The educational consequences of teen childbearing.
A huge literature shows that teen mothers face a variety of detriments across the life course, including truncated educational attainment. To what extent is this association causal? The estimated effects of teen motherhood on schooling vary widely, ranging from no discernible difference to 2.6 fewer years among teen mothers. The magnitude of educational consequences is therefore uncertain, despite voluminous policy and prevention efforts that rest on the assumption of a negative and presumably causal effect. This study adjudicates between two potential sources of inconsistency in the literature—methodological differences or cohort differences—by using a single, high-quality data source: namely, The National Longitudinal Study of Adolescent Health. We replicate analyses across four different statistical strategies: ordinary least squares regression; propensity score matching; and parametric and semiparametric maximum likelihood estimation. Results demonstrate educational consequences of teen childbearing, with estimated effects between 0.7 and 1.9 fewer years of schooling among teen mothers. We select our preferred estimate (0.7), derived from semiparametric maximum likelihood estimation, on the basis of weighing the strengths and limitations of each approach. Based on the range of estimated effects observed in our study, we speculate that variable statistical methods are the likely source of inconsistency in the past. We conclude by discussing implications for future research and policy, and recommend that future studies employ a similar multimethod approach to evaluate findings.


Intracavitary ultrasound (ICARUS): a neuroendoscopic adaptation of intravascular ultrasound for intracerebral hemorrhage evacuation.
Neurosurgeons performing intracerebral hemorrhage evacuation procedures have limited options for monitoring hematoma evacuation and assessing residual hematoma burden intraoperatively. Here, we report the successful neuroendoscopic adaptation of intravascular ultrasound, referred to here as intracavitary ultrasound (ICARUS), in two patients. Pre-evacuation ICARUS demonstrated dense hematomas in both patients. Post-evacuation ICARUS in patient 1 demonstrated significant reduction in clot burden and two focal hyperechoic regions consistent with pockets of hematoma not previously seen with the endoscope or burr hole ultrasound. These areas were directly targeted and resected with the endoscope and suction device. Post-evacuation ICARUS in patient 2 showed significant reduction of hematoma volume without indication of residual blood. ICARUS findings were confirmed on intraoperative DynaCT and postoperative CT 24 hours later. ICARUS is feasibly performed in a hematoma cavity both before and after hematoma aspiration. ICARUS may provide additional information to the operating surgeon and assist in maximizing hematoma removal.


Challenges associated with projecting urbanization-induced heat-related mortality.
Maricopa County, Arizona, anchor to the fastest growing megapolitan area in the United States, is located in a hot desert climate where extreme temperatures are associated with elevated risk of mortality. Continued urbanization in the region will impact atmospheric temperatures and, as a result, potentially affect human health. We aimed to quantify the number of excess deaths attributable to heat in Maricopa County based on three future urbanization and adaptation scenarios and multiple exposure variables. Two scenarios (low and high growth projections) represent the maximum possible uncertainty range associated with urbanization in central Arizona, and a third represents the adaptation of high-albedo cool roof technology. Using a Poisson regression model, we related temperature to mortality using data spanning 1983-2007. Regional climate model simulations based on 2050-projected urbanization scenarios for Maricopa County generated distributions of temperature change, and from these predicted changes future excess heat-related mortality was estimated. Subject to urbanization scenario and exposure variable utilized, projections of heat-related mortality ranged from a decrease of 46 deaths per year (-95%) to an increase of 339 deaths per year (+359%). Projections based on minimum temperature showed the greatest increase for all expansion and adaptation scenarios and were substantially higher than those for daily mean temperature. Projections based on maximum temperature were largely associated with declining mortality. Low-growth and adaptation scenarios led to the smallest increase in predicted heat-related mortality based on mean temperature projections. Use of only one exposure variable to project future heat-related deaths may therefore be misrepresentative in terms of direction of change and magnitude of effects. Because urbanization-induced impacts can vary across the diurnal cycle, projections of heat-related health outcomes that do not consider place-based, time-varying urban heat island effects are neglecting essential elements for policy relevant decision-making.


Our experience with EMLA Cream (for painless venous cannulation in children).
The local analgesic efficacy of EMLA Cream (a eutectic mixture of lidocaine and prilocaine; Astra Pharmaceuticals, Sweden) in reducing the pain at Venous cannulation was investigated in a randommized blind study in 75 children scheduled for elective surgery. In 25 children placebo cream and in 50 children, EMLA cream was applied at the site of venous cannulation 1 hour prior. EMLA Cream was found to be highly effective (84% patients in contrast to 16% patients in placebo group; P less than 0.005). Local side effects of EMLA Cream were negligible.


Axillary lymphoma masquerading as inflammatory breast cancer.
Primary non-Hodgkins lymphoma (NHL) of the breast, and its extranodal spread to the breast resulting from systemic lymphoma, are recognised albeit uncommon conditions. However, lymphoma involving the axilla, presenting with the clinical appearance of inflammatory breast carcinoma (IBC) without infiltration of breast dermal lymphatics has not been reported previously.As highlighted by the two cases presented here, this entity should be considered in the differential diagnosis of patients presenting with clinical IBC. The cases highlight the importance of careful histological analysis to distinguish IBC from NHL, since management strategies and prognosis are quite different.


Numerical simulation of partially coherent broadband optical imaging using the finite-difference time-domain method.
Rigorous numerical modeling of optical systems has attracted interest in diverse research areas ranging from biophotonics to photolithography. We report the full-vector electromagnetic numerical simulation of a broadband optical imaging system with partially coherent and unpolarized illumination. The scattering of light from the sample is calculated using the finite-difference time-domain (FDTD) numerical method. Geometrical optics principles are applied to the scattered light to obtain the intensity distribution at the image plane. Multilayered object spaces are also supported by our algorithm. For the first time, numerical FDTD calculations are directly compared to and shown to agree well with broadband experimental microscopy results.


Time to initiation of modern contraceptive method use after childbirth and its predictors in Southern Ethiopia: a retrospective follow-up study.
Timely initiation of modern contraceptive use is vital to prevent unintended pregnancy and its related morbidities and mortalities. However, there is a scarcity of evidence about the duration of time elapsing from childbirth to initiating modern contraceptive use following childbirth and its associated factors in the study area for evidence-based interventions. Therefore, we aimed to assess the time to initiation of modern contraceptive method use and its predictors in Hossana town, southern Ethiopia. A retrospective follow-up study was conducted at public health facilities in Hosanna town. A total of 503 study participants were included in the study using a systematic random sampling technique. The Box and Whisker plot was used to estimate the time to initiation of modern contraceptive use. A Weibull regression model was applied to identify predictors of time to initiation of modern contraceptive use. Adjusted Hazard Ratio (AHR) with a 95% confidence interval (CI) was used to interpret the strength of the association. The median time to initiation of modern contraceptive use was 6 months, with an interquartile range of 3 months. Husband/partner attending higher education [AHR = 1.64, 95% CI: 1.04, 2.57], women who had parity of more than two [AHR = 1.93, 95% CI: 1.01, 3.67], and women who had communicated with their husband/partner about modern contraceptive methods [AHR = 3.03, 95% CI: 1.41, 6.67] were more likely to initiate modern contraceptive method use within six months after childbirth. In contrast, women with an older age of greater than or equal to 30 years [AHR = 0.32, 95% CI: 0.13, 0.82] and who did not resume sexual intercourse after childbirth [AHR = 0.02, 95% CI: 0.01, 0.03] were less likely to initiate modern contraceptive method use within six months after childbirth. The median time to initiation of modern contraceptive method use after childbirth in the postpartum period was delayed from the World Health Organization recommendation of at most 6 weeks. Emphasis should be given to older women, women with lower parity, and men's participation in contraceptive communication to improve timing for initiation of modern contraceptive use after childbirth and to curb the five-month lag periods.


Extra-oral traction.
In orthodontics, the two main uses of extra-oral forces are in distalizing upper teeth and providing anchorage in the treatment of Class I and Class II malocclusions. This article reviews the theoretical principles behind the use of headgear, outlines the types available, and identifies the most appropriate designs for particular clinical situations. Practical guidelines for managing headgear treatment are also given.


Schistosome antigens in the circulation of chimpanzees infected with Schistosoma japonicum.
Chimpanzees infected with Schistosoma japonicum develop circulating schistosome antigens in their circulation between 6 and 9 weeks post-exposure. The minimum number of circulating antigens ranges from one to three. These antigens also cross-react with an antiserum against S. mansoni adult worms. Clearance of these antigens from the circulation several weeks later typically occurs. Persistence of these antigens could result in the observed renal damage.


Priority given by doctors to continuity of care.
The attitude of 297 general practitioners in the Wessex region to continuity of care was assessed by postal questionnaire; there were 280 complete replies (94% response). One-third of the doctors were asked to define continuity of care; the remaining two-thirds were asked to rank six priorities of practice organization one of which concerned continuity of care. In addition, all doctors were asked whether they used a personal or combined list. A wide variety of definitions for continuity of care was offered but the majority of doctors (61%) specified care by one doctor. Personal continuity was rated highest by significantly more doctors in large practices (list size of 10 000 or more) than in small practices and doctors in large practices were also more likely to use personal lists.


Simple In-House Fabrication of Microwells for Generating Uniform Hepatic Multicellular Cancer Aggregates and Discovering Novel Therapeutics.
Three-dimensional (3D) cell culture models have become powerful tools because they better simulate the in vivo pathophysiological microenvironment than traditional two-dimensional (2D) monolayer cultures. Tumor cells cultured in a 3D system as multicellular cancer aggregates (MCAs) recapitulate several critical in vivo characteristics that enable the study of biological functions and drug discovery. The microwell, in particular, has emerged as a revolutionary technology in the generation of MCAs as it provides geometrically defined microstructures for culturing size-controlled MCAs amenable for various downstream functional assays. This paper presents a simple and economical microwell fabrication methodology that can be conveniently incorporated into a conventional laboratory setting and used for the discovery of therapeutic interventions for liver cancer. The microwells were 400-700 µm in diameter, and hepatic MCAs (Huh-7 cells) were cultured in them for up to 5 days, over which time they grew to 250-520 µm with good viability and shape. The integrability of the microwell fabrication with a high-throughput workflow was demonstrated using a standard 96-well plate for proof-of-concept drug screening. The IC50 of doxorubicin was determined to be 9.3 µM under 2D conditions and 42.8 µM under 3D conditions. The application of photothermal treatment was demonstrated by optimizing concanavalin A-FITC conjugated silica-carbon hollow spheres (SCHSs) at a concentration of 500:200 µg/mL after a 2 h incubation to best bind with MCAs. Based on this concentration, which was appropriate for further photothermal treatment, the relative cell viability was assessed through exposure to a 3 W/cm2 near-infrared laser for 20 min. The relative fluorescence intensity showed an eight-fold reduction in cell viability, confirming the feasibility of using photothermal treatment as a potential therapeutic intervention. The proposed microwell integration is envisioned to serve as a simple in-house technique for the generation of MCAs useful for discovering therapeutic modalities for liver cancer treatment.


