Opinions of general practitioners about psychotherapy and their relationships with mental health professionals in the management of major depression: A qualitative survey.
French general practitioners (GPs) refer their patients with major depression to psychiatrists or for psychotherapy at particularly low rates. This qualitative study aims to explore general practitioners' (GP) opinions about psychotherapy, their relationships with mental health professionals, their perceptions of their role and that of psychiatrists in treating depression, and the relations between these factors and the GPs' strategies for managing depression. In 2011, in-depth interviews based on a semi-structured interview guide were conducted with 32 GPs practicing in southeastern France. Verbatim transcripts were examined by analyzing their thematic content. We identified three profiles of physicians according to their opinions and practices about treatment strategies for depression: pro-pharmacological treatment, pro-psychotherapy and those with mixed practices. Most participants considered their relationships with psychiatrists unsatisfactory, would like more and better collaboration with them and shared the same concept of management in general practice. This concept was based both on the values and principles of practice shared by GPs and on their strong differentiation of their management practices from those of psychiatrists. Several attitudes and values common to GPs might contribute to their low rate of referrals for psychotherapy in France: strong occupational identity, substantial variations in GPs' attitudes and practices regarding depression treatment strategies, representations sometimes unfavorable toward psychiatrists. Actions to develop a common culture and improve cooperation between GPs and psychiatrists are essential. They include systems of collaborative care and the development of interdisciplinary training common to GPs and psychiatrists practicing in the same area.


Neural mechanisms underlying song and speech perception can be differentiated using an illusory percept.
The issue of whether human perception of speech and song recruits integrated or dissociated neural systems is contentious. This issue is difficult to address directly since these stimulus classes differ in their physical attributes. We therefore used a compelling illusion (Deutsch et al. 2011) in which acoustically identical auditory stimuli are perceived as either speech or song. Deutsch's illusion was used in a functional MRI experiment to provide a direct, within-subject investigation of the brain regions involved in the perceptual transformation from speech into song, independent of the physical characteristics of the presented stimuli. An overall differential effect resulting from the perception of song compared with that of speech was revealed in right midposterior superior temporal sulcus/right middle temporal gyrus. A left frontotemporal network, previously implicated in higher-level cognitive analyses of music and speech, was found to co-vary with a behavioural measure of the subjective vividness of the illusion, and this effect was driven by the illusory transformation. These findings provide evidence that illusory song perception is instantiated by a network of brain regions that are predominantly shared with the speech perception network.


Delivery of Curcumin Using Zein-Gum Arabic-Tannic Acid Composite Particles: Fabrication, Characterization, and in vitro Release Properties.
The application of curcumin (Cur) in fat-free food is limited due to its poor water solubility, stability, and bioaccessibility. In this study, zein-gum arabic-tannic acid (zein-GA-TA) composite particles with high physical stability were fabricated to deliver Cur (ZGT-Cur). Their stability and in vitro release properties were also evaluated. The results showed that the thermal and photochemical stability of Cur was improved after loading into composite particles. Meanwhile, the retention rate of Cur in ZGT-Cur composite particles was enhanced compared with Z-Cur or ZG-Cur particles. Fourier transform infrared (FTIR) spectroscopy confirmed that the hydrogen bond within the particles was greatly enhanced after the addition of tannic acid (TA). The in vitro antioxidant activity of Cur in ZGT-Cur composite particles was higher in terms of 2,2'-azino-bis (ABTS) (93.64%) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) (50.41%) compared with Z-Cur or ZG-Cur particles. The bioaccessibility of Cur in ZGT-Cur composite particles was 8.97 times higher than that of free Cur. Therefore, the particles designed in this study will broaden the application of Cur in the food industry by improving its stability and bioaccessibility.


Relationship of response to sleep deprivation and carbamazepine in depressed patients.
The responses of 16 patients with major depressive disorder to one night's sleep deprivation and a subsequent double-blind, placebo-controlled trial of carbamazepine were compared. There was a significant association between the presence or absence of an antidepressant response to each of these treatments. Further studies are required to assess the clinical utility of this relationship and whether it is based on antidepressant response to any agent or is more specific to carbamazepine.


Adaptation of plants to altered shoot orientation relative to the gravity vector.
Wheat Triticum aestivum L., carrots Daucus carota L., Chinese cabbage Brassica pekinensis Rupr., and African marigold Tagetes patula L. were grown at natural and inverted orientation in the Earth gravitational field. Light vector was set unidirectional or opposite directional relative to the gravity vector. Shoot orientation relative to the gravity vector was set natural or invert. Plants grew in the special pots furnished with plane or cylindrical hydrophilic porous membranes. The membrane allowed to stabilize a water potential in the root zone at the fixed level. Seeds were put into a fiber ion-exchange artificial soil overlaying horizontal hydrophilic plates of porous titanium or anchored to porous metal-ceramic tubes. Plants grew at the PPF level 550 +/- 20 micromoles/(m2 s) during 24-hr lighting and at the water potential level at the membrane surface (-1.00) +/- 0.08 kPa. Normal plants were obtained both at the natural and at the inverse shoot orientation in the all experiments. The wheat plants were yielded healthy germinating seeds no matter plant orientation. In the inverse orientation, no negative influence for plant biomass accruing was marked, but the increasing of shoot to root mass ratio was considerable. However carrot root crop mass decreasing was not revealed in the inverse orientation. The results demonstrated substantial dependence of morphological and physiological characteristics of higher plants on the gravity factor.


Palmoplantar pustulosis and sternocostoclavicular arthro-osteitis.
Seventeen patients with shoulder pain and radiographic involvement of the sternoclavicular or sternocostal joints, or both, are described. Eleven of these patients also had palmoplantar pustulosis. Histological examination of the joints showed chronic and subacute inflammation, increased osteoblastic activity, and cartilage degeneration. Propionibacterium acnes was cultured in tissue samples from seven of the 15 biopsied patients, a finding at variance with those of previous reports. The possibility that sternoclavicular arthro-osteitis is of infectious origin should be the subject of further investigation. Non-steroidal anti-inflammatory drugs (NSAIDs) may provide pain relief, possibly owing to their inhibitory action on osteoblasts. In cases of severely restricted movement or severe pain resection of the medial clavicle may be considered.


Cytomegalovirus (CMV) infection and pregnancy-potential for improvements in Australasian maternity health providers' knowledge.
To assess the knowledge, practice and attitudes of maternity clinicians regarding congenital cytomegalovirus (CMV). It is the most common congenital infection, and well-recognized cause of neurodevelopmental disability and hearing loss. New consensus recommendations state all pregnant women and health-care providers should be educated about congenital CMV infection and preventive measures. An email questionnaire was distributed in October 2015 to specialists, diplomates (general practitioners), and trainees of the Royal Australian New Zealand College of Obstetricians and Gynaecologists (RANZCOG), and Victorian and New South Wales midwives. 774 responded: (37.3% specialists, 17.3% diplomates, 16.8% trainees, 28.6% midwives). Clinicians had variable knowledge of fetal sequelae, transmission routes and prevention. Overall, 30.2% felt confident about discussing CMV in pregnancy: less than 10% of midwives (7.4%) and less than half of specialists (47.1%, p < .0001). Only 8.8% of respondents routinely discussed CMV prevention with pregnant women. The majority (69.3%) responded that professional societies should make practice recommendations, and 88% thought more patient information was needed, preferably leaflets. Australasian maternity clinicians lack confidence and knowledge about congenital CMV. Few (<10%) routinely provide advice on prevention. There is urgent need for clinical guidance and patient information to reduce the burden of disease.


Molecular profiling of thyroid nodule fine-needle aspiration cytology.
The differential diagnosis and malignancy risk stratification of thyroid nodules requires multidisciplinary expertise and knowledge of both local ultrasonography practices and the local malignancy rates for a given fine-needle aspiration (FNA) result. Even in such a multidisciplinary setting, FNA cytology has the inherent limitation that indeterminate cytology results cannot distinguish between follicular adenomas, follicular thyroid carcinomas or follicular variant papillary thyroid carcinomas. Accumulating evidence suggests that this limitation can be overcome by using molecular diagnostic approaches. In this Review, we present the advantages and disadvantages of the different molecular diagnostic methodologies, which can be divided into two approaches: those that 'rule out' malignancy (to reduce the overtreatment of benign nodules) and those that 'rule in' malignancy (to optimize surgical planning). We identify microRNA classifiers as potential additional markers for use in a two-step diagnostic approach, consider the potential implications of the reclassification of noninvasive encapsulated follicular variant papillary thyroid carcinomas to noninvasive follicular thyroid neoplasms with papillary-like nuclear features and discuss the cost-effectiveness of molecular testing. Molecular FNA diagnostics is an important complementary addition to FNA cytology that could substantially reduce unnecessary surgery and better define the need for appropriate surgery in patients who have thyroid nodules with indeterminate FNA cytology.


Motoric Cognitive Risk and Incident Dementia in Older Adults.
Motoric cognitive risk (MCR) is a novel predementia syndrome; however, whether it can estimate dementia in a nationwide population or has additive estimation validity over cognitive or motoric components alone remains unknown. To examine whether modified MCR, which incorporates the timed-up-and-go and one-leg-standing tests, improves estimation validity for incident dementia over using cognitive or motoric components alone. This nationwide cohort study evaluated data from individuals aged 66 years who participated in the National Screening Program for Transitional Ages in Korea from January 1, 2009, to December 31, 2013, and examined the association between MCR and incident dementia using Cox proportional hazards regression analysis. Data were collected from the index date (the date on which the participant had the screening) until dementia onset, death, or the end of the follow-up period, whichever came first. The 2 subtypes were defined as subjective cognitive declines with timed-up-and-go impairment or one-leg-standing impairment. The data set was generated with permission from the Korean National Health Insurance Service, and data analysis was conducted from August 2, 2021, to January 31, 2022. Individuals diagnosed with dementia or psychotic disorders or those who had a documented history of dementia medication use before the index date were excluded. The main outcome was incidence of dementia, defined as an individual receiving their first dementia medication with the relevant International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes after the index date. Among the 1 137 530 participants (53.7% women), 15 380 (1.4%) met the MCR criteria for the timed-up-and-go subtype, and 32 910 (2.9%) met the criteria for the one-leg-standing subtype. The mean (SD) follow-up period was 7.02 (1.38) years. Participants with MCR demonstrated an approximately 2-fold higher risk of incident dementia than those without MCR (timed-up-and-go subtype, adjusted hazard ratio, 2.03; 95% CI, 1.94-2.13; one-leg-standing subtype, adjusted hazard ratio, 2.05; 95% CI, 1.98-2.12). In this cohort study of participants aged 66 years of the National Screening Program for Transitional Ages, modified motoric cognitive risk had higher adjusted hazard ratios of incident dementia than individual cognitive or motoric components. Motoric cognitive risk may be a practical screening tool for estimating dementia among individuals in their mid-60s ; however, further investigation of the clinical and neurobiological aspects is necessary.


