Mapping of common rib fracture patterns and the subscapular flail chest associated with operative scapula fractures.
Rib fractures occur in approximately 10% of trauma patients and are associated with more than 50% of patients with scapula fractures. This study investigates the location and patterns of rib fractures and flail chest occurring in patients with operatively treated scapula fractures. Novel frequency mapping techniques of rib fracture patterns in patients who also injure the closely associated scapula can yield insight into surgical approaches and fixation strategies for complex, multiple injuries patients. We hypothesize that rib fractures have locations of common occurrence when presenting with concomitant scapula fracture that requires operative treatment. Patients with one or more rib fractures and a chest computed tomography scan between 2004 and 2018 were identified from a registry of patients having operatively treated scapula fractures. Unfurled rib images were created using Syngo-CT Bone Reading software (Siemens Inc., Munich, Germany). Rib fracture and flail segment locations were marked and measured for standardized placement on a two-dimensional chest wall template. Location and frequency were then used to create a gradient heat map. A total of 1,062 fractures on 686 ribs were identified in 86 operatively treated scapula fracture patients. The mean ± SD number of ribs fractured per patient was 8.0 ± 4.1 and included a mean ± SD of 12.3 ± 7.2 total fractures. Rib fractures ipsilateral to the scapula fracture occurred in 96.5% of patients. The most common fracture and flail segment location was ipsilateral and subscapular; 51.4% of rib fractures and 95.7% of flail segments involved ribs 3 to 6. Patients indicated for operative treatment of scapula fractures have a substantial number of rib fractures that tend to most commonly occur posteriorly on the rib cage. There is a pattern of subscapular rib fractures and flail chest adjacent to the thick bony borders of the scapula. This study enables clinicians to better evaluate and diagnose scapular fracture patients with concomitant rib fractures. Diagnostic test, level IV.


Interleukin-18 enhances monocyte tumor necrosis factor alpha and interleukin-1beta production induced by direct contact with T lymphocytes: implications in rheumatoid arthritis.
At sites of inflammation, T cells exert pathologic effects through direct contact with monocyte/macrophages, inducing massive up-regulation of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha). We examined the regulatory effects of IL-18 on monocyte activation by direct contact with T lymphocytes in rheumatoid arthritis (RA). Activated T cells were isolated from RA synovial fluid. Resting T cells and monocytes were isolated from peripheral blood mononuclear cells. RA synovial T cells or phytohemagglutinin (PHA)-stimulated T cells were fixed by paraformaldehyde and then cocultured with monocytes at a ratio of 4:1. Levels of TNFalpha, IL-1beta, IL-10, and IL-18 were measured by enzyme-linked immunosorbent assay. Expression of adhesion molecules, IL-18 receptor, and TNF receptors was analyzed by flow cytometry. Expression of NF-kappaB p65, phosphorylated IkappaBalpha, and phosphatidylinositol 3-kinase (PI 3-kinase) p110 was analyzed by Western blotting. IL-18 dose-dependently enhanced the production of IL-1beta and TNFalpha, but not IL-10, by monocytes following contact with RA synovial T cells or PHA-prestimulated T cells. NF-kappaB inhibitors N-acetyl-L-cysteine and Bay 11-7085 and PI 3-kinase inhibitor LY294002 inhibited the enhancing effects of IL-18, but MAPK p38 inhibitor SB203580, ERK inhibitor PD98059, and JNK inhibitor SP600125 did not. Increased levels of NF-kappaB in the nucleus, phosphorylated IkappaB, and PI 3-kinase were confirmed in monocytes cocultured with PHA-prestimulated T cells, and the levels were further increased by stimulation with IL-18. Neutralizing antibody to IL-18 inhibited monocyte activation induced by direct contact with PHA-prestimulated T cells. Via cell-cell contact, PHA-prestimulated T cells increased autocrine production of IL-18 by monocytes, which was mediated by activation of the NF-kappaB and PI 3-kinase pathways, and up-regulated the expression of the IL-18 receptor in monocytes. IL-18 up-regulated the expression of the TNF receptors vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) on monocytes. Blocking the binding of the TNF receptors VCAM-1 or ICAM-1 on monocytes to their ligands on stimulated T cells suppressed the IL-18-enhanced production of TNFalpha and IL-1beta in monocytes induced by contact with PHA-prestimulated T cells. IL-18 augments monocyte activation induced by contact with activated T cells in RA synovitis, which is dependent on activation of the NF-kappaB and PI 3-kinase pathways. IL-18 up-regulates the expression of the TNF receptors VCAM-1 and ICAM-1 on monocytes, which mediate the enhancing effects of IL-18 on T cell-monocyte contact.