Promotional effects of calcination temperature and H2O on the catalytic activity of Al-substituted MnAlO catalysts for low-temperature acetone oxidation.
In order to enhance the role of Al in the materials, Al-substituted MnAlO catalysts were synthesized via the hydrothermal-redox method at different calcination temperatures for acetone oxidation. There were Al-substituted α-MnO2 and amorphous aluminum oxide existed with homogeneous dispersion of elements in the catalysts. The surface property, reaction rate, CO2 yield and water resistance of MnAlO catalysts were greatly affected by calcination temperatures. MnAlO-450 catalyst exhibited the best catalytic performance (acetone conversion of 90% at 165 °C) with CO2 yield higher than 99.7%, which was mainly related to the weaker Mn-O bond strength, lower temperature reducibility and abundant Lewis acid sites. The acetone conversion of MnAlO-450 increased by as much as 16% in the presence of 1 vol% H2O compared to that in the absence of H2O at T50 (the temperature for 50% conversion of acetone). The acceleration consumption of ethanol as the main by-product by H2O improved the catalytic performance. This work would shed light on the Al substitution based catalysts for OVOC oxidation with highly efficient and water resistance.


Gut feelings, intuition, and emotions: an exploratory study.
Investigate whether the gut feelings of one person, as measured with an electrogastrogram (EGG), respond to the emotions of a distant person. In a double blind protocol, EGG activity was recorded in an individual relaxing in a heavily shielded chamber while, at a distance, a second person periodically viewed the live video image of the first person along with stimuli designed to evoke positive, negative, calming, or neutral emotions. Twenty-six (26) pairs of healthy adult volunteers. EGG maximum values recorded while the distant person was exposed to emotional stimuli were compared to similar values recorded during exposure to neutral stimuli. EGG maximums were significantly larger on average when the distant person was experiencing positive (p = 0.006) and negative (p = 0.0009) emotions, as compared to neutral emotions. Nonparametric bootstrap procedures were employed to evaluate these differences, and the results survive correction for multiple analyses. EGG activity increases in response to the emotions of a distant person, beyond the influence of ordinary sensory interactions. Relationships commonly reported between gut feelings and intuitive hunches may share a common, poorly understood, perceptive origin.


Schizophrenia: etiology and pharmacotherapy.
Schizophrenia is one of the major psychiatric disorders. Psychosis, in its narrow definition, is restricted to delusions or hallucinations in the absence of insight into their pathological nature. Impairment in psychosocial function is an essential feature of schizophrenia. Research in the last decade has confirmed that schizophrenia is a brain disorder that cannot be attributed solely to psychosocial factors. It is widely accepted from twin and adoption studies that schizophrenia has a significant genetic component. In addition, it is a general belief that schizophrenia is caused by a biological abnormality, even though all attempts to identify that abnormality have been unsuccessful. A major landmark in the history of the understanding and treatment of schizophrenia was the discovery that dopamine D2-blocking agents can control the hallucinations and delusions of schizophrenic patients. However, clinicians have noticed that classical antipsychotics are generally ineffective against the negative symptoms that are prominent in patients with a chronic course. In this article, we will focus on the etiology and pharmacotherapy of schizophrenia.


Methane-Fueled Syntrophy through Extracellular Electron Transfer: Uncovering the Genomic Traits Conserved within Diverse Bacterial Partners of Anaerobic Methanotrophic Archaea.
The anaerobic oxidation of methane by anaerobic methanotrophic (ANME) archaea in syntrophic partnership with deltaproteobacterial sulfate-reducing bacteria (SRB) is the primary mechanism for methane removal in ocean sediments. The mechanism of their syntrophy has been the subject of much research as traditional intermediate compounds, such as hydrogen and formate, failed to decouple the partners. Recent findings have indicated the potential for extracellular electron transfer from ANME archaea to SRB, though it is unclear how extracellular electrons are integrated into the metabolism of the SRB partner. We used metagenomics to reconstruct eight genomes from the globally distributed SEEP-SRB1 clade of ANME partner bacteria to determine what genomic features are required for syntrophy. The SEEP-SRB1 genomes contain large multiheme cytochromes that were not found in previously described free-living SRB and also lack periplasmic hydrogenases that may prevent an independent lifestyle without an extracellular source of electrons from ANME archaea. Metaproteomics revealed the expression of these cytochromes at in situ methane seep sediments from three sites along the Pacific coast of the United States. Phylogenetic analysis showed that these cytochromes appear to have been horizontally transferred from metal-respiring members of the Deltaproteobacteria such as Geobacter and may allow these syntrophic SRB to accept extracellular electrons in place of other chemical/organic electron donors.IMPORTANCE Some archaea, known as anaerobic methanotrophs, are capable of converting methane into carbon dioxide when they are growing syntopically with sulfate-reducing bacteria. This partnership is the primary mechanism for methane removal in ocean sediments; however, there is still much to learn about how this syntrophy works. Previous studies have failed to identify the metabolic intermediate, such as hydrogen or formate, that is passed between partners. However, recent analysis of methanotrophic archaea has suggested that the syntrophy is formed through direct electron transfer. In this research, we analyzed the genomes of multiple partner bacteria and showed that they also contain the genes necessary to perform extracellular electron transfer, which are absent in related bacteria that do not form syntrophic partnerships with anaerobic methanotrophs. This genomic evidence shows a possible mechanism for direct electron transfer from methanotrophic archaea into the metabolism of the partner bacteria.


[Preliminary report of short-course tuberculosis of the spine].
This study consisted of 149 newly diagnosed cases of tuberculosis of the spine; these were alloeated into the following two regimens: 4SHER/5HER and 4SHER/5H3E3R3. 145 cases have completed their chemotherapy. In patients (2.7%) the allocated regimens was modified because of adverse reactions. All of the patients except 9 cases, operative debridment of the spinal focus was performed within 1-3 months of the start of chemotherapy. Some of the results from this study were encouraging: (1) the therapeutic response was favourable in both regimens, and adverse reactions, mainly hepatic toxicity, were rather low, (2) after a four-month initial intensive phase, both intermittent administration for 5 months or daily treatment for 5 month in the continuation phase were of the same high efficacy at the end of treatments as well as during 4-44 months follow-up.


Review of ethnic disparities in access to renal transplantation.
Renal transplantation is the gold standard treatment for patients with end-stage renal disease and is associated with several advantages over dialysis, including increased quality of life, reduced morbidity and mortality, and lower healthcare costs. Barring the constraints of a limited organ supply, the goals of the patient care should focus on attaining renal transplantation while minimizing, or even eliminating, time spent on dialysis. Disparities in access to renal transplantation between African Americans and Caucasians have been extensively documented, with African Americans having significantly poorer access. There is a growing corpus of literature examining the determinants of reduced access among other racial ethnic minority groups, including Hispanics. These determinants include patient and physician preference, socioeconomic status, insurance type, patient education, and immunologic factors. We review these determinants in access to renal transplantation in the United States among all races and ethnicities.


Diet and the diabetic patient.
At the present time, our knowledge regarding the metabolic consequences of various dietary regimens is incomplete and in need of further research. In addition, the composition of a diet for diabetic persons that will result in the best blood glucose control is uncertain and controversial. Whether dietary changes can significantly delay or prevent the long-term complications of diabetes also is not known. Thus, the insistence that certain foods be avoided by the diabetic person or that a specified diet be adhered to rigidly cannot be defended scientifically. In view of the above limitations in our knowledge, perhaps the best approach should be to allow diabetic persons to select their own diet and daily meal plan, as long as the nutrient content is adequate. A diabetic person being treated with insulin or a hypoglycemic drug will have to comply with a dietary regimen consistent in carbohydrate content and time of meal ingestion. This continues to be of vital importance in the management plan. Nevertheless, an insulin or drug regimen usually can be designed to accommodate the individual's usual eating habits and food preferences. Such a flexible approach to diet management should lead to better patient compliance and overall management of the diabetic patient.


Glycogenic acanthosis presenting as leukoplakia on the tongue.
This report describes a rare case of glycogenic acanthosis (GA) located on the tongue of a 72-year-old man. The patient presented with a white plaque that had been on the right side of the tongue for 5 years. Histologically, the lesion was characterised by thickened squamous epithelium with abundant intracellular glycogen deposits. No epithelial dysplasia was noted. This is the first report of GA involving the tongue. This benign condition should be added to the large number of lesions responsible for leukoplakia in this anatomical location.


Bioelectrical impedance analysis before versus after a hemodialysis session in evaluation of nutritional status.
The objective of our study was to evaluate whether bioelectrical impedance analysis (BIA) performed 15 minutes after a hemodialysis (HD) session is clinically useful in nutrition status assessment in comparison with BIA performed before HD. Because of better reliability, it is postulated in the literature that BIA measurements should be performed 1 to 5 hours after HD sessions. However, the measurements 1 to 5 hours after HD sessions are inconvenient in clinical practice. Furthermore, the currently published BIA reference values for the HD population are based on the measurements taken before HD sessions. The study group consisted of 29 HD patients who were in a stable clinical condition. BIA measurements were performed by means of BIA 101 System (Akern RJL Systems, Florence, Italy). The correlation coefficients were surveyed between traditional indices of nutritional status, such as body mass index (BMI) and plasma concentrations of protein, albumin, and nonprotein nitrogen blood urea nitrogen (BUN) (measured before HD) on one hand, and BIA parameters (taken before and 15 minutes after HD) on the other hand. Statistically significant correlations occurred between such BIA parameters as (1) phase angle and BMI or albumin, or total protein or BUN and (2) body cell mass and BMI or BUN. The differences between correlation coefficients achieved either before or after HD were statistically nonsignificant. BIA measurements in the studied group of patients did correlate with traditional indices of nutritional status. The correlation coefficients were not significantly influenced by the time of performing BIA measurements. The obtained correlations confirm that BIA performed 15 minutes after an HD session may be a useful tool in evaluation of nutritional status of stable HD patients in clinical practice.