[Surgical management of acetabulum fractures].
Author reports on the experiences with the operative treatment of 48 acetabular fractures in his Department during 19 years. He thinks that the operative treatment of the acetabular fractures may be successful only after the exact preoperative diagnosis and classification of the type of the fracture. After this the exposure may be chosen. During the operation one has to strive to the exact reconstruction of the articular surfaces and the performance of such stable osteosynthesis that will enable the early movements of the joint without weight bearing. If, because of the severity of the injury, the exact reconstruction of the acetabulum is not possible an effort must be made to create an anatomical situation that will give favourable conditions to late reconstruction operations (arthrodesis or endoprosthesis). Author describes after discussing the classification, diagnosis and treatment of the acetabular fractures his own results: in more than 3/4 of his cases excellent or good late results could be achieved. For this, with correct indication, the performance of the reconstruction operation is suggested.


The effects of natural antioxidants from tomato extract in treated but uncontrolled hypertensive patients.
To evaluate the effect of adding tomato extract to the treatment regime of moderate hypertensives with uncontrolled blood pressure (BP) levels. Fifty four subjects with moderate HT treated with one or two antihypertensive drugs were recruited and 50 entered two double blind cross-over treatment periods of 6 weeks each, with standardized tomato extract or identical placebo. Plasma concentrations of lycopene, nitrite and nitrate were measured and correlated with BP changes. There was a significant reduction of systolic BP after 6 weeks of tomato extract supplementation, from 145.8 +/- 8.7 to 132.2 +/- 8.6 mmHg (p < 0.001) and 140.4 +/- 13.3 to 128.7 +/- 10.4 mmHg (p < 0.001) in the two groups accordingly. Similarly, there was a decline in diastolic BP from 82.1 +/- 7.2 to 77.9 +/- 6.8 mmHg (p = 0.001) and from 80.1 +/- 7.9 to 74.2 +/- 8.5 mmHg (p = 0.001). There was no significant change in systolic and diastolic BP during the placebo period. Serum lycopene level increased from 0.11 +/- 0.09 at baseline, to 0.30 +/- 01.3 micromol/L after tomato extract therapy (p < 0.001). There was a significant correlation between systolic BP and lycopene levels (r = -0.49, p < 0.001). Tomato extract when added to patients treated with low doses of ACE inhibition, calcium channel blockers or their combination with low dose diuretics, had a clinically significant effect-reduction of BP by more than 10 mmHg systolic and more than 5 mmHg diastolic pressure. No side-effects to treatment were recorded and the compliance with treatment was high. The significant correlation between systolic blood pressure values and level of lycopene suggest the possibility of cause-effect relationships.


Health advocacy in nursing: contribution to the reorientation of the Brazilian healthcare model.
Inequalities are the result of the different positions held by individuals in different social spaces, and are related to the distribution of power and property. Health advocacy is a strategy to reduce such inequalities, especially those considered unfair and unnecessary, aiming to fully promote the right to health. This study aims to discuss the contribution of nursing in the field of health advocacy, which includes the right of everyone to a healthy life as one of the strategies for the reorientation of the Brazilian healthcare model.


Guanylate-Binding Protein-Dependent Noncanonical Inflammasome Activation Prevents Burkholderia thailandensis-Induced Multinucleated Giant Cell Formation.
Inflammasomes are cytosolic multiprotein signaling complexes that are activated upon pattern recognition receptor-mediated recognition of pathogen-derived ligands or endogenous danger signals. Their assembly activates the downstream inflammatory caspase-1 and caspase-4/5 (human) or caspase-11 (mouse), which induces cytokine release and pyroptotic cell death through the cleavage of the pore-forming effector gasdermin D. Pathogen detection by host cells also results in the production and release of interferons (IFNs), which fine-tune inflammasome-mediated responses. IFN-induced guanylate-binding proteins (GBPs) have been shown to control the activation of the noncanonical inflammasome by recruiting caspase-4 on the surface of cytosolic Gram-negative bacteria and promoting its interaction with lipopolysaccharide (LPS). The Gram-negative opportunistic bacterial pathogen Burkholderia thailandensis infects epithelial cells and macrophages and hijacks the host actin polymerization machinery to spread into neighboring cells. This process causes host cell fusion and the formation of so-called multinucleated giant cells (MNGCs). Caspase-1- and IFN-regulated caspase-11-mediated inflammasome pathways play an important protective role against B. thailandensis in mice, but little is known about the role of IFNs and inflammasomes during B. thailandensis infection of human cells, particularly epithelial cells. Here, we report that IFN-γ priming of human epithelial cells restricts B. thailandensis-induced MNGC formation in a GBP1-dependent manner. Mechanistically, GBP1 does not promote bacteriolysis or impair actin-based bacterial motility but acts by inducing caspase-4-dependent pyroptosis of the infected cell. In addition, we show that IFN-γ priming of human primary macrophages confers a more efficient antimicrobial effect through inflammasome activation, further confirming the important role that interferon signaling plays in restricting Burkholderia replication and spread. IMPORTANCE The Gram-negative bacteria of the Burkholderia species are associated with human diseases ranging from pneumonia to life-threatening melioidosis. Upon infection through inhalation, ingestion, or the percutaneous route, these bacteria can spread and establish granuloma-like lesions resulting from the fusion of host cells to form multinucleated giant cells (MNGCs). Burkholderia resistance to several antibiotics highlights the importance to better understand how the innate immune system controls infections. Here, we report that interferons protect human epithelial cells against Burkholderia-induced MNGC formation, specifically through the action of the interferon-induced GBP1 protein. Mechanistically, GBP1 acts by inducing caspase-4-dependent cell death through pyroptosis, allowing the infected cells to be quickly eliminated before bacterial spread and the formation of MNGCs. This study provides evidence that interferon-induced innate immune activation, through GBP1 and caspase-4, confers protection against Burkholderia infection, potentially opening new perspectives for therapeutic approaches.


Intermittent hypoxia-related alterations in vascular structure and function: a systematic review and meta-analysis of rodent data.
Obstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure. To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs. We searched PubMed, Embase and Web of Science, and included 125 articles in a meta-analysis, among them 112 using wild-type rodents and 13 using apolipoprotein E knockout (ApoE-/-) mice. We used the standardised mean difference (SMD) to compare results between studies. IH significantly increased mean arterial pressure (+13.90 (95% CI 11.88-15.92) mmHg), and systolic and diastolic blood pressure. Meta-regressions showed that mean arterial pressure change was associated with strain and year of publication. IH altered vasodilation in males but not in females and increased endothelin-1-induced but not phenylephrine-induced vasoconstriction. Intima-media thickness significantly increased upon IH exposure (SMD 1.10 (95% CI 0.58-1.62); absolute values +5.23 (2.81-7.84) µm). This increase was observed in mice but not in rats and was negatively associated with age. Finally, IH increased atherosclerotic plaque size in ApoE-/- mice (SMD 1.08 (95% CI 0.80-1.37)). Our meta-analysis established that IH, independently of other confounders, has a strong effect on vascular structure and physiology. Our findings support the interest of identifying and treating sleep apnoea in routine cardiology practice.


Astrocytoma presenting with apnea and sinus arrest.
Although some vascular lesions of the central nervous system are known to cause abnormalities in the control of breathing, association between astrocytoma and combined cardiorespiratory abnormalities in the adult is distinctly unusual. We present a case of a 52-year-old man whose only features of astrocytoma consisted of episodes of apnea and sinus arrest followed by prolonged alveolar hypoventilation. These abnormalities resolved after resection of the tumor. We conclude that in patients presenting with respiratory and sinus arrest, the search for a cause should not be limited to the cardiac and pulmonary systems, but it must include a possibility of a brain tumor.


Porcine Bone Incorporated With 4-Hexylresorcinol Increases New Bone Formation by Suppression of the Nuclear Factor Kappa B Signaling Pathway.
The objectives of this study were to evaluate the suppression of the nuclear factor kappa B (NF-kB) pathway by 4-hexylresorcinol (4HR), which was activated by tumor necrosis factor-α (TNF-α) in osteoblasts, and new bone formation by 4HR-incorporated porcine bone in an animal model. For the confirmation of successful incorporation of 4HR into porcine bone, scanning electron microscopy (SEM) and Fourier transform-infrared (FT-IR) analysis were performed. High performance liquid chromatography was performed for the analysis of the 4HR release profile from porcine bone. MC 3T3-E1 cells were used for the analysis of the NF-kB signaling pathway activation by western blotting and real-time reverse transcriptase polymerase chain reaction. New bone formation and the analysis of marker protein expression were studied in a rat calvarial critical-sized defect model. Both SEM and FT-IR analysis demonstrated successful incorporation of 4HR into porcine bone. Approximately 30% of 4HR was steadily released from porcine bone for 18 days. 4HR suppressed the NF-kB signaling pathway, which was activated by TNF-α application in MC 3T3-E1 cells. Histological analysis revealed that porcine bone particles with incorporated 4HR showed significantly greater new bone formation than those without 4HR at 4 and 8 weeks after operation (P < 0.05). The expression intensities of alkaline phosphatase, osteoprotegerin, and osteocalcin were also higher in the 4HR-incorporated group. The application of 4HR suppressed the NF-kB signaling pathway in osteoblasts and 4HR-containing porcine bone particles promoted new bone formation in a rat calvarial defect model.


