Self-Synchronized Optoelectronic Oscillator based on an RTD Photo-Detector and a Laser Diode.
We propose and demonstrate a simple and stable low-phase noise optoelectronic oscillator (OEO) that uses a laser diode, an optical fiber delay line and a resonant tunneling diode (RTD) free-running oscillator that is monolithic integrated with a waveguide photo-detector. The RTD-OEO exhibits single-side band phase noise power below -100 dBc/Hz with more than 30 dB noise suppression at 10 kHz from the center free-running frequency for fiber loop lengths around 1.2 km. The oscillator power consumption is below 0.55 W, and can be controlled either by the injected optical power or the fiber delay line. The RTD-OEO stability is achieved without using other high-speed optical/optoelectronic components and amplification.


The role of ultrasound in women who undergo cell-free DNA screening.
The introduction of cell-free DNA screening for aneuploidy into obstetric practice in 2011 revolutionized the strategies utilized for prenatal testing. The purpose of this document is to review the current data on the role of ultrasound in women who have undergone or are considering cell-free DNA screening. The following are Society for Maternal-Fetal Medicine recommendations: (1) in women who have already received a negative cell-free DNA screening screen, ultrasound at 11-14 weeks of gestation solely for the purpose of nuchal translucency measurement (Current Procedural Terminology code 76813) is not recommended (grade 1B); (2) we recommend that diagnostic testing should not be recommended to patients solely for the indication of an isolated soft marker in the setting of a negative cell-free DNA screen (grade 2B); (3) in women with an isolated soft marker without other clinical implications (ie, choroid plexus cyst or echogenic intracardiac focus) and a negative cell-free DNA screen, we recommend describing the finding as not clinically significant or as a normal variant (grade 2B); (4) in women with an isolated soft marker that has no other clinical implication (ie, choroid plexus cyst or echogenic intracardiac focus) and a negative first- or second-trimester screening result, we recommend describing the finding as not clinically significant or as a normal variant (grade 2B); (5) we recommend that all women in whom a structural abnormality is identified by ultrasound should be offered diagnostic testing with chromosomal microarray (grade 1A); and (6) we recommend against routine screening for microdeletions with cell-free DNA screening (grade 1B).


Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanoma.
CD73 is a cell surface enzyme that suppresses T cell-mediated immune responses by producing extracellular adenosine. Growing evidence suggests that targeting CD73 in cancer may be useful for an effective therapeutic outcome. In this study, we demonstrate that administration of a specific CD73 inhibitor, adenosine 5'-(α,β-methylene)diphosphate (APCP), to melanoma-bearing mice induced a significant tumor regression by promoting the release of Th1- and Th17-associated cytokines in the tumor microenvironment. CD8+ T cells were increased in melanoma tissue of APCP-treated mice. Accordingly, in nude mice APCP failed to reduce tumor growth. Importantly, we observed that after APCP administration, the presence of B cells in the melanoma tissue was greater than that observed in control mice. This was associated with production of IgG2b within the melanoma. Depletion of CD20+ B cells partially blocked the anti-tumor effect of APCP and significantly reduced the production of IgG2b induced by APCP, implying a critical role for B cells in the anti-tumor activity of APCP. Our results also suggest that APCP could influence B cell activity to produce IgG through IL-17A, which significantly increased in the tumor tissue of APCP-treated mice. In support of this, we found that in melanoma-bearing mice receiving anti-IL-17A mAb, the anti-tumor effect of APCP was ablated. This correlated with a reduced capacity of APCP-treated mice to mount an effective immune response against melanoma, as neutralization of this cytokine significantly affected both the CD8+ T cell- and B cell-mediated responses. In conclusion, we demonstrate that both T cells and B cells play a pivotal role in the APCP-induced anti-tumor immune response.


[Quantitative contrast angiography of the right ventricle: the normal indices and the problems in analyzing global and regional contractility].
Normal parameters of the right ventricular (RV) volumes, global and regional contractility were obtained in 20 normal subjects (15 men and 7 women, mean age, 47 +/- 8 yrs) by quantitative contrast RV ventriculography. Analysis of different methods of the angiographic RV volumes calculation was made. It was shown, that Ferlinz's method is adequate to get real values for RV. A new method for computer assessment of RV regional contractility was proposed--shrinkage of 5 areas in percent. The most difference (15 and 17%) between "internal" and "external" observer was found in the anterior and anteroapical segments of RV, differences in another segments were not significant (5-8%).


Variability of posterior veins of the left ventricle in the adult human heart.
The frequency of occurrence and topography of the outfow portions of the posterior veins of the left ventricle were observed. One hundred fifty adult human hearts of both sexes from l8 to 85 years of age fixed in a formalin/ethanol solution were examined. Classical macroscopic anatomical examination methods were used. The posterior veins of the left ventricle were always present in the examined heart material, but occurred in varying number (l -4). The outfow portions of these veins were characterized by significant variation with regards to position as well as angle of its outfow.


Factors Affecting the Robustness of Data Inversion for Stable Isotope Measurement Using the Double Spike Method: Insights from Chromium Isotope Analysis.
Stable isotope ratios are widely used to solve environmental, geological, medical, and forensic problems. The double spike technique is considered to be one of the most robust and efficient methods to correct for instrumental mass bias and isotopic fractionation that may occur during sample preparation. However, various hidden errors can arise from data processing and have been largely overlooked in previous studies. Several of these hidden errors were investigated in this work using measurement and synthetic data. Double spike inversion of chromium isotope raw data from 1116 natural samples demonstrated that averaging raw isotope ratios before double spike inversion can add significant errors to inverted isotope values, and such errors can be 1.5 times larger than the true analytical precision. Synthetic data were used to investigate the errors on inverted Cr isotope data caused by spike:analyte ratio and Fe-Ti-V interferences, and the following threshold values are recommended to minimize such errors: 54Crspike/52Crsample ratio greater than 0.5, 56Fe/52Cr less than 0.2, 49Ti/52Cr less than 0.04, and 51V/52Cr less than 1. Sample preparation can potentially lead to large errors in inverted Cr isotope data if preparation-induced isotope fractionation deviates from the exponential law used in the double spike inversion, but such errors can be minimized by achieving >70% Cr yield. Our findings provide important insights for the double spike inversion procedure and assessing the reliability of inverted isotope data for not only the chromium isotope system but also other elements commonly analyzed using the double spike technique.


Modes of (in)tolerance: South African Muslims and same-sex relationships.
In this study we interviewed members of a small, predominantly Muslim community in Johannesburg, South Africa, in order to ascertain attitudes towards people who engage in same-sex practices. We were interested in ascertaining whether community perceptions of homosexuality match the common (Western) assumption that Islam is profoundly homophobic. Our research, while preliminary, shows that although most people condemn same-sex practices on the grounds of religious principle, they also in practice did not act upon these views. Respondents held different views on whether a person is gay or lesbian as result of same-sex behaviour, on the one hand, or same-sex desire, on the other hand. This distinction accords with what was, for them, the difficulty of proving the same-sex practices had occurred given strict Muslim standards of proof. Community attitudes to homosexuality usually involve denial and secrecy in order to maintain the social fabric of daily life and relationships between community members.


