A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance.
The relative short-term efficacy and long-term benefits of pharmacologic versus psychotherapeutic interventions have not been studied for posttraumatic stress disorder (PTSD). This study compared the efficacy of a selective serotonin reup-take inhibitor (SSRI), fluoxetine, with a psychotherapeutic treatment, eye movement desensitization and reprocessing (EMDR), and pill placebo and measured maintenance of treatment gains at 6-month follow-up. Eighty-eight PTSD subjects diagnosed according to DSM-IV criteria were randomly assigned to EMDR, fluoxetine, or pill placebo. They received 8 weeks of treatment and were assessed by blind raters posttreatment and at 6-month follow-up. The primary outcome measure was the Clinician-Administered PTSD Scale, DSM-IV version, and the secondary outcome measure was the Beck Depression Inventory-II. The study ran from July 2000 through July 2003. The psychotherapy intervention was more successful than pharmacotherapy in achieving sustained reductions in PTSD and depression symptoms, but this benefit accrued primarily for adult-onset trauma survivors. At 6-month follow-up, 75.0% of adult-onset versus 33.3% of child-onset trauma subjects receiving EMDR achieved asymptomatic end-state functioning compared with none in the fluoxetine group. For most childhood-onset trauma patients, neither treatment produced complete symptom remission. This study supports the efficacy of brief EMDR treatment to produce substantial and sustained reduction of PTSD and depression in most victims of adult-onset trauma. It suggests a role for SSRIs as a reliable first-line intervention to achieve moderate symptom relief for adult victims of childhood-onset trauma. Future research should assess the impact of lengthier intervention, combination treatments, and treatment sequencing on the resolution of PTSD in adults with childhood-onset trauma.


Towards fast femtosecond laser micromachining of fused silica: The effect of deposited energy.
Femtosecond laser micromachining of glass material using low-energy, sub-ablation threshold pulses find numerous applications in the fields of integrated optics, lab-on-a-chips and microsystems in general. In this paper, we study the influence of the laser-deposited energy on the performance of the micromachining process. In particular, we show that the energy deposited in the substrate affects its etching rate. Furthermore, we demonstrate the existence of an optimal energy deposition value. These results are not only important from an industrial point-of-view but also provide new evidences supporting the essential role of densification and consequently stress-generation as the main driving factor promoting enhanced etching rate following laser exposure.


Complete canine papillomavirus life cycle in pigmented lesions.
Canine papillomaviruses (CPVs) have been identified in various benign and malignant neoplastic skin disorders. The most frequent manifestations of CPV infections are classical warts and pigmented plaques. Although the etiology of canine oral papillomatosis is well established, knowledge about CPVs role in the development of pigmented plaques remains vague. Indeed, as CPV DNA may frequently be found on clinically healthy canine skin, its mere detection in lesions cannot be regarded as a sufficient indicator of causality. Whether CPVs are actually active in pigmented plaques, a requirement for any conceivable involvement, is consequently an open question. To inquire such viral activity, two distinct clinical cases of canine pigmented lesions were evaluated in greater detail. The histological findings in the two cases supported the clinical diagnosis of pigmented viral plaques. Sequencing of amplified DNA from these lesions revealed the genomes of two novel CPV types, i.e. CPV9 and CPV14, both putatively belonging to the genus Chi. Furthermore, transcription and splicing of corresponding CPV mRNA could be shown by RT-PCR in the respective lesions. Finally, viral particles were detected by electron microscopy in homogenates as well as in nuclei of keratinocytes in pigmented lesions. In conclusion, the results link clinical signs of pigmented plaques to histological changes, the presence of CPV specific DNA, viral gene transcription, and the presence of viral particles in and from the lesions. Thus, the findings outline the entire replicative cycle of CPVs in pigmented plaques, which might help understanding the relationship between these viruses and the associated disorders.


Using the National Cancer Database for Outcomes Research: A Review.
The National Cancer Database (NCDB), a joint quality improvement initiative of the American College of Surgeons Commission on Cancer and the American Cancer Society, has created a shared research file that has changed the study of cancer care in the United States. A thorough understanding of the nuances, strengths, and limitations of the database by both readers and investigators is of critical importance. This review describes the use of the NCDB to study cancer care, with a focus on the advantages of using the database and important considerations that affect the interpretation of NCDB studies. The NCDB is one of the largest cancer registries in the world and has rapidly become one of the most commonly used data resources to study the care of cancer in the United States. The NCDB paints a comprehensive picture of cancer care, including a number of less commonly available details that enable subtle nuances of treatment to be studied. On the other hand, several potentially important patient and treatment attributes are not collected in the NCDB, which may affect the extent to which comparisons can be adjusted. Finally, the NCDB has undergone several significant changes during the past decade that may affect its completeness and the types of available data. The NCDB offers a critically important perspective on cancer care in the United States. To capitalize on its strengths and adjust for its limitations, investigators and their audiences should familiarize themselves with the advantages and shortcomings of the NCDB, as well as its evolution over time.


Neurons with strongly negative-charged surface-coats in adult rat brain as detected by staining with cationic iron colloid.
Light microscopy of tissue sections stained either with cationic iron colloid (pH 1.0-2.0) and nuclear fast red or with this colloid and thionin showed that the adult rat brain contains a considerable number of neurons which are strongly negative-charged by being coated with sulfated proteoglycans such as chondroitin sulfates. These neurons are distributed mainly in the cerebral cortex, hippocampus, zona incerta, medial and lateral cerebellar nuclei, ventral pontine nuclei and certain other areas. In the hippocampal formation, the strongly negative-charged cells seem identical with the GABAergic inhibitory interneurons reactive to the lectin Vicia villosa agglutinin. Neurons, including the GABAergic Purkinje's cells, of the cerebellar cortex showed no reaction to our cationic iron colloid at pH values of 1.0-2.0. Many non-GABAergic pyramidal cells in the lamina ganglionalis of cerebral cortex and many non-GABAergic large neurons of the ventral pontine nuclei were highly reactive to our colloid at pH values of 1.0-2.0. This suggests that our cationic iron colloid at pH values of 1.0-2.0 mainly stains certain subtypes of GABAergic neurons as well as some non-GABAergic neurons projecting long associational or commissural fibers.


Effect of methotrexate on intracellular folate pools in purified myeloid precursor cells from normal human bone marrow.
We investigated the effects of the antifolate methotrexate on intracellular folate pools of human myeloid precursor cells (MPCs). Immature MPCs, representing 3.2% of the original marrow population, were selected from normal human bone marrow by immune rosetting. The intracellular folate pools were labeled by incubation with 5 X 10(-8) M [3H]5-formyl-FH4 and were quantitated by high performance liquid chromatography. The predominant folates were 5-methyl-tetrahydrofolate (5-methyl-FH4) (36%), 10-formyl-FH4 (41.4%), 5-formyl-FH4 (12.3%), and FH4 (10.3%). A 12-h exposure to 1 microM methotrexate (MTX) resulted in a 34% reduction in the intracellular concentration of 10-formyl-FH4, a 61% decrease in 5-formyl-FH4, and a 62% decrease in 5-methyl-FH4, as well as the appearance and progressive expansion of the FH2 and 10-formyl-FH2 pools. These changes were maximal after 4 h of incubation with MTX. Paralleling the changes in folates, particularly the increase in FH2, were a 64% reduction in myeloid colony formation and a 77% depression of de novo purine synthesis after 4 h of MTX. We conclude that MTX does not produce quantitative depletion of 10-formyl-FH4 and that its antipurine effect may be mediated by direct inhibition of de novo purine synthesis by FH2 and, at later time points, by MTX polyglutamates.


Rosette-forming ability of thymus-derived lymphocytes in humoral and cell-mediated immunity. II. Helper cell activity.
The technique of velocity sedimentation at unit gravity was used to determine the size and rosette-forming ability of helper cells in nonimmune and immune C57BL/6 mice. Helper T cells were assayed by the ability to cooperate with bone barrow (B) cells in the antibody response to sheep erythrocytes (SRBC) in vivo. 19S helper cells in nonimmune animals were nonrosette-forming small lymphocytes; after immunization with SRBC in complete Freund's adjuvant, 19S helper cells were nonrosette-forming medium lymphocytes. 7S helper cells in immune animals were small lymphocytes which did not form rosettes. No SRBC binding by helper cells was observed under the conditions of rosette formation used.


Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice.
Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse's back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15-17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs' migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans.


Identification of Subject-Specific Immunoglobulin Alleles From Expressed Repertoire Sequencing Data.
The adaptive immune receptor repertoire (AIRR) contains information on an individuals' immune past, present and potential in the form of the evolving sequences that encode the B cell receptor (BCR) repertoire. AIRR sequencing (AIRR-seq) studies rely on databases of known BCR germline variable (V), diversity (D), and joining (J) genes to detect somatic mutations in AIRR-seq data via comparison to the best-aligning database alleles. However, it has been shown that these databases are far from complete, leading to systematic misidentification of mutated positions in subsets of sample sequences. We previously presented TIgGER, a computational method to identify subject-specific V gene genotypes, including the presence of novel V gene alleles, directly from AIRR-seq data. However, the original algorithm was unable to detect alleles that differed by more than 5 single nucleotide polymorphisms (SNPs) from a database allele. Here we present and apply an improved version of the TIgGER algorithm which can detect alleles that differ by any number of SNPs from the nearest database allele, and can construct subject-specific genotypes with minimal prior information. TIgGER predictions are validated both computationally (using a leave-one-out strategy) and experimentally (using genomic sequencing), resulting in the addition of three new immunoglobulin heavy chain V (IGHV) gene alleles to the IMGT repertoire. Finally, we develop a Bayesian strategy to provide a confidence estimate associated with genotype calls. All together, these methods allow for much higher accuracy in germline allele assignment, an essential step in AIRR-seq studies.