The Prognostic Value of Right Atrial and Right Ventricular Functional Parameters in Systemic Sclerosis.
Right ventricular (RV) function is of particular importance in systemic sclerosis (SSc), since common SSc complications, such as interstitial lung disease and pulmonary hypertension may affect RV afterload. Cardiovascular magnetic resonance (CMR) is the gold standard for measuring RV function. CMR-derived RV and right atrial (RA) strain is a promising tool to detect subtle changes in RV function, and might have incremental value, however, prognostic data is lacking. Therefore, the aim of this study was to evaluate the prognostic value of RA and RV strain in SSc. In this retrospective study, performed at two Dutch hospitals, consecutive SSc patients who underwent CMR were included. RV longitudinal strain (LS) and RA strain were measured. Unadjusted cox proportional hazard regression analysis and likelihood ratio tests were used to evaluate the association and incremental value of strain parameters with all-cause mortality. A total of 100 patients (median age 54 [46-64] years, 42% male) were included. Twenty-four patients (24%) died during a follow-up of 3.1 [1.8-5.2] years. RA reservoir [Hazard Ratio (HR) = 0.95, 95% CI 0.91-0.99, p = 0.009] and conduit strain (HR = 0.93, 95% CI 0.88-0.98, p = 0.008) were univariable predictors of all-cause mortality, while RV LS and RA booster strain were not. RA conduit strain proved to be of incremental value to sex, atrial fibrillation, NYHA class, RA maximum volume indexed, and late gadolinium enhancement (p < 0.05 for all). RA reservoir and conduit strain are predictors of all-cause mortality in SSc patients, whereas RV LS is not. In addition, RA conduit strain showed incremental prognostic value to all evaluated clinical and imaging parameters. Therefore, RA conduit strain may be a useful prognostic marker in SSc patients.


Comparison Between Sonography-Based and Surgical Evaluation of Endometriotic Lesions Using the #Enzian Classification - A Retrospective Data Analysis.
To compare the location and sizes of deep endometriosis (DE) lesions evaluated by preoperative transvaginal sonography (TVS) in different #Enzian compartments with intraoperatively assessed DE location and size. Retrospective data analysis of 93 women undergoing TVS and surgery for DE in 2019 at a tertiary referral center for endometriosis. #Enzian compartment C (rectum) showed the highest rate of exact concordance with 74% of cases, which increased to 87% when a tolerance margin of a maximum of 3mm for TVS measurements was taken into account. For compartment B (uterosacral ligaments, parametria) and compartment A (vagina, rectovaginal space), the rates of exact concordance were slightly lower. In compartment O (ovary), high exact concordance rates similar to those observed for compartment C were observed. In compartment T (tubo-ovarian unit), most reliable estimations were seen for slight (TVS T1) and severe adhesions (TVS T3). There were only a few cases of missed lesions as well as false positives on TVS: Sensitivity was 100% for all compartments except for A and B left (97%) and FB (urinary bladder, 86%); specificity was 100% for FB, FI (other intestinal locations), FU (ureters) and O right, 86%-98% for A, B right, C, O left and FO (other extragenital lesions) and 70% for B left. The preoperative evaluation of the location and size of DE lesions by TVS in different #Enzian compartments is accurate, providing a detailed presurgical description of the extent of ovarian and deep endometriosis and associated minor or severe adhesions.


[Analysis of the Cochrane Review: Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2013;1:CD000219].
Acute otitis media is one of the most common infections in children and one of the leading causes for antibiotic prescription. In this paper, we assess and comment the Cochrane systematic review 'Antibiotics for acute otitis media in children', which aimed at assessing the efficacy and safety of antibiotics for acute otitis media in children and identifying subgroups of children who might benefit more than others from antibiotic treatment. This review showed spontaneous resolution of acute otitis media in most children (82%) and a favorable but modest effect of antibiotics, namely in pain control (number needed to treat to benefit: 20), reduction of tympanic membrane perforations and reduction of contralateral acute otitis media. Adverse effects such as vomiting, diarrhea or rash were more common in the antibiotic group (number needed to treat to harm: 14). Thus, for most children, an expectant observational approach during 48-72h without immediate antibiotic prescription seems justified. An additional meta-analysis found that antibiotics appear to be most useful in children with both acute otitis media and otorrhoea and children under two years of age with bilateral acute otitis media.


Implementation of a clinical guideline to decrease laboratory tests in newborns evaluated for early onset sepsis.
Creation of a clinical guideline to reduce the number of complete blood counts (CBCs) obtained on healthy term infants for early onset sepsis (EOS) evaluation secondary to maternal chorioamnionitis. A clinical guideline was introduced at four neonatal intensive care units (NICU) to reduce laboratory tests during EOS evaluation. Measures include frequency and timing of CBCs, culture negative sepsis, length of stay, and readmission rate. Mean number of CBCs per patient significantly decreased (2.31±0.62 versus 1.52±0.65) without increasing trends for patients with culture negative sepsis, length of stay, or re-admission. The clinical guideline demonstrated a significant reduction in the number of CBCs obtained in well-appearing infants admitted to the NICU secondary to maternal chorioamnionitis.


Pollution trees: identifying similarities among complex pollutant mixtures in water and correlating them to mutagenicity.
There are relatively few tools available for computing and visualizing similarities among complex mixtures and in correlating the chemical composition clusters with toxicological clusters of mixtures. Using the "intersection and union ratio (IUR)" and other traditional distance matrices on contaminant profiles of 33 specific water samples, we used "pollution trees" to compare these mixtures. The "pollution trees" constructed by neighbor-joining (NJ), maximum parsimony (MP), and maximum likelihood (ML) methods allowed comparison of similarities among these samples. The mutagenicity of each sample was then mapped to the "pollution tree". The IUR-distance-based measure proved effective in comparing chemical composition and compound level differences between mixtures. We found a robust "pollution tree" containing seven major lineages with certain broad characteristics: treated municipal water samples were different from raw water samples and untreated rural drinking water samples were similar with local water sources. The IUR-distance-based tree was more highly correlated to mutagenicity than were other distance matrices, i.e., MP/ML methods, sampling group, region, or water type. IUR-distance-based "pollution trees" may become important tools for identifying similarities among real mixtures and examining chemical composition clusters in a toxicological context.


The diagnostic role of diffusion-weighted magnetic resonance imaging in hypopharyngeal carcinoma.
The aim of the present study was to assess the role of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) values in hypopharyngeal carcinoma. A total of 40 hypopharyngeal carcinoma tissues and 15 benign lesion tissues were retrospectively analyzed. DWI, and T1- and T2-weighted magnetic resonance imaging (MRI) was performed. The sensitivity, specificity and accuracy of conventional MRI were 97.5, 66.7, and 89.1%, respectively. The mean ADC value [diffusion sensitive factor (b)=1,000× sec/mm2) for hypopharyngeal carcinomas was (1.0285±0.0328)×10-3 mm2/sec, which was significantly lower than the mean ADC value for benign lesions [(1.5333±0.1061)×10-3 mm2/sec; P<0.001]. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) was 0.921 while the optimal threshold for the cut-off point of the ADC was 1.075×10-3 mm2/sec. The mean ADC value of the metastatic nodes was (0.9184±0.0538)×10-3 mm2/sec, lower than the mean value for the benign nodes [(1.2538±0.1145)×10-3 mm2/sec; P=0.005]. Two groups were created according to the mean of the ADC value of hypopharyngeal carcinomas [≤(1.0285±0.0328)×10-3 mm2/sec vs. >(1.0285±0.0328)×10-3 mm2/sec]. The 2-year survival rates of the two groups were 55.6 and 100.0%, respectively (P=0.024). ADC values may aid in distinguishing hypopharyngeal carcinomas from benign lesions and differentiating metastatic lymph nodes of hypopharyngeal squamous cell carcinomas from reactive cervical lymph nodes. In conclusion, mean ADC values may be useful prognostic factors in univariate analysis of hypopharyngeal carcinoma.


Molecular cloning and characterization of a novel protein of Trichinella pseudospiralis excretory-secretory products.
A novel excretory-secretory (ES) protein of Trichinella pseudospiralis was produced. A cDNA library was constructed from mRNA of muscle larvae at 30 days post infection (p.i.) and immunoscreened with the antibody against ES products. A clone, designated Tp22-3, contained a cDNA transcript of 815 bp in length with a single open reading frame which encoded 244-amino acids (28407 Da in the estimated molecular mass). A database search revealed that no sequences had a homology to this predicted protein. The recombinant protein was produced in an Escherichia coli expression system. Stage specific expression of this protein was suggested from the following experiments. An antibody against the recombinant protein could stain proteins migrating at about 28 kDa (which is the expected size from the sequence) on Western blotting of crude extracts or ES products from 30 days p.i. muscle larvae, but failed to stain any proteins in crude extracts from newborn larvae or 15 days p.i. muscle larvae. The antibody reacted to the stichocytes of larvae at 30 days p.i., but did not react to 15 days p.i. muscle larvae. The production of an mRNA transcript for Tp22-3 gene was restricted largely to the 30 days p.i. muscle larvae and adult worms.


Direct improvement of quality of life in colorectal cancer patients using a tailored pathway with quality of life diagnosis and therapy (DIQOL): study protocol for a randomised controlled trial.
Medical treatment in patient-centred care in oncology is broadly managed and regulated in terms of guideline development, cancer centres, and quality assurance by cancer registries. In contrast to this quality management cycle (PDCA), there are no equal standards for patient-reported outcomes like quality of life (QoL). Therefore, the Tumour Centre Regensburg e.V., a population-based regional cancer registry covering a population of more than 2.2 million people in the Upper Palatinate and Lower Bavaria, Germany, designed and implemented a QoL pathway. In a complex intervention with QoL diagnosis and therapy (multidimensional therapeutic network), effectiveness for patients with breast cancer has been demonstrated. To provide local tailored QoL diagnosis and therapy to other cancer patients as well, external validity needs to be extended by adapting the QoL pathway to another tumour entity. The QoL pathway will be tested for colorectal cancer patients in a pragmatic randomised controlled trial. Two hundred twenty primary colorectal cancer patients, surgically treated in one of four hospitals, will be included. QoL is measured in all patients 0, 3, 6, 12, and 18 months after surgery (European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-CR29). In the intervention group, QoL scores are transformed into a QoL profile. This is sent to the coordinating practitioner (general practitioner, internist, or oncologist) with an expert report including treatment recommendations for QoL deficits. The control group receives routine follow-up care attending the guideline recommendations for colorectal cancer without profile or expert report. At the primary endpoint (12 months), the rates of patients with diseased QoL in both groups are compared. This randomised trial is the first complex intervention investigating the effectiveness of an intervention with QoL diagnosis and tailored QoL therapy in colorectal cancer patients. The results will show if this QoL pathway improves the patients' QoL during follow-up care of their disease. ClinicalTrials.gov, NCT02321813 (registered December 2014).