Liquid Biopsy as Surrogate for Tissue for Molecular Profiling in Pancreatic Cancer: A Meta-Analysis Towards Precision Medicine.
Liquid biopsy (LB) is a non-invasive approach representing a promising tool for new precision medicine strategies for cancer treatment. However, a comprehensive analysis of its reliability for pancreatic cancer (PC) is lacking. To this aim, we performed the first meta-analysis on this topic. We calculated the pooled sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio, and diagnostic odds ratio (DOR). A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall accuracy. We finally assessed the concordance rate of all mutations detected by multi-genes panels. Fourteen eligible studies involving 369 patients were included. The overall pooled sensitivity and specificity were 0.70 and 0.86, respectively. The LR+ was 3.85, the LR- was 0.34 and DOR was 15.84. The SROC curve with an AUC of 0.88 indicated a relatively high accuracy of LB for molecular characterization of PC. The concordance rate of all mutations detected by multi-genes panels was 31.9%. LB can serve as surrogate for tissue in the molecular profiling of PC, because of its relatively high sensitivity, specificity and accuracy. It represents a unique opportunity to be further explored towards its introduction in clinical practice and for developing new precision medicine approaches against PC.


Testing the impact of trait prevalence priors in Bayesian-based genetic prediction modeling of human appearance traits.
The prediction of appearance traits by use of solely genetic information has become an established approach and a number of statistical prediction models have already been developed for this purpose. However, given limited knowledge on appearance genetics, currently available models are incomplete and do not include all causal genetic variants as predictors. Therefore such prediction models may benefit from the inclusion of additional information that acts as a proxy for this unknown genetic background. Use of priors, possibly informed by trait category prevalence values in biogeographic ancestry groups, in a Bayesian framework may thus improve the prediction accuracy of previously predicted externally visible characteristics, but has not been investigated as of yet. In this study, we assessed the impact of using trait prevalence-informed priors on the prediction performance in Bayesian models for eye, hair and skin color as well as hair structure and freckles in comparison to the respective prior-free models. Those prior-free models were either similarly defined either very close to the already established ones by using a reduced predictive marker set. However, these differences in the number of the predictive markers should not affect significantly our main outcomes. We observed that such priors often had a strong effect on the prediction performance, but to varying degrees between different traits and also different trait categories, with some categories barely showing an effect. While we found potential for improving the prediction accuracy of many of the appearance trait categories tested by using priors, our analyses also showed that misspecification of those prior values often severely diminished the accuracy compared to the respective prior-free approach. This emphasizes the importance of accurate specification of prevalence-informed priors in Bayesian prediction modeling of appearance traits. However, the existing literature knowledge on spatial prevalence is sparse for most appearance traits, including those investigated here. Due to the limitations in appearance trait prevalence knowledge, our results render the use of trait prevalence-informed priors in DNA-based appearance trait prediction currently infeasible.


[Detection of adenovirus antigens using immunoenzyme analysis].
An enzyme immunoassay test system has been developed for detection of adenovirus antigens, based on avidin--biotin interaction. It is highly sensitive, specific, and effective: it detected adenovirus antigens in 15 percent of 196 patients with acute respiratory diseases (nasopharyngeal washings and aspirates were under study).


Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases.
Telomeres, the protective ends of linear chromosomes, shorten throughout an individual's lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself.


Surgical treatment of thoracic disc herniations via tailored posterior approaches.
We present clinical findings, radiological characteristics and surgical modalities of various posterior approaches to thoracic disc herniations and report the clinical results in 27 consecutive patients. Within an 8-year period 27 consecutive patients (17 female, 10 male) aged 30-83 years (mean 53 years.) were surgically treated for 28 symptomatic herniated thoracic discs in our department. Six of these lesions (21%) were calcified. In all cases surgery was performed via individually tailored posterior approaches. We evaluated the pre- and postoperative clinical status and the complication rate in a retrospective study. Nearly one half of the lesions (46.4%) were located at the three lowest thoracic segments. Clinical symptoms included back pain or radicular pain (77.8%), altered sensitivity (77.8%), weakness (40.7%), impaired gait (51.9%) or bladder dysfunction (22%). Costotransversectomy was performed in 8 patients, 1 lateral extracavitary approach, 2 foraminotomies, 15 transfacet and/or transpedicular approaches and 2 interlaminar approaches were used for removing the pathologies. After a mean follow-up of 38.6 months (3-100 months), complete normalization or reduction of local pain was recorded in 87% of the patients and of radicular pain in 70% of the cases, increased motor strength could be achieved in 55%, sensitivity improved in 76.2% and improvement of myelopathy was noted in 71.4%. Two patients suffered from postoperative impairment of sensory deficits, which in one case was discrete. The overall recovery rate within the modified JOA score was 39.5%. In 1 patient, two revisions were required because of instability and a persisting osteophyte, respectively. The rate of major complications was 7.1% (2/28). Surgical treatment of thoracic disc herniations via posterior approaches tailored to the individual patient produces satisfying results referring to clinical outcome. Posterior approaches remain a viable alternative for a large proportion of patients with symptomatic thoracic disc herniations.


Complete Genome Sequence of Lactobacillus johnsonii Strain Byun-jo-01, Isolated from the Murine Gastrointestinal Tract.
We report here the complete genome sequence of Lactobacillus johnsonii strain Byun-jo-01, which was isolated from the murine gastrointestinal tract. The genome was determined using both PacBio and Illumina sequencing. L. johnsonii strain Byun-jo-01 contains a single circular chromosome of 1,959,519 bp, and its GC content is 34.7%.


Amino acids as cryoprotectants for liposomal delivery systems.
Liposomes provide an efficient delivery system for solubilisation and delivery of both small and macro molecules. However, they suffer from the disadvantage of instability when stored as aqueous dispersions. Cryoprotection of the liposomal systems provides an effective approach to overcome poor stability whilst maintaining formulation characteristics, although, the formulation of a freeze-dried product requires the consideration of not only the selection of an appropriate cryoprotectant, but also needs careful consideration of the processing parameters including pre-freezing conditions, primary and secondary drying protocols along with optimisation of cryoprotectant concentration. This current work investigates the application of amino acids as potential cryoprotectants for the stabilisation of liposomes, and results indicate that amino acids show biphasic nature of stabilisation with 4 mol of cryoprotectant per mole of the lipid exhibiting optimum cryoprotection. The investigations of process parameters showed that the pre-freezing temperatures below the glass transition of the amino acids followed by drying for over 6h resulted in stable formulations. Studies investigating the efficiency of drug retention showed that the cryoprotection offered by lysine was similar to that shown by trehalose, suggesting that amino acids act as effective stabilizers. ESEM analysis was carried out to monitor morphology of the rehydrated liposomes.