Different hunting strategies of generalist predators result in functional differences.
The morphological, physiological, and behavioural traits of organisms are often used as surrogates for actual ecological functions. However, differences in these traits do not necessarily lead to functional differences and/or can be context-dependent. Therefore, it is necessary to explicitly test whether the surrogates have general ecological relevance. To investigate the relationship between the hunting strategies of predators (i.e., how, where, and when they hunt) and their function, we used euryphagous spiders as a model group. We used published data on the diet composition of 76 spider species based on natural prey and laboratory prey acceptance experiments. We computed differences in the position and width of trophic niches among pairs of sympatrically occurring species. Pairs were made at different classification levels, ranked according to the dissimilarity in their hunting strategies: congeners, confamiliars (as phylogenetic proxies for similarity in hunting strategy), species from the same main class of hunting strategy, from the same supra-class, and from different supra-classes. As for niche position computed from the natural prey analyses, species from the same class differed less than species from different classes. A similar pattern was obtained from the laboratory studies, but the congeners differed less than the species from the same classes. Niche widths were most similar among congeners and dissimilar among species from different supra-classes. Functional differences among euryphagous spiders increased continuously with increasing difference in their hunting strategy. The relative frequency of hunting strategies within spider assemblages can, therefore, influence the food webs through hunting strategy-specific predator-prey interactions.


Bronchoalveolar lavage does not alter airway responsiveness in asthmatic subjects.
Bronchoalveolar lavage (BAL) during fiberoptic bronchoscopy is being used increasingly for the investigation of asthma. Airway responsiveness to methacholine is a sensitive indicator of the presence and severity of asthma. Therefore, we studied the effect of BAL on methacholine airway responsiveness in stable asthmatics. Geometric mean methacholine PC20 was 1.34 mg/ml before and 1.80 mg/ml after BAL (p = 0.26) in asthmatics. Immediate symptoms of airway narrowing after BAL occurred only in the 3 asthmatics with moderate to severe hyperresponsiveness. These symptoms were rapidly relieved by inhaled bronchodilator. There was no relationship between the occurrence of symptoms and the amount of topical lidocaine used for local anaesthesia or the volume of lavage fluid returned. The absence of an effect of BAL on airway responsiveness supports the safety of this procedure in the controlled asthmatic patient with near normal FEV1, irrespective of the level of baseline airway responsiveness.


Fat & fabulous: bifunctional lipids in the spotlight.
Understanding biological processes at the mechanistic level requires a systematic charting of the physical and functional links between all cellular components. While protein-protein and protein-nucleic acid networks have been subject to many global surveys, other critical cellular components such as membrane lipids have rarely been studied in large-scale interaction screens. Here, we review the development of photoactivatable and clickable lipid analogues-so-called bifunctional lipids-as novel chemical tools that enable a global profiling of lipid-protein interactions in biological membranes. Recent studies indicate that bifunctional lipids hold great promise in systematic efforts to dissect the elaborate crosstalk between proteins and lipids in live cells and organisms. This article is part of a Special Issue entitled Tools to study lipid functions.


Update on MR imaging of the pulmonary vasculature.
Magnetic resonance imaging (MRI) plays an increasingly important role in the non-invasive evaluation of the pulmonary vasculature. MR angiographic (MRA) techniques provide morphological information, while MR perfusion techniques provide functional information of the pulmonary vasculature. Contrast-enhanced MRA can be performed at high spatial resolution using 3D T1-weighted spoiled gradient echo sequence or at high temporal resolution using time-resolved techniques. Non-contrast MRA can be performed using 3D steady state free precession, double inversion fast spin echo, time of flight or phase contrast sequences. MR perfusion can be done using dynamic contrast-enhanced technique or using non-contrast techniques such as arterial spin labelling and time-resolved imaging of lungs during free breathing with Fourier decomposition analysis. MRI is used in the evaluation of acute and chronic pulmonary embolism, pulmonary hypertension and other vascular abnormalities, congenital anomalies and neoplasms. In this article, we review the different MR techniques used in the evaluation of pulmonary vasculature and its clinical applications.


A phase II study of intraperitoneal radioimmunotherapy with iodine-131-labeled monoclonal antibody OC-125 in patients with residual ovarian carcinoma.
Standard treatment of advanced ovarian cancer is a combination of surgery and chemotherapy. Additional therapies using the i.p. route are considered as a potential means of improving the locoregional control rate. This Phase II study evaluated the efficacy of i.p. radioimmunotherapy (RIT) in patients with minimal residual ovarian adenocarcinoma after primary treatment with surgery and chemotherapy. Between February 1995 and March 1996, six patients with residual macroscopic (<5 mm) or microscopic disease as demonstrated by laparotomy and multiple biopsies received i.p. RIT. All had initial stage III epithelial carcinoma and were treated with debulking surgery and one line (four patients) or two lines (two patients) of chemotherapy. RIT was performed with 60 mg of OC 125 F(ab')2 monoclonal antibody labeled with 4.44 GBq (120 mCi) of 131I injected 5-10 days after the surgical procedure. Systematic laparoscopy or laparotomy with multiple biopsies performed 3 months after RIT in five patients (clinical progression was seen in one patient) showed no change in three patients and progression in two patients. Toxicity was mainly hematological, with grade III neutropenia and thrombocytopenia in two patients. Human antimouse antibody production was demonstrated in all six patients. This study showed little therapeutic benefit from i.p. RIT in patients with residual ovarian carcinoma.


Gastric sarcoid: unusual cause of upper gastrointestinal hemorrhage.
An unusual presentation of sarcoidosis was noted in a patient who developed severe upper gastrointestinal hemorrhage. The bleeding was attributed to a sarcoid ulcer of the stomach. Serial gastroscopic studies demonstrated complete resolution of the ulcer within five months on conventional antacid therapy. The only residual lesions were gastric mucosal nodularities and moderate hyperemia with granulomas on biopsy. Sarcoidosis was diagnosed by positive Kveim test and abnormal diffusing lung capacity despite a normal chest roentgenogram.


Scattering-type Scanning Near-Field Optical Microscopy of Polymer-Coated Gold Nanoparticles.
Scattering-type scanning near-field optical microscopy (s-SNOM) has emerged over the past years as a powerful characterization tool that can probe important properties of advanced materials and biological samples in a label-free manner, with spatial resolutions lying in the nanoscale realm. In this work, we explore such usefulness in relationship with an interesting class of materials: polymer-coated gold nanoparticles (NPs). As thoroughly discussed in recent works, the interplay between the Au core and the polymeric shell has been found to be important in many applications devoted to biomedicine. We investigate bare Au NPs next to polystyrenesulfonate (PSS) and poly(diallyldimethylammonium chloride) (PDDA) coated ones under 532 nm laser excitation, an wavelength matching the surface plasmon band of the custom-synthesized nanoparticles. We observe consistent s-SNOM phase signals in the case of bare and shallow-coated Au NPs, whereas for thicker shell instances, these signals fade. For all investigated samples, the s-SNOM amplitude signals were found to be very weak, which may be related to reduced scattering efficiency due to absorption of the incident beam. We consider these observations important, as they may facilitate studies and applications in nanomedicine and nanotechnology where the precise positioning of polymer-coated Au NPs with nanoscale resolution is needed besides their dielectric function and related intrinsic optical properties, which are also quantitatively available with s-SNOM.


Management of posterior fossa gliomas in children.
Brain tumours form the most common type of solid tumour in children and more that 50% of these are infratentorial. Cerebellar astrocytomas and brain stem gliomas are the commonest posterior fossa glial tumours in children. Cerebellar astrocytomas represent up to 10% of all primary brain tumours and up to 25% of posterior fossa tumors in children, with Low grade gliomas forming the commonest of the cerebellar gliomas. They commonly present with symptoms and signs of raised intracranial pressure due to obstructive hydrocephalus. Radiologically they may be solid or cystic with or without a mural nodule. Surgical excision is the mainstay of treatment and forms the most consistent factor influencing progression free and long term survival. While majority of the tumours are pilocytic astrocytomas, they may also be fibrillary astrocytomas or even high grade tumours. Tumour histology does not appear to be an independent factor in the prognosis of these children, and therefore no palliative treatment after surgery is advocated. Brain stem gliomas account for approximately 10% of all pediatric brain tumours. Cranial nerve signs, ataxia and cerebellar signs with or without symptoms and signs of raised intracranial pressure are classically described symptoms and signs. Radiographic findings and clinical correlates can be used to categorize brain stem tumours into four types: diffuse, focal, exophytic and cervicomedullary. Histologically most brain stem gliomas are fibrillary astrocytomas. Diffuse brain stem gliomas are the most commonly seen tumour in the brain stem. These lesions are malignant high grade fibrillary astrocytomas. Focal tumours of the brain stem are demarcated lesions generally less than 2 cms in size, without associated edema. Most commonly seen in the midbrain or medulla, they form a heterogeneous pathological group, showing indolent growth except when the lesion is a PNET. Dorsally exophytic tumours lie in the fourth ventricle, while cervicomedullary lesions are similar to spinal intramedullary tumours. Expanding lesions are the only lesions amenable for excision while infiltrative and ventral lesions are not.