Family-focused treatment for children and adolescents with bipolar disorder.
The course of bipolar disorder in children and adolescents is highly recurrent and impairing. This article describes the adaptation of family-focused treatment (FFT) for children and adolescents with bipolar disorder. FFT is given in 21 sessions over 9 months, and is usually initiated during the recovery period following an acute episode of depression or (hypo)mania. The treatment consists of an engagement phase followed by psychoeducation, communication enhancement training, and problem-solving skills training. Results of randomized trials in adults and adolescents find that patients with bipolar disorder who receive FFT and pharmacotherapy recover from episodes more quickly and have longer periods of sustained remission than patients who receive briefer forms of therapy and pharmacotherapy. The application of FFT to youth who are genetically at risk for bipolar disorder is described. Problems in disseminating empirically supported family interventions in community settings are discussed.


Behavioral Counseling to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Cardiovascular Risk Factors: US Preventive Services Task Force Recommendation Statement.
Adults who adhere to national guidelines for a healthful diet and physical activity have lower rates of cardiovascular morbidity and mortality than those who do not. All persons, regardless of their risk status for cardiovascular disease (CVD), can gain health benefits from healthy eating behaviors and appropriate physical activity. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention among adults without obesity who do not have cardiovascular risk factors (hypertension, dyslipidemia, abnormal blood glucose levels, or diabetes). The USPSTF reviewed the evidence on whether primary care-relevant counseling interventions to promote a healthful diet, physical activity, or both improve health outcomes, intermediate outcomes associated with CVD, or dietary or physical activity behaviors in adults; interventions to reduce sedentary behaviors; and the harms of behavioral counseling interventions. Counseling interventions result in improvements in healthful behaviors and small but potentially important improvements in intermediate outcomes, including reductions in blood pressure and low-density lipoprotein cholesterol levels and improvements in measures of adiposity. The overall magnitude of benefit related to these interventions is positive but small. The potential harms are at most small, leading the USPSTF to conclude that these interventions have a small net benefit for adults without obesity who do not have CVD risk factors. The USPSTF recommends that primary care professionals individualize the decision to offer or refer adults without obesity who do not have hypertension, dyslipidemia, abnormal blood glucose levels, or diabetes to behavioral counseling to promote a healthful diet and physical activity. Existing evidence indicates a positive but small benefit of behavioral counseling for the prevention of CVD in this population. Persons who are interested and ready to make behavioral changes may be most likely to benefit from behavioral counseling. (C recommendation).


Mono- and combination therapy of long-acting bronchodilators and inhaled corticosteroids in advanced COPD.
Beta-2 adrenergic agonists are sympathomimetic agents that stimulate bronchodilation by activation of adenyl cyclase to produce cyclic 3'5' adenosine monophosphate (AMP). Short-acting beta-agonists (SABAs) have a 3- to 6-hour duration of action, and the duration of action of long-acting beta-agonists (LABAs) exceeds 12 hours. Because of their rapid onset of action, SABAs are effective for rescue from symptoms of chronic obstructive pulmonary disease (COPD). LABAs-salmeterol and formoterol-have been shown to significantly improve lung function, health status, and symptom reduction, compared with ipratropium. Despite safety concerns over the use of LABAs as monotherapy in asthma the use of these medications in COPD has generally been described as safe. Novel bronchodilators for COPD in late-stage development include the beta-agonists indacterol and carmoterol. Parasympathetic activity in the large and medium-size airways is mediated through the muscarinic receptors and results in airway smooth-muscle contraction, mucus secretion, and possibly increased ciliary activity. Although short-acting ipratropium has been used as monotherapy or in combination with albuterol the use of long-acting antimuscarinics is superior in improving health outcomes. The use of tiotropium results in improved health status, dyspnea, and exercise capacity, and reduced hyperinflation and COPD exacerbation rate in patients with moderate to severe COPD. Analysis of prospective clinical trial data shows a mortality reduction in subjects treated with tiotropium, despite retrospective review of insurance claims that show an enhanced mortality. Theophylline is a nonselective phosphodiesterase inhibitor that acts as both a weak bronchodilator and a respiratory stimulant. Novel approaches include using the inhalation route to reduce side effects and combination with inhaled corticosteroids (ICS). However, because of its potential adverse effects and narrow therapeutic index, it should only be used when symptoms persist despite optimal bronchodilator therapy. Current guidelines highlight that for COPD patients uncontrolled by bronchodilator monotherapy, combination therapy is recommended. These include LABA/ICS and LAMA/LABA combinations. Bronchodilators and their combination with ICS are central to the management of COPD. The choice of agents is based primarily on disease stage, individual response, cost, side effect profile, and availability.


Altered distributions of bone tissue mineral and collagen properties in women with fragility fractures.
Heterogeneity of bone tissue properties is emerging as a potential indicator of altered bone quality in pathologic tissue. The objective of this study was to compare the distributions of tissue properties in women with and without histories of fragility fractures using Fourier transform infrared (FTIR) imaging. We extended a prior study that examined the relationship of the mean FTIR properties to fracture risk by analyzing in detail the widths and the tails of the distributions of FTIR properties in biopsies from fracture and non-fracture cohorts. The mineral and matrix properties of cortical and trabecular iliac crest tissue were compared in biopsies from women with a history of fragility fracture (+Fx; n=21, age: mean 54±SD 15y) and with no history of fragility fracture (-Fx; n=12, age: 57±5y). A subset of the patients included in the -Fx group were taking estrogen-plus-progestin hormone replacement therapy (HRT) (-Fx+HRT n=8, age: 58±5y) and were analyzed separately from patients with no history of HRT (-Fx-HRT n=4, age: 56±7y). When the FTIR parameter mean values were examined by treatment group, the trabecular tissue of -Fx-HRT patients had a lower mineral:matrix ratio (M:M) and collagen maturity (XLR) than that of -Fx+HRT patients (-22% M:M, -18% XLR) and +Fx patients (-17% M:M, -18% XLR). Across multiple FTIR parameters, tissue from the -Fx-HRT group had smaller low-tail (5th percentile) values than that from the -Fx+HRT or +Fx groups. In trabecular collagen maturity and crystallinity (XST), the -Fx-HRT group had smaller low-tail values than those in the -Fx+HRT group (-16% XLR, -5% XST) and the +Fx group (-17% XLR, -7% XST). The relatively low values of trabecular mineral:matrix ratio and collagen maturity and smaller low-tail values of collagen maturity and crystallinity observed in the -Fx-HRT group are characteristic of younger tissue. Taken together, our data suggest that the presence of newly formed tissue that includes small/imperfect crystals and immature crosslinks, as well as moderately mature tissue, is an important characteristic of healthy, fracture-resistant bone. Finally, the larger mean and low-tail values of mineral:matrix ratio and collagen maturity noted in our -Fx+HRT vs. -Fx-HRT biopsies are consistent with greater tissue age and greater BMD arising from decreased osteoclastic resorption in HRT-treated patients.


Special visual effect of art glazes explained by the radiative transfer equation.
We present the first modeling of the light scattered by a paint layer in a bidirectional configuration. The studied medium is composed of small concentrated pigments embedded in an oil binder. The color is modulated by changing the number of paint layers, called glazes. The radiative transfer equation is established for incoherent light scattered by the pigments with use of a collimated illumination. The equation is solved by use of the auxiliary function method. This new method, applied here for the first time to a practical case, allows for exact computations of the scattered flux for any incident and collected directions. Spectroscopic and goniometric measurements are implemented in bidirectional and back-scattered configurations. The excellent agreement between the measurement and the simulation validates the assumptions used for the glaze model and proves the effectiveness of the auxiliary function method.


Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.
Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. OBJECTIVES: To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 19 August 2020. We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' 2.0 tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, mortality (time to event), improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events (AEs), and serious adverse events (SAEs). This is the second living update of our review. We included 19 studies (2 RCTs, 8 controlled NRSIs, 9 non-controlled NRSIs) with 38,160 participants, of whom 36,081 received convalescent plasma. Two completed RCTs are awaiting assessment (published after 19 August 2020). We identified a further 138 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 73 are randomised (3 reported in a study registry as already being completed, but without results). We did not identify any completed studies evaluating hyperimmune immunoglobulin. We did not include data from controlled NRSIs in data synthesis because of critical risk of bias. The overall certainty of evidence was low to very low, due to study limitations and results including both potential benefits and harms. Effectiveness of convalescent plasma for people with COVID-19 We included results from two RCTs (both stopped early) with 189 participants, of whom 95 received convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. We are uncertain whether convalescent plasma decreases all-cause mortality at hospital discharge (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.22 to 1.34; 1 RCT, 86 participants; low-certainty evidence). We are uncertain whether convalescent plasma decreases mortality (time to event) (hazard ratio (HR) 0.64, 95% CI 0.33 to 1.25; 2 RCTs, 189 participants; low-certainty evidence). Convalescent plasma may result in little to no difference in improvement of clinical symptoms (i.e. need for respiratory support) at seven days (RR 0.98, 95% CI 0.30 to 3.19; 1 RCT, 103 participants; low-certainty evidence). Convalescent plasma may increase improvement of clinical symptoms at up to 15 days (RR 1.34, 95% CI 0.85 to 2.11; 2 RCTs, 189 participants; low-certainty evidence), and at up to 30 days (RR 1.13, 95% CI 0.88 to 1.43; 2 studies, 188 participants; low-certainty evidence). No studies reported on quality of life. Safety of convalescent plasma for people with COVID-19 We included results from two RCTs, eight controlled NRSIs and nine non-controlled NRSIs assessing safety of convalescent plasma. Reporting of safety data and duration of follow-up was variable. The controlled studies reported on AEs and SAEs only in participants receiving convalescent plasma. Some, but not all, studies included death as a SAE. The studies did not report the grade of AEs. Fourteen studies (566 participants) reported on AEs of possible grade 3 or 4 severity. The majority of these AEs were allergic or respiratory events. We are very uncertain whether convalescent plasma therapy affects the risk of moderate to severe AEs (very low-certainty evidence). 17 studies (35,944 participants) assessed SAEs for 20,622 of its participants. The majority of participants were from one non-controlled NRSI (20,000 participants), which reported on SAEs within the first four hours and within an additional seven days after transfusion. There were 63 deaths, 12 were possibly and one was probably related to transfusion. There were 146 SAEs within four hours and 1136 SAEs within seven days post-transfusion. These were predominantly allergic or respiratory, thrombotic or thromboembolic and cardiac events. We are uncertain whether convalescent plasma therapy results in a clinically relevant increased risk of SAEs (low-certainty evidence). We are uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. There was limited information regarding grade 3 and 4 AEs to determine the effect of convalescent plasma therapy on clinically relevant SAEs. In the absence of a control group, we are unable to assess the relative safety of convalescent plasma therapy. While major efforts to conduct research on COVID-19 are being made, recruiting the anticipated number of participants into these studies is problematic. The early termination of the first two RCTs investigating convalescent plasma, and the lack of data from 20 studies that have completed or were due to complete at the time of this update illustrate these challenges. Well-designed studies should be prioritised. Moreover, studies should report outcomes in the same way, and should consider the importance of maintaining comparability in terms of co-interventions administered in all study arms. There are 138 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 73 are RCTs (three already completed). This is the second living update of the review, and we will continue to update this review periodically. Future updates may show different results to those reported here.


Effect of Morus alba L. (mulberry) leaves on anxiety in mice.
The aim of the present work is to evaluate the anxiolytic effect of a methanolic extract of Morus alba L. leaves in mice. The hole-board test, elevated plus-maze paradigm, open field test, and light/dark paradigm were used to assess the anxiolytic activity of the methanolic extract of M. alba L. Morus alba extract (50, 100, and 200 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were administered 30 min before the tests. The results showed that the methanolic extract of M. alba significantly increased the number and duration of head poking in the hole-board test. In the elevated plus-maze, the extract significantly increased the exploration of the open arm in similar way to that of diazepam. At a dose of 200 mg/kg i.p. the extract significantly increased both the time spent in and the entries into the open arm by mice. Further, in the open field test, the extract significantly increased rearing, assisted rearing, and number of squares traversed, all of which are demonstrations of exploratory behavior. In the light/dark paradigm, the extract produced significant increase in time spent in the lighted box as compared to vehicle. The spontaneous locomotor activity count, measured using an actophotometer, was significantly decreased in animals pretreated with M. alba extract, indicating a remarkable sedative effect of the plant. The results of the present study suggest that a methanolic extract of M. alba leaves may possess an anxiolytic effect.


The activation dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha 6 beta 1 integrin.
Macrophages require activation with either PMA (Mercurio, A. M., and L. M. Shaw. 1988. J. Cell Biol. 107:1873-1880) or interferon-gamma (Shaw, L. M., and A. M. Mercurio. 1989. J. Exp. Med. 169:303-308) to adhere to a laminin substratum. In the present study, we identified an integrin laminin receptor on macrophages and characterized cellular changes that occur in response to PMA activation that facilitate laminin adhesion. A monoclonal antibody (GoH3) that recognizes the integrin alpha 6 subunit (Sonnenberg, A., H. Janssen, F. Hogervorst, J. Calafat, and J. Hilgers. 1987. J. Biol. Chem. 262:10376-10383) specifically inhibited adhesion to laminin-coated surfaces. This antibody precipitated an alpha 6 beta 1 heterodimer (Mr 130/110 kD) from 125I surface-labeled macrophages. The amount of radiolabeled receptor on the cell surface did not increase after PMA activation. Thus, the induction of laminin adhesion cannot be attributed to de novo or increased surface expression of alpha 6 beta 1. By initially removing the Triton X-100-soluble fraction of macrophages and then disrupting the remaining cytoskeletal framework, we observed that 75% of the alpha 6 beta 1 heterodimer on the cell surface is anchored to the cytoskeleton in macrophages that had adhered to a laminin substratum in response to PMA. Significant cytoskeletal anchoring of this receptor was not observed in macrophages that had adhered to fibronectin or tissue culture plastic, nor was it seen in nonadherent cells. PMA also induced phosphorylation of the cytoplasmic domain of the alpha 6 subunit, but not the beta 1 subunit. Phosphorylated alpha 6 was localized to the cytoskeletal fraction only in macrophages plated on a laminin substratum. In summary, our results support a mechanism for the regulation of macrophage adhesion to laminin that involves specific and dynamic matrix integrin-cytoskeletal interactions that may be facilitated by integrin phosphorylation.


Detection and functional studies of p60-65 (Tac antigen) on activated human B cells.
A monoclonal antibody, AT-1, is shown to precipitate a p60-65 molecule identical to the Tac antigen. With AT-1, the expression of IL-2 receptors by normal activated human B cells from peripheral blood and tonsils is documented by biosynthetic and immunofluorescence studies. AT-1 precipitated a p60-65 protein from [35S]methionine-labeled activated B cells, similar to that from activated T cells. The interleukin 2 (IL-2) receptor appeared shortly after activation with anti-IgM and B cell-stimulatory factor(s). Its expression reached its peak at 60-72 h with approximately 50% of the B blasts stained by AT-1. Other modes of activation of B cells, by T cell-independent, formalin-treated staphylococci and Epstein-Barr virus, and by T cell-dependent pokeweed mitogen, also induced IL-2 receptor expression. The functional significance of this finding was investigated using recombinant IL-2 (rIL-2). While rIL-2 did not induce resting B cells to proliferate in the presence of anti-IgM, it induced activated B cells to proliferate in the absence of other factors. On the other hand, rIL-2 did not induce the differentiation of these activated B lymphocytes. These data suggest that IL-2 may play a significant role in B cell activation.


Interplay Between Conceptual Expectations and Movement Predictions Underlies Action Understanding.
Recent accounts of understanding goal-directed action underline the importance of a hierarchical predictive architecture. However, the neural implementation of such an architecture remains elusive. In the present study, we used functional neuroimaging to quantify brain activity associated with predicting physical movements, as they were modulated by conceptual-expectations regarding the purpose of the object involved in the action. Participants observed object-related actions preceded by a cue that generated both conceptual goal expectations and movement goal predictions. In 2 tasks, observers judged whether conceptual or movement goals matched or mismatched the cue. At the conceptual level, expected goals specifically recruited the posterior cingulate cortex, irrespectively of the task and the perceived movement goal. At the movement level, neural activation of the parieto-frontal circuit, including inferior frontal gyrus and the inferior parietal lobe, reflected unpredicted movement goals. Crucially, this movement prediction error was only present when the purpose of the involved object was expected. These findings provide neural evidence that prior conceptual expectations influence processing of physical movement goals and thereby support the hierarchical predictive account of action processing.


Effects of animal-assisted therapy on patients' anxiety, fear, and depression before ECT.
To determine whether animal-assisted therapy (AAT) is associated with reductions in fear, anxiety, and depression in psychiatric patients before electroconvulsive therapy (ECT). Before their scheduled ECT treatment, 35 patients were assigned on alternate days to the treatment condition, consisting of a 15-minute AAT session, and the standard (comparison) condition, consisting of 15 minutes with magazines. Visual analogue scales were used to measure anxiety, fear, and depression before and after treatment and standard conditions. The effect of AAT on fear was significant in both the mixed-model, repeated-measures analysis of covariance (ANCOVA) (p = 0.0006) and the secondary analysis (p = 0.0050), which covaried out all of the demographic conditions (gender, race, marital status, pet ownership, age), condition order, and the pretest rating. The effect of AAT on anxiety approached significance in the ANCOVA (p = 0.0982), but in the secondary analysis, the effect was not significant (p = 0.6498). The AAT effect on depression was not significant in ANCOVA (p = 0.7665) or in the secondary analysis (p = 0.9394). A least squares mean analysis showed that AAT reduced fear by 37% and anxiety by 18%. There was no demonstrated effect of AAT on depression. Animal-assisted therapy may have a useful role in psychiatric and medical therapies in which the therapeutic procedure is inherently fear-inducing or has a negative societal perception.


Crystal templating through liquid-liquid phase separation.
Controlled induction of crystal nucleation is a highly desirable but elusive goal. Attempts to speed up crystallization, such as high super saturation or working near a liquid-liquid critical point, always led to irregular and uncontrollable crystal growth. Here, we show that under highly nonequilibrium conditions of spinodal decomposition, water crystals grow as thin wires in a template-less formation of "Haareis". This suggests that such nonequilibrium conditions may be employed more widely as mechanisms for crystal growth control.


Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma.
The goal of this study was to comprehensively identify CpG island methylation alterations between pancreatic cancers and normal pancreata and their associated gene expression alterations. We employed methylated CpG island amplification followed by CpG island microarray, a method previously validated for its accuracy and reproducibility, to analyze the methylation profile of 27,800 CpG islands covering 21 MB of the human genome in nine pairs of pancreatic cancer versus normal pancreatic epithelial tissues and in three matched pairs of pancreatic cancer versus lymphoid tissues from the same individual. This analysis identified 1,658 known loci that were commonly differentially methylated in pancreatic cancer compared with normal pancreas. By integrating the pancreatic DNA methylation status with the gene expression profiles of the same samples before and after treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, and the histone deacetylase inhibitor, trichostatin A, we identified dozens of aberrantly methylated and differentially expressed genes in pancreatic cancers including a more comprehensive list of hypermethylated and silenced genes that have not been previously described as targets for aberrant methylation in cancer. We expected that the identification of aberrantly hypermethylated and silenced genes will have diagnostic, prognostic, and therapeutic applications.


Evolution, substrate specificity and subfamily classification of glycoside hydrolase family 5 (GH5).
The large Glycoside Hydrolase family 5 (GH5) groups together a wide range of enzymes acting on β-linked oligo- and polysaccharides, and glycoconjugates from a large spectrum of organisms. The long and complex evolution of this family of enzymes and its broad sequence diversity limits functional prediction. With the objective of improving the differentiation of enzyme specificities in a knowledge-based context, and to obtain new evolutionary insights, we present here a new, robust subfamily classification of family GH5. About 80% of the current sequences were assigned into 51 subfamilies in a global analysis of all publicly available GH5 sequences and associated biochemical data. Examination of subfamilies with catalytically-active members revealed that one third are monospecific (containing a single enzyme activity), although new functions may be discovered with biochemical characterization in the future. Furthermore, twenty subfamilies presently have no characterization whatsoever and many others have only limited structural and biochemical data. Mapping of functional knowledge onto the GH5 phylogenetic tree revealed that the sequence space of this historical and industrially important family is far from well dispersed, highlighting targets in need of further study. The analysis also uncovered a number of GH5 proteins which have lost their catalytic machinery, indicating evolution towards novel functions. Overall, the subfamily division of GH5 provides an actively curated resource for large-scale protein sequence annotation for glycogenomics; the subfamily assignments are openly accessible via the Carbohydrate-Active Enzyme database at http://www.cazy.org/GH5.html.


Stable association of herpes simplex virus with target membranes is triggered by low pH in the presence of the gD receptor, HVEM.
Using a liposome-binding assay, we investigated the requirements for activation of herpes simplex virus (HSV) into a state capable of membrane interaction. Virions were mixed with liposomes along with the ectodomain of one of three gD receptors (HVEMt, nectin-1t, or nectin-2t) and incubated under different pH and temperature conditions. Virions failed to associate with liposomes in the presence of nectin-1 or nectin-2 at any temperature or pH tested. In contrast, HVEMt triggered association of HSV with liposomes at pH 5.3 or 5.0 when incubated at 37 degrees C, suggesting that HVEM binding and mildly acidic pH at a physiological temperature provide coactivation signals, allowing virus association with membranes. Virions incubated with HVEMt at 37 degrees C without liposomes rapidly lost infectivity upon exposure to pH 5.0, suggesting that these conditions lead to irreversible virus inactivation in the absence of target membranes. Consistent with the idea that soluble receptor molecules provide a trigger for HSV entry, HVEMt promoted virus entry into receptor-deficient CHO K1 cells. However, in B78H1 cells, HVEMt promoted virus entry with markedly lower efficiency. Interestingly, HSV entry into receptor-bearing CHO K1 cells has been shown to proceed via a pH-dependent manner, whereas HSV entry into receptor-bearing B78H1 cells is pH independent. Based on these observations, we propose that the changes triggered by HVEM and mildly acidic pH that allow liposome association are similar or identical to changes that occur during pH-dependent HSV entry.


Metabolic response to carbohydrate ingestion during exercise in males and females.
The present study investigated potential sex-related differences in the metabolic response to carbohydrate (CHO) ingestion during exercise. Moderately endurance-trained men and women (n = 8 for each sex) performed 2 h of cycling at approximately 67% Vo(2 max) with water (WAT) or CHO ingestion (1.5 g of glucose/min). Substrate oxidation and kinetics were quantified during exercise using indirect calorimetry and stable isotope techniques ([(13)C]glucose ingestion, [6,6-(2)H(2)]glucose, and [(2)H(5)]glycerol infusion). In both sexes, CHO ingestion significantly increased the rates of appearance (R(a)) and disappearance (R(d)) of glucose during exercise compared with WAT ingestion [males: WAT, approximately 28-29 micromol x kg lean body mass (LBM)(-1) x min(-1); CHO, approximately 53 micromol x kg LBM(-1) x min(-1); females: WAT, approximately 28-29 micromol x kg LBM(-1) x min(-1); CHO, approximately 61 micromol x kg LBM(-1) x min(-1); main effect of trial, P < 0.05]. The contribution of plasma glucose oxidation to the energy yield was significantly increased with CHO ingestion in both sexes (from approximately 10% to approximately 20% of energy expenditure; main effect of trial, P < 0.05). Liver-derived glucose oxidation was reduced, although the rate of muscle glycogen oxidation was unaffected with CHO ingestion (males: WAT, 108 +/- 12 micromol x kg LBM(-1) x min(-1); CHO, 108 +/- 11 micromol x kg LBM(-1) x min(-1); females: WAT, 89 +/- 10 micromol x kg LBM(-1) x min(-1); CHO, 93 +/- 11 micromol x kg LBM(-1) x min(-1)). CHO ingestion reduced fat oxidation and lipolytic rate (R(a) glycerol) to a similar extent in both sexes. Finally, ingested CHO was oxidized at similar rates in men and women during exercise (peak rates of 0.70 +/- 0.08 and 0.65 +/- 0.06 g/min, respectively). The present investigation suggests that the metabolic response to CHO ingestion during exercise is largely similar in men and women.


Adaptation and validation of Richmond Compulsive Buying Scale in Chinese population.
Compulsive buying (CB) is a behavioral addiction that is conceptualized as an obsessive-compulsive and impulsive-control disorder. The Richmond Compulsive Buying Scale (RCBS), a six-item self-reporting instrument that has been validated worldwide, was developed based on this theoretical background. This study aimed to adapt RCBS to the Chinese population (RCBS-TC) to guide future national and international prevalence studies. This methodological study was conducted in two phases. Phase 1 involved the forward and backward translation of RCBS, the content and face validation of the RCBS, and the evaluation of its translation adequacy. Phase 2 involved the psychometric testing of RCBS-TC for its internal consistency, stability, and construct validity using confirmatory factor analysis (CFA). In Phase 1, RCBS-TC obtained satisfactory item-level (I-CVI = 83.3%-100%) and scale-level content validity index (CVI/AVE = 97.2%), comprehensibility (100%), and translation adequacy [intraclass correlation coefficient (ICC) = 0.858]. In Phase 2, based on data collected from 821 adults, RCBS-TC demonstrated a satisfactory internal consistency (Cronbach's α = .88; corrected item-total correlation coefficients = 0.61-0.78) 2-week test-retest reliability (ICC = 0.82 based on 61 university students). For construct validation, the CFA results indicated that the corrected first-order two-factor models were acceptable with the same goodness-of-fit indices (χ2/df = 8.56, CFI = 0.99, NFI = 0.98, IFI = 0.99, and RMSEA = 0.09). The 2-week test-retest reliability of RCBS-TC (n = 61) was also satisfactory (ICC = 0.82). This methodological study adopted appropriate and stringent procedures to ensure that the translation and validation of RCBS-TC was of quality. The results indicate that this scale has a satisfactory reliability and validity for the Chinese population.


A randomised controlled trial of three very brief interventions for physical activity in primary care.
Very brief interventions (VBIs) for physical activity are promising, but there is uncertainty about their potential effectiveness and cost. We assessed potential efficacy, feasibility, acceptability, and cost of three VBIs in primary care, in order to select the most promising intervention for evaluation in a subsequent large-scale RCT. Three hundred and ninety four adults aged 40-74 years were randomised to a Motivational (n = 83), Pedometer (n = 74), or Combined (n = 80) intervention, delivered immediately after a preventative health check in primary care, or control (Health Check only; n = 157). Potential efficacy was measured as the probability of a positive difference between an intervention arm and the control arm in mean physical activity, measured by accelerometry at 4 weeks. For the primary outcome the estimated effect sizes (95 % CI) relative to the Control arm for the Motivational, Pedometer and Combined arms were respectively: +20.3 (-45.0, +85.7), +23.5 (-51.3, +98.3), and -3.1 (-69.3, +63.1) counts per minute. There was a73% probability of a positive effect on physical activity for each of the Motivational and Pedometer VBIs relative to control, but only 46 % for the Combined VBI. Only the Pedometer VBI was deliverable within 5 min. All VBIs were acceptable and low cost. Based on the four criteria, the Pedometer VBI was selected for evaluation in a large-scale trial. Current Controlled Trials ISRCTN02863077 . Retrospectively registered 05/10/2012.