Acute HIV-infection: report of a case and a review of recent developments.
A patient is reported with a typical acute HIV-infection. He presented with an infectious mononucleosis-like illness, which included fever, malaise, sore throat, myalgia, swollen glands and a rash. Seroconversion, documented by serial immunoblotting, occurred within a period of four days. If a patient with a glandular fever-like illness belongs to one of the risk groups, an acute HIV-infection should be seriously considered. In a recent study an association was found between the clinical course of acute HIV-infection and the subsequent course. Treatment of asymptomatic HIV-infected patients is discouraged, except if included in a clinical trial.


Seroprevalence of H7N9 infection among humans: A systematic review and meta-analysis.
In spring 2013, a novel avian-origin influenza A (H7N9) virus emerged in mainland China. The burden of H7N9 infection was estimated based on systematic review and meta-analysis. The systematic search for available literature was conducted using Chinese and English databases. We calculated the pooled seroprevalence of H7N9 infection and its 95% confidence interval by using Freeman-Tukey double arcsine transformation. Out of 16 890 records found using Chinese and English databases, 54 articles were included in the meta-analysis. These included studies of a total of 64 107 individuals. The pooled seroprevalence of H7N9 infection among humans was 0.122% (95% CI: 0.023, 0.275). In high-risk populations, the highest pooled seroprevalence was observed among close contacts (1.075%, 95% CI: 0.000, 4.357). The seroprevalence among general population was (0.077%, 95% CI: 0.011, 0.180). Our study discovered that asymptomatic infection of H7N9 virus did occur, even if the seroprevalence among humans was low.


Fast visible light photoelectric switch based on ultralong single crystalline V₂O₅ nanobelt.
A photoelectric switch with fast response to visible light (<200 μs), suitable photosensitivity and excellent repeatability is proposed based on the ultralong single crystalline V₂O₅ nanobelt, which are synthesized by chemical vapor deposition and its photoconductive mechanism can well be explained by small polaron hopping theory. Our results reveal that the switch has a great potential in next generation photodetectors and light-wave communications.


Imidacloprid and acetamiprid synergistically downregulate spaetzle and myD88 of the Toll pathway in haemocytes of the European honeybee (Apis mellifera).
Pollinator health has been of critical concern over the last few decades. The prevalence of the honeybee Colony Collapse Disorder (CCD), changing climate, and the rise of vector-borne honeybee diseases by Varroa destructor, have played a major role in the rapid decline of global honeybee populations. Honeybees are environmentally and economically significant actors in biodiversity. The impact of agricultural practices, such as pesticide use, has exacerbated the negative effects on honeybees. We demonstrate the synergistic effect of cocktails of the neonicotinoids imidacloprid and acetamiprid on honeybee haemocytes. Two genes responsible for critical immune responses, spaetzle and myD88, are consistently dysregulated following exposure to either neonicotinoid alone or as a mixture with or without an immune challenge. The 2018 ban of neonicotinoids in Europe, followed by the 2020 reauthorisation of imidacloprid in France and the current consideration to reinstate acetamiprid underscores the need to evaluate their cumulative impact on honeybee health.


X-ray Transparent Microfluidic Chip for Mesophase-Based Crystallization of Membrane Proteins and On-Chip Structure Determination.
Crystallization from lipidic mesophase matrices is a promising route to diffraction-quality crystals and structures of membrane proteins. The microfluidic approach reported here eliminates two bottlenecks of the standard mesophase-based crystallization protocols: (i) manual preparation of viscous mesophases and (ii) manual harvesting of often small and fragile protein crystals. In the approach reported here, protein-loaded mesophases are formulated in an X-ray transparent microfluidic chip using only 60 nL of the protein solution per crystallization trial. The X-ray transparency of the chip enables diffraction data collection from multiple crystals residing in microfluidic wells, eliminating the normally required manual harvesting and mounting of individual crystals. We validated our approach by on-chip crystallization of photosynthetic reaction center, a membrane protein from Rhodobacter sphaeroides, followed by solving its structure to a resolution of 2.5 Å using X-ray diffraction data collected on-chip under ambient conditions. A moderate conformational change in hydrophilic chains of the protein was observed when comparing the on-chip, room temperature structure with known structures for which data were acquired under cryogenic conditions.


Lead poisoning in a historical perspective.
Lead poisoning existed and was already known in Antiquity but was forgotten, at least in the literature, until the end of the Middle Ages, where it was mentioned sporadically. In the 19th century this disease, which reached epidemic dimensions during the period of industrialization, was "rediscovered." Several comprehensive clinical articles appeared in the literature. The clinical picture deepened during the beginning of the 20th century, and preventive efforts were started. However, the concept of poisoning remained strictly clinical. During the latter half of the 20th century a new concept emerged: subclinical and early forms became recognized as undesirable effects. This led to a substantial lowering of hygienic standards. Pediatric poisoning has also been a serious problem during the 20th century. After the 1920s, environmental pollution by lead caused by the introduction of tetraethyl lead in gasoline became an alarming public health problem. The use became restricted in the 1980s; its effects on blood lead levels are now evident. Today's research focuses on the effects of low exposure, often with the aim of defining noneffect levels for different types of effects.


In Silico Evaluation of the Potential Impact of Bioanalytical Bias Difference between Two Therapeutic Protein Formulations for Pharmacokinetic Assessment in a Biocomparability Study.
Formulation changes at later stages of biotherapeutics development require biocomparability (BC) assessment. Using simulation, this study aims to determine the potential effect of bias difference observed between the two formulations after spiking into serum in passing or failing of a critical BC study. An ELISA method with 20% total error was used to assess any bias differences between a reference (RF) and test formulations (TF) in serum. During bioanalytical comparison of these formulations, a 9% difference in bias was observed between the two formulations in sera. To determine acceptable level of bias difference between the RF and TF bioanalytically, two in silico simulations were performed. The in silico analysis showed that the likelihood of the study meeting the BC criteria was >90% when the bias difference between RF and TF in serum was 9% and the number of subjects was ≥20 per treatment arm. An additional simulation showed that when the bias difference was increased to 13% and the number of subjects was <40, the likelihood of meeting the BC criteria decreased to 80%. The result from in silico analysis allowed the bioanalytical laboratory to proceed with sample analysis using a single calibrator and quality controls made from the reference formulation. This modeling approach can be applied to other BC studies with similar situations.


The age and size of the universe.
Modern distance determinations to galaxies were reviewed and placed on a uniform and self-consistent scale. Based on eight separate but not entirely independent techniques, the distance to the Virgo cluster was found to be 15.8 +/- 1.1 megaparsec. Twelve different determinations yield a Coma/Virgo distance ratio of 5.52 +/- 0.13 and hence a Coma distance of 87 +/- 6 megaparsec. With a cosmological redshift of 7210 kilometers per second, this gives a Hubble parameter H(0) (local) of 83 +/- 6 kilometers per second per megaparsec. From the velocity-distance relation of rich clusters of galaxies, the ratio of the value of H(0) (global) to the value of H(0) (local) was determined to be 0.92 +/- 0.08. In other words, the cluster data do not show a statistically significant difference between the local and global values of the Hubble parameter. If one nevertheless adopts this relation between H(0) (global) and H(0) (local), then the value of H(0) (global) is 76 +/- 9 kilometers per second per megaparsec. This observed value differs at the approximately 3sigma level (where sigma is the standard deviation of the distribution) from values in the range 36 less, similar H(0) less, similar50 kilometers per second per megaparsec, which are derived from stellar evolutionary theory in conjunction with standard cosmological models with a density parameter (Omega) that is equal to 1 and a cosmological constant (lambda) that is equal to 0.


