Disruption of magnetic orientation in hatchling loggerhead sea turtles by pulsed magnetic fields.
Loggerhead sea turtles (Caretta caretta) derive both directional and positional information from the Earth's magnetic field, but the mechanism underlying magnetic field detection in turtles has not been determined. One hypothesis is that crystals of biogenic, single-domain magnetite provide the physical basis of the magnetic sense. As a first step toward determining if magnetite is involved in sea turtle magnetoreception, hatchling loggerheads were exposed to pulsed magnetic fields (40 mT, 4 ms rise time) capable of altering the magnetic dipole moment of biogenic magnetite crystals. A control group of turtles was treated identically but not exposed to the pulsed fields. Both groups of turtles subsequently oriented toward a light source, implying that the pulsed fields did not disrupt the motivation to swim or the ability to maintain a consistent heading. However, when swimming in darkness under conditions in which turtles normally orient magnetically, control turtles oriented significantly toward the offshore migratory direction while those that were exposed to the magnetic pulses did not. These results are consistent with the hypothesis that at least part of the sea turtle magnetoreception system is based on magnetite. In principle, a magnetite-based magnetoreception system might be involved in detecting directional information, positional information, or both.


Antinociceptive effects of racemic AM1241 and its chirally synthesized enantiomers: lack of dependence upon opioid receptor activation.
Cannabinoid CB(2) receptors represent a therapeutic target that circumvents unwanted central side effects (e.g., psychoactivity and/or addiction) associated with activation of CB(1) receptors. One of the primary investigative tools used to study functions of the CB(2) receptor is the aminoalkylindole (R,S)-AM1241. However, (R,S)-AM1241 has been described as an atypical CB(2) agonist which produces antinociception mediated indirectly by opioid receptors. (R,S)-AM1241 and its enantiomers, (R)-AM1241 and (S)-AM1241, were evaluated for antinociception in response to thermal (Hargreaves) and mechanical (von Frey) stimulation. Pharmacological specificity was established using antagonists for CB(1) (rimonabant [SR141716]) and CB(2) (SR144528). The opioid antagonist naloxone was administered locally in the paw or systemically to evaluate the contribution of opioid receptors to CB(2)-mediated antinociception produced by (R,S)-AM1241, (R)-AM1241, and (S)-AM1241. Comparisons were made with the opioid analgesic morphine. (R,S)-AM1241, (R)-AM1241, and (S)-AM1241 (0.033-10 mg/kg i.p.) produced antinociception to thermal, but not mechanical, stimulation of the hindpaw in naive rats. Antinociception produced by (R,S)-AM1241 and (S)-AM1241 exhibited an inverted U-shaped dose response curve. (R)-AM1241 produced greater antinociception than either (S)-AM1241 or (R,S)-AM1241 at the lowest (0.033 and 0.1 mg/kg i.p.) and highest (10 mg/kg i.p.) doses. Similar levels of antinociception were observed at intermediate doses. (R,S)-AM1241, (R)-AM1241, and (S)-AM1241 each produced CB(2)-mediated antinociception that was blocked by SR144528 but not by rimonabant. Local and systemic naloxone blocked morphine-induced antinociception but did not block antinociceptive effects of (R,S)-AM1241, (R)-AM1241, or (S)-AM1241. The antinociceptive effects of the CB(2)-selective cannabinoid (R,S)-AM1241 and its enantiomers, (R)-AM1241 and (S)-AM1241, are not dependent upon opioid receptors.


Enhancing pediatric workforce diversity and providing culturally effective pediatric care: implications for practice, education, and policy making.
This policy statement serves to combine and update 2 previously independent but overlapping statements from the American Academy of Pediatrics (AAP) on culturally effective health care (CEHC) and workforce diversity. The AAP has long recognized that with the ever-increasing diversity of the pediatric population in the United States, the health of all children depends on the ability of all pediatricians to practice culturally effective care. CEHC can be defined as the delivery of care within the context of appropriate physician knowledge, understanding, and appreciation of all cultural distinctions, leading to optimal health outcomes. The AAP believes that CEHC is a critical social value and that the knowledge and skills necessary for providing CEHC can be taught and acquired through focused curricula across the spectrum of lifelong learning. This statement also addresses workforce diversity, health disparities, and affirmative action. The discussion of diversity is broadened to include not only race, ethnicity, and language but also cultural attributes such as gender, religious beliefs, sexual orientation, and disability, which may affect the quality of health care. The AAP believes that efforts must be supported through health policy and advocacy initiatives to promote the delivery of CEHC and to overcome educational, organizational, and other barriers to improving workforce diversity.


Audiological and genetic features of the mtDNA mutations.
Significant difference in the incidence of mitochondrial DNA (mtDNA) mutations was found between the Chinese and USA populations. The identification of the mtDNA A1555G mutation in a large proportion of Chinese probands with nonsyndromic sensorineural hearing loss (NSHL) provides a molecular explanation for the high prevalence of aminoglycoside-induced deafness in China. The aim was to characterize the audiological and genetic features of NSHL due to mutations in mtDNA. The mtDNA and audiogram analyses were performed in 498 NSHL patients (290 from China and 208 from the USA) with and without history of aminoglycoside exposure. A PCR and restriction enzyme digestion protocol was used for mutational screening and the European Workshop on Genetic Hearing Loss criteria were applied for audiological classification. All Chinese probands (15.5%) with mtDNA mutation were found to carry the homoplasmic mtDNA A1555G mutation, whereas four probands (1.9%) from the USA were found to carry the mtDNA A1555G and two (1%) had mtDNA G7444A. Approximately 63% of the probands with mtDNA mutations had post-lingual hearing loss and 56.8% of them had a medical history of exposure to aminoglycosides. Hearing losses are bilateral, sensorineural, and symmetric. The main audiogram shapes found were sloping.


SCAN-ECHO for Pain Management: Implementing a Regional Telementoring Training for Primary Care Providers.
The Specialty Care Access Network-Extension for Community Health Outcomes (SCAN-ECHO) is a video teleconferencing-based training program where primary care providers are trained by a specialty care team to provide specialty care. A multidisciplinary team of pain management specialists at the Cleveland Veterans Affairs Medical Center established such a program for pain management; a description and preliminary effectiveness assessment of this training program is presented. Primary care provider participants in the Specialty Care Access Network program in pain management completed pre- and post-training questionnaires. A subset of these participants also participated in a group session semistructured interview. Twenty-four primary care providers from Cleveland, South Texas, or Wisconsin Veterans Affairs Medical Centers who regularly attended pain management SCAN-ECHO sessions during 2011, 2012, 2013, or 2014 completed pre- and post-training questionnaires. Pre- and post-training questionnaires were conducted to measure confidence in treating and knowledge of pain management. Questionnaire responses were tested for significance using R. Qualitative data were analyzed using inductive coding and content analysis. Statistically significant increases in confidence ratings and scores on knowledge questionnaires were noted from pre- to post-pain management SCAN-ECHO training. Program participants felt more knowledgeable and reported improved communication between specialty and primary care providers. This pilot study reveals positive outcomes in terms of primary care providers' confidence and knowledge in treating patients with chronic pain. Results suggest that involving primary care providers in a one-year academic project such as this can improve their knowledge and skills and has the potential to influence their opioid prescribing practices.


[The course of alcoholic embryopathy].
Pediatric examinations were performed in 71 children with fetal alcohol syndrome (FAS). A subgroup of these patients underwent neurological and psychiatric assessment and psychological testing. Psychopathology was also studied in a matched control group. After a period of 3-4 years various subgroups of these children were re-examined. Follow-up examinations revealed that with increasing age dysmorphic signs became less apparent in children with FAS. Furthermore, neurologic performance improved and EEG-recordings revealed less pathological patterns. These positive findings were confirmed by the observation that these patients also experienced an improvement with regard to psychiatric status and cognitive functions. But it must be stated that the affected children did not become normal in all psychiatric areas. Hyperactivity and distractability seem to be the major handicaps for a normal school career of these children.


The Efficacy, Adverse Effects and Economic Implications of Oral Versus Intravenous Methylprednisolone for the Treatment of Optic Neuritis: A Systematic Review.
Optic neuritis may occur in a variety of conditions, including as a manifestation of multiple sclerosis. Despite significant research into the efficacy of corticosteroids as a first-line treatment, the optimal route of administration has not been well defined. This review aims to explore the efficacy, adverse effects and economic implications of using oral versus intravenous methylprednisolone to treat acute optic neuritis. A systematic search of the databases PubMed/MEDLINE, Embase and CENTRAL was performed to July 2022, prior to data collection and risk of bias analysis in accordance with the PRISMA guidelines. Six articles fulfilled the inclusion criteria. The results showed that in the treatment of acute optic neuritis, oral methylprednisolone has a non-inferior efficacy and adverse effect profile in comparison to intravenous methylprednisolone. In a cost analysis, oral methylprednisolone to be more cost-effective than intravenous methylprednisolone. Oral methylprednisolone has comparable efficacy and adverse effect profiles to intravenous methylprednisolone for the treatment of optic neuritis. The analysis suggests oral administration is more cost-effective than intravenous administration; however, further analyses of the formal cost-benefit ratio are required.


Neurochemical mechanisms underlying alcohol withdrawal.
More than 50 years ago, C.K. Himmelsbach first suggested that physiological mechanisms responsible for maintaining a stable state of equilibrium (i.e., homeostasis) in the patient's body and brain are responsible for drug tolerance and the drug withdrawal syndrome. In the latter case, he suggested that the absence of the drug leaves these same homeostatic mechanisms exposed, leading to the withdrawal syndrome. This theory provides the framework for a majority of neurochemical investigations of the adaptations that occur in alcohol dependence and how these adaptations may precipitate withdrawal. This article examines the Himmelsbach theory and its application to alcohol withdrawal; reviews the animal models being used to study withdrawal; and looks at the postulated neuroadaptations in three systems-the gamma-aminobutyric acid (GABA) neurotransmitter system, the glutamate neurotransmitter system, and the calcium channel system that regulates various processes inside neurons. The role of these neuroadaptations in withdrawal and the clinical implications of this research also are considered.