Healthcare professionals' intentions to use clinical guidelines: a survey using the theory of planned behaviour.
Finnish clinical guidelines are evolving toward integration of knowledge modules into the electronic health record in the Evidence-Based Medicine electronic Decision Support project. It therefore became important to study which factors affect professionals' intention to use clinical guidelines generally in their decision-making on patient care. A theory-based approach is a possible solution to explore determinants of professionals' behaviour. The study's aim was to produce baseline information for developers and implementers by using the theory of planned behaviour. A cross-sectional internet-based survey was carried out in Finnish healthcare organisations within three hospital districts. The target population (n = 2,252) included physicians, nurses, and other professionals, of whom 806 participated. Indicators of the intention to use clinical guidelines were observed by using a theory-based questionnaire. The main data analysis was done by means of multiple linear regressions. The results indicated that all theory-based variables--the attitude toward the behaviour, the subjective norm, and the perceived behaviour control--were important factors associated with the professionals' intention to use clinical practice guidelines for their area of specialisation in the decisions they would make on the care of patients in the next three months. In addition, both the nurse and the physician factors had positive (p < 0.01) effects on this intention in comparison to other professionals. In the similar models for all professions, the strongest factor for the physicians was the perceived behaviour control, while the key factor for the nurses and the other professionals was the subjective norm. This means that context- and guideline-based factors either facilitate or hinder the intention to use clinical guidelines among physicians and, correspondingly, normative beliefs related to social pressures do so for nurses and other healthcare professionals. The results confirm suggestions that the theory of planned behaviour is a suitable theoretical basis for implementing clinical guidelines in healthcare practices. Our new finding was that, in general, profession had an effect on intention to use clinical guidelines in patient care. Therefore, the study reaffirms the general contention that different strategies need to be in place when clinical guidelines are targeted at different professional groups.


Docetaxel in the treatment of metastatic castration-resistant prostate cancer (mCRPC): an observational study in a single institution.
Treatment with docetaxel in combination with prednisone is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). For patients failing first-line docetaxel no standard has emerged. The outcome in routine daily clinical practice of a cohort of unselected chemotherapy-naïve mCRPC patients treated with docetaxel plus methylprednisolone as first- and further-line treatment in a single institution was investigated. Data from the medical records of patients treated with docetaxel plus methylprednisolone either in a three-weekly (75 mg/m(2)) (D3) or a three-of-four-weekly (35 mg/m(2))(D1) schedule as first- or further-line treatment were analysed with respect to clinical and prostate-specific antigen (PSA) response, time-on-treatment (TOT), treatment-free interval (TFI), overall survival time (OS) and toxicity and were compared to the results of the registration study TAX 327. Out of 41 patients, 28 and 13 received first-line docetaxel according to the D3 and the D1 schedules respectively. An overall PSA response ≥50% was achieved in thirty patients (73%). In ten patients (24%) the PSA level was normalised. The median OS of the total population was 18.7 months. No significant differences were observed between the D3 and the D1 regimens with respect to PSA response, duration of PSA response, TOT, TFI and OS. Patients obtaining a normalisation of PSA level achieved a significantly superior OS, TOT and TFI compared to those without normalisation of PSA. Second-line treatment with docetaxel in nine patients induced a normalisation in PSA level in two (22%). The TOT and TFI from the start of second-line treatment, was significantly superior in docetaxel compared to non-docetaxel treated patients. Treatment with docetaxel was well-tolerated and only two patients were withdrawn for non-haematological toxicity during first- and further-line treatment. There were no differences in either subjective or objective side-effects between both treatment schedules. The results of the retrospective analysis of non-selected patients with mCRPC treated with docetaxel chemotherapy are in line with the data from TAX 327. Normalisation of PSA during first-line treatment with docetaxel is associated with a better survival irrespective of second- or further-line treatment used. Retreatment with docetaxel in second- or further-line remains a treatment option in docetaxel-sensitive patients.


Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae.
A proof-of-concept study evaluating the potential of Streptococcus pneumoniae Pneumococcal Surface Protein A (PspA) as a passive immunization target was conducted. We describe the generation and isolation of several broadly reactive mouse anti-PspA monoclonal antibodies (mAbs). MAb 140H1 displayed (i) 98% strain coverage, (ii) activity in complement deposition and opsonophagocytic killing (OPK) assays, which are thought to predict the in vivo efficacy of anti-pneumococcal mAbs, (iii) efficacy in mouse sepsis models both alone and in combination with standard-of-care antibiotics, and (iv) therapeutic activity in a mouse pneumonia model. Moreover, we demonstrate that antibody engineering can significantly enhance anti-PspA mAb effector function. We believe that PspA has promising potential as a target for the therapy of invasive pneumococcal disease by mAbs, which could be used alone or in conjunction with standard-of-care antibiotics.


Overall survival and functional results of prostate-sparing cystectomy: a matched case-control study.
To compare two matched groups of men with bladder transitional cell carcinoma (TCC) who underwent prostate-sparing cystectomy (PSC) or conventional radical cystoprostatectomy (CRC). Twenty-three men who have undergone PSC with the diagnosis of bladder TCC (Ta-T2) from 2003 to 2008 in Tehran, Iran were included in the study as the experimental group. The control group composed of 27 men with comparable tumor characteristics and age range, who had non-nerve-sparing radical cystoprostatectomy and orthotopic ileal W pouch reconstruction in the same center. All the procedures were performed by the same surgical group under the supervision of different attending staff. Mean follow-up period was 39 months in PSC and 35 months in CRC group. The 5-year overall survival was 47% and 30% in PSC and CRC groups, respectively. Median survival was 48 months in PSC and 36 months in CRC group, using Kaplan-Meier survival analysis (P > .05). Impotence was observed in 16.6% in PSC and in 83.3% in CRC group (P = .002). Mean International Index of Erectile Function-5 score of the PSC group was 19.8 compared with 5.7 in the CRC group (P = .003). Only one patient in each group was completely incontinent. Urethral anastomosis stricture occurred in 2 patients in CRC group. Patients who underwent PSC did not show decreased overall survival compared to CRC, which provided better functional results.


Unravelling the biosynthesis of pyriculol in the rice blast fungus Magnaporthe oryzae.
Pyriculol was isolated from the rice blast fungus Magnaporthe oryzae and found to induce lesion formation on rice leaves. These findings suggest that it could be involved in virulence. The gene MoPKS19 was identified to encode a polyketide synthase essential for the production of the polyketide pyriculol in the rice blast fungus M. oryzae. The transcript abundance of MoPKS19 correlates with the biosynthesis rate of pyriculol in a time-dependent manner. Furthermore, gene inactivation of MoPKS19 resulted in a mutant unable to produce pyriculol, pyriculariol and their dihydro derivatives. Inactivation of a putative oxidase-encoding gene MoC19OXR1, which was found to be located in the genome close to MoPKS19, resulted in a mutant exclusively producing dihydropyriculol and dihydropyriculariol. By contrast, overexpression of MoC19OXR1 resulted in a mutant strain only producing pyriculol. The MoPKS19 cluster, furthermore, comprises two transcription factors MoC19TRF1 and MoC19TRF2, which were both found individually to act as negative regulators repressing gene expression of MoPKS19. Additionally, extracts of ΔMopks19 and ΔMoC19oxr1 made from axenic cultures failed to induce lesions on rice leaves compared to extracts of the wild-type strain. Consequently, pyriculol and its isomer pyriculariol appear to be the only lesion-inducing secondary metabolites produced by M. oryzae wild-type (MoWT) under these culture conditions. Interestingly, the mutants unable to produce pyriculol and pyriculariol were as pathogenic as MoWT, demonstrating that pyriculol is not required for infection.


Peristaltic pulse dynamic compression of the lower extremity enhances flexibility.
This study investigated the effects of peristaltic pulse dynamic compression (PPDC) on range-of-motion (ROM) changes in forward splits. Serious stretching usually involves discomfort and large time investments. Tissue structural changes and stretch tolerance have heretofore been considered the primary mechanisms of enhanced ROM. The PPDC treatment was computer controlled. Circumferential and segmented inflation pressures were induced by feet to hip leggings. Nine subjects, experienced in stretching and a forward split position, volunteered. The subjects were familiarized with the protocol and randomly assigned to an initial condition: experimental (PPDC), or control (CONT). The study involved a crossover design. Second conditions were tested within 1-5 days. All tests were 2 trials of right and left forward splits. Split flexibility was assessed by measuring the height of the anterior superior iliac spine of the rear leg from the floor. Pelvic posture was controlled by rear leg position. The PPDC treatment was 15 minutes of seated PPDC. The control condition was the same except that leggings were not inflated. Pressures of 5 cells in the leggings were set at factory defaults, 70 mm Hg sequentially. Difference score results indicated statistically significant (p ≤ 0.05) differences by condition and the condition by leg interaction. The rapid acute changes in ROM (PPDC: right 25.3%, left 33.3%; CONT: right 12.2%, left 1.0%) support the premise that changes in ROM were dependent on mechanisms other than tissue structural changes and/or stretch tolerance. PPDC provides a means of rapidly enhancing acute ROM requiring less discomfort and time.