Normalizing Flows for Microscopic Many-Body Calculations: An Application to the Nuclear Equation of State.
Normalizing flows are a class of machine learning models used to construct a complex distribution through a bijective mapping of a simple base distribution. We demonstrate that normalizing flows are particularly well suited as a Monte Carlo integration framework for quantum many-body calculations that require the repeated evaluation of high-dimensional integrals across smoothly varying integrands and integration regions. As an example, we consider the finite-temperature nuclear equation of state. An important advantage of normalizing flows is the ability to build highly expressive models of the target integrand, which we demonstrate enables precise evaluations of the nuclear free energy and its derivatives. Furthermore, we show that a normalizing flow model trained on one target integrand can be used to efficiently calculate related integrals when the temperature, density, or nuclear force is varied. This work will support future efforts to build microscopic equations of state for numerical simulations of supernovae and neutron star mergers that employ state-of-the-art nuclear forces and many-body methods.


Effect of low-level laser therapy on patient reported measures of oral mucositis and quality of life in head and neck cancer patients receiving chemoradiotherapy--a randomized controlled trial.
Chemoradiotherapy (CRT)-induced oral mucositis (OM) adversely affects a patient's oral functions and quality of life (QOL). Low-level laser therapy (LLLT) showed some preventive and curative effects against clinically reported objective measures of OM in few trials including our recently published study. There is dearth of evidence regarding the effects of LLLT on patient's subjective experience of OM and QOL. Hence, we did this study to evaluate the effects of LLLT on a patient's reported measures of OM and QOL in head and neck cancer (HNC) patients receiving CRT. This triple blinded study randomized 220 HNC patients scheduled for CRT (three weekly Cisplatin + RT = 66 Gray (2 Gy/session), five fractions/week for 6.5 weeks, total 33 fractions) into laser (110) and placebo (110) groups. The laser group received LLLT (Technomed Electronics Advanced Laser Therapy 1000, He-Ne, λ = 632.8 nm, power density = 24 mW/cm(2), dosage = 3.0 J at each point, total dose/session = 36-40 J, spot size 1 cm(2), irradiation time/point 125 s) before each radiation session, while the placebo group did not receive laser therapy. Methodology was similar to our recently published study (Gautam et al. Radiother Oncol 104:349-354, 2012). In this part of our study, a blinded assessor collected subjective outcomes of the patient's reported measures of OM using Oral Mucositis Weekly Questionnaire-Head and Neck (OMWQ-HN) and QOL using Functional Assessment of Cancer Treatment-Head and Neck (FACT-HN) Questionnaire. Data were analyzed using repeated measure ANOVA through general linear model. Statistical significance was kept at p < 0.05. Results analysis revealed that OMWQ-HN (F = 12.199, df = 6,1314, p < 0.001) and FACT-HN (p < 0.05) scores were significantly lower in LLLT than placebo group patients. Also, a significant reduction (p < 0.001) in incidence of severe OM, need for opioid analgesics, and total parenteral nutrition was observed. LLLT was effective in improving the patient's subjective experience of OM and QOL in HNC patients receiving CRT.


The efficacy of corticosteroids therapy in patients with moderate to severe SARS-CoV-2 infection: a multicenter, randomized, open-label trial.
We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.


The Use of Event-Related Potentials and Machine Learning to Improve Diagnostic Testing and Prediction of Disease Progression in Parkinson's Disease.
Current tests of disease status in Parkinson's disease suffer from high variability, limiting their ability to determine disease severity and prognosis. Event-related potentials, in conjunction with machine learning, may provide a more objective assessment. In this study, we will use event-related potentials to develop machine learning models, aiming to provide an objective way to assess disease status and predict disease progression in Parkinson's disease.


A comparison of two dosing regimens of zidovudine in Thai adults with early symptomatic HIV infection. Conducting clinical HIV trials in South-East Asia.
To compare the clinical and immunological efficacy, and tolerance of two dosage regimens of zidovudine (ZDV) in an adult Thai population with early symptomatic human immunodeficiency virus (HIV) disease and to identify important clinical issues associated with conducting HIV trials in South-East Asia. HIV-infected Thai adults, with early symptomatic HIV disease and CD4 lymphocyte counts less than 400/mm3, who were managed in the infectious diseases clinics at two university teaching hospitals in Bangkok, Thailand, were enrolled in a randomised, open-label, dose-regimen comparison trial of ZDV. Two oral ZDV dosing regimens: regimen A, 100 mg tid+200 mg nocte (ZDV-A) vs regimen B, 250 mg bid (ZDV-B) were compared. The main outcome measures were: 1. Clinical efficacy: rate of progression to acquired immunodeficiency syndrome (AIDS) or death. 2. Immunologic efficacy: changes in CD4 lymphocyte numbers compared to baseline; rate of decline of CD4 lymphocyte numbers to less than 100/mm3. 3. Toxicity, as defined by clinical symptomatology and laboratory parameters. Two hundred and four patients were enrolled (103 ZDV-A; 101 ZDV-B) of whom 195 were followed beyond baseline. Patients were typical of those encountered with HIV in Thailand: mean age 33 years; 89% male; 88% heterosexual HIV acquisition; mean baseline CD4 lymphocyte count 241/mm3. Follow-up while on therapy was comparable for the two groups (mean+/-SD): 533+/-236 days (ZDV-A) vs 592+/-210 days (ZDV-B). One hundred and eleven patients (57%; 51 ZDV-A; 60 ZDV-B) were treated for at least 22 months (669+/-30 days). Clinical and immunological outcomes for ZDV-A and ZDV-B, including rate of progression to AIDS or death, development of non-AIDS-defining opportunistic infections, mean changes in CD4 lymphocyte numbers/mm3, difference in area under the CD4:time distribution curve and difference in the rate of decline of CD4 lymphocyte numbers to less than 100/mm3, were not significantly different. The presence of oral hairy leukoplakia or unintentional weight loss of 10-20% at enrollment were significantly associated with the later development of AIDS (p=0.03 and 0.04, respectively). ZDV-associated toxicity was similar for both regimens. Maintaining protocol adherence and appropriate clinical follow-up emerged as important practical issues. In Thai adults, ZDV 100 mg tid+200 mg nocte and ZDV 250 mg bid have similar clinical and immunological efficacy. Rates of ZDV toxicity are comparable to those reported in non-Asian populations. Despite limitations in medical care access and maintaining long-term follow-up, successful trials of antiretroviral agents are feasible in South-East Asia and multi-drug treatment trials should be pursued in appropriate institutions.