[The ultrastructure of portions of the cat spinal cord gray matter connected to fibers of different descending tracts].
Definite ultrastructural features were found in the regions of the cat spinal grey matter connected with different descending pathways, especially in the structure of dendritic membranes and relative quantities of axon terminals. Two types of destructive changes in myelinated axons and axon terminals in these regions were observed during experimental degeneration of descending fibres. Axon terminals of small size and F-type vesicles were subjected to degeneration after pyramidal tract lesion, while large terminals of both S-type and F-type were affected after sectioning of extrapyramidal tracts.


Anti-Inflammatory Activity of Fucan from Spatoglossum schröederi in a Murine Model of Generalized Inflammation Induced by Zymosan.
Fucans from marine algae have been the object of many studies that demonstrated a broad spectrum of biological activities, including anti-inflammatory effects. The aim of this study was to verify the protective effects of a fucan extracted from the brown algae Spatoglossum schröederi in animals submitted to a generalized inflammation model induced by zymosan (ZIGI). BALB/c mice were first submitted to zymosan-induced peritonitis to evaluate the treatment dose capable of inhibiting the induced cellular migration in a simple model of inflammation. Mice were treated by the intravenous route with three doses (20, 10, and 5 mg/kg) of our fucan and, 1 h later, were inoculated with an intraperitoneal dose of zymosan (40 mg/kg). Peritoneal exudate was collected 24 h later for the evaluation of leukocyte migration. Doses of the fucan of Spatoglossum schröederi at 20 and 10 mg/kg reduced peritoneal cellular migration and were selected to perform ZIGI experiments. In the ZIGI model, treatment was administered 1 h before and 6 h after the zymosan inoculation (500 mg/kg). Treatments and challenges were administered via intravenous and intraperitoneal routes, respectively. Systemic toxicity was assessed 6 h after inoculation, based on three clinical signs (bristly hair, prostration, and diarrhea). The peritoneal exudate was collected to assess cellular migration and IL-6 levels, while blood samples were collected to determine IL-6, ALT, and AST levels. Liver tissue was collected for histopathological analysis. In another experimental series, weight loss was evaluated for 15 days after zymosan inoculation and fucan treatment. The fucan treatment did not present any effect on ZIGI systemic toxicity; however, a fucan dose of 20 mg/kg was capable of reducing the weight loss in treated mice. The treatment with both doses also reduced the cellular migration and reduced IL-6 levels in peritoneal exudate and serum in doses of 20 and 10 mg/kg, respectively. They also presented a protective effect in the liver, with a reduction in hepatic transaminase levels in both doses of treatment and attenuated histological damage in the liver at a dose of 10 mg/kg. Fucan from S. schröederi presented a promising pharmacological activity upon the murine model of ZIGI, with potential anti-inflammatory and hepatic protective effects, and should be the target of profound and elucidative studies.


Allele-specific expression at the androgen receptor alpha gene in a hybrid unisexual fish, the Amazon molly (Poecilia formosa).
The all-female Amazon molly (Poecilia formosa) is the result of a hybridization of the Atlantic molly (P. mexicana) and the sailfin molly (P. latipinna) approximately 120,000 years ago. As a gynogenetic species, P. formosa needs to copulate with heterospecific males including males from one of its bisexual ancestral species. However, the sperm only triggers embryogenesis of the diploid eggs. The genetic information of the sperm donor typically will not contribute to the next generation of P. formosa. Hence, P. formosa possesses generally one allele from each of its ancestral species at any genetic locus. This raises the question whether both ancestral alleles are equally expressed in P. formosa. Allele-specific expression (ASE) has been previously assessed in various organisms, e.g., human and fish, and ASE was found to be important in the context of phenotypic variability and disease. In this study, we utilized Real-Time PCR techniques to estimate ASE of the androgen receptor alpha (arα) gene in several distinct tissues of Amazon mollies. We found an allelic bias favoring the maternal ancestor (P. mexicana) allele in ovarian tissue. This allelic bias was not observed in the gill or the brain tissue. Sequencing of the promoter regions of both alleles revealed an association between an Indel in a known CpG island and differential expression. Future studies may reveal whether our observed cis-regulatory divergence is caused by an ovary-specific trans-regulatory element, preferentially activating the allele of the maternal ancestor.


Explaining Mexican American workers' hearing protection use with the health promotion model.
Mexican American workers are vulnerable to noise-induced hearing loss, the most common occupational disease in the United States. The purpose was to test the applicability of the Health Promotion Model to Mexican American workers' use of hearing protection devices. A correlational descriptive design and path analysis were used to determine the relationships between cognitive-perceptual factors, modifying factors and use of hearing protection devices. A questionnaire was completed by a total of 119 workers in three garment manufacturing plants. Interviews were conducted with the occupational health nurse or safety director in each plant to determine the policy regarding hearing protection also. Factors that directly influenced the use of hearing protection devices were a clinical definition of health, benefits of and barriers to use of hearing protection devices, self-efficacy in the use of hearing protection devices and perceived health status (R2 =.25, p <.01). An exploratory analysis allowing a direct relationship of modifying factors with the dependent variable explained additional variance in use of hearing protection devices through the contribution of situational factors (R2 =.55, p <.01). Important factors related to Mexican American workers' use of hearing protection devices were identified to provide direction for nursing interventions. Future research should further test the explanatory capabilities of the Health Promotion Model, explore the importance of situational influences on health behavior, and ensure reliable measures of all model components for this population.


[Activation of glutamatergic system of the medial septal region facilitates the epileptogenesis].
The influence of L-glutamate injected into the medial septal region (MSR) on the epileptogenesis evoked by perforant path stimulation was investigated in waking guinea pigs. In animals injected with saline ("control") and L-glutamate ("glutamate"), field potentials (EEG) of the hippocampus and the MSR were recorded before the injections and during epileptogenesis. The delivery of L-glutamate to the MSR induced an increase in theta activity both in the MSR and the hippocampus. During kindling, the seizure behaviour and secondary epileptiform discharges were observed earlier in the glutamate group than in control animals. In the process of epileptogenesis, theta oscillations almost disappeared in all animals, but in the glutamate group this happened much earlier. The correlation between hippocampal and septal EEGs dramatically decreased in the animals with glutamate injections, and in the controls the decrease was not significant. These results contribute to understanding the mechanisms of temporal lobe epilepsy.


Cementless femoral prostheses cost more to implant than cemented femoral prostheses.
Prosthetic cost contributes greatly to the overall expense of THA. A key question, therefore, in the selection of implant technique is whether any price difference exists between a cementless and a cemented femoral prosthesis. We evaluated the price difference between the most commonly used cemented and cementless femoral stems at three high-volume academic medical centers. Each hospital's costs for prostheses from the manufacturers were recorded. The average cost of implanting a cementless femoral prosthesis was $296 more than the average cost of implanting a cemented femoral stem, even with the additional expense of two batches of bone cement and the accessories commonly used to achieve a third-generation cementing technique. The price difference was less variable if the cost of the prostheses from only the primary implant supplier for each institution was considered. As the number of THAs performed per year continues to escalate, implantation of a cemented femoral component remains an attractive method of fixation from an economic standpoint. Level III, economic and decision analysis. See the Guidelines for Authors for a complete description of levels of evidence.


Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats.
There are conflicting reports on the effect of soy and its components on mammary carcinogenesis in adult female rats, mainly because of different rodent models that are used in chemoprevention studies. The present study was undertaken to compare the tumor-preventative effects of soy protein isolate (SPI) and two of its isoflavones in a "standard" model that had been used for the identification of many chemopreventive agents. Six groups of female Sprague-Dawley rats were provided with modified cornstarch AIN-76A diets supplemented as follows: no additional agents (control), purified genistein (200 mg/kg diet), purified daidzein (200 mg/kg diet), genistein + daidzein (100 mg/kg diet each), SPI containing normal levels of isoflavones (SPI-n), or SPI depleted of isoflavones (SPI-d). Mammary carcinomas were induced by 7,12-dimethylbenz[a]anthracene (DMBA) introduced 1 wk after the animals began consuming the experimental diets. At the end of the study (120 days after DMBA treatment), no significant differences were found among the six groups with respect to tumor incidence or survival, nor was there a significant reduction in tumor multiplicity in the genistein or genistein + daidzein group. However, there was a 32% reduction in tumor multiplicity in the daidzein and SPI-n groups relative to the control group (P < 0.05). The most effective diet was SPI-d, which produced a 50% reduction in tumor multiplicity relative to the control (P < 0.01). The difference between the SPI-d group and the daidzein or SPI-n group was not significant. Median tumor latency was increased from 53 days in the control group to 68 days in the daidzein group and to 72 days in the SPI-d group, but these differences were not statistically significant. These results show that daidzein and SPI (with normal or low levels of isoflavones) are effective inhibitors of DMBA-induced mammary tumors in adult rats.


Small airway immunoglobulin A profile in emphysema-predominant chronic obstructive pulmonary disease.
Due to airway remodeling and emphysematous destruction in the lung, the two classical clinical phenotypes of chronic obstructive pulmonary disease (COPD) are emphysema and bronchiolitis. The present study was designed to investigate the levels of small airway immunoglobulin A (IgA) in COPD with "emphysema phenotype." The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation. Thirty patients (20 with COPD and ten healthy smokers) undergoing lung resection surgery for a solitary peripheral nodule were included. The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital. The presence of small airway IgA expression was determined in the lung by immunohistochemistry. In vivo, Wistar rats were exposed to silica by intratracheal instillation. Rats were sacrificed at 15 and 30 days after exposure of silica (n = 10 for each group). We also evaluated airway IgA from rats. Small airway secretory IgA (sIgA), dimeric IgA (dIgA), and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1-2 COPD patients showed no difference compared with smoking control subjects (5.15 ± 1.53 vs. 6.03 ± 0.85; 1.94 ± 0.66 vs. 1.67 ± 0.04; 41.69 ± 21.02 vs. 28.44 ± 9.45, all P > 0.05). dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema (51.89 ± 24.81 vs. 31.49 ± 9.28, P = 0.03). The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels (r = 0.45, P = 0.047), but not associated with the severity of disease by spirometric measurements (forced expiratory volume in the first second %pred, P > 0.05). Likewise, in the rat study, significant differences in sIgA, dIgA, dIgA/sIgA, mean linear intercept, mean alveoli number, and mean airway thickness of bronchioles (VV airway, all P < 0.01) were only observed between control rats and those exposed for 30 days. However, in the group exposed for 15 days, although the VV airway was higher than that in normal rats (27.61 ± 2.26 vs. 20.39 ± 1.99, P < 0.01), there were no significant differences in IgA and emphysema parameters between the two groups (all P > 0.05). Airway IgA concentrations in mild and moderate COPD patients are directly associated with the severity of COPD with "emphysema phenotype" preceding severe airway limitation. This finding suggests that small airway IgA might play an important role in the pathophysiology of COPD, especially emphysema phenotype.