Anogenital Human Papillomavirus and HIV Infection in Rwandan Men Who Have Sex With Men.
Men who have sex with men (MSM) have a high prevalence of anal and penile human papillomavirus (HPV) infections with MSM living with HIV (MSMLH) bearing the highest rates. Data on anogenital high-risk HPV (hrHPV) among MSM in Rwanda and the associated risk factors are scant. We recruited 350 self-identified MSM aged 18 years living in Kigali, Rwanda, with 300 recruited from the community and 50 from partner clinics. Anal and penile specimens from all participants were analyzed for hrHPV using the AmpFire platform. Logistic regression was used to calculate crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (95% CIs) as a measure of association between various factors and anal and penile hrHPV infection prevalence. Anal hrHPV prevalence was 20.1%, was positively associated with having receptive anal sex with more partners (aOR: 9.21, 95% CI: 3.66 to 23.14), and was negatively associated with having insertive anal sex with more partners (aOR: 0.28, 95% CI: 0.12 to 0.66). Penile hrHPV prevalence was 35.0%, was negatively associated with having receptive anal sex with more partners (aOR: 0.29, 95% CI: 0.13 to 0.66), and differed significantly by HIV status, with 55.2% and 29.7% for MSMLH and HIV-negative MSM, respectively (P < 0.01). Penile hrHPV prevalence was higher than that of anal hrHPV and it was significantly higher in Rwandan MSMLH than in HIV-negative MSM. The prevalence of anal and penile HPV infections is likely variable at different locations in Africa, according to a number of factors including HIV status and sexual practices.


Marine origin collagens and its potential applications.
Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role, existing different types according with their specific organization in distinct tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches. Also, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are from bovine and porcine origin, but other ways are making their route, such as recombinant production, but also extraction from marine organisms like fish. Different organisms have been proposed and explored for collagen extraction, allowing the sustainable production of different types of collagens, with properties depending on the kind of organism (and their natural environment) and extraction methodology. Such variety of collagen properties has been further investigated in different ways to render a wide range of applications. The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation.


Twenty-five Years of Research on Childhood Anxiety Disorders: Publication Trends Between 1982 and 2006 and a Selective Review of the Literature.
We examined trends in publications on childhood anxiety disorders over the past 25 years. A PsycINFO search was carried out to find relevant research articles published between 1982 and 2006. Results indicated a gradual and significant rise in the frequency of publications on childhood anxiety disorders during the past 25 years, and this increase was particularly strong for post-traumatic stress disorder, obsessive-compulsive disorder, social phobia, and multiple anxiety disorders. Most studies concerned the phenomenology of childhood anxiety disorders (i.e., >50%). Considerable less research has been conducted on the etiology, intervention, and assessment of these disorders in youths. Nevertheless, the conclusion seems warranted that the research on childhood anxiety disorders has made significant advancements during the past decades. This notion is supported by a selective review of the literature, which highlights important developments in this field of study.


Factors affecting ultraviolet-A photon emission from β-irradiated human keratinocyte cells.
The luminescence intensity of 340±5 nm photons emitted from HaCaT (human keratinocyte) cells was investigated using a single-photon-counting system during cellular exposure to (90)Y β-particles. Multiple factors were assessed to determine their influence upon the quantity and pattern of photon emission from β-irradiated cells. Exposure of 1 x 10(4) cells/5 mL to 703 μCi resulted in maximum UVA photoemission at 44.8 x 10(3)±2.5 x 10(3) counts per second (cps) from live HaCaT cells (background: 1-5 cps); a 16-fold increase above cell-free controls. Significant biophoton emission was achieved only upon stimulation and was also dependent upon presence of cells. UVA luminescence was measured for (90)Y activities 14 to 703 μCi where a positive relationship between photoemission and (90)Y activity was observed. Irradiation of live HaCaT cells plated at various densities produced a distinct pattern of emission whereby luminescence increased up to a maximum at 1 x 10(4) cells/5 mL and thereafter decreased. However, this result was not observed in the dead cell population. Both live and dead HaCaT cells were irradiated and were found to demonstrate different rates of photon emission at low β activities (⩽400 μCi). Dead cells exhibited greater photon emission rates than live cells which may be attributable to metabolic processes taking place to modulate the photoemissive effect. The results indicate that photon emission from HaCaT cells is perturbed by external stimulation, is dependent upon the activity of radiation delivered, the density of irradiated cells, and cell viability. It is postulated that biophoton emission may be modulated by a biological or metabolic process.


Dysregulated overexpression of Sox9 induces fibroblast activation in pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease associated with unremitting fibroblast activation including fibroblast-to-myofibroblast transformation (FMT), migration, resistance to apoptotic clearance, and excessive deposition of extracellular matrix (ECM) proteins in the distal lung parenchyma. Aberrant activation of lung-developmental pathways is associated with severe fibrotic lung disease; however, the mechanisms through which these pathways activate fibroblasts in IPF remain unclear. Sry-box transcription factor 9 (Sox9) is a member of the high-mobility group box family of DNA-binding transcription factors that are selectively expressed by epithelial cell progenitors to modulate branching morphogenesis during lung development. We demonstrate that Sox9 is upregulated via MAPK/PI3K-dependent signaling and by the transcription factor Wilms' tumor 1 in distal lung-resident fibroblasts in IPF. Mechanistically, using fibroblast activation assays, we demonstrate that Sox9 functions as a positive regulator of FMT, migration, survival, and ECM production. Importantly, our in vivo studies demonstrate that fibroblast-specific deletion of Sox9 is sufficient to attenuate collagen deposition and improve lung function during TGF-α-induced pulmonary fibrosis. Using a mouse model of bleomycin-induced pulmonary fibrosis, we show that myofibroblast-specific Sox9 overexpression augments fibroblast activation and pulmonary fibrosis. Thus, Sox9 functions as a profibrotic transcription factor in activating fibroblasts, illustrating the potential utility of targeting Sox9 in IPF treatment.


Oesophageal perforation as a complication of primary pulmonary tuberculous lymphadenopathy in children.
Involvement of the oesophagus by tuberculosis is rare, and erosion and perforation of the oesophagus by tuberculous lymphadenopathy is an unusual complication of primary pulmonary tuberculosis. There are very few reports describing both CT and contrast swallow appearances of these lesions. To describe the CT and contrast swallow appearances of oesophageal erosion and perforation by lymphadenopathy as a complication of primary pulmonary tuberculosis in children. Imaging of three children with confirmed pulmonary tuberculosis and oesophageal perforation was retrospectively reviewed. Tuberculosis was confirmed by culture in all three patients. Contrast swallow demonstrated a contained leak in two patients and a tracheo-oesophageal fistula in one. Two patients had mediastinal air and one patient had a mediastinal collection on CT. All patients had features diagnostic of pulmonary tuberculosis on CT. The imaging features comprise leakage of contrast medium with or without fistula formation on contrast swallow, large low-density lymph nodes on CT, and mediastinal air. The use of retrievable stents is a promising idea in this condition.


Evidence for similar early but not late representation of possible and impossible objects.
The perceptual processes that mediate the ability to efficiently represent object 3D structure are still not fully understood. The current study was aimed to shed light on these processes by utilizing spatially possible and impossible objects that could not be created in real 3D space. Despite being perceived as exceptionally unusual, impossible objects still possess fundamental Gestalt attributes and valid local depth cues that may support their initial successful representation. Based on this notion and on recent findings from our lab, we hypothesized that the initial representation of impossible objects would involve common mechanisms to those mediating typical object perception while the perceived differences between possible and impossible objects would emerge later along the processing hierarchy. In Experiment 1, participants preformed same/different classifications of two markers superimposed on a display containing two objects (possible or impossible). Faster reaction times were observed for displays in which the markers were superimposed on the same object ("object-based benefit"). Importantly, this benefit was similar for possible and impossible objects, suggesting that the representations of the two object categories rely on similar perceptual organization processes. Yet, responses for impossible objects were slower compared to possible objects. Experiment 2 was designed to examine the origin of this effect. Participants classified the location of two markers while exposure duration was manipulated. A similar pattern of performance was found for possible and impossible objects for the short exposure duration, with differences in accuracy between these two types of objects emerging only for longer exposure durations. Overall, these findings provide evidence that the representation of object structure relies on a multi-level process and that object impossibility selectively impairs the rendering of fine-detailed description of object structure.


Hepatitis B virus HBx protein induces transcription factor AP-1 by activation of extracellular signal-regulated and c-Jun N-terminal mitogen-activated protein kinases.
The HBx protein of hepatitis B virus is a dual-specificity activator of transcription, stimulating signal transduction pathways in the cytoplasm and transcription factors in the nucleus, when expressed in cell lines in culture. In the cytoplasm, HBx was shown to stimulate the Ras-Raf-mitogen-activated protein kinase (MAP kinase) cascade, which is essential for activation of transcription factor AP-1. Here we show that HBx protein stimulates two independently regulated members of the MAP kinase family when expressed transiently in cells. HBx protein stimulates the extracellular signal-regulated kinases (ERKs) and the c-Jun N-terminal kinases (JNKs). HBx activation of ERKs and JNKs leads to induction and activation of AP-1 DNA binding activity involving transient de novo synthesis of c-Fos protein and prolonged synthesis of c-Jun, mediated by N-terminal phosphorylation of c-Jun carried out by HBx-activated JNK. New c-Jun synthesis was blocked by coexpression with a dominant-negative MAP kinase kinase (MEK kinase, MEKK-1), confirming that HBx stimulates the prolonged synthesis of c-Jun by activating JNK signalling pathways. Activation of the c-fos gene was blocked by coexpression with a Raf-C4 catalytic mutant, confirming that HBx induces c-Fos by acting on Ras-Raf linked pathways. HBx activation of ERK and JNK pathways resulted in prolonged accumulation of AP-1-c-Jun dimer complexes. HBx activation of JNK and sustained activation of c-jun, should they occur in the context of hepatitis B virus infection, might play a role in viral transformation and pathogenesis.