Projections from the parahippocampal region to the prefrontal cortex in the rat: evidence of multiple pathways.
The purpose of the present study was to investigate, by means of anterograde tracing methods, the detailed organization of the parahippocampal-prefrontal projections in the rat brain. Efferents from the perirhinal cortex were found to terminate principally in both the ventromedial (prelimbic and infralimbic cortices) and lateral (agranular insular cortex) regions of the prefrontal cortex. Terminal fields were observed mainly in the superficial layers of the prefrontal cortex. Projections arising from the dorsolateral entorhinal cortex, which borders the perirhinal cortex along its ventral extent, were similarly directed to the ventromedial and lateral prefrontal cortices but also encompassed other frontal areas (dorsomedial and orbital prefrontal regions). Terminal fields of entorhinal projections were also found in the superficial layers of the prefrontal cortex. A third pathway, taking its source in the post-rhinal cortex, presented striking topographical differences with the two other output systems. Hence, post-rhinal efferences terminated only in the ventrolateral orbital area. The results indicate that two main routes originate from the parahippocampal region to reach the prefrontal cortex. One pathway involves the rostral and lateral portions of the parahippocampal region (perirhinal and dorsolateral entorhinal cortices), and the other relies on its most caudal region, the post-rhinal cortex. The presence of such different multiple parahippocampal-prefrontal pathways may have functional relevance for learning and memory processes.


Genetic association analysis of 77,539 genomes reveals rare disease etiologies.
The genetic etiologies of more than half of rare diseases remain unknown. Standardized genome sequencing and phenotyping of large patient cohorts provide an opportunity for discovering the unknown etiologies, but this depends on efficient and powerful analytical methods. We built a compact database, the 'Rareservoir', containing the rare variant genotypes and phenotypes of 77,539 participants sequenced by the 100,000 Genomes Project. We then used the Bayesian genetic association method BeviMed to infer associations between genes and each of 269 rare disease classes assigned by clinicians to the participants. We identified 241 known and 19 previously unidentified associations. We validated associations with ERG, PMEPA1 and GPR156 by searching for pedigrees in other cohorts and using bioinformatic and experimental approaches. We provide evidence that (1) loss-of-function variants in the Erythroblast Transformation Specific (ETS)-family transcription factor encoding gene ERG lead to primary lymphoedema, (2) truncating variants in the last exon of transforming growth factor-β regulator PMEPA1 result in Loeys-Dietz syndrome and (3) loss-of-function variants in GPR156 give rise to recessive congenital hearing impairment. The Rareservoir provides a lightweight, flexible and portable system for synthesizing the genetic and phenotypic data required to study rare disease cohorts with tens of thousands of participants.


Early intravenous thrombolysis with recombinant tissue-type plasminogen activator in vertebrobasilar ischemic stroke.
The optimal therapy of vertebrobasilar ischemic stroke is under debate. In the case of underlying basilar artery occlusion, intra-arterial thrombolysis is recommended. Because this pathologic condition is rarely found and the procedure is time consuming and restricted to specialized centers, the question arises whether early intravenous thrombolysis could also effectively be applied in vertebrobasilar ischemic stroke. To determine if early intravenous thrombolysis could be used effectively in vertebrobasilar ischemic stroke. A case series of 12 consecutive patients with acute vertebrobasilar ischemia were followed up 3 months after thrombolytic treatment at the Department of Neurology of the University Hospital of Cologne, Cologne, Germany, a primary care and referral center. Patients with clinically diagnosed moderate to severe vertebrobasilar ischemic stroke with clearly determined symptom onset were treated with intravenous recombinant tissue-type plasminogen activator within 3 hours after symptom onset following a protocol similar to that of the National Institute of Neurological Disorders and Stroke study. On admission, 7 patients exhibited moderate to severe brainstem symptoms without impairment of consciousness and 5 patients had impairment of consciousness, of whom 2 were comatose. Of 12 patients, 10 had a favorable outcome after 3 months defined as full independence (Barthel index score of 100) or return to premorbid condition. One patient had a poor outcome with complete dependency due to reocclusion after primarily successful thrombolysis, and 1 patient died of severe brainstem infarction and additional space occupying parietal hemorrhage. Favorable outcome could be achieved in the majority of 12 consecutive patients with moderate to severe vertebrobasilar ischemic stroke treated with intravenous recombinant tissue-type plasminogen activator within 3 hours after symptom onset.


A new quantitative (two-photon extracellular polar-tracer imaging-based quantification (TEPIQ)) analysis for diameters of exocytic vesicles and its application to mouse pancreatic islets.
We have developed an imaging approach to estimate the diameter of exocytic vesicles that are smaller than the resolution of an optical microscope and present within intact tissue. This approach is based on two-photon excitation imaging of polar tracers in the extracellular medium, is designated TEPIQ (two-photon extracellular polar-tracer imaging-based quantification), and has three variants. TEPIQ analysis of DeltaV measures vesicle volume with a fluid-phase tracer, sulforhodamine B (SRB). TEPIQ analysis of DeltaS determines vesicle surface area with a polar membrane tracer, FM1-43. TEPIQ analysis of DeltaV/DeltaS estimates vesicle diameter from the SRB/FM1-43 fluorescence ratio. TEPIQ analysis is insensitive to microscope settings because the same setup is used for calibration and actual experiments. We tested the validity of TEPIQ with glucose-induced exocytosis from beta-cells within pancreatic islets. The three TEPIQ variants yielded estimates for the mean diameter of exocytic vesicles of between 340 and 390 nm, consistent with the size of insulin granules. TEPIQ analysis relies on the combination of two-photon excitation imaging, the narrow intercellular spaces of intact tissue, and the presence of diffusible polar tracers in the extracellular medium. It allows quantitative imaging of exocytosis within secretory organs, yielding estimates of vesicle diameter with nanometer resolution.


Photoacoustic/ultrasound dual imaging of human thyroid cancers: an initial clinical study.
We reported an initial clinical study of in vivo human thyroid by a photoacoustic/ultrasound handheld probe. Our dual-modality system is based on a high-end clinical ultrasound machine. Both healthy and cancerous thyroids were imaged non-invasively, and we compared the photoacoustic imaging with color Doppler ultrasound. The results of photoacoustic thyroid imaging could reveal many blood vessels that were not sensitive for Doppler ultrasound. Our study demonstrated that photoacoustic imaging could provide important complementary information for traditional ultrasound thyroid examination, which has a great potential for clinical diagnosis.


Multilocus Mitochondrial Mutations Do Not Directly Affect the Efficacy of Gene Therapy for Leber Hereditary Optic Neuropathy.
Clinical trials of gene therapy for Leber hereditary optic neuropathy (LHON) were conducted in 9 volunteers with the mitochondrial mutation, G11778A in ND4. The purpose of this study was to investigate whether multilocus mitochondrial mutations directly influence the efficacy of gene therapy for LHON. Nine volunteers with LHON participated in a clinical trial with intravitreal injection of an adenoviral vector expressing wild-type ND4. Patients were subsequently divided into 2 groups: according to the differences in therapy efficacy and based on improvements in visual acuity. Full mitochondrial DNA sequences of the 2 groups of patients were generated and compared using PubMed, PolyPhen, and PROVEAN. Furthermore, the association between the detected mutations and clinical effects of gene therapy was analyzed. Best-corrected visual acuity (BCVA) significantly improved (≥0.3 log of minimum angle of resolution [logMAR]) in 7 patients 6 months after gene therapy, whereas there was no significant change in BCVA (<0.3 logMAR) of the remaining 2 patients. All 9 patients carried the G1178A mutation in addition to other nonsynonymous mutations. Among these mutations, some were predicted to be neutral and deleterious. Meanwhile, different mitochondrial mutations in the group in which treatment was ineffective, compared with those in responders, were at nucleotide positions 6569 (CO1; Patient 3), 9641 (CO3; Patient 3), and 4491 (ND2; Patient 5). Detection of the 3 primary mitochondrial mutations causing LHON is sufficient for screening before gene therapy; sequencing of the entire mitochondrial genome is unnecessary before treatment. Patients with LHON can respond to targeted gene therapy irrespective of additional multilocus mitochondrial mutations.


[Hemiconvulsion-hemiplegia syndrome: two case reports with findings from magnetic resonance imaging of the brain in diffusion-weighted sequences].
Hemiconvulsion-hemiplegia (HH) syndrome is characterised by prolonged hemiclonic seizures followed by, very often permanent, hemiplegia. We report the cases of two patients with HH syndrome; in addition, the paper also includes a discussion of the value of neuroimaging in its diagnosis, including the use of magnetic resonance imaging (MRI) of the brain in diffusion-weighted sequences, and its clinical-radiological progression. Case 1: a 16-month-old female who was admitted to hospital owing to right-side hemiclonic seizures, with a febrile condition, that lasted at least 30 minutes, and persistent hemiparesis on the right-hand side of the body. Results of an initial computerised tomography (CT) brain scan were normal. Brain MRI at 3 days: T2 weighted sequences were normal; diffusion-weighted sequences showed lowered diffusion in the temporoparietooccipital region in the left hemisphere. Brain CT scan at 6 months: hemiatrophy on the left-hand side of the brain. Paresis of the right hand continues at the age of 4 years and 8 months; no further seizures have occurred and the patient's psychic development is normal. Case 2: a female aged 2 years and 6 months who was admitted to the Paediatric Intensive Care Unit owing to right-side hemiclonic seizures, with a feverish condition, lasting between 35-40 minutes, with persistent hemiplegia on the right-hand side of the body. The patient had a history of psychomotor retardation secondary to chromosome pathology; findings from a brain CT scan were normal. CT scan at 48 hours after the episode: edema in the left hemisphere of the brain. Brain MRI at 7 days following hospital admission: extensive involvement of the left hemisphere of the brain could be seen in T2 weighted sequences and in diffusion-weighted sequences. CT scan at 3 months: hemiatrophy on the left-hand side of the brain. Hemiparesis persists at the age of 5 years and 4 months; the patient has had no further seizures and attends specialised schooling. Although rare in our environment, HH syndrome can be seen in the context of hemiclonic febrile conditions. MRI of the brain in diffusion-weighted sequences may be the only means of proving the initial brain lesion.