Human periodontal ligament derived progenitor cells: effect of STRO-1 cell sorting and Wnt3a treatment on cell behavior.
STRO-1 positive periodontal ligament cells (PDLCs) and unsorted PDLCs have demonstrated potential for periodontal regeneration, but the comparison between unsorted cells and the expanded STRO-1 sorted cells has never been reported. Additionally, Wnt3a is involved in cell proliferation thus may benefit in vitro PDLC expansion. The aim was to evaluate the effect of STRO-1 cell sorting and Wnt3a treatment on cell behavior of human PDLCs (hPDLCs). STRO-1 positive hPDLCs were sorted and the sorted cells were expanded and compared with their unsorted parental cells. Thereafter, hPDLCs were treated with or without Wnt3a and the cell proliferation, self-renewal, and osteogenic differentiation were evaluated. No differences were measured between the expanded STRO-1-sorted cells and unsorted parental cells in terms of proliferation, CFU, and mineralization capacity. Wnt3a enhanced the proliferation and self-renewal ability of hPDLCs significantly as displayed by higher DNA content values, a shorter cell population doubling time, and higher expression of the self-renewal gene Oct4. Moreover, Wnt3a promoted the expansion of hPDLCs for 5 passages without affecting cell proliferation, CFU, and osteogenic capacity. Expanded STRO-1-sorted hPDLCs showed no superiority compared to their unsorted parental cells. On the other hand, Wnt3a promotes the efficient hPDLC expansion and retains the self-renewal and osteogenic differentiation capacity.


[Application of direct fluorescence technique in the diagnosis of superficial mycosis ].
A Direct Microscopic Exam (DME)--in 40x with KOH at 40% and heat--applied on materials obtained by scraping from injuries on patients infected with superficial mycosis, results effective in the detection and identification of infectious organisms based on their morphological features. This exam requires the ability of an experienced medical professional due to the fact that the mycotic element are not typical or are found in very small amounts. In this study we applied the calcofluor white and fluorescence technique together with the DME with KOH at 40% and heat. In order to do it, 100 samples obtained by scraping from skin of small and big folds and nails from feet and hands, were analyzed. We found a lower percentage of positive (+) DME with KOH at 40% and heat, than with the calcofluor white and Fluorescence Technique, an 84% and 90% respectively. Through the latter, a higher amount of elements with fungi (hifas, macro and microconidias) were observed, and it was possible to clearly see the morphological characteristics of these elements.


[Polyneuropathic pain therapy with a patient suffering from generalized castrate- resistant prostate cancer - clinical case report].
Tapentadol is a µ -opioid receptors agonist as well as an inhibitor of noradrenaline reuptake. This pharmacologic profile of tapentadol makes it a suitable drug of choice in nociceptive and neuropathic pain control. This clinical report pressents a 65year old man with poorly differentiated prostate cancer - Gleason score 8 (4 + 4) with metastatic bone disease. Besides the initial application of bisphosphonates, the patient had been treated with androgen deprivation therapy (cyproterone acetate + leuprolide acetate) for the period of 18 months. This therapy was terminated due to an increase of PSA levels. Subsequently, the patient underwent palliative docetaxelbased chemotherapy. There were eight cycles applied with positive clinical and laboratory effect. However, the further application was limited by the averse effects, namely the peripheral neuropathy manifested by pain in arms and legs. The peripheral neuropathy had progressive tendency even after the end of chemotherapy, and supportive treatment with gabapentin and amitryptiline failed to succeed. Four months after zoledronic acid monotherapy, the patient was started on tapentadol in 50-mg dose b.i.d., consequently escalated to 100 mg b.i.d. (to this point, 25 µg of transdermal fentanyl were used for pain management). Significant relief from neuropathic discomfort was observed three weeks from the onset of tapentadol therapy. Patients state of health normalized within three months after the initiation of therapy. Consequently, the patient was able to receive docetaxel chemotherapy again, without any neuropathic pain exacerbation on the maintenance dose of tapentadol 50 mg b.i.d. Tapentadol administration resulted in stable and longtime relief from neuropathic pain which is a frequent side effect in the course of castrate-resistant prostate cancer therapy with taxanes.


Resveratrol and Curcumin Improve Intestinal Mucosal Integrity and Decrease m6A RNA Methylation in the Intestine of Weaning Piglets.
N 6-Methyladenosine (m6A) is the most prevalent modification on eukaryotic messenger RNA (mRNA). Resveratrol and curcumin, which can exert many health-protective effects, may have a relationship with m6A RNA methylation. We hypothesized that the combination of resveratrol and curcumin could affect growth performance, intestinal mucosal integrity, m6A RNA methylation, and gene expression in weaning piglets. One hundred and eighty piglets weaned at 28 ± 2 days were fed a control diet or supplementary diets (300 mg/kg of antibiotics; 300 mg/kg of each resveratrol and curcumin; 100 mg/kg of each resveratrol and curcumin; 300 mg/kg of resveratrol; 300 mg/kg of curcumin) for 28 days. The results showed that the combination of resveratrol and curcumin improved growth performance and enhanced intestinal mucosal integrity and functions in weaning piglets. Resveratrol and curcumin also increased intestinal antioxidative capacity and mRNA expression of tight junction proteins. Furthermore, resveratrol and curcumin decreased the content of m6A and decreased the enrichment of m6A on the transcripts of tight junction proteins and on heme oxygenase-1 in the intestine. Our findings indicated that the combination of resveratrol and curcumin increased growth performance, enhanced intestine function, and protected piglet health, which may be associated with changes in m6A methylation and gene expression, suggesting that curcumin and resveratrol may be a potential natural alternative to antibiotics.


Isoniazid preventive treatment among child contacts of adults with smear-positive tuberculosis in The Gambia.
Setting: Greater Banjul area of The Gambia. Objectives: To evaluate uptake, adherence and completion of treatment among tuberculosis (TB) exposed children in The Gambia when isoniazid preventive treatment (IPT) is delivered at home Design: Child (age <5 years) contacts of adults with smear-positive TB were prospectively enrolled. Following symptom screening, tuberculin skin testing and clinical evaluation where indicated, those without disease were placed on daily isoniazid, provided monthly at home. Adherence was assessed by pill counts and IsoScreen™ urine test. Results: Of 404 contacts aged <5 years, 368 (91.1%) were offered IPT. Of the 328 (89.4%) for whom consent was received and who commenced IPT, 18 (5.5%) dropped out and 310 (94.5%) remained on IPT to the end of the 6-month regimen. Altogether, 255/328 children (77.7%, 95%CI 73.2-82.2) completed all 6 months, with good adherence. The IsoScreen test was positive in 85.3% (435/510) of all tests among those defined as having good adherence by pill count and in 16% (8/50) of those defined as having poor adherence (P < 0.001). A cascade of care analysis showed an overall completion rate with good adherence of 61% for all child contacts. Conclusion: Home-delivered IPT among child contacts of adults with smear-positive TB in The Gambia achieved verifiable high uptake and adherence rates. System rather than patient factors are likely to determine the success of IPT at national level.


Racial discrimination and blood pressure: the CARDIA Study of young black and white adults.
This study examined associations between blood pressure and self reported experiences of racial discrimination and responses to unfair treatment. Survey data were collected in year 7 (1992/93) of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective multisite community-based investigation. Participants included 831 Black men, 1143 Black women, 1006 White men, and 1106 White women 25 to 37 years old. Systolic blood pressure among working-class Black adults reporting that they typically accepted unfair treatment and had experienced racial discrimination in none of seven situations was about 7 mm Hg higher than among those reporting that they challenged unfair treatment and experienced racial discrimination in one or two of the situations. Among professional Black adults, systolic blood pressure was 9 to 10 mm Hg lower among those reporting that they typically challenged unfair treatment and had not experienced racial discrimination. Black-White differences in blood pressure were substantially reduced by taking into account reported experiences of racial discrimination and responses to unfair treatment. Research on racial/ ethnic distributions of blood pressure should take into account how discrimination may harm health.