Initial Validation of the 12-Item Tampa Scale of Kinesiophobia in a Retrospective Sample of Adults with Chronic Headache.
An area of emerging interest in chronic pain populations concerns fear of pain and associated fear of movement (kinesiophobia)-a cognitive appraisal pattern that is well-validated in non-headache chronic pain. However, there is limited research on whether this construct can be measured in a similar manner in headache populations. The current project details a confirmatory factor analysis of the 12-Item Tampa Scale of Kinesiophobia (TSK-12) using a clinical dataset from 210 adults with diverse headache diagnoses presenting for care at a multidisciplinary pain clinic. One item (concerning an "accident" that initiated the pain condition) was excluded from analysis. Results of the confirmatory factor analysis for the remaining 12 items indicated adequate model fit for the previously established 2-factor structure (activity avoidance and bodily harm/somatic focus subscales). In line with previous literature, total TSK-12 scores showed moderate correlations with pain severity, pain-related interference, positive and negative affect, depressive and anxious symptoms, and pain catastrophizing. The current study is the first to examine the factor structure of the TSK-12 in an adult headache population. The results support the relevance of pain-related fear to the functional and psychosocial status of adults with chronic headache, though model fit of the TSK-12 could be characterized as adequate rather than optimal. Limitations of the study include heterogeneity in headache diagnosis and rates of comorbid non-headache chronic pain in the sample. Future studies should replicate these findings in more homogenous headache groups (e.g., chronic migraine) and examine associations with behavioral indices and treatment response.


Transition-metal-catalyzed site-selective C7-functionalization of indoles: advancement and future prospects.
C7-Decorated indoles are important structural motifs present in a plethora of bioactive and pharmaceutical compounds. Early stage developments for C7 modifications were realized through directed metallation (DOM) and subsequent quenching with suitable electrophiles or by halogenation with Cu(ii) halides. Direct C-7 functionalization of indoles is comparatively difficult compared to functionalization at C-2 and C-3 positions owing to the inherent reactivity of the pyrrole-type ring. However, recently transition-metal-catalyzed auxiliary assisted site-selective C-7 functionalization of indoles has emerged as an elegant synthetic tool for carbon-carbon and carbon-heteroatom bond formation to diversify the indoles. This article covers the advancement, application and mechanistic underpinnings of the evolved transformations of the otherwise inert C7-H bond up to October 2018.


Aryl hydrocarbon receptor polymorphisms and dioxin resistance in Atlantic killifish (Fundulus heteroclitus).
The aryl hydrocarbon receptor (AHR) gene encodes a ligand-activated transcription factor through which planar halogenated aromatic hydrocarbons (HAHs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as well as polynuclear aromatic hydrocarbons (PAHs) cause altered gene expression and toxicity. To understand the role of AHR genetic variability in differential sensitivity to HAHs and PAHs, we are currently studying a population of the teleost Fundulus heteroclitus (Atlantic killifish) that has evolved genetic resistance to the toxic and biochemical effects of these compounds. Here, we report that the killifish AHR1 locus is highly polymorphic and that the frequencies of the major allele types differ between dioxin-sensitive and dioxin-resistant populations. Twenty-five single nucleotide polymorphisms (SNPs), nine of which are non-synonymous, were identified in the AHR1 coding sequence. Seven identified alleles were assigned to three groups, designated AHR1*1, AHR1*2 and AHR1*3. AHR1*1 alleles were under-represented in a population of dioxin- and polychlorinated biphenyl (PCB)-resistant fish from a PCB-contaminated Superfund site (New Bedford Harbor, Massachusetts, USA) compared to dioxin-sensitive fish from a less contaminated reference site (Scorton Creek, Massachusetts, USA). To determine the possible role of these AHR1 variants in differential HAH sensitivity, we expressed representative variant proteins from the two most divergent allelic groups (AHR1*1 and AHR1*3) by in-vitro transcription and translation and assessed their functional properties. AHR1*1A and AHR1*3A proteins displayed similar binding capacities and affinities for [H]TCDD. In transient transfection assays using mammalian cells, AHR1*1A and AHR1*3A exhibited similar abilities to support TCDD-dependent transactivation of a luciferase reporter gene under control of AHR-responsive enhancer elements. We discuss the possibility of other functional differences in AHR1 variants or their interaction with other killifish loci (AHR2, AHRR) that may contribute to differences in dioxin sensitivity.


[Obesity, inflammation and insulin resistance: which role for adipokines].
Adipose tissue is now recognized as an endocrine organ involved in regulating physiologic and pathologic processes including inflammation. It synthesizes and secretes hormones such as leptin and adiponectin. It can secrete other products namely adipokines including cytokines and chemokines. The release of adipokines by either adipocytes or adipose tissue-infiltrated macrophages leads to a chronic sub-inflammatory state that likely plays a major role in cardiovascular complications linked to obesity and insulin resistance.


Identification of a hyaluronic acid-binding protein that interferes with the preparation of high-buoyant-density proteoglycan aggregates from adult human articular cartilage.
Adult human articular cartilage contains a hyaluronic acid-binding protein of Mr 60 000-75 000, which contains disulphide bonds essential for this interaction. The molecule can compete with proteoglycan subunits for binding sites on hyaluronic acid, and can also displace proteoglycan subunits from hyaluronic acid if their interaction is not stabilized by the presence of link proteins. The abundance of this protein in the adult accounts for the reported inability to prepare high-buoyant-density proteoglycan aggregates from extracts of adult human cartilage [Roughley, White, Poole & Mort (1984) Biochem. J. 221, 637-644], whereas the deficiency of the protein in newborn human cartilage allows the normal recovery of proteoglycan aggregates from this tissue. The protein shares many common features with a hyaluronic acid-binding region derived by proteolytic treatment of a proteoglycan aggregate preparation, and this may also represent its origin in the cartilage, with its production increasing during tissue maturation.


Anti-electrostatic cation⋯π-hole and cation⋯lp-hole interactions are stabilized via collective interactions.
Collective interactions are a novel type of bond between metals and AX3 fragments with an electropositive central atom, A, and electronegative X substituents. Here, using electrostatic potential maps and state-of-the-art bonding analysis tools we have shown that collective interactions are anti-electrostatic cation⋯π-Hole or cation⋯lp-Hole interactions.


A new methodological approach in nursing research: an actor, partner, and interaction effect model for family outcomes.
Methodological and statistical challenges have been identified in family research when the parental dyad is under study. The purposes of this article are to review the literature on methodological and statistical procedures in research on families, and to introduce an analysis technique that is new to the nursing literature, the actor-partner interdependence model (APIM). The use and interpretation of the APIM method is illustrated through an example of families of young children with asthma. In the APIM an actor effect is the impact a person has on his or her own outcome, whereas a partner effect is the impact a member of a dyad has on his or her partner's outcome. The main findings from the data example indicate that family adaptation is influenced by the actor effect of resiliency factors (sense of coherence and family hardiness), the partner effect of caregiving demands, as well as by both the actor and partner effects of family demands. The APIM method gives new insight into how parental data can be analyzed by taking both the individual and the partner contribution into account when studying family phenomena. Knowing how outcomes may be influenced not only by individuals (via an actor effect) but also by their partners (through a partner effect) enriches our understanding of how families function.


Incense, sparklers and cigarettes are significant contributors to indoor benzene and particle levels.
The increased use of incense, magic candles and other flameless products often produces indoor pollutants that may represent a health risk for humans. Today, in fact, incense and air fresheners are used inside homes as well as in public places including stores, shopping malls and places of worship. As a source of indoor contamination, the impact of smoke, incense and sparklers on human health cannot be ignored. In the present work, we report the results of an emission study regarding particles (PM10 and particle number concentration, PNC) and benzene, produced by various incense sticks and sparklers. The results obtained for benzene, PM10 and PNC, showed a strong negative influence on air quality when these products were used indoors. Various incense sticks gave completely different benzene results: from a small increase of the benzene concentration in the air, just slightly above the background levels of ambient air, to very high concentrations, of more than 200 µg/m of benzene in the test room after the incense sticks had been tested.


Older firefighters are susceptible to age-related impairments in heat dissipation.
The aging-induced reduction in whole-body heat loss (HL) capacity generates concerns regarding the continued participation of older workers in occupations such as firefighting. We compared HL and change in body heat storage (S) during intermittent exercise in warm/dry and warm/humid conditions among older male firefighters (OLDER, n = 9, age = 54.7 ± 2.1 yr), older (age-matched) nonfirefighters (NON-FF, n = 9, age = 52.8 ± 1.2 yr), and young firefighters (YOUNG, n = 6, age = 26.7 ± 0.8 yr). We measured evaporative heat loss and dry heat exchange via the Snellen whole-body direct calorimeter while participants performed four 15-min bouts of cycling at 400 W of metabolic heat production separated by 15-min recovery periods in warm/dry (35 °C, 20% relative humidity) and warm/humid (35 °C, 60% relative humidity) conditions. We found no differences (P > 0.05) in HL or cumulative S (ΔS) between OLDER and NON-FF in the warm/dry (ΔS: OLDER = 233 ± 26 kJ, NON-FF = 270 ± 29 kJ) or warm/humid (ΔS: OLDER = 548 ± 24 kJ, NON-FF = 504 ± 47 kJ) conditions. The OLDER and NON-FF had lower HL than the YOUNG during exercise in both environmental conditions (P < 0.05). The OLDER stored 40% (P > 0.05) and 46% (P = 0.004) more heat than YOUNG in the warm/dry and warm/humid conditions, respectively. The NON-FF stored 63% (P = 0.016) and 34% (P = 0.025) more heat than the YOUNG in the dry and humid conditions, respectively. Older firefighters and age-matched nonfirefighters demonstrate similar HL and S during work in the heat. Moreover, HL is significantly reduced in older compared to younger firefighters during exercise in both warm/dry and warm/humid conditions. Consequently, older firefighters may be more susceptible to thermal injury while on duty than their younger counterparts.


Administration of Corticosteroids, Ascorbic Acid, and Thiamine Improves Oxygenation after Thoracoscopic Esophagectomy.
The activity of corticosteroids, ascorbic acid, and thiamine against oxidative and inflammatory responses was evaluated in patients undergoing esophagectomy. This study was undertaken to investigate the effect of this combined therapy on lung dysfunction following esophagectomy. In this retrospective before-after study, we compared the clinical course of consecutive patients undergoing thoracoscopic esophagectomy treated with the combination of corticosteroids, ascorbic acid, and thiamine between June and December 2018 with a control group treated with corticosteroids alone between January 2016 and May 2018. Outcomes included oxygenation (arterial partial pressure of oxygen (PaO2)/fractional concentration of inspired oxygen (FiO2) ratios), duration of mechanical ventilation and intensive care unit (ICU) length of stay. In all, 17 patients were included in this study (6 in the combination therapy group and 11 patients in the control group). Mean PaO2/FiO2 ratios in the combined therapy group were significantly higher than in the control group at all points during the observation period (p <0.001). In the combined therapy group, the duration of mechanical ventilation and ICU stay were significantly shorter (p <0.001, p = 0.009). This study suggests that combined therapy including corticosteroids, ascorbic acid, and thiamine may be effective in improving oxygenation after esophagectomy. Additional studies are required to confirm these preliminary findings.