The effect of different angle kappa on higher-order aberrations after small incision lenticule extraction.
This study aimed to compare higher-order aberrations (HOAs) after small incision lenticule extraction (SMILE) in patients with different angle kappa. This is a retrospective report in which 341 right eyes of 341 patients who were subjected to SMILE, which used coaxially sighted corneal light reflex (CSCLR) as the treatment zone centered, treated by the same experienced surgeon (LHB) for correction of myopia and myopic astigmatism, preoperative and postoperative spherical equivalent (SE), angle kappa, total higher-order aberrations (total HOA), spherical aberration (SA), vertical coma (VC), horizontal coma (HC), oblique trefoil (OT), and horizontal trefoil (HT), were compared. SMILE showed outstanding performance in terms of safety, efficacy, and predictability. In addition, a comparison of preoperative and postoperative HOAs exhibited the difference of total HOA (P < 0.01), SA (P < 0.01), VC (P < 0.01), and HC (P < 0.01), which was statistically significant; however, for OT and HT with the longer follow-up time, the statistical difference gradually decreased. For stratification of angle kappa into groups based on decantation, angle kappa was divided into three major groups: r < 0.1 mm, 0.1 ≤ r < 0.2 mm, and r ≥ 0.2 mm; the changes of SA (F = 4.127, P = 0.021) and OT (F = 3.687, P = 0.031) exhibited significant difference after 1 year of SMILE. We performed a correlation analysis of all preoperative and postoperative parameters, and the results indicated that the preoperative total HOA was negatively correlated with preoperative cylindrical diopter (DC), and postoperative total HOA, SA, and coma were affected by spherical diopter (DS) and SE. Moreover, we also found a significant difference of SA and VC in the early postoperative with preoperative. SA was positively correlated with Y values and r of 1 year after SMILE. All of the analyzed parameters in the three groups, except for the trefoil, gradually increased over time; however, the trefoil could gradually stabilize over time. We also divided angle kappa into four groups by quadrants; the result showed that the effects of higher-order aberrations were markedly different from the various quadrants. Patients with large angle kappa were able to increase VC and SA postoperatively, and higher HOAs were more significant in patients with high myopia. The differences in quadrants exhibited a diversity of HOAs; this could be attributed to the corneal surface reestablishment and the alteration of angle kappa, but the trend was not apparent. Although all patients displayed increased HOAs after SMILE, the potential application of CSCLR as the treatment zone centered still showed excellent safety, efficacy, and predictability.


Gene mdpC plays a regulatory role in the methyl-tert-butyl ether degradation pathway of Methylibium petroleiphilum strain PM1.
Among the few bacteria known to utilize methyl tert-butyl ether (MTBE) as a sole carbon source, Methylibium petroleiphilum PM1 is a well-characterized organism with a sequenced genome; however, knowledge of the genetic regulation of its MTBE degradation pathway is limited. We investigated the role of a putative transcriptional activator gene, mdpC, in the induction of MTBE-degradation genes mdpA (encoding MTBE monooxygenase) and mdpJ (encoding tert-butyl alcohol hydroxylase) of strain PM1 in a gene-knockout mutant mdpC(-). We also utilized quantitative reverse transcriptase PCR assays targeting genes mdpA, mdpJ and mdpC to determine the effects of the mutation on transcription of these genes. Our results indicate that gene mdpC is involved in the induction of both mdpA and mdpJ in response to MTBE and tert-butyl alcohol (TBA) exposure in PM1. An additional independent mechanism may be involved in the induction of mdpJ in the presence of TBA.


Aesthetic Concepts and Interdisciplinary Approach in a Patient With Bilateral Cleft Lip and Palate and Missing Premaxilla: A Case Report.
The smile is an important part of the individual's facial expression, it allows the communication of emotions and ideas. However, its aesthetics can be severely compromised in patients with cleft lip and palate due to multiple missing, malformed and malposed teeth, abnormal soft tissue morphology, upper lip scar tissue, and altered anatomy in the lower third of the face. This clinical case reports the interdisciplinary treatment approach of a young male patient with complete bilateral cleft lip and palate and missing premaxilla. Prosthodontic rehabilitation included a zirconia-based fixed dental prosthesis, with pink porcelain to camouflage the bony defect and restore the facial and dental aesthetics. Maxillary second premolars received lithium disilicate crowns to obtain a more harmonious smile line and adequate occlusion. A resin-bonded fixed partial denture restored a missing mandibular central incisor. Tooth proportions, gingival contours and facial ratios routinely used in noncleft patients, were used to achieve a consonant smile. The final restorations satisfied the patient's expectations, restored an aesthetically pleasant smile, and provided an adequate occlusion.


Prodromal symptoms associated with acute coronary syndrome acute symptom presentation.
Prodromal symptoms (PS), indicative of myocardial ischemia, are frequently unrecognized by individuals prior to an acute coronary syndrome (ACS). ACSs are the leading cause of death worldwide. This study describes (1) the prevalence and association of PS with patients' baseline ACS-related acute symptoms of pain intensity and state anxiety and (2) the relationship of PS to co-morbidity. An exploratory sub-analysis was performed. Cross sectional data identified prodromal predictors of ACS pain intensity (numeric rating scale 0-10 (NRS)) and state anxiety (Speilberger state-trait anxiety personality inventory (STAI)). ACS patients (n=121) admitted to a community rural emergency department completed the prodromal symptom screening scale (PS-SS) and reported baseline cardiac pain intensity, state, and trait anxiety. Increased ACS pain intensity was associated with PS. Median pain scores were higher by two points for those with prodromal headache, p=0.006, and anxiety, p=0.017, and one point higher for those with sleep disturbances, p=0.012. PS were not associated with state or trait anxiety. Hypertensive individuals were 7.5 times more likely to experience prodromal fatigue prior to their ACS event. Results extend current knowledge of the predictive value that prodromal headache, sleep disturbance and anxiety may have on individuals' acute symptom presentation. A prospective, prognostic study is required in order to determine whether PS are predictive of adverse cardiac events and if PS are a stronger predictor of ACS acute symptom presentation, compared with typical ACS-related co-morbidities.


[Neonatal alloimmune neutropenia is a frequently overlooked diagnosis in neonates].
Neonatal alloimmune neutropenia (NIN) results from the destruction of foetal neutrophils by maternal immunoglobulin G-class neutrophil-reactive antibodies crossing the foeto-placental barrier. We report two cases of neonatal patients presenting with unspecific symptoms and persisting neutropenia accompanied by thrombocytosis. Both were subsequently diagnosed with NIN. These two cases of persisting neutropenia highlight the diversity of symptoms and the diagnostic challenges remaining in NIN. Furthermore, the cases remind us that neutropenia in neonates may be rooted in several different pathophysiological mechanisms.