Host responses in periodontal diseases.
Great progress has been made in our understanding of the pathogenesis of periodontal disease, the primary role of bacteria as etiologic agents, and the critical modifying role of host responses. It is useful to consider several stages in the pathogenesis of periodontal disease - (a) colonization, (b) invasion, (c) destruction, and (d) healing - and to place into perspective the various host responses as they may affect each of these four stages (Table 5). With respect to colonization, although very little direct evidence is available, it is reasonable to suggest that antibodies, either secretory or serum-derived, acting by virtue of their ability to block attachment, could inhibit colonization by immune reduction of adherence mechanisms. With respect to invasion of the tissue, it appears that phagocytes, particularly the neutrophils, are important, acting in concert with opsonic antibody and complement in ingesting and killing the periodontal microflora before or during the early invasive process. A major advance in our understanding of the pathogenesis of periodontal diseases is the realization that the virulence of periodontopathic bacteria relates to their leukaggressive properties, allowing them to evade neutrophil protective mechanisms. Invasion of the periodontal tissues by bacterial products may be inhibited by the complexing of these products with antibody with the formation of antigen-antibody complexes that are phagocytosed and digested, particularly by scavenger phagocytes such as the macrophage. With respect to the destructive phase of periodontal disease, it is clear that the direct effect of lymphocytes mediated either through direct cytotoxic activity, or through biologically-active destructive lymphokines (such as alpha-lymphotoxin and osteoclast activating factor), can lead to tissue destruction. Macrophages, through the production of monokines, collagenase, and reactive oxygen species, can also lead to tissue destruction. The direct effects of bacterial toxins or enzymes which can lead to tissue destruction can be inhibited by complexing with antitoxic or enzyme-neutralizing antibodies. With respect to healing and fibrosis, very little direct information is available; however, it is possible that the lymphocytes and macrophages affect fibrosis by the production of chemotactic factors for fibroblasts which would be expected to bring them to the area of periodontal inflammation and also by production of fibroblast-activating factors, which then cause the fibroblasts to proliferate and produce collagen which replaces lost collagen or results in fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)


Atrial fibrillation and thromboembolic risk: what is the extent of adherence to guidelines in clinical practice?
Atrial fibrillation (AF) is the most common cardiac rhythm disorder in clinical practice, with a growing prevalence in recent decades. Through the use of thromboembolic risk scores it is possible to adjust thromboprophylaxis to individual risk. The aim of this study was to evaluate the conformity of antithrombotic therapy prescribed at hospital discharge with the guidelines in patients with AF and its influence on long-term morbidity and mortality. We performed a retrospective analysis, based on medical records and phone interview, of consecutive patients admitted to an internal medicine department over a one-year period with a diagnosis of AF or atrial flutter--ICD-9-CM 427.31/32. We determined individual thromboembolic risk in accordance with the ACC/AHA/ESC risk categories, and assessed conformity of antithrombotic therapy with the guidelines. Independent predictors of long-term (378 +/- 241 days) mortality and mortality or readmission were identified by multivariate analysis. The study population consisted of 174 patients with a diagnosis of AF, 59.8% (104) female, mean age 77 +/- 10 years. Hypertension (65.7%) and heart failure (61.3%) were the most prevalent comorbidities. Most patients (82.7%) were stratified as high thromboembolic risk and the remainder as moderate risk. The antithrombotic therapy prescribed at hospital discharge was documented in 155 patients, 126 (81.3%) with high thromboembolic risk. Of the latter group of patients, oral anticoagulation (OAC) was prescribed in 65 (51.6%) and proposed but contraindicated in 24 (19.0%). In patients with moderate thromboembolic risk, therapeutic options were divided between OAC (69.0%), antiplatelet therapy (17.2%) and no thromboprophylaxis (13.8%). Overall there was discordance between the therapy instituted and the guidelines in 25.8% of patients. Age 85 years or over was the only independent predictor of death (HR 1.92; 95% CI 0.94-3.91), while OAC (HR 0.43; 95% CI 0.27-0.70) and male gender (HR 0.58; 95% CI 0.36-0.94) were independent protective factors against death or hospital readmission. In this study, patients admitted with AF were mainly elderly, women and with high thromboembolic risk. The prescription rate of OAC in patients at high risk was lower than recommended in the guidelines, which were not followed in a quarter of patients. The main therapeutic option in cases of moderate risk was OAC. OAC use was the only modifiable factor able to improve prognosis of patients with AF, and it is thus crucial to ensure adherence to the guidelines in daily clinical practice.


Clathrin-mediated endocytosis regulates occludin, and not focal adhesion, distribution during epithelial wound healing.
Vesicle trafficking has long been suggested to play mechanistic roles in regulating directed cell migration. Recent evidence demonstrates that specific cell types and modes of migration involve transport of particular cargo through particular pathways. Epithelial wound healing is essential in tissue repair. However, investigations into the mechanisms regulating cell migration have mainly focused upon other models such as fibroblast-derived cells. Roles for vesicle trafficking pathways in regulating directed cell migration have been identified in recent studies, but mechanisms through which endocytosis might be involved in epithelial wound healing have not been as well studied. Therefore, we analysed potential regulatory roles for endocytosis pathways during epithelial cell motility, with a particular focus on cell adhesion. Specifically, and in contrast to studies in fibroblasts, we find no evidence for a link between endocytosis and the distribution of focal adhesions. However, the localisation of occludin, an essential component of tight junctions, is regulated through endocytosis. We identified epithelial monolayer wounding as a stimulus for endocytosis of occludin and have shown that internalisation of occludin from the wound edge occurs through clathrin-mediated endocytosis (CME) into a rab5-positive compartment. Thus, these studies have evaluated mechanistic roles for dynamin-dependant, CME and caveolar endocytosis during epithelial wound healing and have provided contrasting observations between analyses of cell motility in fibroblast models and epithelial cells. In conclusion, these studies have identified a novel mechanism for regulation of occludin during wound healing.


Enhanced air sparging for groundwater remediation using alginate gel-based removable hydraulic barriers.
The objective of this study was to investigate the effect of a removable physical barrier on the air sparging performance using a lab-scale aquifer model was investigated. The barrier was installed in water-saturated porous media, prior to the air sparging, by injecting calcium chloride aqueous solution into the aquifer with pre-applied alginate solution. Changes in the air flow direction and air flux at the media surface during air sparging were evaluated. With a hydrogel barrier set at the center of the media, the airflow detoured the barrier resulting in a bimodal air flux distribution at the media surface. While employing two gel-formed barriers positioned away from the media's center, the airflow concentrated specifically on the gap between the barriers. The hydrogel was successfully removed using a sodium bicarbonate solution (1.0 mol/L). Using the hydrogel barrier, the performance of air sparging was significantly enhanced for removing contaminants [tetrachloroethene (PCE) and n-hexane mixture] due to increased air flux; 9.8% of PCE applied (7.8 g) was removed during 120 min air sprging for the gel barrier system whereas no PCE was removed for the control. Alginate gel did not show significant sorption capacity for PCE. It was stable in the contaminant up to 68 days with reasonable loss of its mass. Findings of this study present a promising option for air sparging process specifically targeting the contaminant source zone in the aquifer.


Clinical genetics and outcome of left ventricular non-compaction cardiomyopathy.
In this study, we aimed to clinically and genetically characterize LVNC patients and investigate the prevalence of variants in known and novel LVNC disease genes. Left ventricular non-compaction cardiomyopathy (LVNC) is an increasingly recognized cause of heart failure, arrhythmia, thromboembolism, and sudden cardiac death. We sought here to dissect its genetic causes, phenotypic presentation and outcome. In our registry with follow-up of in the median 61 months, we analysed 95 LVNC patients (68 unrelated index patients and 27 affected relatives; definite familial LVNC = 23.5%) by cardiac phenotyping, molecular biomarkers and exome sequencing. Cardiovascular events were significantly more frequent in LVNC patients compared with an age-matched group of patients with non-ischaemic dilated cardiomyopathy (hazard ratio = 2.481, P = 0.002). Stringent genetic classification according to ACMG guidelines revealed that TTN, LMNA, and MYBPC3 are the most prevalent disease genes (13 patients are carrying a pathogenic truncating TTN variant, odds ratio = 40.7, Confidence interval = 21.6-76.6, P < 0.0001, percent spliced in 76-100%). We also identified novel candidate genes for LVNC. For RBM20, we were able to perform detailed familial, molecular and functional studies. We show that the novel variant p.R634L in the RS domain of RBM20 co-segregates with LVNC, leading to titin mis-splicing as revealed by RNA sequencing of heart tissue in mutation carriers, protein analysis, and functional splice-reporter assays. Our data demonstrate that the clinical course of symptomatic LVNC can be severe. The identified pathogenic variants and distribution of disease genes-a titin-related pathomechanism is found in every fourth patient-should be considered in genetic counselling of patients. Pathogenic variants in the nuclear proteins Lamin A/C and RBM20 were associated with worse outcome.


Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital.
To examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC) in patients undergoing resection at Johns Hopkins Hospital (JHH; Baltimore, MD). Between August 30, 1993, and February 28, 2005, a total of 908 patients underwent PD for PC at JHH. A prospective database was reviewed to determine which patients received fluorouracil (FU) -based CRT. Excluded patients had metastatic disease, died 60 or fewer days after PD, received preoperative therapy, an experimental vaccine, adjuvant chemotherapy or radiation alone. The final cohort includes 616 patients. The median follow-up was 17.8 months (interquartile range, 9.7 to 33.5 months). Overall median survival was 17.9 months (95% CI, 16.3 to 19.5 months). Groups were similar with respect to tumor size, nodal status, and margin status, but the CRT group was younger (P < .001), and less likely to present with a severe comorbid disease (P = .001). Patients with carcinomas larger than 3 cm (P = .001), grade 3 and 4 (P < .001), margin-positive resection (P = .001), and complications after surgery (P = .017) had poor long-term survival. Patients receiving CRT experienced an improved median (21.2 v 14.4 months; P < .001), 2-year (43.9% v 31.9%), and 5-year (20.1% v 15.4%) survival compared with no CRT. After controlling for high-risk features, CRT was still associated with improved survival (relative risk = 0.74; 95% CI, 0.62 to 0.89). These data suggest that adjuvant concurrent FU-based CRT significantly improves survival after PD for PC when compared with patients not receiving CRT. These data support the use of combined adjuvant CRT for PC.


Arabidopsis proteome responses to the smoke-derived growth regulator karrikin.
Karrikins are butenolide plant growth regulators in smoke from burning plant material that have proven ability to promote germination and seedling photomorphogenesis. However, the molecular mechanisms underlying these processes are unclear. Here we provide the first proteome-wide analysis of early responses to karrikin in plants (Arabidopsis seedlings). Image analysis of two-dimensionally separated proteins, Rubisco-depleted proteomes and phosphoproteomes, together with LC-MS profiling, detected >1900 proteins, 113 of which responded to karrikin treatment. All the differentially abundant proteins (except HSP70-3) are novel karrikin-responders, and most are involved in photosynthesis, carbohydrate metabolism, redox homeostasis, transcription control, proteosynthesis, protein transport and processing, or protein degradation. Our data provide functionally complementary information to previous identifications of karrikin-responsive genes and evidence for a novel karrikin signalling pathway originating in chloroplasts. We present an updated model of karrikin signalling that integrates proteomic data and is supported by growth response observations. Karrikin has shown promising potential in agricultural applications, yet this process is poorly understood at the molecular level. To the best of our knowledge, this is the first survey of early global proteomic responses to karrikin in plants (Arabidopsis seedlings). The combination of label-free LC-MS profiling and 2-DE analyses provided highly sensitive snapshots of protein abundance and quantitative information on proteoform-level changes. These results present evidence of proteasome-independent karrikin signalling pathways and provide novel targets for detailed mechanistic studies using, e.g., mutants and transgenic plants.