Comparing the effects of problem-based and conventional curricula in an international sample.
In this article, the authors review 15 studies that compare various educational outcomes of problem-based, community-oriented medical curricula with those of conventional programs. The data suggest that problem-based curricula provide a student-centered learning environment and encourage an inquisitive style of learning in their students as opposed to the rote memorization and short-term learning strategies induced by conventional medical education. In addition, community-oriented schools appear to influence the career preferences of their students. The few data available show that significantly larger proportions of graduates from these schools seek careers in primary care. Some of the studies reviewed suggest that students in conventional programs perform somewhat better on traditional measures of academic achievement than do students in problem-based curricula. However, these differences, if any, tend to be very small. Data with respect to performance on instruments measuring clinical competence are inconclusive. Finally, the authors discuss the difficulties involved in carrying out comparative research at the curriculum level.


Changes in DNA methylation persist over time in males with severe alcohol use disorder-A longitudinal follow-up study.
Treatment strategies for alcohol use disorder (AUD) aim for abstinence or harm reduction. While deranged biochemical parameters reverse with alcohol abstinence, whether molecular changes at the epigenetic level reverse is not clearly understood. We investigated whether the reduction from high alcohol use reflects DNA methylation at the gene-specific and global level. In subjects seeking treatment for severe AUD, we assessed gene-specific (aldehyde dehydrogenase [ALDH2]/methylene tetrahydrofolate reductase [MTHFR]) and global (long interspersed elements [LINE-1]) methylation across three-time points (baseline, after detoxification and at an early remission period of 3 months), in peripheral blood leukocytes. We observed that both gene-specific and global DNA methylation did not change over time, irrespective of the drinking status at 3 months (52% abstained from alcohol). Further, we also compared DNA methylation in AUD subjects with healthy controls. At baseline, there was a significantly higher gene-specific DNA methylation (ALDH2: p < .001 and MTHFR: p = .001) and a significant lower global methylation (LINE-1: p = .014) in AUD as compared to controls. Our results suggest that epigenetic changes at the DNA methylation level associated with severe AUD persist for at least 3 months of treatment.


[The influence of leu-enkephalin on the bile secretion function in the rat liver during pharmacological modulation of the autonomous nervous system].
In acute experiments on rats the influence of ley-enkephalin (1 mkg/100 g) on liver bile secretion function and changes of organic contents of bile were studied. For studying the influence of opioid peptide under conditions of altered state of adreno- and cholinoreceptors, the antagonists of alpha- and beta-adrenoreceptors phentolamin (25 mkg/100 g) and obzidan (5 mkg/100 g), and the blocker of M-holinoreceptors atropine (2 mkg/100 g) were used. The pharmacological modulation of autonomous nervous systems alters the effects of ley-enkephalin on cholesecretions. Opioid peptide in the presence of antagonists of alpha-adrenoreceptors stimulates the processes of bile acids conjugation, in the presence of antagonists of beta-adrenoreceptors it cancels the effects of ley-enkephalin. The antagonists M-holinoreceptors reverse the effects of ley-enkephalin for the opposite ones: the synthesis and transport of free bile asides and cholisterine are suppressed.


Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four Vlambda6 proteins.
Primary (AL) amyloidosis results from the pathologic deposition of monoclonal light chains as amyloid fibrils. Studies of recombinant-derived variable region (VL) fragments of these proteins have shown an inverse relationship between thermodynamic stability and fibrillogenic potential. Further, ionic interactions within the VL domain were predicted to influence the kinetics of light chain fibrillogenicity, as evidenced from our analyses of a relatively stable Vlambda6 protein (Jto) with a long range electrostatic interaction between Asp and Arg side chains at position 29 and 68, respectively, and an unstable, highly fibrillogenic Vlambda6 protein (Wil) that had neutral amino acids at these locations. To test this hypothesis, we have generated two Jto-related mutants designed to disrupt the interaction between Asp 29 and Arg 68 (JtoD29A and JtoR68S). Although the thermodynamic stabilities of unfolding for these two molecules were identical, they exhibited very different kinetics of fibril formation: the rate of JtoD29A fibrillogenesis was slow and comparable to the parent molecule, whereas that of JtoR68S was significantly faster. High-resolution X-ray diffraction analyses of crystals prepared from the two mutants having the same space group and unit cell dimensions revealed no significant main-chain conformational changes. However, several notable side-chain alterations were observed in JtoR68S, as compared with JtoD29A, that resulted in the solvent exposure of a greater hydrophobic surface and modifications in the electrostatic potential surface. We posit that these differences contributed to the enhanced fibrillogenic potential of the Arg 68 mutant, since both Jto mutants lacked the intrachain ionic interaction and were equivalently unstable. The information gleaned from our studies has provided insight into structural parameters that in addition to overall thermodynamic stability, contribute to the fibril forming propensity of immunoglobulin light chains.


Off-resonance angiography: a new method to depict vessels--phantom and rabbit studies.
To evaluate the utility of inversion recovery with on-resonant water suppression (IRON) in combination with injection of the long-circulating monocrystalline iron oxide nanoparticle (MION)-47 for contrast material-enhanced magnetic resonance (MR) angiography. Experiments were approved by the institutional animal care committee. Eleven rabbits were imaged at baseline before injection of a contrast agent and then serially 5-30 minutes, 2 hours, 1 day, and 3 days after a single intravenous bolus injection of 80 micromol of MION-47 per kilogram of body weight (n = 6) or 250 micromol/kg MION-47 (n = 5). Conventional T1-weighted MR angiography and IRON MR angiography were performed on a clinical 3.0-T imager. Signal-to-noise and contrast-to-noise ratios were measured in the aorta of rabbits in vivo. Venous blood was obtained from the rabbits before and after MION-47 injection for use in phantom studies. In vitro blood that contained MION-47 appeared signal attenuated on T1-weighted angiograms, while characteristic signal-enhanced dipolar fields were observed on IRON angiograms. In vivo, the vessel lumen was signal attenuated on T1-weighted MR angiograms after MION-47 injection, while IRON supported high intravascular contrast by simultaneously providing positive signal within the vessels and suppressing background tissue (mean contrast-to-noise ratio, 61.9 +/- 12.4 [standard deviation] after injection vs 1.1 +/- 0.4 at baseline, P < .001). Contrast-to-noise ratio was higher on IRON MR angiograms than on conventional T1-weighted MR angiograms (9.0 +/- 2.5, P < .001 vs IRON MR angiography) and persisted up to 24 hours after MION-47 injection (76.2 +/- 15.9, P < .001 vs baseline). IRON MR angiography in conjunction with superparamagnetic nanoparticle administration provides high intravascular contrast over a long time and without the need for image subtraction.


Sagittal alignment of the lumbar spine in a Turkish population.
To understand the normal lumbar spine in the sagittal plane, and the range of lumbar lordosis. This study was carried out in the Department of Anatomy, School of Medicine, Duzce University, Duzce, Turkey in the year 2005. We retrospectively reviewed T1-weighed sagittal spin-echo MRIs of the lumbar spine in 413 individuals (188 male, 225 female) aged between 13-82 years, and evaluated the angle of lumbar lordosis (ALL), sacrohorizontal angle (SHA), and lumbosacral angle (LSA). The ALL and SHA were significantly greater in females than in males (p<0.05). Weak, but significant correlations were detected between age and ALL, SHA, and LSA for females (p<0.05). The LSA was significantly greater for individuals over 41 years (p<0.05) when the entire study group was considered, and it was also significantly greater for individuals over 51 years in females (p<0.05). The LSA was significantly greater in the 7th decade than in the 3rd decade (p<0.05). The results of this study provide insight into the sagittal alignment of the lumbar region for a Turkish population, and can serve as a reference for further clinical studies to improve the planning of spinal surgery.


Metal levels in the liver, muscle, gill, intestine, and gonad of Lake Van fish (Chalcalburnus tarichi) with abnormal gonad.
Recently, an increasing number of studies have shown that Lake Van--the biggest soda lake in the world--is polluted due to an increasing population. Studies have shown abnormalities in the Lake Van fish (Chalcalburnus tarichi), the sole fish species that inhabits the lake. Unlike the vitellogenic and mature oocytes in normal gonads, abnormal gonads show large amounts of connective tissue and young oocytes. In this study, metal levels (nickel [Ni], copper [Cu], cobalt [Co], iron [Fe], zinc [Zn], cadmium [Cd], lead [Pb], and manganese [Mn]) in the muscle, liver, gill, intestine, and gonad of Lake Van fish with normal and abnormal gonads were assessed. Further, the metal contents in the wastewater from the wastewater treatment facility situated near Lake Van in Van City were assessed. All the metal levels, except that of Zn, were high in the Lake Van environment (P<0.05). The highest metal content in the tissues was for Fe, while the lowest level was for Co. The Pb level was found to be very high in both fish groups. Cd was not found in the tissues of both fish groups. The levels of Fe, Cu, Pb, and Mn were not significant in the tissues of both normal and abnormal fish groups. Zn level was significantly high in the livers and gonads of fish with abnormal gonads, and Co level was significantly high only in the livers (P<0.05). Consequently, high levels of Zn in the liver and gonads and high levels of Co in the liver may be factors causing the abnormal gonads in the Lake Van fish.


Thoracoscopy in the diagnosis and treatment of thoracoabdominal stab injuries.
Occult diaphragmatic injuries are associated with significant mortality, if the diagnosis is delayed. We report our experience in diagnostic and therapeutic thoracoscopy in a selected group of patients with stab wounds of thoracoabdominal region. The patients who underwent thoracoscopic management of thoracoabdominal stab injuries between June 2001-December 2005 were included into the study. The data were retrospectively analyzed. Ninety-three patients with abdominal and thoracoabdominal stab wounds underwent videoendoscopic management. Among them, eleven selected patients with thoracoabdominal stab injuries were managed by thoracoscopy. The procedures were performed under general (n=10) or local anesthesia (n=1). Diaphragmatic injuries were repaired by intracorporeal sutures in three cases and bleeding was controlled in another two cases by electrocautery coagulation. The procedures were simply diagnostic in six patients. The mean operating time and hospital stay were 35 minutes and 3.5 days respectively. There was neither intraoperative or early postoperative complication, nor mortality. Thoracoscopy is a safe and efficient tool in the diagnosis and treatment of diaphragmatic stab injuries.