Relationship between liver fat content and lifestyle factors in adults with metabolic syndrome.
The aim of this study was to investigate the associations between liver fat content (LFC), sedentary behaviour (SB), physical activity (PA), fitness, diet, body composition, and cardiometabolic risk factors in adults with metabolic syndrome. A total of 44 sedentary adults (mean age 58 [SD 7] years; 25 women) with overweight or obesity participated. LFC was assessed with magnetic resonance spectroscopy and imaging, SB and PA with hip-worn accelerometers (26 [SD 3] days), fitness by maximal bicycle ergometry, body composition by air displacement plethysmography and nutrient intake by 4-day food diaries. LFC was not independently associated with SB, PA or fitness. Adjusted for sex and age, LFC was associated with body fat%, body mass index, waist circumference, triglycerides, alanine aminotransferase, and with insulin resistance markers. There was and inverse association between LFC and daily protein intake, which persisted after further adjusment with body fat%. LFC is positively associated with body adiposity and cardiometabolic risk factors, and inversely with daily protein intake. SB, habitual PA or fitness are not independent modulators of LFC. However, as PA is an essential component of healthy lifestyle, it may contribute to liver health indirectly through its effects on body composition in adults with metabolic syndrome.


Intravenous Versus Wetting Solution Magnesium Sulphate to Counteract Epinephrine Cardiac Adverse Events in Abdominal Liposuction: A Randomized Controlled Trial.
The increased frequency of liposuction has resulted in more complications being reported. Adding epinephrine to the wetting solution could induce some cardiac adverse effects, some of which may be fatal. For instance, magnesium sulfate (MgSO4) is known for its cardioprotective effects. This study aimed to evaluate the efficacy of intravenous (IV) versus wetting solution containing MgSO4 in decreasing such cardiac adverse events during abdominal liposuction. This randomized controlled study included 129 adult cases undergoing abdominal liposuction under general anesthesia. The participants were divided into 3 groups: Group I (control group) was only subjected to the injection of the wetting fluid (1 mL 1/1000 epinephrine added to every 1000 mL of normal saline), group II was subjected to IV MgSO4 (40 mg/kg over 1 minute) at the same time of installing the wetting solution, and group III was subjected to MgSO4 (40 mg/kg) added to the wetting solution. Intraoperative isoflurane consumption, intraoperative heart rate (HR), mean arterial pressure (MAP), and postoperative pain scores were significantly lower in the MgSO4 groups (groups II and III) than group I. Cardiac adverse events (sinus tachycardia and premature ventricular contractions (PVCs)) were also significantly less frequent in groups II and III compared to group I. Adding MgSO4, either through IV or subcutaneous routes, is associated with lower intraoperative HR, MAP, and postoperative pain scores and a remarkable decrease in epinephrine-induced cardiac adverse events during liposuction.


Systemic absorption of fluoride from alginate impression material in humans.
Thirty minutes after routine alginate impressions in five adult subjects, plasma fluoride levels increased by an average of 2.6 times over control values. Urinary fluoride excretion rates increased approximately 2.9 times during the first two hours after the impressions. Average whole saliva fluoride levels at 15 minutes were over 100 times the average control concentration. When small amounts of alginate were deliberately ingested, plasma fluoride levels and urinary excretion rates increased sharply.


Revisiting Cationic Phosphorus Dendrimers as a Nonviral Vector for Optimized Gene Delivery Toward Cancer Therapy Applications.
Gene delivery, one important cancer-therapy mode, still remains to be challenging because of the shortage of highly efficient and safe nonviral vectors. Here, we revisit the development of cationic phosphorus dendrimers by synthesizing them with different generations (G1-3) and surface ligands (1-(2-aminoethyl) pyrrolidine, 1-(3-aminopropyl) piperidine, or 1-(2-aminoethyl) piperidine) for optimized gene delivery toward cancer-gene-therapy applications. First, the synthesized dendrimer derivatives were employed to condense plasmid DNA (pDNA) encoding enhanced green fluorescent protein (EGFP) to optimize their gene-delivery efficiency by varying the dendrimer generations and surface polycationic ligands. We show that all dendrimer/pDNA polyplexes display good cytocompatibility, and the 1-(2-aminoethyl) pyrrolidine-modified protonated G1 dendrimers (1-G1) display the best gene-delivery efficiency to HeLa cells under the same conditions through flow cytometry and fluorescence microscopic imaging analyses. Hence, 1-G1 dendrimers were then used as a vector to transfect pDNA encoding both EGFP and p53 protein for cancer-gene-therapy applications. Our results reveal that under the optimized conditions, the transfection of pDNA induces the significant p53 protein expression as verified through the resulted cell cycle arrest (regulation of p21 and Cdk4/Cyclin-D1 expression) and Western blotting. The cancer-gene-therapy potential of the polyplexes was finally validated through therapy of a xenografted tumor model after intratumoral injection without systemic toxicity. The developed cationic 1-G1 dendrimers may be adopted as a powerful vector system for gene therapy of cancer, as well as for highly effective gene therapy of other diseases.


High throughput functional assays for P2X receptors.
Adenosine triphosphate (ATP) activates two receptor superfamilies, metabotropic P2Y and ionotropic P2X receptors. The P2X receptors are nonselective cation channels that are widely expressed on excitable cells including neurons, glia, and smooth muscle cells. The protocols in this unit are useful for evaluating ligands that interact with P2X receptors on native cells or that are cloned and expressed in recombinant heterologous cell systems. Calcium imaging methods are described for the pharmacological characterization of fast or slowly desensitizing P2X receptors. While these methods are readily applicable to a wide variety of ligand-gated ion channels, the protocols provided herein detail how they can be used to measure activation of homomeric P2X3 (fast desensitizing) and heteromeric P2X2/3 (slowly desensitizing) receptors. Appropriate agonists and/or calcium dyes can be substituted to assess activity at other P2X receptor subtypes. An additional protocol is provided for measuring P2X7 receptor-mediated pore formation in THP-1, a native human acute monocytic leukemia cell line that can be used to study homomeric P2X7 (non-desensitizing) receptors that are expressed on macrophages and microglial cells.


Allelic loss at chromosomes 3p, 8p, 13q, and 17p associated with poor prognosis in head and neck cancer.
Little is known about the molecular genetic events that contribute to the pathogenesis of squamous cell carcinoma of the upper aerodigestive tract. Previous molecular genetic studies have been limited to the identification of mutations of the p53 (also known as TP53) tumor suppressor gene, activation of a limited set of oncogenes, allelic loss at 3p and other locations, and occasional association with human papillomavirus infection. Our purpose was to screen tumor tissue and blood from patients with squamous cell carcinoma of the upper aerodigestive tract for loss of heterozygosity at polymorphic loci corresponding to each of the autosomal chromosomes and to identify the locations of additional putative tumor suppressor genes, other than RB (also known as RB1) and p53, that may contribute to the pathogenesis of this disease. Tumor tissue and blood were obtained from 68 consecutive patients with squamous cell carcinoma of the upper aerodigestive tract. In all cases, tumor tissue was obtained from the center of the surgical specimen. The relative absence of non-neoplastic tissue was confirmed by frozen-section histologic examination of immediately adjacent tissue. Initially, 30 paired tissue and blood samples were tested for loss of heterozygosity by polymerase chain reaction (PCR) to amplify 43 different highly polymorphic sequences containing small oligonucleotide repeats. After PCR amplification, with unique oligonucleotides flanking the repeat, visualization and sizing of the alleles on DNA sequencing gels were performed. Specific loss of heterozygosity was distinguished from random genetic loss due to generalized chromosomal instability if it occurred in more than 20% of specimens tested for a particular marker. Significant loss of heterozygosity (> 20%) occurred at alleles at chromosome bands 3p21 (32%), 3p25-26 (56%), 8pter-21.1 (31%), 13q14 (27%), and 17p12 (45%). Loss of heterozygosity at more than two loci was significant with a poor prognosis (P = .039). These findings demonstrate that squamous cell carcinoma of the upper aerodigestive tract exhibits genetic alterations at multiple loci and that allelic loss at more than two locations is indicative of a poor prognosis (the likelihood of the patient dying of disease). While tumor suppressor genes at 3p (VHL), 13q (RB), and 17p (p53) have been identified, altered genes at other loci on 3p and on 8p have not yet been characterized. Furthermore, the genotype at these loci for squamous cell carcinoma of the upper aerodigestive tract has prognostic importance and may identify the patients who should receive the most aggressive treatment.


U.S. Policies for school health education: opportunities for advocacy at the local, state, and national levels.
Children in K-12 settings comprise roughly one fifth of the population of the United States and are a cohort that has long drawn the interest of health educators. Early education and prevention efforts reduce human suffering, contribute to preparation for classroom learning, affect long-term health, and contain health costs due to preventable diseases. Despite the possible positive impact of a comprehensive approach, no broad-based federal legislation mandates regular school health education. Instead, the current state of school health education policy is a cobbled-together set of policies subsumed under existing laws. The purpose of this article is to provide information about the key legislation that is being used to promote school health education in the United States. Furthermore, the authors suggest opportunities for lobbying for the continuance of existing legislation and advocating for state and local operationalization of these policies. Finally, health educators are rallied to consider raising the issue of advocating for a more complete legislative strategy for school health education.