Parental age and risk of schizophrenia: a case-control study.
Advanced paternal age has been suggested as a possible risk factor for schizophrenia. It is not known whether this is explained by known risk factors for schizophrenia, including sibship characteristics, death of a parent before first hospital admission, season and place of birth, and family history of psychiatric illness, or by socioeconomic factors. We investigated the risk of schizophrenia associated with parental age, adjusting for known risk factors for schizophrenia, including family psychiatric history, and controlling for socioeconomic and demographic factors. We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history. Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83). Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia.


Resistance of Salmonellae isolated in 1959 and 1960 to tetracyclines and chloramphenicol.
The resistance of cultures of Salmonella typhimurium to tetracyclines and chloramphenicol has been examined periodically. Although none of 200 cultures isolated prior to 1948 was resistant to the antibiotics, 5% of 100 cultures from man and 9% of 100 cultures from fowls which were isolated in 1956 and 1957 were resistant to tetracyclines. Among 158 cultures isolated from man and 100 cultures isolated from fowls in 1959 and 1960, 13.9 and 29%, respectively, were resistant to tetracyclines. In the last series, cultures resistant to chloramphenicol were found for the first time. Among 150 cultures of other Salmonella serotypes from man and 137 similar cultures isolated from fowls in 1959 and 1960, 5.3 and 8%, respectively, were found resistant to tetracyclines. There is no obvious explanation for the higher percentage of resistant strains occurring in S. typhimurium than in other serotypes.


17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway.
Osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability. The importance of chondrocytes in the pathogenesis of OA is unequivocal. 17β-estradiol (E2) has a potential protective effect against OA. However, the mechanism of E2 in OA chondrocytes remains unclear. In this study, we investigated the regulative effect of E2 on cell growth and the relationship between E2 and the PI3K/Akt pathway in rat OA model chondrocytes (pretreated with interleukin-1β). We found that E2 induced chondrocyte proliferation, and increased the expression level of Akt simultaneously, especially the expression level of P-Akt. Furthermore, the inhibition of P-Akt could block chondrocyte proliferation induced by E2. These results suggest that PI3K/Akt activation induced by E2 may be an important factor in the mechanism of E2 in cell proliferation in rat OA model chondrocytes, and help further understanding the role of E2 in OA progression.


Inactivation of the cannabinoid receptor CB1 prevents leukocyte infiltration and experimental fibrosis.
Cannabinoids are derivates of the marijuana component Δ(9) -tetrahydrocannabinol that exert their effects on mesenchymal cells and immune cells via CB1 and CB2 receptors. The aim of the present study was to evaluate the role of CB1 in systemic sclerosis. CB1-deficient (CB1(-/-) ) mice and wild-type littermates (CB1(+/+) mice) were injected with bleomycin. CB1 signaling was activated in vivo with the selective agonist N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA). Bone marrow transplantation experiments were performed to investigate whether the phenotype of CB1(-/-) mice was mediated by leukocytes or mesenchymal cells. The role of CB1 was also investigated in the TSK-1 mouse model. CB1(-/-) mice were protected from bleomycin-induced dermal fibrosis, with reduced dermal thickening, hydroxyproline content, and myofibroblast counts. Inactivation of CB1 decreased the number of infiltrating T cells and macrophages in lesional skin. In contrast, activation of CB1 with ACEA increased leukocyte infiltration and enhanced the fibrotic response to bleomycin. The phenotype of CB1(-/-) mice was mimicked by transplantation of CB1(-/-) mouse bone marrow into CB1(+/+) mice, demonstrating that CB1 exerts its profibrotic effects indirectly by regulating leukocyte infiltration. Consistently, knockdown of CB1 did not prevent fibrosis in the inflammation-independent TSK-1 mouse model. We demonstrate that the cannabinoid receptor CB1 is crucial for leukocyte infiltration and secondary fibroblast activation and that inactivation of CB1 exerts potent antifibrotic effects in inflammation-driven models of fibrosis.


Lymphoma growth in vivo: electronic discrimination between tumor and stroma cells.
Moloney lymphoma cells are larger than normal cells of mouse spleen, lymph-node, and thymus. Use of electronic cell-size anaylsis in conjunction with specific immunocytolysis permits difjerential counting of host and tumor cells. Increase of lymphoma cells occurs first in spleen and then in lymph nodes; in thymus it occurs only during the terminal stages of tumor growth.


A robust type I interferon gene signature from blood RNA defines quantitative but not qualitative differences between three major IFNβ drugs in the treatment of multiple sclerosis.
We analysed gene expression microarray data from whole blood samples from 228 multiple sclerosis (MS) patients either untreated or treated with one of three alternative commonly used interferon beta (IFNβ) disease modifying drugs: Avonex (×1 weekly), Betaseron (every second day) or Rebif (×3 weekly). Patient injections were not timed to coordinate sample collections, thus providing a global transcriptomic profile for each population of patients studied. Three hundred and fifty one genes were significantly differentially expressed by at least one of the IFNβ drugs. Despite the different drug sources with distinct injection and dosage protocols, a striking similarity was found in the identity and functional classes of the differentially expressed genes induced. Using the 25 most-upregulated genes, we defined a robust IFNβ gene expression signature that quantifies the IFN activation state per blood sample collected irrespective of the type of IFNβ therapy. This 25-gene signature also defined basal IFN activation states among untreated MS patients, which differed among individuals but remained relatively constant per patient with time. The maximum drug-induced IFN-activation state was similar for all three drugs despite a 1.7-2.0-fold diminished average effect for Avonex. This and a more erratic effect of Avonex per patient across longitudinal measurements is likely a result of its reduced injection frequency. In summary, we have defined a robust blood-derived type I IFN gene signature from MS patients. This signature could potentially serve to generically quantify the systemic Type I IFN activation status for any other clinical manifestation, inclusive of other autoimmune diseases.


Inhibition of very long chain acyl-CoA dehydrogenase during cardiac ischemia.
The heart utilizes primarily fatty acids for energy production. During ischemia, however, diminished oxygen supply necessitates a switch from beta-oxidation of fatty acids to glucose utilization and glycolysis. Molecular mechanisms responsible for these alterations in metabolism are not fully understood. Mitochondrial acyl-CoA dehydrogenase catalyzes the first committed step in the beta-oxidation of fatty acids. In the current study, an in vivo rat model of myocardial ischemia was utilized to determine whether specific acyl-CoA dehydrogenases exhibit ischemia-induced alterations in activity, identify mechanisms responsible for changes in enzyme function, and assess the effects on mitochondrial respiration. Very long chain acyl-CoA dehydrogenase (VLCAD) activity declined 34% during 30 min of ischemia. Loss in activity appeared specific to VLCAD as medium chain acyl-CoA dehydrogenase activity remained constant. Loss in VLCAD activity during ischemia was not due to loss in protein content. In addition, activity was restored in the presence of the detergent Triton X-100, suggesting that changes in the interaction between the protein and inner mitochondrial membrane are responsible for ischemia-induced loss in activity. Palmitoyl-carnitine supported ADP-dependent state 3 respiration declined as a result of ischemia. When octanoyl-carnitine was utilized state 3 respiration remained unchanged. State 4 respiration increased during ischemia, an increase that appears specific to fatty acid utilization. Thus, VLCAD represents a likely site for the modulation of substrate utilization during myocardial ischemia. However, the dramatic increase in mitochondrial state 4 respiration would be predicted to accentuate the imbalance between energy production and utilization.


Long-Term Cortisol Concentration in Scalp Hair of Asthmatic Children Using Inhaled Corticosteroids: A Case-Control Study.
Inhaled corticosteroids (ICS) can interfere with the hypothalamic-pituitary-adrenal (HPA) axis and may lead to adrenal insufficiency, resulting in a decrease of cortisol production. Cortisol levels measured in scalp hair provide a marker for long-term cortisol exposure. Data regarding hair cortisol concentration (HCC) in asthmatic children with ICS therapy are scarce. The aim of this study is to compare HCC in asthmatic children under ICS treatment with a healthy control group. We set up a case-control study measuring the cortisol concentration in scalp hair in asthmatic children (N = 80) treated with ICS and healthy controls (N = 252) aged 4-18 years. Anthropometric characteristics and hair samples from the posterior vertex were obtained. At least 5 mg of the most proximal 3 cm of hair was used for each hair sample. HCC was analyzed by liquid chromatography-tandem mass spectrometry. HCC did not significantly differ between asthmatic children using ICS and healthy controls (p = 0.950) after adjustment for age, gender, height, body mass index, and socioeconomic status. No correlation was found between budesonide dosage and HCC levels (r = -0.031, p = 0.78). There was no evidence of suppression of basal cortisol production, as measured in scalp hair, in asthmatic children using ICS, compared to healthy controls. No conclusions can be drawn on the HPA-axis stress response in these children.


Kinetics of metabolic pathways. A system in vitro to study the control of flux.
A method for determining Control Coefficients is proposed for systems studied in vitro and applied to a model pathway. Rat liver extract, which converts glucose into glycerol 3-phosphate, was used with the addition to the incubation mixture of fructose-bisphosphate aldolase, triose-phosphate isomerase and glycerol-3-phosphate dehydrogenase as 'auxiliary' enzymes, which leaves all the control on the first three enzymes. The flux of the metabolic pathway was recorded by assaying NADH decay. Flux Control Coefficients (CJE) of hexokinase, glucose-6-phosphate isomerase and phosphofructokinase were calculated by titration of the system with increasing quantities of extraneous enzymes. It is shown that the summation property is fulfilled. The applicability of this procedure to study the control in any metabolic pathway is discussed. Possible relevance of the method to conditions in vivo and its limitations are considered.