Neural progenitor cells transplanted into the uninjured brain undergo targeted migration after stroke onset.
Endogenous neural stem cells normally reside in their niche, the subventricular zone, in the uninjured rodent brain. Upon stroke, these cells become more proliferative and migrate away from the subventricular zone into the surrounding parenchyma. It is not known whether this stroke-induced behavior is due to changes in the niche or introduction of attractive cues in the infarct zone, or both. A related question is how transplanted neural stem cells respond to subsequent insults, including whether exogenous stem cells have the plasticity to respond to subsequent injuries after engraftment. We addressed this issue by transplanting neural progenitor cells (NPCs) into the uninjured brain and then subjecting the animal to stroke. We were able to follow the transplanted NPCs in vivo by labeling them with superparamagnetic iron oxide particles and imaging them via high-resolution magnetic resonance imaging (MRI) during engraftment and subsequent to stroke. We find that transplanted NPCs that are latent can be activated in response to stroke and exhibit directional migration into the parenchyma, similar to endogenous neural NPCs, without a niche environment.


[Chronic instability and fixed dislocation of the shoulder].
Chronic instabilities may be traumatic or atraumatic, unidirectional or multidirectional. It is important to distinguish between symptomatic instability and asymptomatic hyperlaxity. Posttraumatic, unidirectional anterior instability without hyperlaxity is the most common form of instability. The patient presents apprehension, the sulcus-sign is negative. Posttraumatic, unidirectional instability with hyperlaxity is due to an adequate trauma, both the apprehension test and the sulcus sign are positive. The treatment of traumatic instability is surgically with respect to the underlying pathology of the ligaments, labrum and capsule. The "golden standard" is the reconstruction of the capsulolabral complex. The repetitive microtraumatic instability is seen in overhead athletes with elongation or disruption of the capsule. The typical patient presents with painful subluxations, the instability may be unidirectional or multidirectional. The treatment is conservatively. Multidirectional instability with hyperlaxity is defined as symptomatic instability in at least two directions of instability with multidimensional hyperlaxity. These individuals will also report on pain rather than instability. The apprehension test is positive in at least two directions, the sulcus sign is positive as well. The patients are responsive to an intensive rehabilitation program for 6-12 months. Open capsular shift or thermal capsular shrinkage may be successful after failed conservative treatment. Multidirectional instability without hyperlaxity is extremely rare and is due to more than one adequate trauma with traumatic instability in different directions. The apprehension test is positive, the sulcus sign negative. The treatment is surgically. The fixed dislocation is posterior in most of the cases and frequently being missed primarily. It is seen in unconscious, multiple-injured patients or after grand mal or electroshock seizures. The reduction may be either closed or open depending on the interval between trauma and diagnosis. Voluntary instability represents a subset of individuals with atraumatic instability. The patients can dislocate and reduce their shoulder, have no pain and do not develop arthritis. They do not require a special therapy.


Chemoattractant factors in breast milk from allergic and nonallergic mothers.
The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. Recently, we showed that allergic mothers had higher concentrations of IL-4 and lower concentrations of ovalbumin-specific IgA in their breast milk than nonallergic mothers. The aim of this study was to investigate the concentrations of chemokines and cytokines that are chemotactic to cells involved in allergic reactions in breast milk from allergic and nonallergic mothers. Cytokine and chemokine concentrations were determined with ELISA in colostrum and mature milk samples from 23 mothers with and 25 mothers without atopic symptoms. IL-8 was detected in all milk samples. RANTES (regulated on activation, normal T cell expressed and secreted), eotaxin, and IL-16 were detected in 50%, 76%, and 48%, respectively, in colostrum and less commonly in mature milk. Macrophage inflammatory protein-1alpha, however, could not be detected in any of the samples. The concentrations of IL-8 and RANTES were higher in breast milk from allergic, compared with nonallergic, mothers. In conclusion, the presence of chemoattractant factors in breast milk may be responsible for the traffic of leukocytes from the maternal circulation to the breast milk. The higher concentrations of RANTES and IL-8 in allergic mothers may partly explain the controversy regarding the protective effect of breast-feeding against the development of allergy by stronger chemotaxis and activation of cells involved in allergic diseases, and possibly by elevated IgE production.


Effect of CO(2)-Milliwatt laser on peripheral nerves: part II. A histological and functional study.
In order to further explore the role of laser for microneural repair, the early and late effects of CO(2) laser irradiation on intact rat sciatic nerves were investigated. A total of 48 rat sciatic nerves were exposed to 100-mW laser power with a pulse duration of 1.0 s and a spot size of 320 microm. In one-half of the nerves, albumin solder was applied to the nerve followed by laser irradiation. The results were evaluated up to 94 days after surgery with functional toe-spreading test, and light and transmission electron microscopy. Irradiation of the nerve resulted in almost no deficit in the motor function. A subperineurial degeneration of myelinated and unmyelinated axons is observed in the first 2 weeks after laser irradiation, while the central part of the nerve remains undamaged. The degeneration is followed by axonal regeneration with subsequent maturation of nerve fibres in time. No excessive intraneural or extraneural scarring was seen. In the soldered nerves, the solder elicits an inflammatory reaction upon the epineurium in the first week after irradiation. By week 1, the solder is completely absorbed. After 2 weeks, the inflammatory reaction ceases and by week 4, no residual reaction is seen. At 12 weeks, only minimally disarranged epineurium is seen with otherwise normal neural architecture. In conclusion, CO(2) laser irradiation at 100 mW with pulses of 1.0 s has no long term negative effects on nerve function and morphology. Therefore, these laser settings can be safely applied for laser-assisted nerve repair.


Enhancement of natural cytotoxicity by beta-endorphin.
The role of enkephalins, beta-endorphin, or other neuropeptides produced by the nervous system in the alteration of immune responsiveness is generally unknown. The present studies were undertaken to investigate the role of these neuropeptides in the modulation of human spontaneous cytotoxicity induced by natural killer (NK) cells. Natural cytotoxicity was measured by using a standard 51Cr release assay with radiolabeled K562 cells. NK activity was significantly enhanced by both beta-endorphin (30.5 +/- 11.5%, M +/- SE, relative enhancement at 50:1, effector:target (E:T) ratio, 10(-14)M beta-endorphin) and methionine-enkephalin (met-enkephalin) (27.4 +/- 9.7% relative enhancement at 10(-9)M). The magnitude of relative enhancement significantly correlated with increasing concentrations of beta-endorphin. Leucine-enkephalin, alpha-endorphin, and morphine did not augment NK activity. The enhancement of NK activity with beta-endorphin increased at all E:T ratios tested. Naloxone inhibited the augmentation of NK activity produced by beta-endorphin and met-enkephalin. By using a combination of a standard 51Cr release and soft agarose single cell analysis assays, beta-endorphin increased both the number of E:T cell conjugates and the number of active killer cells among target-binding cells. The maximal effector cell recycling capacity was increased by 170%. These studies provide new insight into the mechanisms by which neuropeptides produced by the nervous system can alter immune responsiveness.


Molecular beam epitaxy growth and post-growth annealing of FeSe films on SrTiO3: a scanning tunneling microscopy study.
Low temperature scanning tunneling microscopy and spectroscopy are used to investigate the atomic and electronic structure evolution of FeSe films grown on SrTiO3 as a function of post-growth annealing. Single unit cell FeSe films are found to bond strongly with the underlying substrate, and become superconductive with diminishing chemical bond disorders at the interface via post-annealing. For thicker FeSe films, post-annealing removes excess Se in the films and leads to a transition from semiconductor into metallic behaviors. In double and multilayer films, strain-induced complex textures are observed and suggested to be the main cause for the absent superconductivity.


Developmental pathways to adolescent cannabis abuse and dependence: child maltreatment, emerging personality, and internalizing versus externalizing psychopathology.
Child maltreatment is strongly associated with adolescent psychopathology and substance abuse and dependence. However, developmental processes unfolding from childhood into adolescence that delineate this trajectory are not well understood. The current study used path analysis in a structural equation modeling framework to examine multiple mediator models, including ego control, ego resiliency, and internalizing and externalizing symptoms to investigate this developmental process. Participants were 415 children, assessed across 3 waves of data, (i.e., at ages 7 to 9, 10 to 12, and 13 to 15). The sample included maltreated (n = 259) and nonmaltreated (n = 156) children; groups were comparable in sociodemographic characteristics. Findings support an transactional-ecological model by revealing a developmental sequence in which severity of early childhood maltreatment potentiates less adaptive childhood personality functioning, followed by externalizing problems in preadolescence, and ultimately adolescent cannabis abuse and dependence symptoms. A developmental pathway from child maltreatment to adolescent cannabis abuse and dependence symptoms via personality and preadolescent internalizing problems was not supported. Understanding developmental pathways by which maltreatment experiences increase risk for substance abuse and dependence symptoms in youth has far-reaching implications for the treatment and prevention of substance use disorders.


The ontogeny of vasoactive intestinal polypeptide-like and substance P-like immunoreactivity in the digestive tract of the sheep.
Using the technique of indirect immunofluorescence cytochemistry, the development of structures showing vasoactive intestinal polypeptide-like (VIP-l.i.) and substance P-like (SP-l.i.) immunoreactivity was studied in the gut of the fetal sheep and of new-born lambs. The fetuses were obtained by hysterotomy at known stages of gestation. VIP-l.i. immunoreactivity was first detected at mid-gestation (70 d) in neuronal structures in the myenteric plexus of the oesophagus and the forestomachs. SP-l.i. immunoreactivity was detectable at 50 d of gestation in neuronal structures in the myenteric and submucous plexuses of the forestomachs and abomasum and in the myenteric plexus of the rectum. SP-l.i. immunoreactivity was also seen in open-type endocrine cells in the abomasal epithelium. Subsequently, VIP-l.i. staining progressively appeared caudally from the oesophagus and later cranially from the rectum. By birth the full adult staining pattern had developed in all regions except the colon. SP-l.i. was found to progress cranially and caudally from the forestomachs and abomasum and also cranially from the rectum and by birth the gut showed staining fully representative of the adult distribution. The SP-reactive endocrine cells appeared progressively along the intestine as the fetus developed and by birth were found predominantly in the small and large intestine with only a few in the abomasum.