Validation of a decision support tool for wastewater treatment selection.
Wastewater treatment selection is a complex task usually addressed by applying separate tools for the correct assessment of multi-criteria evaluation. Novedar_EDSS integrates technical, environmental, economic and social assessment capabilities in one single platform. The aim of this work is to evaluate and demonstrate the capabilities of this environmental decision support system (EDSS). For that purpose, 4 case studies of real projects were selected to validate the results in the EDSS by comparing them with those from the study of alternatives performed by the decision makers. Moreover, 1 conceptual case study was applied to support the selection of the most properly strategy for plant retrofitting. Results have demonstrated that the EDSS provides key aspects when deciding the retrofitting process to apply and, when compared to real projects, it recommends analogue treatments as those applied in the projects, ranking them in the same order. Therefore, results in the validation process performed show that this tool provides a reliable basis to support decision makers to select properly treatment alternatives in wastewater treatment plant pre-design.


Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin.
The basal-like subtype of breast cancer is characterized by a triple-negative (TN) phenotype (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2/neu negative). TN breast cancers share similar gene expression profiles and DNA repair deficiencies with BRCA1-associated breast cancers. BRCA1-mutant cells exhibit sensitivity to gemcitabine, cisplatin, and poly(ADP-ribose) polymerase (PARP) inhibition; therefore, we hypothesized that TN cancer cells may also exhibit sensitivity to these drugs. In this study, we report that TN breast cancer cells are more sensitive to these drugs compared with non-TN breast cancer cells. Moreover, combination treatments indicated that PARP inhibition by the small-molecule inhibitor PJ34 or siRNA knockdown synergized with gemcitabine and cisplatin in TN cells but not in luminal cancer cells. TN cells exhibited reduced repair of UV-induced cyclobutane pyrimidine dimers after PARP inhibition, suggesting that the synergistic effect of PJ34 and gemcitabine or cisplatin reflected inefficient nucleotide excision repair. Mechanistic investigations revealed that in TN cells, PJ34 reduced the levels of ΔNp63α with a concurrent increase in p73 and its downstream target p21. Thus, the sensitivity to combination treatment seemed to be mediated by sustained DNA damage and inefficient DNA repair triggering p63/p73-mediated apoptosis. Our results suggest a novel therapeutic strategy to treat women with TN breast cancer, an aggressive disease that presently lacks effective treatment options.


Response-locked brain dynamics of word production.
The cortical regions involved in the different stages of speech production are relatively well-established, but their spatio-temporal dynamics remain poorly understood. In particular, the available studies have characterized neural events with respect to the onset of the stimulus triggering a verbal response. The core aspect of language production, however, is not perception but action. In this context, the most relevant question may not be how long after a stimulus brain events happen, but rather how long before the production act do they occur. We investigated speech production-related brain activity time-locked to vocal onset, in addition to the common stimulus-locked approach. We report the detailed temporal interplay between medial and left frontal activities occurring shortly before vocal onset. We interpret those as reflections of, respectively, word selection and word production processes. This medial-lateral organization is in line with that described in non-linguistic action control, suggesting that similar processes are at play in word production and non-linguistic action production. This novel view of the brain dynamics underlying word production provides a useful background for future investigations of the spatio-temporal brain dynamics that lead to the production of verbal responses.


The evolution of anisogamy: the adaptive significance of damage, repair and mortality.
Classic theory on the evolution of anisogamy focuses on the trade-off between gamete productivity and provisioning and mechanisms associated with post-zygotic survival. In this article, the role of mortality acting on both zygotes and gametes is explored as a factor influencing the evolution of different sized gametes. In particular, variable mortality through differential survival or metabolic damage is shown to affect the persistence of isogamy, the evolution of more than two sexes and the evolution of anisogamy. Evolutionary stable isogamous states are shown to be locally unstable and disruptive selection can induce the evolution of anisogamy. Analysis of both the isogamous and anisogamous ESS points reveals that the persistence of either of these conditions is not always assured. The implications of variable survival on the evolution of anisogamy are discussed.


Impaired in vivo insulin clearance in patients with severe target-cell resistance to insulin.
The concentration of insulin in plasma is determined by both its rate of secretion and its rate of clearance from the plasma compartment. The effect of marked insulin resistance on insulin clearance in vivo has not been determined in man. We have employed the euglycemic insulin clamp technique to measure insulin sensitivity and insulin clearance in 16 control subjects and in 4 subjects with marked target-cell resistance to insulin. Two insulin-resistant patients had reduced receptor concentration on peripheral mononuclear cells, and two patients had normal receptor number and affinity. During 80-mU/m2/min insulin clamp studies, the clearance rate in each insulin-resistant patient was lower than that in any controls; the mean insulin clearance rate was 511 +/- 74 ml/m2/mon in control subjects and 205 ml/m2/min (P less than 0.001) in insulin-resistant patients. These findings demonstrate an association between marked target-cell resistance to insulin and impaired in vivo insulin clearance, and suggest an important role for receptor-mediated pathways in insulin clearance in vivo.


Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes to the aggressive phenotype of glioblastoma through regulation of poor prognosis-associated signatures. Restitution of ZBTB18 expression reverses the phenotype and impairs tumor-forming ability. These results indicate that ZBTB18 functions as a tumor suppressor in GBM through the regulation of genes associated with phenotypically aggressive properties.Implications: This study characterizes the role of the putative tumor suppressor ZBTB18 and its regulation by promoter hypermethylation, which appears to be a common mechanism to silence ZBTB18 in the mesenchymal subtype of GBM and provides a new mechanistic opportunity to specifically target this tumor subclass. Mol Cancer Res; 15(8); 998-1011. ©2017 AACR.


Neural tube defects: from a proteomic standpoint.
Neural tube defects (NTDs) are congenital birth defects classified according to their resulting morphological characteristics in newborn patients. Current diagnosis of NTDs relies largely on the structural evaluation of fetuses using ultrasound imaging, with biochemical characterization used as secondary screening tools. The multigene etiology of NTDs has been aided by genetic studies, which have discovered panels of genes mutated in these diseases that encode receptors and cytoplasmic signaling molecules with poorly defined functions. Animal models ranging from flies to mice have been used to determine the function of these genes and identify their associated molecular cascades. More emphasis is now being placed on the identification of biochemical markers from clinical samples and model systems based on mass spectrometry, which open novel avenues in the understanding of NTDs at protein, metabolic and molecular levels. This article reviews how the use of proteomics can push forward the identification of novel biomarkers and molecular networks implicated in NTDs, an indispensable step in the improvement of patient management.


Curricula Challenges and Informatics Competencies for Nurse Educators.
Nursing informatics competencies are fundamental to nursing practice in all areas of nursing work, including direct patient care, administration and education. The recent activity relating to the development of nursing informatics competencies for beginning level nurses has exposed a paucity of understanding of the requirements for nursing informatics competencies for nurse educators. So, whilst the challenge of educating faculty to teach informatics has been limited, research into such competencies is required to meet this challenge. This paper describes the challenges and issues associated with nursing informatics competency development for faculty, outlines the capabilities of faculty, and presents a vision for the future of informatics education for faculty. The final requirement of the introduction of new competencies is to determine appropriate evaluation measures that reflect the requirements of all stakeholders.


Exploiting temporal network structures of human interaction to effectively immunize populations.
Decreasing the number of people who must be vaccinated to immunize a community against an infectious disease could both save resources and decrease outbreak sizes. A key to reaching such a lower threshold of immunization is to find and vaccinate people who, through their behavior, are more likely than average to become infected and to spread the disease further. Fortunately, the very behavior that makes these people important to vaccinate can help us to localize them. Earlier studies have shown that one can use previous contacts to find people that are central in static contact networks. However, real contact patterns are not static. In this paper, we investigate if there is additional information in the temporal contact structure for vaccination protocols to exploit. We answer this affirmative by proposing two immunization methods that exploit temporal correlations and showing that these methods outperform a benchmark static-network protocol in four empirical contact datasets under various epidemic scenarios. Both methods rely only on obtainable, local information, and can be implemented in practice. For the datasets directly related to contact patterns of potential disease spreading (of sexually-transmitted and nosocomial infections respectively), the most efficient protocol is to sample people at random and vaccinate their latest contacts. The network datasets are temporal, which enables us to make more realistic evaluations than earlier studies--we use only information about the past for the purpose of vaccination, and about the future to simulate disease outbreaks. Using analytically tractable models, we identify two temporal structures that explain how the protocols earn their efficiency in the empirical data. This paper is a first step towards real vaccination protocols that exploit temporal-network structure--future work is needed both to characterize the structure of real contact sequences and to devise immunization methods that exploit these.


Outcomes of radialization for radial longitudinal deficiency: 20 limbs with minimum 5-year follow-up.
We report functional and cosmetic outcomes in 14 patients (six bilateral and eight unilateral) with type IV radial longitudinal deficiency who underwent radialization. Follow-up ranged from 5 to 19 years. Outcome measures were grip and pinch strengths, Percival and Sykes score, Vilkki score, Cattaneo grading, and a questionnaire to patients. Radiological assessment included the hand-forearm angle, the hand-forearm position, and ulna length and width. At final follow-up, the length of the affected ulna was 56% of the length of the normal ulna. The distal ulna hypertrophied to 97% of the opposite distal radius and a median loss of correction of hand-forearm angle was 9°. All hands improved on Vilkki severity grade and on the Cattaneo functional and aesthetic grading. We conclude that radialization is an effective procedure in these cases, but secondary procedures may be required for the long-term maintenance of wrist alignment and hand function. Level of evidence: IV.