FDG-PET predicts outcomes of treated bone metastasis following palliative radiotherapy in patients with hepatocellular carcinoma.
To determine the utility of FDG-PET in predicting long-term infield tumour control after RT in patients with metastatic hepatocellular carcinoma (HCC) to bone. Among 223 patients with HCC skeletal metastases diagnosed, we reviewed 22 patients with 45 total sites treated with RT who had at least two FDG-PETs prior to and after RT. The median RT dose was 42 Gy (range, 22-48) with a median fraction of 3 Gy (range, 2-8). Helical tomotherapy was generally offered for lesions that received higher RT dose (36%). The intrahepatic control rate in all patients was 73% at the time of referral. The ratio of tumour SUV to blood-pool activity SUV (SUV-ratio) was calculated. The primary end-points were infield progression-free survival (infield-PFS) and infield event-free survival (infield-EFS; recurrent and intractable pain or skeletal-related events). Among 45 sites, 20 had tumour progression and 21 developed events in the previously treated area. A higher SUV-ratio before RT, SUV-ratio decline and higher radiation dose were independently and significantly correlated with better infield-PFS (both P<0.05). The tumours with a pre-RT SUV-ratio≥3.0 and SUV-ratio decline≥40% had significantly better infield-PFS and EFS than those with either a pre-RT SUV-ratio<3.0 or SUV-ratio decline<40% (both P<0.05). FDG-PET may help to predict outcomes of infield tumour control following palliative RT for treatment of HCC bone metastases. Tumours with low metabolic uptake before RT or with a minor decline in post-RT SUV-ratio showed poor long-term infield tumour control.


Pathogenesis of Autographa californica M nucleopolyhedrovirus in fifth instar Spodoptera frugiperda.
We have characterized infection and pathogenesis of an Autographa californica M nucleopolyhedrovirus recombinant, AcMNPV-hsp70/lacZ, carrying the lacZ reporter gene, in penultimate (fifth) instar Spodoptera frugiperda. Bioassays revealed that while <0.1 p.f.u. of budded virus was required to generate an LD(50) by intrahaemocoelic injection, approximately 6000 occlusions were required orally to achieve the same mortality in newly moulted fifth instar (5(0)) larvae. In pathogenesis experiments, 78 % of the 5(0) larvae inoculated orally with 6000 occlusions of AcMNPV-hsp70/lacZ were LacZ-positive at 8 h post-inoculation (p.i.) and 50 % had LacZ signals in tracheal cells indicating that in these larvae infection had been transmitted from the midgut to secondary target cells. At 24 h p.i., maximum numbers of midgut and midgut-associated tracheal foci were observed (mean of 35 foci per infected larva), and 88 % of the larvae were LacZ-positive. The extremely low foci-per-occlusion ratio (0.006) indicated that successful infection of midgut cells was the primary barrier to fatal infection. A second barrier involved the loss of infected tracheal cells associated with the midgut. At 24 h p.i., 88 % of the inoculated larvae had a systemic infection, but in bioassays only 51 % succumbed to polyhedrosis disease. The absence of melanized tracheal cells in the insects throughout the time-course suggested that the larvae that cleared their infections (38 %) did so by a mechanism other than a classical immune response.


A novel in silico Nuss procedure for pectus excavatum patients.
The purpose of this study is to suggest a novel in silico Nuss procedure that can predict the results of chest wall deformity correction. Three-dimensional (3D) geometric and finite element model of the chest wall were built from the 15-year-old male adolescent patient's computed tomography (CT) image with pectus excavatum of the mild deformity. A simulation of anterior translating the metal bar (T) and a simulation of maintaining equilibrium after 180-degree rotation (RE) were performed respectively. A RE simulation using the chest wall finite element model with intercostal muscles (REM) was also performed. Finally, the quantitative results of each in silico Nuss procedure were compared with those of postoperative patient. Furthermore, various mechanical indicators were compared between simulations. This confirmed that the REM simulation results were most similar to the actual patient's results. Through two clinical indicators that can be compared with postoperative patient and mechanical indicators, the authors consider that the REM of silico Nuss procedure proposed in this study is best simulated the actual surgery.


Reversible Bergman cyclization by atomic manipulation.
The Bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology. Here we demonstrate a reversible Bergman cyclization for the first time. We induced the on-surface transformation of an individual aromatic diradical into a highly strained ten-membered diyne using atomic manipulation and verified the products by non-contact atomic force microscopy with atomic resolution. The diyne and diradical were stabilized by using an ultrathin NaCl film as the substrate, and the diyne could be transformed back into the diradical. Importantly, the diradical and the diyne exhibit different reactivity, electronic, magnetic and optical properties associated with the changes in the bond topology, and spin multiplicity. With this reversible, triggered Bergman cyclization we demonstrated switching on demand between the two reactive intermediates by means of selective C-C bond formation or cleavage, which opens up the field of radical chemistry for on-surface reactions by atomic manipulation.


Impact of blunted perception of dyspnea on medical care use and expenditure, and mortality in elderly people.
Dyspnea is an alarming symptom responsible for millions of patient visits each year. Poor perception of dyspnea might be reasonably attributed to an inappropriately low level of fear and inadequate earlier medical treatment for both patients and physicians, resulting in subsequent intensive care. This study was conducted to evaluate medical care use and cost, and mortality according to the perception of dyspnea in community-dwelling elderly people. We analyzed baseline data from a community-based Comprehensive Geriatric Assessment in 2002. The perception of dyspnea in 479 Japanese community-dwelling elderly people with normal lung function was measured in August 2002. The sensation of dyspnea during breathing with a linear inspiratory resistance of 10, 20, and 30 cmH(2)O/L/s was rated using the Borg scale. According to the perception of dyspnea, we divided the elderly into tertiles and compared all hospitalizations, out-patient visits, costs, and death through computerized linkage with National Health Insurance beneficiaries claims history files between August 2002 and March 2008. In-patient hospitalization days and medical care costs significantly increased with the blunted perception of dyspnea, resulting in an increase in total medical-costs with blunted perception of dyspnea. With low perception group as reference, the hazard ratios of all-cause mortality were 0.65 (95% CI 0.23-1.89) for intermediate perception group and 0.31 (0.10-0.97) for high perception group, indicating the mortality rate also significantly increased with the blunted perception of dyspnea after multivariates adjustment (p = 0.04). The blunted perception of dyspnea is related to hospitalization, large medical costs, and all-cause mortality in community-dwelling elderly people. These findings provide a rational for preventing serious illness with careful monitoring of objective conditions in the elderly.


Reliability of outer lesion secondary caries as a predictor of wall lesions.
To assess the reliability of in vitro developed secondary caries outer lesions as an indicator of presence and extent of wall lesions. Class I occlusal cavities were cut in 132 extracted premolars: 12 teeth were not restored, 120 restored with one of 20 different restoration combinations of silver amalgam, base and varnish. Specimens were aged in 1% NaCl for up to 1 year where after 80 restored and 12 unrestored teeth were subjected to an in vitro bacterial challenge for 36 days, the other 40 specimens were similarly incubated in an acidified broth (pH = 4.0). Sections were prepared for polarized light microscopy and outer and wall lesion areas, outer lesion width, wall lesion length and enamel thickness measured. Data were subjected to Fisher's exact test and Pearson Correlation. There was a significant association (P < 0.05) between outer and wall lesions in all cariously challenged specimen groups. Sensitivity was high 95-96% but specificity was 26% for acid broth, 68% for restored bacterial and 100% for unrestored specimens. Restoration variables impacted widely on specificity. Correlation values were too low to show clinically relevant associations between wall and outer lesion size. Frequency distribution showed that wall lesions extending beyond the dentin-enamel junction were generally associated with potentially remineralizable outer lesions.


Clinical utility during inpatient rehabilitation of a clinical prediction rule for ambulation prognosis following spinal cord injury.
Objective: Mobility prognosis is a key focus during rehabilitation following spinal cord injury (SCI). The goal of this study was to prospectively evaluate the clinical utility of the van Middendorp clinical prediction rule (CPR).Design: Observational studySetting: Inpatient rehabilitation unitParticipants: Physical therapists and their patients with acute SCI and SCI disorders (SCI/D) for whom long-term ambulation prognosis was judged difficult to determine.Interventions: N/AOutcome Measures: CPR-determined probability of ambulation, therapist reported clinical utility (yes/no), shared with the patient (yes/no), useful for motivation/setting realistic expectations, and Functional Independence Measure (FIM) Locomotion walk score.Results: Five therapists and 52 patients (8 non-traumatic SCI/D) participated. 91% had lesions classified as AIS C or D. The median [IQR] for CPR probability of ambulation was 96.0 [86.5,99.0] for traumatic SCI and 80.0 [64.5, 94.5] for non-traumatic SCI/D. Clinical utility was reported for 45% of those with SCI and 88% with non-traumatic SCI/D. Therapists with less experience were more likely to report clinical utility and share with their patients. Ambulation probability was higher for patients who did not meet their FIM goal. CPR probability was correlated with discharge FIM only for non-traumatic SCI/D.Conclusion: The CPR was not predictive of inpatient rehabilitation outcomes, in fact outcomes varied widely for individuals with similar probabilities emphasizing the importance of clinical judgement and continued need to identify individual factors that affect ambulation. However, greater utility in establishing prognosis and goal setting was noted for clinicians with less experience and for individuals with non-traumatic SCI/D.


Short-term exposure to hydrogen peroxide during oocyte maturation improves bovine embryo development.
Recent studies have shown that short-term exposure of oocytes to a stressor such as hydrostatic pressure or osmotic stress might induce stress tolerance in embryos. The aim of the present study was to investigate the consequences of short-term hydrogen peroxide (H(2)O(2)) exposure to bovine in vitro matured cumulus-oocyte complexes (COCs) on subsequent preimplantation embryo development and apoptosis. In the first experiment, mature COCs were incubated in H(2)O(2) at concentrations ranging between 0.01 and 100 micromol/l, and subsequently fertilized and cultured. Oocyte incubation with 50-100 micromol/l of H(2)O(2) resulted in a significantly higher blastocyst yield (47.3%) in comparison with control medium (31.8%), while apoptotic cell ratio was inversely related with H(2)O(2) concentration. In the second experiment, we showed that the stress tolerance after H(2)O(2) exposure was not mediated by increased glutathione content in treated oocytes nor by enhanced fertilization or penetration. Further research should concentrate on the potential role of players that have been associated with stress tolerance in somatic cell lines.