Interpenetrating graphene network bct-C40: a promising anode material for Li ion batteries.
The stable sp2-C atoms in graphite enable its excellent structural and electrochemical stability as an anode material for Li-ion battery applications, while the limited Li-storage capacity of graphite also originates from the sp2 hybridization. Herein, from first-principles calculations, we show that a synergistic effect of sp2 and sp3 hybridized C atoms can substantially enhance the Li-storage performance in carbon-based anodes, using bct-C40 as an example, which is constructed with interconnected graphene layers (sp2 hybridized C atoms) and the connecting points are composed of sp3-C atoms. Charge transfer from sp2-C atoms to sp3-C atoms has been found, leading to unoccupied electronic states forming around the Fermi level. Furthermore, we found that the unoccupied electronic states are contributed by the pz orbital of the sp2-C atoms, resulting in stronger interactions between C atoms and intercalated Li atoms. As a result, the Li intercalation concentration in bct-C40 can reach as high as LiC2.5 (corresponding to a capacity of 893 mA h g-1), much higher than that of LiC6 in graphite (372 mA h g-1). Furthermore, bct-C40 inherits good structural and electrochemical stability, a metallic electronic structure, and low Li-ion migration energy barriers (0.067-0.112 eV) from the sp2 hybridized graphene structures, therefore very good Li-storage performance is expected, indicating that bct-C40 can be used as a high-performance anode material for lithium ion batteries. Our study provides new insights into the functionality of sp2- and sp3-C atoms in carbon-based anode materials and is helpful for the designing of new carbon-based anodes.


Composition and activity of the photosynthetic apparatus in temperature-sensitive mutants of higher plants.
Six nuclear mutants of corn, six of soybean, and seven of cotton displayed low temperature-induced virescence when grown in controlled environments. For the group of plants studied, an increase in leaf chlorophyll a/b ratio was correlated with a temperature-sensitive biosynthetic sequence leading to a reduction in total chlorophyll content. These pigment alterations were reflected in the composition and quantity of the two major chlorophyll-protein complexes of chloroplast membranes. Changes in the amount of the major light-harvesting chlorophyll-protein complex was a prime consequence of the nuclear mutations. A decrease in the light-harvesting chlorophyll component of the light reaction centers of the leaf may account for the decrease in size of the photo-synthetic unit frequently noted in chlorophyll-deficient mutants. Variations in the concentration of the chlorophyll-protein complexes in the chloroplast lamellae may be causally related to variations in CO(2) compensation points of mutant soybean and cotton plants.


Electrochemical behavior and electrogenerated chemiluminescence of star-shaped D-A compounds with a 1,3,5-triazine core and substituted fluorene arms.
We report the synthesis, electrochemistry, and electrogenerated chemiluminescence of a series of star-shaped donor-acceptor (D-A) molecules. The star-shaped molecules consist of an electron-deficient 1,3,5-triazine core with three fluorene arms substituted with diarylamino (TAM1-TAM3) or carbazolyl (TAM4) electron donors. Cyclic voltammetry of TAM1-TAM3 shows that the reduction consists of one wave of single electron transfer to the core, while the oxidation exhibits a single peak of three sequential electron-transfer processes, with the formation of a trication. The carbazole-containing molecule TAM4 after oxidation undergoes a subsequent rapid chemical reaction to produce a dimer (via the overall coupling of two radical cations with the loss of two protons). The dimer electrooxidizes more easily than the monomer of TAM4. With continuous cycling on the oxidation side, a conductive polymer film is formed on the surface of the working electrode. Because of the presence of the acceptor (triazine) center and strong donors in the arms (diarylamine or carbazole), TAM1-TAM3 exhibit large solvatochromic effects with emissions ranging from deep blue (428 nm) to orange-red (575 nm) depending on the solvent polarity. These star-shaped molecules show high PL quantum yields of 0.70-0.81. The electrogenerated chemiluminescence (ECL) of TAM1-TAM3 in nonaqueous solutions showed strong ECL that could be seen with the naked eye in a well-lit room. Because the enthalpy of annihilation is higher than the energy required for formation of the singlet excited state, the ECL emission is believed to be generated via S-route annihilation. However, TAM4 shows weak annihilation ECL because of the production of polymer film on the electrode surface during oxidation cycles. However, by limiting the potential region only to the reduction side and using benzoyl peroxide (BPO) as a coreactant, strong ECL of TAM4 can be obtained.


Genetic characterization of an H5N1 avian influenza virus from a vaccinated duck flock in Vietnam.
This study reports the genetic characterization of a highly pathogenic avian influenza virus subtype H5N1 isolated from a moribund domestic duck in central Vietnam during 2012. In the moribund duck's flock, within 6 days after vaccination with a commercial H5N1 vaccine (Re-5) to 59-day-old birds, 120 out of 2,000 ducks died. Genetic analysis revealed a substantial number of mutations in the HA gene of the isolate in comparison with the vaccine strains, Re-1 and Re-5. Similar mutations were also found in selected Vietnamese H5N1 strains isolated since 2009. Mutations in the HA gene involved positions at antigenic sites associated with antibody binding and also neutralizing epitopes, with some of the mutations resulting in the modification of N-linked glycosylation of the HA. Those mutations may be related to the escape of virus from antibody binding and the infection of poultry, interpretations which may be confirmed through a reverse genetics approach. The virus also carried an amino acid substitution in the M2, which conferred a reduced susceptibility to amantadine, but no neuraminidase inhibitor resistance markers were found in the viral NA gene. Additional information including vaccination history in the farm and the surrounding area is needed to fully understand the background of this outbreak. Such understanding and expanded monitoring of the H5N1 influenza viruses circulating in Vietnam is an urgent need to provide updated information to improve effective vaccine strain selection and vaccination protocols, aiding disease control, and biosecurity to prevent H5N1 infection in both poultry and humans.


How all stars works: an examination of program effects on mediating variables.
Prevention research continues to focus on school-based substance use programs aimed at adolescents. These programs are designed to reduce substance use and risk behavior by targeting key mediators, such as normative beliefs, which in turn reduce substance use. All Stars is a newly developed program that was recently evaluated in a randomized field trial in 14 middle schools in Lexington and Louisville, Kentucky. The authors examined targeted and nontargeted variables as possible mediators of program effectiveness. Findings indicate that All Stars achieved reductions in substance use and postponed sexual activity when teachers were successful at altering targeted mediators: normative beliefs, lifestyle incongruence, and manifest commitment to not use drugs. The program was not successful when it was delivered by specialists. At least in part, this failure is attributable to specialists' inability to change mediators as intended by the program.


Knockdown of AHR1A but not AHR1B exacerbates PAH and PCB-126 toxicity in zebrafish (Danio rerio) embryos.
Various environmental contaminants are known agonists for the aryl hydrocarbon receptor (AHR), which is highly conserved across vertebrate species. Due to gene duplication events before and after the divergence of ray- and lobe-finned fishes, many teleosts have multiple AHR isoforms. The zebrafish (Danio rerio) has three identified AHRs: AHR1A and AHR1B, the roles of which are not yet well elucidated, and AHR2, which has been shown to mediate the toxicity of various anthropogenic compounds including dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). In this study, we sought to explore the role of the two AHR1 isoforms in PAH- and PCB-induced toxicity in zebrafish embryos utilizing morpholino gene knockdown of the AHR isoforms. Knockdown of AHR1B did not affect the toxicity of PAH mixtures or PCB-126, whereas knockdown of AHR1A exacerbated the cardiac toxicity caused by PAH mixtures and PCB-126. Knockdown of AHR1A did not impact the mRNA expression of CYP1A, CYP1B1, and CYP1C1 in exposed embryos, but it did result in increased CYP1 activity in exposed embryos. As has been shown previously, knockdown of AHR2 resulted in protection from PAH- and PCB-induced cardiac deformities and prevented CYP1 enzyme activity in exposed embryos. Co-knockdown of AHR1A and AHR2 resulted in an intermediate response compared to knockdown of AHR1A and AHR2 individually; co-knockdown did not exacerbate nor protect from PAH-induced deformities and embryos exhibited an intermediate CYP1 enzyme activity response. In contrast, co-knockdown of AHR1A and AHR2 did protect from PCB-126-induced deformities. These results suggest that AHR1A is not a nonfunctional receptor as previously thought and may play a role in the normal physiology of zebrafish during development and/or the toxicity of environmental contaminants in early life stages.


Efficacy and Safety of Switching from Sitagliptin to Ipragliflozin in Obese Japanese Patients with Type 2 Diabetes Mellitus: A Single-Arm Multicenter Interventional Study.
Dipeptidyl peptidase-4 inhibitors have limited efficacy in improving glycemic control for obese Japanese patients with type 2 diabetes mellitus. Sodium-glucose co-transporter 2 inhibitors are recommended for use in patients with type 2 diabetes with obesity. Nevertheless, there has been no previously published study on the effect of switching from dipeptidyl peptidase-4 inhibitors to sodium-glucose co-transporter 2 inhibitors on the systemic and organic effects in obese Japanese patients with type 2 diabetes. We evaluated the efficacy and safety of switching from sitagliptin to ipragliflozin for 24 weeks in obese Japanese patients with inadequately controlled type 2 diabetes. Fifty-one obese patients with type 2 diabetes (body mass index > 25 kg/m2) treated with sitagliptin (50 mg) and metformin but with inadequate glycemic control (glycosylated hemoglobin [HbA1c] > 7.5% and < 9.0%) were enrolled. After a 4-week observation period, sitagliptin was switched to ipragliflozin (50 mg) for 24 weeks. The primary outcome was the change in HbA1c from baseline to the end of treatment. The secondary outcomes were changes in clinical characteristics and other biochemical variables. Fifty-one patients with an average HbA1c of 8.37 ± 0.48% and body mass index of 28.8 ± 3.8 kg/m2 were enrolled. Fifty patients completed the study, one patient stopped ipragliflozin at 4 weeks because of the development of hyperosmolar hyperglycemic syndrome. No significant change in HbA1c from baseline to the end of treatment was observed (- 0.02 ± 0.75%). However, fasting plasma glucose was reduced (- 16.2 ± 28.4 mg/dL, p < 0.001), and biochemical variables associated with insulin resistance, oxidative stress, and hepatic and renal functions showed significant improvements. No severe adverse effects were observed, except in the one aforementioned case. Switching from sitagliptin to ipragliflozin did not alter HbA1c in obese patients with type 2 diabetes, while improving parameters related to organ homeostasis. These data provide novel information useful for selecting oral anti-diabetic agents for patients with type 2 diabetes with obesity, a risk factor for developing various complications of diabetes. Japan Registry of Clinical Trials identifier: jRCT#031190022.