Molecular Graphics of Convex Body Fluids.
Coarse-grained modeling of molecular fluids is often based on nonspherical convex rigid bodies like ellipsoids or spherocylinders representing rodlike or platelike molecules or groups of atoms, with site-site interaction potentials depending both on the distance among the particles and the relative orientation. In this category of potentials, the Gay-Berne family has been studied most extensively. However, conventional molecular graphics programs are not designed to visualize such objects. Usually the basic units are atoms displayed as spheres or as vertices in a graph. Atomic aggregates can be highlighted through an increasing amount of stylized representations, e.g., Richardson ribbon diagrams for the secondary structure of proteins, Connolly molecular surfaces, density maps, etc., but ellipsoids and spherocylinders are generally missing, especially as elementary simulation units. We fill this gap providing and discussing a customized OpenGL-based program for the interactive, rendered representation of large ensembles of convex bodies, useful especially in liquid crystal research. We pay particular attention to the performance issues for typical system sizes in this field. The code is distributed as open source.


Elastomeric-ligated vs self-ligating appliances: a pilot study examining microbial colonization and white spot lesion formation after 1 year of orthodontic treatment.
To (1) evaluate the use of adenosine triphosphate (ATP)-driven bioluminescence for quantification of total plaque bacteria in orthodontic patients, (2) compare plaque bacteria amounts at the bracket-tooth interface with use of elastomeric-ligated and self-ligating brackets after 1 year of orthodontic treatment, and (3) analyze formation of white spot lesions by photographic evaluation and laser-light fluorescence (DIAGNOdent). Thirteen subjects had fixed orthodontic appliances placed where lateral incisors were bonded with either elastomeric-ligated or self-ligating brackets. Plaque bacteria were collected from incisor surfaces after 1 year and quantified using plating methods and ATP-driven bioluminescence. White spot lesions were evaluated by photographic and DIAGNOdent determinations. A 2 x 2 x 2 mixed-design ANOVA was conducted to determine differences in plaque retention between elastomeric-ligated and self-ligating brackets. ATP-driven bioluminescence values correlated to numbers of total plaque bacteria (r = 0.80). However, unlike findings published in the original pilot study, which described increased plaque retention with elastomeric-ligated brackets at 5 weeks postbonding, there were no significant differences in bacterial numbers or ATP-driven bioluminescence values surrounding the elastomeric-ligated vs self-ligating brackets after 1 year of orthodontic treatment. Based on photographic and DIAGNOdent determinations, white spot lesions were found relatively equally on teeth bonded with either bracket type. DIAGNOdent measurements were found to have moderate sensitivity (0.71) and good specificity (0.88) when compared to white spot lesions determined using photographic evaluation. ATP-driven bioluminescence can be used as an accurate assessment of total plaque bacteria in orthodontic patients. After 1 year of orthodontic treatment for patients in this pilot study, there appeared to be no differences in retention of plaque bacteria or white spot lesions comparing the bracket types. The use of DIAGNOdent has some limitations, but may prove to be useful to monitor white spot lesions longitudinally.


Experimental study on the electrical impedance of bone and the effect of direct current on the healing of fractures.
An experimental study of the electrical impedance of cortical bone and medullary cavity and on the effect of a D.C. or a periodically interrupted D.C. on the healing of fractures in rabbits, suggests that the bone behaves as a capacitance of about 20 muF in parallel with a high D.C. resistance. Also a 10 muA periodically interrupted D.C. current stimulates osteogenesis.


Mediterranean diet and essential tremor. A case-control study.
Higher adherence to the Mediterranean diet (MeDi) has been related to lower Alzheimer's disease risk. Some dietary factors have been studied in patients with essential tremor (ET), but the MeDi's effect has not been investigated. Adherence to the MeDi was calculated from a food frequency questionnaire administered in a case-control study of environmental epidemiology of ET in the New York Tri-State area. Logistic regression models were used to examine whether adherence to the MeDi predicted ET (vs. control) outcome. The models adjusted for age, gender, ethnicity, education, caloric intake, body mass index, smoking, ethanol consumption, coffee intake and blood harmane concentrations. 148 ET cases adhered less to MeDi (0-9 scale with higher scores indicating higher adherence) than 250 controls (mean 4.3 +/- 1.7 vs. 4.7 +/- 1.7; p = 0.03). Higher adherence to MeDi was associated with lower odds for ET [0.78 (0.61-0.99); p = 0.042]. As compared to subjects at the lowest MeDi adherence tertile, those at the middle tertile had lower ET odds [0.41 (0.16-1.05)], while subjects at the highest tertile had an even lower ET odds [0.29 (0.10-0.82); p for trend 0.021]. Compared to controls, ET cases adhered less to MeDi. The gradual reduction in ET odds with higher MeDi adherence tertiles suggests a possible dose-response effect. The mechanisms that underlie this association merit further study.


Upper cervical spine instability in pseudoachondroplasia.
Pseudoachondroplasia (PSACH) is a rare autosomal dominant skeletal dysplasia associated with os odontoideum and atlantoaxial instability. This study aims to define the characteristics of upper cervical spine instability in patients with PSACH and analyze the relation between the incidence of upper cervical instability and os odontoideum. Fifteen patients (10 women and 5 men) with PSACH of Korean ethnicity with mean age of 23.7 years (range, 3-44 years) at presentation to our hospital with varied complaints, including short stature, limb deformity, neck pain, and neurological symptoms, were evaluated clinicoradiologically for upper cervical spine instability. The patients were separated into group 1 (n = 9) with os odontoideum and group 2 (n = 6) without os odontoideum. Comparisons were made using parameters such as instability index, rotational instability, atlantodens interval and space available for cord, and analysis done to correlate cervical instability with age and Japanese Orthopedic Association (JOA) score. Significant differences were found statistically when the 2 groups were compared on the basis of the space available for the cord (SAC), JOA scoring, and rotational instability. Linear relationship was found between instability and age and JOA score. Incidence of os odontoideum was 60% in our study group. Os odontoideum led to an increase in the incidence of upper cervical spine instability. Instability increased with the age. The presence of os odontoideum and atlantoaxial instability did not warrant for surgery because no signs of cervical myelopathy developed or progressed in our patients during the follow-up period, but these patients should undergo regular clinical and radiological evaluation. Level IV prognostic study.


Resident away rotations allow adaptive neurosurgical training.
Subspecialization of physicians and regional centers concentrate the volume of certain rare cases into fewer hospitals. Consequently, the primary institution of a neurological surgery training program may not have sufficient case volume to meet the current Residency Review Committee case minimum requirements in some areas. To ensure the competency of graduating residents through a comprehensive neurosurgical education, programs may need for residents to travel to outside institutions for exposure to cases that are either less common or more regionally focused. We sought to evaluate off-site rotations to better understand the changing demographics and needs of resident education. This would also allow prospective monitoring of modifications to the neurosurgery training landscape. We completed a survey of neurosurgery program directors and query of data from the Accreditation Council of Graduate Medical Education to characterize the current use of away rotations in neurosurgical education of residents. We found that 20% of programs have mandatory away rotations, most commonly for exposure to pediatric, functional, peripheral nerve, or trauma cases. Most of these rotations are done during postgraduate year 3 to 6, lasting 1 to 15 months. Twenty-six programs have 2 to 3 participating sites and 41 have 4 to 6 sites distinct from the host program. Programs frequently offset potential financial harm to residents rotating at a distant site by support of housing and transportation costs. As medical systems experience fluctuating treatment paradigms and demographics, over time, more residency programs may adapt to meet the Accreditation Council of Graduate Medical Education case minimum requirements through the implementation of away rotations.


Maternal and paternal recreational drug use and sudden infant death syndrome.
To determine whether maternal or paternal use of cocaine, opiates, or marijuana during conception and pregnancy and postnatally increases the risk of sudden infant death syndrome (SIDS) during the first year of the infant's life. This is an important issue and may prove useful in further decreasing the rate of SIDS. A case-control study was conducted consisting of 239 infants who died of SIDS in southern California between 1989 and 1992, and 239 healthy infants who were matched on the basis of birth hospital, date of birth, age, and sex. Specific drug use at the period of conception, during pregnancy and breastfeeding, and in the presence or vicinity of the infant was ascertained by telephone for the white, African American, Hispanic, Asian American, and Pacific Islander case and control fathers and mothers. Maternal recreational drug use during pregnancy was not associated with the risk of SIDS after adjusting for maternal smoking during pregnancy (adjusted odds ratio [OR] = 2.0; 95% confidence interval [CI], 0.6-6.5). There were statistically significant differences between case and control fathers' use of marijuana during conception (OR = 2.2; 95% CI, 1.2-4.2; P =.01), during pregnancy (OR = 2.0; 95% CI, 1.0-4.1; P =.05), and postnatally (OR = 2.8; 95% CI, 1.1-7.3; P =.04) and the risk of SIDS, while adjusting for paternal smoking and alcohol use. There was no association between maternal recreational drug use and SIDS. Paternal marijuana use during the periods of conception and pregnancy and postnatally were significantly associated with SIDS. The role of paternal psychoactive drug use, especially the relationship between marijuana and SIDS, is an understudied area; however, before any definitive role for the father can be confirmed, these findings should be investigated and replicated in future studies.