[Exploration and practice of post-marketing survival benefit evaluation of Chinese patent medicine for cancer].
Traditional Chinese medicine(TCM) is an important feature of cancer treatment in China. The methods to tap the advantages of TCM, reasonably evaluate and accurately apply Chinese patent medicines have become current research hotspots and difficulties. TCM takes syndrome differentiation and treatment as the core, with the characteristics of overall regulation and multi-targets efficacy. Therefore, the post-marketing survival benefit evaluation of Chinese patent medicines for cancer is different from that in modern medicine. The primary treatment goals in cancer patients include to improve the disease control rate and prolong their survival time. At present, Chinese patent medicines for cancer patients are lacking indepth studies on survival benefit at the post-marketing stage. In addition, the characteristics of individualized treatment with TCM have also increased the complexity of clinical research on TCM. Therefore, it is of certain practical significance and necessity to evaluate the survival benefit of Chinese patent medicines for cancer after marketing. Based on this, in this paper, we first summarized the technical methodological means of survival benefit evaluation at this stage, and then explored the post-marketing survival benefit evaluation of Chinese patent medicines for cancer from three aspects: the evaluation of cancer treatment effect based on survival time and quality of life, treatment-related toxicity and the auxiliary effect of TCM, and the improvement effect for tumor-related symptoms. Based on the practices of early clinical researches, and according to the insufficient efficacy evaluation of current clinical research on Chinese patent medicines, this paper proposed to improve the evaluation system for clinical researches on Chinese patent medicines, establish the evaluation method with TCM characteristics, clarify the dominant population, lay a theoretical foundation for the evaluation of post-marketing survival benefits of Chinese patent medicines for cancer in the future, and promote the modernization process of TCM.


A study of vascular permeability in normal skeletal muscle and inflammatory myopathies using a fluorescein dye technique with percutaneous needle biopsy.
Percutaneous needle biopsy of the vastus lateralis muscle was performed immediately prior to the intravenous injection of 5 ml of 20% fluorescein sodium, in 2 control subjects and 2 patients with polymyositis. Repeat biopsies were performed 5, 10 and 15 minutes after injection. Similar biopsies were taken prior to, and 10 minutes after, fluorescein injection in 1 control subject and 15 patients with a variety of inflammatory muscle conditions including polymyositis, some of whom were on treatment with corticosteroids. Apart from one patient, with polymyalgia rheumatica, increased penetration of dye was found only in those patients with polymyositis, particularly around areas of cellular infiltration, necrosis and phagocytosis and in the periphery of muscle fibres. Corticosteroid therapy appeared to reduce the amount of dye permeating muscle tissue in patients with polymyositis. It is suggested that reducing the abnormally increased vascular permeability in damaged muscle from patients with polymyositis may represent one mode of action of corticosteroids in this condition, and that the amount of fluorescein permeating muscle may be helpful in the diagnosis where conventional clinical and histological criteria are not conclusive.


An assessment of a hospital-based pregnancy testing service.
A proposal to withdraw the hospital-based pregnancy testing service provoked a local debate in which a range of strongly held but conflicting opinions were expressed. It was agreed to seek more detailed information before making any final decision. The authors describe their investigations and findings about the use of the service and the views of its consumers. Subsequently, a solution was reached for a novel but more appropriate form of service provision. It is argued that when planning changes in service provision health authorities should obtain information from and consult widely with all consumers.


Task-oriented and bottle feeding adversely affect the quality of mother-infant interactions after abnormal newborn screens.
To examine effects of newborn screening and neonatal diagnosis on the quality of mother-infant interactions in the context of feeding. Study compared the quality of mother-infant feeding interactions among 4 groups of infants classified by severity of newborn screening and diagnostic results: cystic fibrosis (CF), congenital hypothyroidism, heterozygote CF carrier, and healthy with normal newborn screening. The Parent-Child Early Relational Assessment and a task-oriented item measured the quality of feeding interactions for 130 dyads, infant ages 3 to 19 weeks (M = 9.19, SD = 3.28). The Center for Epidemiologic Studies Depression Scale and State-Trait Anxiety Inventory measured maternal depression and anxiety. Composite Indicator Structure Equation Modeling showed that infant diagnostic status and, to a lesser extent, maternal education predicted feeding method. Mothers of infants with CF were most likely to bottle feed, which was associated with more task-oriented maternal behavior than breastfeeding. Mothers with low task-oriented behavior showed more sensitivity and responsiveness to infant cues, as well as less negative affect and behavior in their interactions with their infants than mothers with high task-oriented scores. Mothers of infants with CF were significantly more likely to have clinically significant anxiety and depression than the other groups. However, maternal psychological profile did not predict feeding method or interaction quality. Mothers in the CF group were the least likely to breastfeed. Research is needed to explicate long-term effects of feeding methods on quality of mother-child relationship and ways to promote continued breastfeeding after a neonatal CF diagnosis.


Spectrophotometric study on the thermodynamics of binding of alpha- and beta-cyclodextrin towards some p-nitrobenzene derivatives.
Binding properties of native alpha- and beta-cyclodextrin towards some nitrobenzene derivatives have been studied by means of UV-vis spectrophotometry. The former host is able to form complexes having 1:1 and 1:2 stoichiometric ratios with these guests, while only 1:1 complexes are detected with the latter host. A careful analysis of the thermodynamic parameters for complexation equilibria, under the perspective of the enthalpy-entropy compensation effect, reveals that binding abilities of the two different hosts are subject to different features.


[A flavinogenic mutant of the yeast Pichia guilliermondii with impaired iron transport].
A mutant of the yeast Pichia guilliermondii was produced by means of UV; the mutant was capable of riboflavin overproduction in the presence of high concentrations of iron in the medium. The content of total and non-hemin iron and cytochrome c, and the activity of catalase, were lower in the cells of the mutant than in the parent cells, while the activity of riboflavin synthetase was higher. The content of iron in the cells increased when the mutant was cultivated on media with citric acid, siderochromes of Klebsiella aerogenes, Neurospora crassa, Rhodotorula glutinis, cultural broth of Pichia ohmeri, and autolysate of brewer's yeast, whereas the flavinogenous activity of the cells decreased. Rotenone inhibited respiration of the intact cells of the mutant producing elevated amounts of riboflavin; therefore, flavinogenesis was not regulated by non-hemin iron on the first segment of the respiratory chain. Overproduction of riboflavin in the mutant of Pichia guilliermondii was proved to be a recessive property.


Characteristics of select and non-select U15 male soccer players.
Baseline characteristics of 31 healthy male U15 soccer players who were classified as select or non-select at the end of the season were compared. Players were 14.4 ± 0.54 years (13.6-15.3 years) at baseline; characteristics included body size, proportions and composition, estimated maturity status, several functional capacities, and coach classifications of potential in the sport. Decisions regarding selection or non-selection were made about two months after baseline. Select and non-select U15 soccer players differed significantly in estimated maturity status, body size, proportions and estimated muscle mass, functional tests related to speed, power and strength, and coach evaluation of potential, specifically tactical skills on offense and skills associated with creativity and decision making. When age and biological maturity status were statistically controlled, select and non-select players differed significantly only on the vertical jump, grip strength, and coach ratings of tactical skills on offense and of creativity and decision making. Results of stepwise discriminant analysis highlighted the importance of coach evaluation of tactical skills associated with offense, and of power and strength in distinguishing select from non-select players. The results highlight the advantages of advanced biological maturity status among adolescent male soccer players and also the importance of coach perceptions of talent. The latter implies a need for further study of the basis of coach perceptions, specifically how they are influenced by and perhaps interact with player characteristics at different ages, and how the perceptions influence playing time and player behaviors and interactions.


Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer.
We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.


Blood product transfusions and reactions.
Blood product transfusions are an essential component of the practice of emergency medicine. From acute traumatic hemorrhage to chronic blood loss necessitating transfusion for symptomatic anemia, familiarity with individual blood products and their indications for transfusion is an essential tool for every emergency physician (EP). Although the focus of this article is primarily on the transfusion of red blood cells, many of the concepts are applicable to the transfusion of all blood products. EPs must be fully familiar with both the individual blood components and the potential reactions and complications of these transfusions.


Combining machine learning with knowledge-based modeling for scalable forecasting and subgrid-scale closure of large, complex, spatiotemporal systems.
We consider the commonly encountered situation (e.g., in weather forecast) where the goal is to predict the time evolution of a large, spatiotemporally chaotic dynamical system when we have access to both time series data of previous system states and an imperfect model of the full system dynamics. Specifically, we attempt to utilize machine learning as the essential tool for integrating the use of past data into predictions. In order to facilitate scalability to the common scenario of interest where the spatiotemporally chaotic system is very large and complex, we propose combining two approaches: (i) a parallel machine learning prediction scheme and (ii) a hybrid technique for a composite prediction system composed of a knowledge-based component and a machine learning-based component. We demonstrate that not only can this method combining (i) and (ii) be scaled to give excellent performance for very large systems but also that the length of time series data needed to train our multiple, parallel machine learning components is dramatically less than that necessary without parallelization. Furthermore, considering cases where computational realization of the knowledge-based component does not resolve subgrid-scale processes, our scheme is able to use training data to incorporate the effect of the unresolved short-scale dynamics upon the resolved longer-scale dynamics (subgrid-scale closure).


Enzymatic synthesis of magnetic nanoparticles.
We report the first in vitro enzymatic synthesis of paramagnetic and antiferromagnetic nanoparticles toward magnetic ELISA reporting. With our procedure, alkaline phosphatase catalyzes the dephosphorylation of l-ascorbic-2-phosphate, which then serves as a reducing agent for salts of iron, gadolinium, and holmium, forming magnetic precipitates of Fe45±14Gd5±2O50±15 and Fe42±4Ho6±4O52±5. The nanoparticles were found to be paramagnetic at 300 K and antiferromagnetic under 25 K. Although weakly magnetic at 300 K, the room-temperature magnetization of the nanoparticles found here is considerably greater than that of analogous chemically-synthesized LnxFeyOz (Ln = Gd, Ho) samples reported previously. At 5 K, the nanoparticles showed a significantly higher saturation magnetization of 45 and 30 emu/g for Fe45±14Gd5±2O50±15 and Fe42±4Ho6±4O52±5, respectively. Our approach of enzymatically synthesizing magnetic labels reduces the cost and avoids diffusional mass-transfer limitations associated with pre-synthesized magnetic reporter particles, while retaining the advantages of magnetic sensing.


[Hemothorax associated with von Recklinghausen's disease; report of a case].
We report a case of hemothorax in a patient with von Recklinghausen's disease. A 40-year-old male was transfered to our hospital because of sudden severe right back pain. Chest computed tomography (CT) scan showed right hemothorax that ruptured intercostal artery. He underwent selective angiography that demonstrated a pseud aneurhysm in the 10th intercostals artery and treated with endovascular coil embolization. We conducted surgical right thoracic drainage on post embolization day 7. In the 2 year since his embolization and operation, there has been no recurrence of hemothorax.


Detection of acanthamoeba in tap water and contact lens cases using polymerase chain reaction.
To detect the presence of Acanthamoeba in Hong Kong tap water and the contamination of contact lens cases using a polymerase chain reaction (PCR) method. Tap water was collected from the bathroom sink of 100 households in Hong Kong and tested for the presence of Acanthamoeba by means of PCR amplification. Characteristics of homes were noted with respect to age, building type, and location. A sample of 100 contact lens cases were collected from regular users of contact lenses and tested for the presence of Acanthamoeba by PCR. Ten percent of water samples were contaminated by Acanthamoeba. The risk for contamination was higher in older properties, those located in the urban area of Kowloon, and those in which the bathroom tap was served by a water tank. Only one contact lens case yielded Acanthamoeba. The subject admitted poor compliance with lens care routines. Levels of Acanthamoeba detected using PCR were somewhat higher than previously reported in Hong Kong. Older plumbing and poorly maintained water storage tanks may increase the risk of Acanthamoeba contamination. Poor compliance with care of the lens case, allowing for the build up of biofilm may increase the risk of Acanthamoeba contamination of the case and possible Acanthamoeba keratitis.


Evaluation of USDA approved antimicrobials on the reduction of Salmonella and Campylobacter in ground chicken frames and their effect on meat quality.
The main objective of this study was to examine the efficacy of USDA approved antimicrobials in reducing Salmonella Heidelberg (S. H.) and Campylobacter jejuni (C. j.) in ground chicken frames and to determine the treatment effects on total aerobic counts and meat color. Six antimicrobials (0.1% peracetic acid [PAA], 0.6% cetylpyridinium chloride [CPC], 0.005% sodium hypochlorite, 1.5% acidified lactic acid [ALA], 0.3% propionic acid, and 0.1% lauric arginate [LAE]) applied as dip treatments were evaluated in their efficacy in reducing S. Heidelberg and C. jejuni. Fresh chicken frames were spot inoculated with nalidixic acid resistant S. H. and C. j. (ATCC 33291) to achieve a recovery level of ca. 3 log CFU/g in the ground product. Frames were dipped for 10 s in each antimicrobial solution and each treatment was replicated on 3 frames. Three separate replications were conducted for this experiment. Frames were blended, and ground samples similar to mechanically separated chicken (MSC) were obtained and stored at 4°C for 24 hours. Samples were analyzed after grinding on d zero (2 h) and d one (24 h) to determine reduction in S. H. and C. j. counts in MSC. PAA and LAE treatments had the highest reductions on Salmonella counts (P ≤ 0.05), both treatments resulting in 0.9 log CFU/g reduction as compared to control on d zero. PAA and CPC reduced Salmonella counts by 1.4 and 0.9 log CFU/g, respectively, on d one; PAA, propionic acid, ALA, and LAE resulted in one log CFU/g reductions of C. j. as compared to control on d one. There was no significant difference among the treatments in their ability to reduce C. j. on d one. The treatments had no effect on total aerobic counts. The findings from the study indicate that PAA, CPC, and LAE can reduce S. H. in ground chicken frames, whereas all the antimicrobials tested in the study, except chlorine, have the ability to reduce C. j. in ground chicken frames, a product similar to commercial MSC.