Quantification of pulmonary perfusion with free-breathing dynamic contrast-enhanced MRI--a pilot study in healthy volunteers.
The assessment of pulmonary perfusion using dynamic contrast-enhanced (DCE) MRI is still limited in the clinical routine due to the necessity of breath holding. An acquisition technique for the quantitative assessment of pulmonary perfusion in free breathing was investigated in our study. 10 healthy male volunteers underwent pulmonary DCE-MRI on a 1.5 T scanner. Each volunteer was examined twice: (a) in breath-hold half expiration and (b) during shallow free breathing. The pulmonary parenchyma was segmented automatically. The pulmonary plasma flow (PPF) and pulmonary plasma volume (PPV) were determined pixel-wise using a one-compartment model. All examinations were of diagnostic image quality. The measured mean values of the PPV were significantly lower in the breath-hold technique than during free breathing ((10.2 ± 2.8) ml/100 ml vs. (12.7 ± 3.9) ml/100 ml); p < 0.05). A significant difference was also observed between both PPF measurements (mean PPF (206.2 ± 104.0) ml/100 ml/min in breath-hold technique vs. (240.6 ± 114.0) ml/100 ml/min during free breathing; p < 0.05). Free-breathing DCE-MRI appears to be suitable for the quantitative assessment of the pulmonary perfusion in healthy volunteers. The proposed segmentation and quantification approach does not suffer from the increased motion, as compared to the breath-holding measurement. The increased PPV and PPF during free breathing are in accordance with the results of previous studies concerning breathing influence on perfusion parameters. Overall, free-breathing DCE-MRI may be a promising technique for the assessment of pulmonary perfusion in various pathologies.


Development of a computational pregnant female phantom and calculation of fetal dose during a photon breast radiotherapy.
The incidence of carcinoma during pregnancy is reported to be 1:1000-1:1500 pregnancies with the breast carcinoma being the most commonly diagnosed. Since the fetus is most sensitive to ionizing radiation during the first two trimesters, there are mixed clinical opinions and no uniform guidelines on the use of radiotherapy during pregnancy. Within this study the pregnant female phantom in the second trimester, that can be used for radiotherapy treatment planning (as DICOM data), Monte Carlo simulations (as voxelized geometry) and experimental dosimetry utilizing 3D printing of the molds (as .STL files), was developed. The developed phantom is based on MRI images of a female patient in her 18th week of pregnancy and CT images after childbirth. Phantom was developed in such a manner that a pregnant female was scanned "in vivo" using MRI during pregnancy and CT after childbirth. For the treatment of left breast carcinoma, 3D conformal radiotherapy was used. The voxelized geometry of the phantom was used for Monte Carlo (MC) simulations using Monte Carlo N-Particle transport codeTM 6.2 (MCNP). The modeled photon breast radiotherapy plan, applied to the phantom, indicated that the fetus dose is 59 mGy for 50 Gy prescribed to the breast. The results clearly indicate that only 9.5% of the fetal dose is caused by photons that are generated in the accelerator head through scattering and leakage, but the dominant component is scattered radiation from the patient's body.


Lonidamine: basic science and rationale for treatment of prostatic proliferative disorders.
Normal and hyperplastic prostatic tissues concentrate citrate within the epithelium; however, a unique biochemical property within prostate epithelial cells renders them dependent on glycolysis, rather than the citric acid cycle, for energy production. Lonidamine, an orally administered small molecule that inhibits glycolysis by the inactivation of hexokinase, may represent a unique and novel approach to the treatment of benign prostatic hyperplasia (BPH). Results of a phase II trial of lonidamine in BPH (described elsewhere in this supplement) are encouraging. Lonidamine is already used in the treatment of several cancers in other countries. Its target-specific nature renders it a safe compound for administration; in cancer therapy, patients have been treated with 40 times the daily dose used in the BPH trial, with negligible toxicity.


Gossypol and gossypolone enantiomers in tissues of rainbow trout fed low and high levels of dietary cottonseed meal.
Gossypol is an antifertilizing agent in males and females. However, gossypol and its metabolite, gossypolone, have also gained interest because of their anticarcinogenic activities. This paper examines for the first time both enantiomers of tissue gossypol and gossypolone in mature rainbow trout fed two diets containing low (15%) and high (60%) levels of cottonseed meal (CM) for 9 months. The gossypol concentration was highest in liver followed by kidney, intestine, testis, blood plasma, stomach, and muscle. Gossypol was detected in muscles of fish fed low- and high-CM diets (0.31 +/- 0.03 and 1.95 +/- 0.59 microg of total gossypol/g, wet basis, respectively). The (+)-gossypol enantiomer was predominantly retained in all tissues. The ratio of (-)- to total gossypol ranged from 30 to 44% in fish fed the high-CM diet and from 23 to 30% in fish fed the low-CM diet except for muscle tissue (44%). Higher gossypolone concentrations were found in intestine than in liver. Gossypolone, however, was not detected in blood plasma, muscle, and testis of fish fed the low-CM diet. The ratio of gossypolone to gossypol was highest in muscle (1.75), followed by intestine (1.59), stomach (1.50), kidney (0.43), liver (0.34), testis (0.28), and blood plasma (0.27). This study indicated that the retention of the (-)-gossypol enantiomer is dependent on dietary concentrations and that the oxidative conversion of gossypol to gossypolone occurs more actively in the digestive tract and muscle than in other tissues in rainbow trout.


Influencing College and Higher Education Choices in Disadvantaged Hispanic High School Students Through a School-Based Health Club.
Statistics representing professional health care providers do not adequately reflect the shift in the nation's diverse population. Latinos are significantly underrepresented at all levels of appropriate academic programs critical for entry to health profession careers. This project describes the implementation of a student-run, faculty-facilitated Future Nurse and Health Club at a school (with majority Latino students) to emphasize the importance of higher education in health care. Demographic and psychosocial profiles of club members were also developed to understand community needs. The Future Nurse and Health Club was established in partnership with faculty and researchers representing a university-based nursing program, school officials, and community leaders. Both quantitative and qualitative data were collected from club members and their parents using a variety of techniques including questionnaires and focus groups. The findings of the study highlighted a variety of student- and parent-related factors including poor lifestyle habits and perceptions of support that could potentially influence Latino high school students' interest and progress in health care-related higher education. A school-based health career club involving active participation of parents and students with support from health care professionals such as academic nursing faculty has the potential to simultaneously raise student interest in health-related careers and health needs of their community.


Atomic force microscopy study of DNA flexibility on short length scales: smooth bending versus kinking.
The apparently anomalous flexibility of DNA on short length scales has attracted a lot of attention in recent years. We use atomic force microscopy (AFM) in solution to directly study the DNA bending statistics for small lengths down to one helical turn. The accuracy of experimental estimates could be improved due to a large data volume and a refined algorithm for image processing and measuring bend angles. It is found that, at length scales beyond two helical turns (7 nm), DNA is well described by the harmonic worm-like chain (WLC) model with the bending persistence length of 56 nm. Below this threshold, the AFM data are also described by the WLC model assuming that the accuracy of measured bend angles is limited by the physical width of the double helix. We conclude that the double helical DNA behaves as a uniform elastic rod even at very short length scales. Strong bends due to kinks, melting bubbles and other deviations from the WLC model are statistically negligible.


Portable oxygen concentrators versus oxygen cylinder during walking in interstitial lung disease: A randomized crossover trial.
Ambulatory oxygen therapy is often provided to patients with interstitial lung disease (ILD). Lightweight portable oxygen concentrators (POCs) provide an alternative to traditional portable systems such as compressed oxygen cylinders; however, their efficacy in patients with ILD has not been assessed. This study aimed to evaluate the clinical performance of three ambulatory oxygen systems (two different POCs and a compressed oxygen cylinder) during 6-min walk tests (6MWTs) in patients with ILD and exertional desaturation. A total of 20 participants with ILD of varying aetiologies who demonstrated exertional desaturation to <90% on room air during 6MWT were recruited. Each participant performed two 6MWTs while breathing room air. On a subsequent day, two further 6MWTs were performed, in random order: one breathing oxygen via a POC (either the Inogen One G2 POC or the EverGo POC at the setting of 6) and one with a compressed oxygen cylinder (at 5 L/min). There were no significant differences in nadir oxygen saturation (SpO2 ) during 6MWTs using different portable oxygen devices (Trial 1: mean SpO2 for Inogen One G2 POC: 82.3 ± 3.5% vs oxygen cylinder: 80.3 ± 2.2%, P = 0.14; Trial 2: mean SpO2 for EverGo POC: 85.7 ± 7.7% vs oxygen cylinder: 86.1 ± 6.1%, P = 0.79). The mean 6-min walk distances were not significantly different among the three devices. The performance of the Inogen One G2 POC and the EverGo POC had comparable performance with that of the compressed oxygen cylinder during walking in patients with ILD and exertional desaturation.


Inter-laboratory validation of a thin film microextraction technique for determination of pesticides in surface water samples.
The primary goal of the present study is the inter-laboratory evaluation of a thin film microextraction (TFME) technique to be used as an alternative approach to liquid-liquid extraction (LLE). Polydimethylsiloxane/divinylbenzene (PDMS/DVB) and PDMS/DVB-carbon mesh supported membranes were used for the extraction of 23 targeted pesticides, while a thermal desorption unit (TDU) was employed to transfer these analytes to a GC/MS instrument for separation and detection. After optimization of the most critical parameters, both membranes were capable of achieving limits of detection (LOD) in the low ng L-1 range while demonstrating excellent robustness, withstanding up to 100 extractions/desorption cycles. Furthermore, limits of quantification (LOQ) between 0.025 and 0.50 μg L-1 were achieved for the 23 compounds selected from several classes of pesticides with a wide range of polarities. A wide linear range of 0.025-10.0 μg L-1 with strong correlation to response (R2 > 0.99) was attained for most of the studied analytes. Both membranes showed good accuracy and repeatability at three levels of concentration. Moreover, the method was also validated through blind split analyses of 18 surface water samples, collected within 3 months, using TFME at the University of Waterloo and LLE at Maxxam Analytics (Mississauga, ON) which is an accredited commercial analytical laboratory. Good agreement between the two methods was achieved with accuracy values ranging from 70 to 130%, for the majority of analytes in the samples collected. At the concentration levels investigated, 90% of the analytes were quantifiable by TFME, whereas only 53% of the compounds were reportable using the LLE method particularly at concentrations lower than 1 μg L-1. The comparison of TFME and LLE from several analytical aspects demonstrated that the novel TFME method gave similar accuracy to LLE, while providing additional advantages including higher sensitivity, lower sample volume, thus reduced waste production, and faster analytical throughput. Given the sensitivity, simplicity, low cost, accuracy, greenness and relatively fast procedure of TFME, it shows great potential for adoption in analytical laboratories as an alternative to LLE.