Examining Preparatory Testing and Other Factors Associated With Performance on the Multistate Pharmacy Jurisprudence Examination.
Objective. To evaluate whether the score on the Pre-Multistate Pharmacy Jurisprudence Examination (Pre-MPJE) predicts pharmacy students' performance on the MPJE, and to determine whether demographics, pre-pharmacy school factors, or pharmacy school factors affect MPJE outcomes.Methods. We performed a retrospective review of pharmacy school graduates' (N = 156) MPJE scores, Pre-MPJE scores, demographics, pre-pharmacy school academic performance factors, and pharmacy school academic performance factors. Bivariate and correlational analyses were conducted along with multiple linear regression models to determine the influence of variables on the MPJE total scaled score.Results. A total of 136 pharmacy school graduates were included, with most being female (59%) and non-Hispanic White students (75%). The score on the Pre-MPJE was not significantly correlated with students' first-attempt MPJE pass-fail outcome or total scaled score. Factors that were correlated with passing the MPJE were a younger age at graduation, a higher pharmacy law course grade, Pharmacy Curriculum Outcomes Assessment (PCOA) examination scores, specifically scaled total scores and scaled scores for content areas 1-4 and final pharmacy school grade point average (GPA). The MPJE total scaled score was correlated with a higher pre-pharmacy school GPA, pharmacy law course grade, PCOA total and content area 1-4 scaled scores, and final pharmacy school GPA. However, regression models found that the greatest variance in MPJE total scaled score was contributed by the pharmacy law course grade. The total scaled score on the PCOA contributed to some variance for all MPJE takers, but only the pharmacy law course grade significantly influenced the in-state MPJE total scaled score.Conclusion. The findings did not show that the Pre-MPJE score was a predictor for passing the MPJE or for the MPJE total scaled score. The most important determinant of the MPJE total scaled score was a student's performance in the pharmacy law course.


Focused ultrasound to displace renal calculi: threshold for tissue injury.
The global prevalence and incidence of renal calculi is reported to be increasing. Of the patients that undergo surgical intervention, nearly half experience symptomatic complications associated with stone fragments that are not passed and require follow-up surgical intervention. In a clinical simulation using a clinical prototype, ultrasonic propulsion was proven effective at repositioning kidney stones in pigs. The use of ultrasound to reposition smaller stones or stone fragments to a location that facilitates spontaneous clearance could therefore improve stone-free rates. The goal of this study was to determine an injury threshold under which stones could be safely repositioned. Kidneys of 28 domestic swine were treated with exposures that ranged in duty cycle from 0%-100% and spatial peak pulse average intensities up to 30 kW/cm(2) for a total duration of 10 min. The kidneys were processed for morphological analysis and evaluated for injury by experts blinded to the exposure conditions. At a duty cycle of 3.3%, a spatial peak intensity threshold of 16,620 W/cm(2) was needed before a statistically significant portion of the samples showed injury. This is nearly seven times the 2,400-W/cm(2) maximum output of the clinical prototype used to move the stones effectively in pigs. The data obtained from this study show that exposure of kidneys to ultrasonic propulsion for displacing renal calculi is well below the threshold for tissue injury.


You Should Be the Specialist! Weak Mental Rotation Performance in Aviation Security Screeners - Reduced Performance Level in Aviation Security with No Gender Effect.
Aviation security screeners analyze a large number of X-ray images per day and seem to be experts in mentally rotating diverse kinds of visual objects. A robust gender-effect that men outperform women in the Vandenberg & Kuse mental rotation task has been well documented over the last years. In addition it has been shown that training can positively influence the overall task-performance. Considering this, the aim of the present study was to investigate whether security screeners show better performance in the Mental Rotation Test (MRT) independently of gender. Forty-seven security screeners of both sexes from two German airports were examined with a computer based MRT. Their performance was compared to a large sample of control subjects. The well-known gender-effect favoring men on mental rotation was significant within the control group. However, the security screeners did not show any sex differences suggesting an effect of training and professional performance. Surprisingly this specialized group showed a lower level of overall MRT performance than the control participants. Possible aviation related influences such as secondary effects of work-shift or expertise which can cumulatively cause this result are discussed.


Unusual transformations in the biosynthesis of the antibiotic phosphinothricin tripeptide.
Phosphinothricin tripeptide (PTT, phosphinothricylalanylalanine) is a natural-product antibiotic and potent herbicide that is produced by Streptomyces hygroscopicus ATCC 21705 (ref. 1) and Streptomyces viridochromogenes DSM 40736 (ref. 2). PTT has attracted widespread interest because of its commercial applications and unique phosphinic acid functional group. Despite intensive study since its discovery in 1972 (see ref. 3 for a comprehensive review), a number of steps early in the PTT biosynthetic pathway remain uncharacterized. Here we report a series of interdisciplinary experiments involving the construction of defined S. viridochromogenes mutants, chemical characterization of accumulated intermediates, and in vitro assay of selected enzymes to examine these critical steps in PTT biosynthesis. Our results indicate that early PTT biosynthesis involves a series of catalytic steps that to our knowledge has not been described so far, including a highly unusual reaction for carbon bond cleavage. In sum, we define a pathway for early PTT biosynthesis that is more complex than previously appreciated.


Itch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors.
Chronic itch is a highly debilitating condition affecting about 10% of the general population. The relay of itch signals is under tight control by inhibitory circuits of the spinal dorsal horn, which may offer a hitherto unexploited therapeutic opportunity. Here, we found that specific pharmacological targeting of inhibitory α2 and α3GABAA receptors reduces acute histaminergic and non-histaminergic itch in mice. Systemic treatment with an α2/α3GABAA receptor selective modulator alleviates also chronic itch in a mouse model of atopic dermatitis and in dogs sensitized to house dust mites, without inducing sedation, motor dysfunction, or loss of antipruritic activity after prolonged treatment. Transsynaptic circuit tracing, immunofluorescence, and electrophysiological experiments identify spinal α2 and α3GABAA receptors as likely molecular targets underlying the antipruritic effect. Our results indicate that drugs targeting α2 and α3GABAA receptors are well-suited to alleviate itch, including non-histaminergic chronic itch for which currently no approved treatment exists.


Increased expression of Nox1 in neointimal smooth muscle cells promotes activation of matrix metalloproteinase-9.
Vascular injury causes neointimal hypertrophy, which is characterized by redox-mediated matrix degradation and smooth muscle cell (SMC) migration and proliferation. We hypothesized that, as compared to the adjacent medial SMCs, neointimal SMCs produce increased superoxide via NADPH oxidase, which induces redox-sensitive intracellular signaling to activate matrix metalloproteinase-9 (MMP-9). Two weeks after balloon injury, rat aorta developed a prominent neointima, containing increased expression of NADPH oxidase and reactive oxygen species (ROS) as compared to the medial layer. Next, SMCs were isolated from either the neointima or the media and studied in culture. Neointimal-derived SMCs exhibited increased Nox1 expression and ROS levels as compared to medial SMCs. Neointimal SMCs had higher cell growth rates than medial SMCs. ROS-dependent ERK1/2 phosphorylation was greater in neointimal SMCs. MMP-9 activity, as detected by gel zymography, was greater in neointimal SMCs under resting and stimulated conditions and was prevented by expression of an antisense to Nox1 or treatment with an ERK1/2 inhibitor. Following vascular injury, the increased expression of Nox1 in SMCs within the neointima initiates redox-dependent phosphorylation of ERK1/2 and subsequent MMP-9 activation.


[An experimental study on the use of the Hilbert operator as a method of signal preprocessing for the determination of oxygen saturation in retinal vessels].
For the non-invasive measurement of the oxygen saturation in human retinal vessels, the light reflected by a vessel and its surroundings is evaluated. Differences in the absorption and scattering properties of the optical media provide so-called vessel profiles, but the central vessel section is often disturbed by a regular reflex. In order to eliminate this reflex, a method based on the Hilbert transform is presented, which can be used for the determination of logarithmic differences between the reflected light on and that beside the vessel. The data for our investigations were produced by simulation of the radiation transport in multi-layered tissue. A linear regression between expected and measured values based on 40 pairs was used for the evaluation of the proposed method. A linear relationship was shown to exist.


Expression of S100A8 correlates with inflammatory lung disease in congenic mice deficient of the cystic fibrosis transmembrane conductance regulator.
Lung disease in cystic fibrosis (CF) patients is dominated by chronic inflammation with an early and inappropriate influx of neutrophils causing airway destruction. Congenic C57BL/6 CF mice develop lung inflammatory disease similar to that of patients. In contrast, lungs of congenic BALB/c CF mice remain unaffected. The basis of the neutrophil influx to the airways of CF patients and C57BL/6 mice, and its precipitating factor(s) (spontaneous or infection induced) remains unclear. The lungs of 20-day old congenic C57BL/6 (before any overt signs of inflammation) and BALB/c CF mouse lines maintained in sterile environments were investigated for distinctions in the neutrophil chemokines S100A8 and S100A9 by quantitative RT-PCR and RNA in situ hybridization, that were then correlated to neutrophil numbers. The lungs of C57BL/6 CF mice had spontaneous and significant elevation of both neutrophil chemokines S100A8 and S100A9 and a corresponding increase in neutrophils, in the absence of detectable pathogens. In contrast, BALB/c CF mouse lungs maintained under identical conditions, had similar elevations of S100A9 expression and resident neutrophil numbers, but diverged in having normal levels of S100A8. The results indicate early and spontaneous lung inflammation in CF mice, whose progression corresponds to increased expression of both S100A8 and S100A9, but not S100A9 alone. Moreover, since both C57BL/6 and BALB/c CF lungs were maintained under identical conditions and had similar elevations in S100A9 and neutrophils, the higher S100A8 expression in the former (or suppression in latter) is a result of secondary genetic influences rather than environment or differential infection.