Detection of tuberculosis-associated compounds from human skin by GCxGC-TOFMS.
Tuberculosis (TB) remains a global health concern. This study aimed to investigate the potential of human skin volatile organic compounds (VOCs) as prospective biomarkers for TB diagnosis. It employed a non-invasive approach using a wearable silicone rubber band for VOC sampling, comprehensive gas chromatography - time of flight mass spectrometry (GCxGC-TOFMS), and chemometric techniques. Both targeted and untargeted biochemical screening was utilized to explore biochemical differences between healthy individuals and those with TB infection. Results confirmed a correlation between compounds found in this study, and those reported for TB from other biofluids. In a comparison to known TB-associated compounds from other biofluids our analysis established the presence of 27 of these compounds emanating from human skin. Additionally, 16 previously unreported compounds were found as potential biomarkers. The diagnostic ability of the VOCs selected by statistical methods was investigated using predictive modelling techniques. Artificial neural network multi-layered perceptron (ANN) yielded two compounds, 1H-indene, 2,3 dihydro-1,1,3-trimethyl-3-phenyl; and heptane-3-ethyl-2-methyl, as the most discriminatory, and could differentiate between TB-positive (n = 15) and TB-negative (n = 23) individuals with an area under the receiver operating characteristic curve (AUROC) of 92 %, a sensitivity of 100 % and a specificity of 94 % for six targeted features. For untargeted analysis, ANN assigned 3-methylhexane as the most discriminatory between TB-positive and TB- negative individuals. An AUROC of 98.5 %, a sensitivity of 83 %, and a specificity of 88 % were obtained for 16 untargeted features as chosen by high performance variable selection. The obtained values compare highly favourable to alternative diagnostic methods such as breath analysis and GeneXpert. Consequently, human skin VOCs hold considerable potential as a TB diagnostic screening test.


Vitamin C Enhances Antiviral Functions of Lung Epithelial Cells.
Vitamin C is well documented to have antiviral functions; however, there is limited information about its effect on airway epithelial cells-the first cells to encounter infections. Here, we examined the effect of vitamin C on human bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) cells, and observed that sodium-dependent vitamin C transporter 2 (SVCT2) was the primary vitamin C transporter. Transcriptomic analysis revealed that treating BEAS-2B cells with vitamin C led to a significant upregulation of several metabolic pathways and interferon-stimulated genes (ISGs) along with a downregulation of pathways involved in lung injury and inflammation. Remarkably, vitamin C also enhanced the expression of the viral-sensing receptors retinoic acid-inducible gene 1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5), which was confirmed at the protein and functional levels. In addition, the lungs of l-gulono-γ-lactone oxidase knockout (GULO-KO) mice also displayed a marked decrease in these genes compared to wild-type controls. Collectively, our findings indicate that vitamin C acts at multiple levels to exert its antiviral and protective functions in the lungs.


[Bipolar disorder. Follow-up of lithium therapy in a clinic].
Lithium carbonate is the drug of choice in the prophylactic treatment of bipolar disorder. The purpose of this article is to describe the effective functioning of lithium in a clinical way in our hospital under the control of university graduates in nursing. During the first ten months of its use, 40 patients have been included which led to 122 appointments, absenteeism being 8.62%. 20% (8/40) of the lithium intoxications at the start of the follow-up were inferior to 0.5% mmol/l while at the end, only 5.3% (2/38) fell below 0.5% mmol/l. The average of the lithium intoxications at the end of the study period was significantly higher than in the moment of entrance to the program (p = 0.009). During the study period, three relapses were registered.


Effects of isradipine on cocaine-induced subjective mood.
We hypothesized that in humans, as in animals, isradipine, a dihydropyridine-class calcium channel antagonist, would antagonize cocaine's rewarding effects, based on preclinical evidence that isradipine inhibits cocaine-mediated increases in mesolimbic dopamine (DA), thereby reducing cocaine's abuse liability. Confirmation of our hypothesis would make isradipine a promising medication for treating cocaine dependence. Eighteen male and female volunteers (mean age, 32.6 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a double-blind, placebo-controlled, crossover study. Subjects received placebo or sustained-release (SR) low-dose or high-dose isradipine (15 or 30 mg), plus placebo or low-dose or high-dose cocaine HCl (0.325 or 0.650 mg/kg), for 9 treatment sessions separated by a 2-day interval. Standardized assessments of abuse liability, including a choice procedure to determine preference for cocaine with and without isradipine over monetary incentives, were conducted at scheduled intervals. Cocaine administration produced dose-related prototypic increases in stimulant-related effects, including euphoria, and drug preference over monetary incentives. Isradipine lacked any stimulant or abuse liability effects or the propensity to elicit craving, and it did not antagonize any of cocaine's stimulant-related effects associated with its abuse liability. In conclusion, SR isradipine (up to 30 mg) does not antagonize cocaine's rewarding effects in cocaine-dependent individuals. While higher isradipine doses may have been more effective at antagonizing cocaine reward, we could not test such doses due to the risk of serious adverse events. Also, isradipine-mediated inhibition of mesolimbic DA release may be an ineffective treatment of cocaine dependence.


Activity Modification and Knee Strengthening for Osgood-Schlatter Disease: A Prospective Cohort Study.
Osgood-Schlatter disease (OSD) affects 1 in 10 adolescents. There is a lack of evidence-based interventions, and passive approaches (eg, rest and avoidance of painful activities) are often prescribed. To investigate an intervention consisting of education on activity modification and knee-strengthening exercises designed for adolescents with OSD. Case series; Level of evidence, 4. This study included 51 adolescents (51% female; age range, 10-14 years) with OSD. The 12-week intervention consisted of an activity ladder designed to manage patellar tendon loading and pain, knee-strengthening exercises, and a gradual return to sport. The primary outcome was the global reporting of change at 12 weeks, evaluated with a 7-point Likert scale (successful outcome was considered "much improved" or "improved"). Additional endpoints were at 4, 8, 26, and 52 weeks. Secondary outcomes included the Knee injury and Osteoarthritis Outcome Score (KOOS), objective strength, and jump performance. Adolescents reported a mean pain duration of 21 months at enrollment. After 12 weeks, 80% reported a successful outcome, which increased to 90% at 12 months. At 12 weeks, 16% returned to playing sport, which increased to 69% at 12 months. The KOOS subscores of Pain, Activities of Daily Living, Sport and Recreation, and Quality of Life improved significantly (7-20 points), and there were improvements in knee extension strength (32%; P < .001), hip abduction strength (24%; P < .001), and jumping for distance (14%; P < .001) and height (19%; P < .001) at 12 weeks. An intervention consisting of activity modification, pain monitoring, progressive strengthening, and a return-to-sport paradigm was associated with improved self-reported outcomes, hip and knee muscle strength, and jumping performance. This approach may offer an alternative to passive approaches such as rest or wait-and-see, often prescribed for adolescents with OSD. NCT02799394 (ClinicalTrials.gov identifier).


Cost-Effectiveness of Follow-Up of Chronic Coughers in Detecting Smear-Positive Tuberculosis in South Ethiopia.
In Ethiopia, no studies assessing the cost-effectiveness of follow-up of smear-negative chronic coughers in detecting smear-positive tuberculosis (TB) (PTB+) cases have been reported. This article describes the cost-effectiveness of community-based follow-up of smear-negative chronic coughers in detecting PTB+ cases. Two alternative strategies of TB case finding, namely community-based follow-up of smear-negative chronic coughers and passive TB case finding, were compared. Participants were selected randomly in the active TB case finding approach, while purposively in the passive TB case finding strategy. In November 2012 and January 2015, costs related to TB diagnosis were collected using structured questionnaires from sample of 60 patients in each strategy. Data on health system cost and direct and indirect costs incurred by patients and their caretakers were collected in Ethiopian Birr and converted into USD for analysis. Exchange rate for the data collection period of chronic coughers was 1 USD = 18.16 ETB and for passive case finding period was 1 USD = 20.24 ETB. Cost-effectiveness was calculated in terms of cost per PTB+ cases detected. The overall cost of TB case finding was lower under active case finding approach than under passive TB case finding approach (USD 27.4 vs. 27.6). Active case finding approach was cost-effective by 43.4% and it is highly cost-effective when the duration of follow-up is reduced to 7 months or less. Active case finding approach is a cost-effective approach of TB case finding. The cost benefit obtained could be even higher when the follow-up duration is minimized.


An updated view of plasmid conjugation and mobilization in Staphylococcus.
The horizontal gene transfer facilitated by mobile genetic elements impacts almost all areas of bacterial evolution, including the accretion and dissemination of antimicrobial-resistance genes in the human and animal pathogen Staphylococcus aureus. Genome surveys of staphylococcal plasmids have revealed an unexpected paucity of conjugation and mobilization loci, perhaps suggesting that conjugation plays only a minor role in the evolution of this genus. In this letter we present the DNA sequences of historically documented staphylococcal conjugative plasmids and highlight that at least 3 distinct and widely distributed families of conjugative plasmids currently contribute to the dissemination of antimicrobial resistance in Staphylococcus. We also review the recently documented "relaxase-in trans" mechanism of conjugative mobilization facilitated by conjugative plasmids pWBG749 and pSK41, and discuss how this may facilitate the horizontal transmission of around 90% of plasmids that were previously considered non-mobilizable. Finally, we enumerate unique sequenced S. aureus plasmids with a potential mechanism of mobilization and predict that at least 80% of all non-conjugative S. aureus plasmids are mobilizable by at least one mechanism. We suggest that a greater research focus on the molecular biology of conjugation is essential if we are to recognize gene-transfer mechanisms from our increasingly in silico analyses.