Feasibility of performance-based functional assessment in brain tumour survivors.
Rehabilitation and exercise interventions are beneficial for the physical and psychological health of cancer survivors. Current clinic-based performance status measures do not accurately capture the survivor's functioning, or rehabilitation and exercise needs. Our primary objective was to explore the feasibility of performing a performance-based functional assessment with brain tumour survivors as a means to inform needs for rehabilitation and exercise. A feasibility study was conducted with survivors of brain and other neurological cancers attending new patient or follow-up clinics. Survivors were assessed using the Short Physical Performance Battery (SPPB), grip strength and Rosow-Breslau Physical Activity Self-Assessment (RSB). We approached 40 survivors with brain tumours, and 30 agreed to participate in the study. The SPPB was inversely correlated with Eastern Cooperative Oncology Group (ECOG) scores (r = -.73; p < .01), but scores on the SPPB for individuals classified as ECOG 1 ranged from 5 to 12 out of 12, indicating a large variability in functional scores within this ECOG grade. Implementation of objective functional testing is feasible in the neuro-oncology outpatient clinic. The SPPB appears to best inform the functional status of survivors with brain tumours, facilitating more individualised exercise and rehabilitation referrals.


Presynaptic modulation of parallel fibre signalling to Bergmann glia.
Transmission at the parallel fibre-Purkinje neurone synapse of the cerebellum can be depressed by a number of presynaptic receptors: endocannabinoid (CB1), metabotropic glutamate (mGluR4), adenosine (A1) and GABA (GABA(B)), which have been implicated in both short- and long-term synaptic plasticity. Stimulation of parallel fibres also activates glutamate receptors and transporters on the Bergmann glial cell that forms a sheath around the synapse. The resulting glial extrasynaptic currents (ESC) exhibit short- and long-term plasticity, which differs from the plasticity of adjacent synapses. This functional independence could arise from differential modulation of presynaptic release sites targeted to synapses or glia, but the sensitivity of glial ESC to these inhibitory pathways is unknown. Here I show that all four presynaptic receptors depress parallel fibre-Bergmann glial cell signalling with similar potency to synaptic transmission. Depression of glial ESC is accompanied by a decrease in paired pulse ratio. However, application of receptor antagonists had no effect on ESC amplitude, indicating that tonic activation of these pathways does not occur, and antagonists failed to block the activity-dependent depression of glial ESC observed during tetanic or low frequency stimulation. These data suggest that modulation of presynaptic glutamate release does not underlie glial plasticity.


Oxidative modifications of apoB-100 by exposure of low density lipoproteins to HOCL in vitro.
Although the products of oxidation of the lipid components of LDL have been studied extensively, much less is known about the specific products of oxidative modification of the apoprotein. We reacted native LDL and LDL that had been treated with HOCl with 2,4-dinitrophenylhydrazine (DNPH), delipidated and trypsinized the protein, and analyzed the products by HPLC. Although tryptic digests of native LDL and LDL oxidized by limited quantities of HOCl showed similar patterns by HPLC with detection at 220 nm, oxidized LDL showed several discrete peaks at 365 nm, which is characteristic of hydrazones formed with aldehydes and ketones, commonly termed protein carbonyls. Native LDl showed no peaks in the chromatograms at 365 nm. Peptides absorbing at 365 nm were isolated by HPLC and characterized. In most cases, the probable sites of modification on the peptides could be implied by failure of an anticipated amino acid to appear in the expected sequence. Of the 14 peptides isolated and characterized to date, eight peptides contained Cys residues. In other peptides, Lys, Trp, and Met were identified as amino acid residues apparently modified by HOCl treatment of LDL. Thirteen of the peptides identified are from trypsin-releasable peptides located on the surface of unoxidized native LDL. Our studies suggest a selective process of modification of apoB-100 by HOCl and the approaches used in the present studies should be useful for the characterization of the mechanisms of oxidation of this and other proteins.


[Effects of life style intervention on obesity-related vascular dysfunction in children].
To evaluate the reversibility of obesity-related arterial dysfunction and thickening carotid intima-media through dietary and/or exercise intervention programs. Seventy-eight 9 to 12 year-old overweight children, were randomly assigned to group A: only dietary modification, group B: diet plus a supervised structured exercise program for 6 weeks (SE) and subsequently for 1 year (CE). The prospectively defined primary end points were assessed through ultrasound-derived arterial endothelial function (endothelium-dependent dilation) of the brachial artery and intima-media thickness of common carotid artery. At 6 weeks, both interventions were associated with improved arterial endothelial function [group A: (6.36 +/- 0.81)% vs. (5.32 +/- 0.84)%, P < 0.01; group B: (7.46 +/- 0.91)% vs. (5.20-0.87)%, P < 0.01]. A combination of diet and exercise were associated with a significantly greater improvement in endothelial function than on diet alone (P < 0.01). At 1 year, there appeared significantly less thickening of the carotid wall in group CE [(0.57 +/- 0.05) mm vs. (0.59 +/- 0.07) mm, P < 0.001]. Compared with children in group SE [(6.38-1.04)% vs. (5.22 +/- 0.96)%, P < 0.05], vascular function appeared significantly better in group CE [(8.29 +/- 0.78)% vs. (5.38 +/- 0.65)%, P < 0.001]. Obesity-related vascular dysfunction in young children was partially reversible with diet alone but more obvious when combined with exercise training for 6 weeks. Sustained improvements at 1 year was seen in those who persisted in diet program plus regular exercise.


Therapeutic efficacy and renal effects of cefonicid in the treatment of difficult urinary tract infections.
EFFICACY, renal effects and nephrotoxicity of the cephalosporin cefonicid (CEF) were evaluated in 11 adult patients with urinary tract infection and varying renal function (creatinine cl 19-161 ml/min, mean 75). CEF was administered i.m. for 7 days at a daily dose adjusted to renal function of the patients. At the 4th day and at the end of the treatment urine cultures were negative in all cases; a recurrence of the infection was observed in 4 patients 10 days after completion of therapy. Renal effects and nephrotoxicity: CEF neither modified plasma creatinine, urea, uric acid and their renal clearances nor glomerular filtration rate. Only the urinary enzyme activity of alanine aminopeptidase increased slightly at the end of the therapy. It returned to basal values in the post-treatment period. Urinary enzyme activities of gamma-glutamyltransferase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase and lysozyme were unmodified during and after treatment with CEF. These results indicate that CEF is an effective antimicrobial agent which does not influence renal function, nor cause nephrotoxic effects.


Specificity and efficiency of editing of mismatches involved in the formation of base-substitution mutations by the 3'----5' exonuclease activity of phage T4 DNA polymerase.
The specificity and efficiency of base-mispair editing by the 3'----5' exonuclease activity of phage T4 DNA polymerase has been measured using a sensitive infectivity assay. A series of oligodeoxynucleotide primer chains was synthesized chemically. These primers, when hybridized to phi X174 single-stranded DNAs containing an amber codon, result in a mispaired nucleotide at the 3'-hydroxyl end of the primer chain within the amber codon. DNA synthesis on these primer X templates without the removal of the mispaired terminal nucleotide results in the formation of heteroduplex molecules that yield viable revertants upon transfection into an amber nonsuppressor host. This method permits determination of the efficiency of editing of a mismatch to 1 in 10(6) mismatches that escape editing and allows all eight mispairs that can yield viable revertants at an amber codon to be studied. The results of experiments with primers hybridizing to phi X174 am16 and am3 codons show that the order of mispair editing by T4 DNA polymerase is Ttemplate X Gprimer less than (A X G, T X C) less than (T X T, G X A, G X G, A X C) less than A X A. The efficiency of editing depends upon the mispair, as well as the neighboring DNA sequence. Under these conditions of synthesis, the 3'----5' exonuclease activity, depending upon the mispair and DNA sequences beyond the nearest neighbors, is estimated to contribute a factor of from 2.3 X 10(3)- to greater than 10(6)-fold to the accuracy of T4 DNA polymerase.


Resonance overlap, secular effects, and nonintegrability: an approach from ensemble theory.
The time evolution of a classical multiresonance nonintegrable Hamiltonian system with few degrees of freedom is analyzed on the ensemble level. Time-dependent perturbation analysis is applied to the Liouville equation to determine the most secular series for the time evolution of the expectation value of some physical observables. In contrast to the so-called lambda(2) t expansion for thermodynamic systems, which is well known in nonequilibrium statistical physics, we find a square root of lambda t expansion in small nonintegrable systems with few degrees of freedom. This asymptotic expansion exists only on the level of ensemble but not on the level of trajectories. Moreover, the time symmetry of this expansion is broken as in nonequilibrium statistical mechanics. The relation of the Chirikov overlapping criterion to our approach is discussed.


Perfusion and metabolism imaging studies in Parkinson's disease.
Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are important tools in the evaluation of brain blood flow and glucose metabolism in Parkinson's disease (PD). However, conflicting results are reported in the literature depending on the type of imaging data analysis employed. The present review gives a comprehensive summary of the perfusion and metabolism literature in the field of PD research, including quantitative PET studies, normalized PET and SPECT studies, autoradiography studies in animal models of PD, and simulation studies of PD data. It is concluded that PD most likely is characterized by widespread cortical hypometabolism, probably even at early disease stages. Widespread subcortical hypermetabolism is probably not a feature of PD, although certain small basal ganglia structures, such as the external pallidum, may display true hypermetabolism in the absolute sense. This observation is also in agreement with the animal literature.


Ischaemic renal injury.
Ischaemic renal injury is becoming one of the main causes of end-stage renal failure. The appearance of new diagnostic methods, as well as the evidence that surgery or percutaneous transluminal angioplasty techniques are capable of inducing a significant degree of recovery in a subset of patients, are encouraging events. The identification of the precise cellular pathogenetic mechanisms of ischaemic injury is an area for future research.


[Changes in prices of taxed sugar-sweetened beverages and nonessential energy dense food in rural and semi-rural areas in Mexico].
To estimate changes in prices associated with the implementation of the tax to sugar sweetened beverages (SSB) and to nonessential energy dense food in 2014. Price data were collected in rural and semi-rural areas in December 2013, and April and December 2014. Fixed effects models were used to estimate changes in prices of beverages and nonessential energy dense food, stratified by region, retailer and package size. The SSB tax did not pass completely through prices: prices increased on average 0.73 pesos per liter. For nonessential energy dense food, the tax passed completely or was overshifted for cookies, cereal bars and cereal boxes. The potential effect of the taxes on consumption could be attenuated in rural areas as the pass through prices was incomplete.