Locus-specific proteome decoding reveals Fpt1 as a chromatin-associated negative regulator of RNA polymerase III assembly.
Transcription of tRNA genes by RNA polymerase III (RNAPIII) is tuned by signaling cascades. The emerging notion of differential tRNA gene regulation implies the existence of additional regulatory mechanisms. However, tRNA gene-specific regulators have not been described. Decoding the local chromatin proteome of a native tRNA gene in yeast revealed reprogramming of the RNAPIII transcription machinery upon nutrient perturbation. Among the dynamic proteins, we identified Fpt1, a protein of unknown function that uniquely occupied RNAPIII-regulated genes. Fpt1 binding at tRNA genes correlated with the efficiency of RNAPIII eviction upon nutrient perturbation and required the transcription factors TFIIIB and TFIIIC but not RNAPIII. In the absence of Fpt1, eviction of RNAPIII was reduced, and the shutdown of ribosome biogenesis genes was impaired upon nutrient perturbation. Our findings provide support for a chromatin-associated mechanism required for RNAPIII eviction from tRNA genes and tuning the physiological response to changing metabolic demands.


The TEL/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways.
The TEL/PDGF beta R fusion protein is the product of the t(5;12) translocation in patients with chronic myelomonocytic leukemia. The TEL/PDGF beta R is an unusual fusion of a putative transcription factor, TEL, to a receptor tyrosine kinase. The translocation fuses the amino terminus of TEL, containing the helix-loop-helix (HLH) domain, to the transmembrane and cytoplasmic domain of the PDGF beta R. We hypothesized that TEL/PDGF beta R self-association, mediated by the HLH domain of TEL, would lead to constitutive activation of the PDGF beta R tyrosine kinase domain and cellular transformation. Analysis of in vitro-translated TEL/ PDGF beta R confirmed that the protein self-associated and that self-association was abrogated by deletion of 51 aa within the TEL HLH domain. In vivo, TEL/PDGF beta R was detected as a 100-kDa protein that was constitutively phosphorylated on tyrosine and transformed the murine hematopoietic cell line Ba/F3 to interleukin 3 growth factor independence. Transformation of Ba/F3 cells required the HLH domain of TEL and the kinase activity of the PDGF beta R portion of the fusion protein. Immunoblotting demonstrated that TEL/PDGF beta R associated with multiple signaling molecules known to associate with the activated PDGF beta R, including phospholipase C gamma 1, SHP2, and phosphoinositol-3-kinase. TEL/PDGF beta R is a novel transforming protein that self-associates and activates PDGF beta R-dependent signaling pathways. Oligomerization of TEL/PDGF beta R that is dependent on the TEL HLH domain provides further evidence that the HLH domain, highly conserved among ETS family members, is a self-association motif.


Lack of serum bactericidal activity in preschool children two years after a single dose of serogroup C meningococcal polysaccharide-protein conjugate vaccine.
There is an increased risk of invasive meningococcal disease during the teenage years. A cohort of children vaccinated with a single dose of meningococcal C protein-polysaccharide conjugate (MenC) vaccine in early childhood during the U.K. catch up campaign will enter this age group during the coming decade. The duration of protective immunity against invasive meningococcal C disease provided by this single dose regimen is uncertain.A serum bactericidal titer of <1/8 correlates with susceptibility to invasive meningococcal disease. We assessed this correlate of protection in a cohort of children approximately 2 years after a single dose of vaccine. Serum bactericidal activity was assessed in 94 children (median age, 4.0 years) at a median time of 1.8 years after vaccination. Of the 94 children, 59 (63%) had a serum bactericidal titer <1/8. The data from this study add to previous evidence indicating that immunity wanes rapidly after vaccination with serogroup C meningococcal glycoconjugate vaccines in infancy and early childhood. Such observations suggest that booster doses of MenC vaccine may be needed to maintain the successful contribution this vaccine has made to child health in the United Kingdom.


Rare Case of Pulmonary Tuberculosis with Hematogenous Spread to Larynx and Skin.
Tuberculosis is an infectious disease with various clinical and radiological symptoms which are determined primarily by the immune system of the host towards the infection with Mycobacterium tuberculosis. The infection with M. tuberculosis can be limited to an organ or it can spread through hematogenous or lymphatic route to other organs (especially cases of younger or older people). Tuberculosis always needs bacteriological or histopathological confirmation. Matherial and method: We present the case of a 62 year old woman investigated and treated in our Hospital in 2009-2010 for Pulmonary tuberculosis complicated with Laryngeal Tuberculosis and Skin Tuberculosis (confirmed by histopathological exams). We intend to focus our case report on the cutaneous form of tuberculosis because of its rareness and clinical interest. Cutaneous tuberculosis is a very rare form of extrapulmonary tuberculosis and can be highly variable in its clinical appearance, significance and prognosis. Lesions of the skin are a real challenge for dermatologists. The treatment of cutaneous tuberculosis in most cases is the same as for pulmonary tuberculosis leading to regression and healing of the skin lesions.


An Iridium-Stabilized Borenium Intermediate.
Exploration of new organometallic systems based on polyhedral boron clusters has the potential to solve challenging chemical problems such as the stabilization of reactive intermediates and transition-state-like species postulated for E-H (E = H, B, C, Si) bond activation reactions. We report on facile and clean B-H activation of a hydroborane by a new iridium boron cluster complex. The product of this reaction is an unprecedented and fully characterized transition metal-stabilized boron cation or borenium. Moreover, this intermediate bears an unusual intramolecular B···H interaction between the hydrogen originating from the activated hydroborane and the cyclometallated metal-bonded boron atom of the boron cluster. This B···H interaction is proposed to be an arrested insertion of hydrogen into the Bcage-metal bond and the initiation step for iridium "cage-walking" around the upper surface of the boron cluster. The "cage-walking" process is supported by the hydrogen-deuterium exchange observed at the boron cluster, and a mechanism is proposed on the basis of theoretical methods with a special focus on the role of noncovalent interactions. All new compounds were isolated and fully characterized by NMR spectroscopy and elemental analysis. Key compounds were studied by single crystal X-ray diffraction and X-ray photoelectron spectroscopy.


Assessment of public health educator practice: health educator responsibilities.
This study presents a method for better understanding how practicing health educators in local health departments spend their time. The purpose of this study was to document the daily practice of health educators in the 10 areas of responsibility as defined by a competency-based framework for graduate-level health educators. The results of the current study present the average percentage of time health educators spent carrying out each area of responsibility and the percentage of health educators that did not carry out activities related to a specific area of responsibility. For example, the greatest percentage of time was spent implementing programs (21.2%), and approximately 60% of the health educators in the sample did not conduct research nor did they participate in activities to advance the profession. These findings have implications for the professional preparation of health educators and for their continuing education. The current study contains several suggestions for future research in this area.