Genes and gene clusters related to genotype and drought-induced variation in saccharification potential, lignin content and wood anatomical traits in Populus nigra.
Wood is a renewable resource that can be employed for the production of second generation biofuels by enzymatic saccharification and subsequent fermentation. Knowledge on how the saccharification potential is affected by genotype-related variation of wood traits and drought is scarce. Here, we used three Populus nigra L. genotypes from habitats differing in water availability to (i) investigate the relationships between wood anatomy, lignin content and saccharification and (ii) identify genes and co-expressed gene clusters related to genotype and drought-induced variation in wood traits and saccharification potential. The three poplar genotypes differed in wood anatomy, lignin content and saccharification potential. Drought resulted in reduced cambial activity, decreased vessel and fiber lumina, and increased the saccharification potential. The saccharification potential was unrelated to lignin content as well as to most wood anatomical traits. RNA sequencing of the developing xylem revealed that 1.5% of the analyzed genes were differentially expressed in response to drought, while 67% differed among the genotypes. Weighted gene correlation network analysis identified modules of co-expressed genes correlated with saccharification potential. These modules were enriched in gene ontology terms related to cell wall polysaccharide biosynthesis and modification and vesicle transport, but not to lignin biosynthesis. Among the most strongly saccharification-correlated genes, those with regulatory functions, especially kinases, were prominent. We further identified transcription factors whose transcript abundances differed among genotypes, and which were co-regulated with genes for biosynthesis and modifications of hemicelluloses and pectin. Overall, our study suggests that the regulation of pectin and hemicellulose metabolism is a promising target for improving wood quality of second generation bioenergy crops. The causal relationship of the identified genes and pathways with saccharification potential needs to be validated in further experiments.


Research into the pathogenesis of macular corneal dystrophy.
The morphology and histochemical attributes of the lesions in macular corneal dystrophy have been well characterized and thus far found to be restricted to the cornea. This inherited metabolic storage disease is thought to be a localized mucopolysaccharidosis and an enzymatic defect in the degradation of corneal keratan sulphate is suspected. Studies on cell cultures of fibroblasts from diseased corneas have as yet failed to extend our knowledge about the pathogenesis of the disorder. Such investigations have included the use of acridine orange and metachromatic dyes, assays for lysosomal enzymes, biochemical analyses of cells and media, as well as kinetic studies on the synthesis and degradation of radioactive glycosaminoglycans. Despite the lack of supportive evidence, the cell culture data nevertheless remain consistent with the hypothesis that macular corneal dystrophy is a disorder of keratan sulphate I catabolism, since the synthesis of keratan sulphate by corneal fibroblasts normally decreases markedly in culture. Studies on corneal explants with macular dystrophy have provided significant positive information about this dystrophy. Freshly excised corneas with macular dystrophy synthesize considerably less keratan sulphate than normal corneas, while they produce excessive amounts of glycopeptides which still need to be characterized.


pFDR and pFNR estimation for brain networks construction.
Recent developments in the study of brain functional connectivity are widely based on graph theory. In the current analysis of brain networks, there is no unique way to derive the adjacency matrix, which is a useful representation for a graph. Its entries, containing information about the existence of links, are identified by thresholding the correlation between the time series that characterized the dynamic behavior of the nodes. In this work, we put forward a strategy to choose a suitable threshold on the correlation matrix considering the problem of multiple comparisons in order to control the error rates. In this context we propose to control the positive false discovery rate (pFDR) and a similar measure involving false negatives, called the positive false nondiscovery rate (pFNR). In particular, we provide point and interval estimators for pFNR and a method for balancing the two types of error, demonstrating it by using functional magnetic resonance imaging data and Monte Carlo simulations.


Vagal nerve stimulation in prevention and management of coronary heart disease.
Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by appropriate vagal stimulation that is anti-inflammatory in nature. Acetylcholine, the principal vagal neurotransmitter, is a potent anti-inflammatory molecule. Polyunsaturated fatty acids (PUFAs) augment acetylcholine release, while acetylcholine can enhance the formation of prostacyclin, lipoxins, resolvins, protectins and maresins from PUFAs, which are anti-inflammatory and anti-arrhythmic molecules. Furthermore, plasma and tissue levels of PUFAs are low in those with CHD and atherosclerosis. Hence, vagal nerve stimulation is beneficial in the prevention of CHD and cardiac arrhythmias. Thus, measurement of catecholamines, acetylcholine, various PUFAs, and their products lipoxins, resolvins, protectins and maresins in the plasma and peripheral leukocytes, and vagal tone by heart rate variation could be useful in the prediction, prevention and management of CHD and cardiac arrhythmias.


Qualitative exploration of sociocultural determinants of health inequities of Dalit population in Dhaka City, Bangladesh.
In recent years, Bangladesh has made remarkable advances in health outcomes; however, the benefits of these gains are unequally shared among citizens and population groups. Dalits (jaat sweepers), a marginalised traditional working community, have relatively poor access to healthcare services. This study sought to explore the sociopolitical and cultural factors associated with health inequalities among Dalits in an urban setting. An exploratory qualitative study design was adopted. Fourteen in-depth interviews, five focus group discussions and seven key informant interviews were conducted. The acquired data were analysed using an iterative approach which incorporated deductive and inductive methods in identifying codes and themes. This study was conducted in two sweeper communities in Dhaka city. Participants were Dalit men and women (in-depth interviews, mean age±SD 30±10; and focus group discussions), and the community leaders and non-governmental organisation workers (key informant interviews). The health status of members of these Dalit groups is determined by an array of social, economic and political factors. Dalits (untouchables) are typically considered to fall outside the caste-based social structure and existing vulnerabilities are embedded and reinforced by this identity. Dalits' experience of precarious access to healthcare or poor healthcare is an important manifestation of these inequalities and has implications for the economic and social life of Dalit populations living together in geographically constrained spaces. The provision of clinical healthcare services alone is insufficient to mitigate the negative effects of discriminations and to improve the health status of Dalits. A better understanding of the precise influences of sociocultural determinants of health inequalities is needed, together with the identification of the strategies and programmes needed to address these determinants with the aim of developing more inclusive health service delivery systems.


Optical scanning cryptography for secure wireless transmission.
We propose a method for secure wireless transmission of encrypted information. By use of an encryption key, an image or document is optically encrypted by optical heterodyne scanning and hence encryption is performed on the fly. We call this technique optical scanning cryptography. The output of the heterodyne encrypted signal is at radio frequency and can be directly sent through an antenna to a secure site for digital storage to be prepared for decryption. In the secure site, an identical optical scanning system to that used for encryption is used, together with a decryption key, to generate an electrical signal. The electrical signal is then processed and sent to a computer to be used for decryption. Utilizing the stored information received from the encryption stage and the electrical information from the secure site, a digital decryption unit performs a decryption algorithm. If the encryption key and the decryption key are matched, the decryption unit will decrypt the image or document faithfully. The overall cryptosystem can perform the incoherent optical processing counterpart of the well-known coherent double-random phase-encoding technique. We present computer simulations of the idea.


Prevalence of self-reported activity and sedentary behaviors among 4th-, 8th-, and 11th-grade Texas public school children: the school physical activity and nutrition study.
Few studies have compared physical activity (PA) and sedentary activity (SA) by grade and ethnicity, specifically including elementary school students. A cross-sectional probability-based design was used to provide data by ethnicity (African American, Hispanic, and White/Other), gender, and grade (4th, 8th, and 11th) from 2000 to 2002. Two validated questionnaires (elementary and secondary) assessed self-reported PA and SA. Point-prevalence estimates and 95% confidence intervals were computed. Over 70% of students reported vigorous PA on > or = 3 days/week, but < 50% participated in daily physical education. A significant percentage (30% to 50%) of students reported > or = 3 hours per day in SA. Fourth-grade boys and girls reported equal PA; however, 8th and 11th grade girls reported lowered vigorous PA. African American 8th- and 11th-grade boys reported the highest PA, but African American children also reported the highest prevalence of SA. Findings from this study highlight the disparities in physical and sedentary activities by gender, grade, and race/ethnicity, and the need to address these differences with programs and policy. In general, grade level and gender differences were more striking and consistent than racial/ethnic differences.


Frameworks and primary healthcare policy.
Healthcare reform in Canada needs to start with primary care reform, putting patients and their caregivers at the centre of the health system. Although the directions are well accepted, primary care reform requires changes to organizational structures (moving toward multidisciplinary practice) and to physician remuneration to be effective. Without action on these system-level enablers, little real action will be able to occur in repositioning the healthcare system.


Adaptation of a weight management program for a potential lung transplant candidate.
Obesity is a relative contraindication for heart and lung transplantation at most transplant centers. Surgical risks are higher for obese patients, and 1 study suggests that obesity is significantly correlated with higher posttransplant death rates in cardiac transplantation. Obesity is a restrictive disease that contributes to exercise intolerance in patients with lung disease. A weight management group was formed at a transplant center to help obese patients with heart and/or lung disease lose weight and maintain their goal weight, with the hope of decreasing their waiting time to be listed for transplantation and their incidence of weight-related complications. Some patients experienced symptomatic improvement, which delayed their need for heart or lung transplantation.


eNORA2 Exact NOE Analysis Program.
We have recently developed an NMR protocol to extract exact distances between nuclei in proteins from an exact interpretation of NOESY buildup intensities (eNOEs). This enabled us to calculate multistate structural ensembles that exhibit realistic spatial sampling and long-range correlations. Our initial studies were laborious and required a deep understanding of the underlying spin dynamics. Here, we present a MatLab package that integrates all data processing steps required to convert intensities of assigned peaks in NOESY series into upper and lower distance limits for structure calculation. Those steps include organization of the data in object format, extraction of autorelaxation and cross-relaxation rate constants by fitting of diagonal peak decays and cross peak buildups, validation of the data, correction for spin diffusion, graphical display of the results, and generation of distance limits in CYANA compatible format. The analysis may be carried out using a full relaxation matrix or a simplified "divide and conquer" approach that allows for partial deuteration of protons. As the program does not require expertise beyond that of standard resonance assignment/structure calculation, it is suitable for experts and nonexperts alike.