Anterior keratouveitis secondary to Hydroa vaccineforme: a role for ophthalmic slit-lamp examination in this condition?
The authors report the case of an 8-year-old girl of Caucasian origin who attended the Emergency Eye Clinic with a 3-week history of a red, light sensitive left eye during the month of April. Her Snellen visual acuities were 6/5 right and 6/9 left. Examination revealed perilimbal injection and anterior chamber inflammation in the left eye consistent with an anterior uveitis. Inferior stromal haze and fine keratic precipitates were noted in the left cornea. Intraocular pressures were normal, with no vitritis and healthy looking discs, maculae and peripheral retina. Systemic examination revealed a papular rash over the face consistent with previously diagnosed Hydroa vaccineforme. With intensive topical steroids the inflammation gradually resolved.


Malignant pleural mesothelioma in Turkey, 2000-2002.
Both asbestos and erionite related malignant pleural mesothelioma (MPM) is a serious health problem in Turkey. Erionite has a higher potency in the lung than asbestos and familial clustering of malignant mesothelioma suggests a genetic predisposition to this cancer among affected individuals. Neither Simian virus 40 (SV40) nor human herpes virus 8 (HHV-8) are co-factors in the pathenogenesis of environmentally induced mesothelioma. A survival advantage has been demonstrated in patients with asbestos-induced mesothelioma compared with erionite-induced mesothelioma. This together with the proliferation index (PI) can be used as an independent prognostic factor for patients with malignant pleural mesothelioma. It is envisaged that the application of these prognostic approaches together with the new TNM staging system will allow investigations to be more precisely carried out and evaluated.


Comparing willingness to pay for telemedicine across a chronic heart failure and hypertension population.
This paper presents estimates of the willingness to pay for a new telemedicine technology in the absence of market data. The study utilizes a contingent valuation method to determine patient willingness to pay for access to telemedicine services. Willingness to pay was assessed in two populations: patients who are being treated for chronic heart failure (CHF) and patients who are being treated for hypertension. Patients who were approached to participate in these studies were asked about their preference for using telemedicine technologies. We find that patient willingness to pay has the expected negative relationship between price and the likelihood of purchase and that patients with CHF are less responsive to price changes than those with hypertension.


The development process and urbanisation in a newly organised state: a case study of Haryana.
"This paper examines the impact of emergence of Haryana [India] as a new state in 1966 on its development and concomitant urbanisation process. The analysis is based on data for individual towns for all the post-Independence censuses of 1951 to 1981. It was found that urban growth in the state was far more rapid during the post-1966 period than that during the pre-1966 phase. The spatial picture of urban growth also changed somewhat."


Pneumonitis caused by saikokeisikankyou-tou, an herbal drug.
A 57-year-old man was admitted to our hospital because of dyspnea and abnormal shadow on chest roentgenogram. He had received two herbal drugs: Saikokeisikankyou-tou (SKT) for one month and Licium Halimifolium Mil (LHM) for two weeks. After admission, all medication was stopped and his symptoms were gradually diminished. Transbronchial lung biopsy specimens showed interstitial pneumonia. Lymphocyte stimulation test, skin test and challenge test were positive to these herbal drugs. We diagnosed him as drug-induced pneumonitis. This is the first report on pneumonitis caused by Saikokeisikankyou-tou diagnosed by lymphocyte stimulation test, skin test and challenge test.


Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults.
GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein. We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 +/- 14.5 yr; 122 +/- 7.7 cm; 36.7 +/- 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout. Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline. In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intima-media thickness and in the number of atherosclerotic carotid plaques.


Construction of macroscopic cytomimetic vesicle aggregates based on click chemistry: controllable vesicle fusion and phase separation.
Vesicle-vesicle aggregation to mimic cell-cell aggregation has attracted much attention. Here, hyperbranched polymer vesicles (branched-polymersomes, BPs) with a cell-like size were selected as model membranes, and the vesicle aggregation process, triggered by click chemistry of the copper-catalysed azide-alkyne cycloaddition reaction, was systematically studied. For this purpose, azide and alkynyl groups were loaded on the membranes of BPs through the co-assembly method to obtain N(3)-BPs and Alk-BPs, respectively. Subsequently, macroscopic vesicle aggregates were obtained when these two kinds of functional BPs were mixed together with the ratio of azide to alkynyl groups of about 1:1. Both the vesicle fusion events and lateral phase separation on the vesicle membrane occurred during such a vesicle aggregation process, and the fusion rate and phase-separation degree could be controlled by adjusting the clickable group content. The vesicle aggregation process with N(3) -micelles as desmosome mimics to connect with Alk-BPs through click-chemistry reaction was also studied, and large-scale vesicle aggregates without vesicle fusion were obtained in this process. The present work has extended the controllable cytomimetic vesicle aggregation process with the use of covalent bonds, instead of noncovalent bonds, as the driving force.


Strain-Gradient Position Mapping of Semiconductor Quantum Dots.
We introduce a nondestructive method to determine the position of randomly distributed semiconductor quantum dots (QDs) integrated in a solid photonic structure. By setting the structure in an oscillating motion, we generate a large stress gradient across the QDs plane. We then exploit the fact that the QDs emission frequency is highly sensitive to the local material stress to map the position of QDs deeply embedded in a photonic wire antenna with an accuracy ranging from ±35 nm down to ±1 nm. In the context of fast developing quantum technologies, this technique can be generalized to different photonic nanostructures embedding any stress-sensitive quantum emitters.


Dosage individualization of erythropoietin using a profile-dependent support vector regression.
The external administration of recombinant human erythropoietin is the chosen treatment for those patients with secondary anemia due to chronic renal failure in periodic hemodialysis. The objective of this paper is to carry out an individualized prediction of the EPO dosage to be administered to those patients. The high cost of this medication, its side-effects and the phenomenon of potential resistance which some individuals suffer all justify the need for a model which is capable of optimizing dosage individualization. A group of 110 patients and several patient factors were used to develop the models. The support vector regressor (SVR) is benchmarked with the classical multilayer perceptron (MLP) and the Autoregressive Conditional Heteroskedasticity (ARCH) model. We introduce a priori knowledge by relaxing or tightening the epsilon-insensitive region and the penalization parameter depending on the time period of the patients' follow-up. The so-called profile-dependent SVR (PD-SVR) improves results of the standard SVR method and the MLP. We perform sensitivity analysis on the MLP and inspect the distribution of the support vectors in the input and feature spaces in order to gain knowledge about the problem.


Primary Localized Cutaneous Nodular Amyloidosis on Scalp Successfully Treated with Excision.
Primary localized cutaneous nodular amyloidosis (PLCNA) is the rarest form of cutaneous amyloidosis, characterized by nodular deposits of light chain amyloids in the dermis and subcutaneous tissue, without apparent systemic involvement. One or several nodules are preferably located on the extremities, trunk, or face. The most useful stain for detecting amyloid fibrils is Congo red, which, when combined with polarized light, makes amyloid proteins appear apple-green under a microscope. Immunohistochemical staining can help identify the exact type of amyloid proteins. Although the exact etiology of PLCNA is unclear, removal of nodules by shaving or surgical excision has shown good results. To the best of our knowledge, only seven cases of PLCNA have yet been reported in the Korean literature. In three of these cases, the patients had lesions on the scalp. Herein, we present a case of a 34-year-old male with PLCNA on the scalp with all the results of immunohistochemical evaluation.


High-performance liquid chromatographic determination of strychnine in grain baits.l.
A simple and rapid high-performance liquid chromatographic procedure is described for the determination of strychnine. Grain baits containing strychnine alkaloid are ground, mixed, and extracted by shaking with chloroform. Without further cleanup, extract filtrates are injected directly into a liquid chromatograph. Chromatography is complete within 7 min and peak heights are used for quantitation. Separations were made on a 30 cm times 4 mm id stainless steel column packed with mu Porasil (8-12 mum silica). The eluting solvent was methanol-chloroform (10+90) at a flow rate of 2.0 ml/min. Recovery of spiked samples ranged from 91.5 to 95.2%. Confirmation of strychnine from a commercial sample was made by high resolution mass spectrometry with mass agreement to 1.2 ppm.


Benzyl isothiocyanate inhibits oncogenic actions of leptin in human breast cancer cells by suppressing activation of signal transducer and activator of transcription 3.
Molecular effects of obesity, a well-established risk factor for breast cancer progression, are mediated by adipocytokine leptin. Given the important role of leptin in breast cancer growth and metastasis, novel strategies to antagonize biological effects of this adipocytokine are much desired. We showed previously that benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables (e.g. garden cress), confers significant protection against mammary carcinogenesis in a transgenic mouse model. The present study provides first evidence for the efficacy of BITC against oncogenic effects of leptin. The BITC treatment circumvented leptin-induced clonogenicity and anchorage-independent growth of MDA-MB-231 and MCF-7 human breast cancer cells. Leptin-stimulated migration and invasion of these cells was also inhibited in the presence of BITC. Analysis of the underlying molecular mechanisms revealed that BITC treatment suppressed leptin-induced Stat3 phosphorylation and cyclin D1 transactivation. The BITC-mediated inhibition of MDA-MB-231 xenograft growth correlated with a modest yet significant decrease in levels of Tyr705 phosphorylated Stat3. The BITC treatment efficiently inhibited Stat3 and SRC1 recruitment to cyclin D1 promoter in a chromatin immunoprecipitation analysis. Furthermore, overexpression of constitutively active Stat3 imparted significant protection against BITC-mediated inhibition of cyclin D1 transactivation, whereas RNA interference of Stat3 resulted in a significant increase in BITC-mediated inhibition of cyclin D1 transactivation in the presence of leptin. These results indicate that Stat3 plays an important role in BITC-mediated inhibition of leptin-induced cyclin D1 transactivation. In conclusion, BITC could potentially be a rational therapeutic strategy for breast carcinoma in obese patients with high leptin levels.