Synthesis, structure, and reactivity of fluorous phosphorus/carbon/phosphorus pincer ligands and metal complexes.
Reactions of the diphosphine 1,3-C6H4(CH2PH2)2 and fluorous alkenes H2C=CHR(fn)(R(fn)=(CF2)(n-1)CF3; n = 6, 8) at 75 degrees C in the presence of AIBN give the title ligands 1,3-C6H4(CH2P(CH2CH2R(fn))2)2(3-R(fn)) and byproducts 1,3-C6H4(CH3)(CH2P(CH2CH2R(fn))2)(4-R(fn)) in 1 : 3 to 1 : 5 ratios. Workups give -R(fn) in 4--17% yields. Similar results are obtained photochemically. Reaction of 1,3-C6H4(CH2Br)2 and HP(CH2CH2R(f8))2 (5) at 80 degrees C (neat, 1 : 2 mol ratio) gives instead of simple substitution the metacyclophane [1,3-C6H4(CH2P(CH2CH2R(f8))2 CH2-1,3-C(6)H(4)CH(2)P[lower bond 1 end](CH2CH2R(f8))2C[upper bond 1 end]H2](2+)2Br-, which upon treatment with LiAlH(4) yields 3-R(f8)(20%), 4-R(f8), and other products. Efforts to better access 3-R(f8), either by altering stoichiometry or using various combinations of the phosphine borane (H3B)PH(CH2CH2R(f8))2 and base, are unsuccessful. Reactions of 3-R(fn) with Pd(O2CCF3)2 and [IrCl(COE)2]2(COE=cyclooctene) give the palladium and iridium pincer complexes (2,6,1-C6H3(CH2 P(CH2CH2R(fn))(2)(2)Pd(O2CCF3)(10-R(fn); 80-90%) and (2,6,1-C6H3(CH2P(CH2CH2R(f8))2)2)Ir(Cl)(H)(11-R(f8); 29%), which exhibit CF3C6F(11)/toluene partition coefficients of >96 : <4. The crystal structure of 10-R(f8) shows CH2CH2R(f8) groups with all-anti conformations that extend in parallel above and below the palladium square plane to create fluorous lattice domains. NMR monitoring shows a precursor to 11-R(f8) that is believed to be a COE adduct.


Parental participation in religious services and parent and child well-being: findings from the National Survey of America's Families.
Using data from the 1999 and 2002 National Survey of America's Families, a large-scale nationally representative sample, this study finds that parental religious attendance is positively associated with parent self-rated health, parent mental well-being, positive parenting attitudes, child health, and child school engagement. Although the strength of these associations varies to some extent according to socio-demographic factors, the interactive patterns are not consistently predictable. Moreover, parental health and well-being and positive attitudes toward parenting appear to be important pathways linking parental religious attendance to child well-being. These findings suggest that opportunities for participation in local religious services offered by faith-based organizations may be fruitful avenues through which the government and society can help American families enhance parent and child well-being.


Targeted RNA-Sequencing Enables Detection of Relevant Translocations and Single Nucleotide Variants and Provides a Method for Classification of Hematological Malignancies-RANKING.
Patients with hematological malignancies (HMs) carry a wide range of chromosomal and molecular abnormalities that impact their prognosis and treatment. Since no current technique can detect all relevant abnormalities, technique(s) are chosen depending on the reason for referral, and abnormalities can be missed. We tested targeted transcriptome sequencing as a single platform to detect all relevant abnormalities and compared it to current techniques. We performed RNA-sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in bone marrow from 136 patients with a primary diagnosis of HM. We then applied machine learning to expression profile data to perform leukemia classification, a method we named RANKING. Gene fusions for all the genes in the panel were detected, and overexpression of the genes EVI1, CCND1, and BCL2 was quantified. Single nucleotide variants/indels were analyzed in acute myeloid leukemia (AML), myelodysplastic syndrome and patients with acute lymphoblastic leukemia (ALL) using a virtual myeloid (54 genes) or lymphoid panel (72 genes). RANKING correctly predicted the leukemia classification of all AML and ALL samples and improved classification in 3 patients. Compared to current methods, only one variant was missed, c.2447A>T in KIT (RT-PCR at 10-4), and BCL2 overexpression was not seen due to a t(14; 18)(q32; q21) in 2% of the cells. Our RNA-sequencing method also identified 6 additional fusion genes and overexpression of CCND1 due to a t(11; 14)(q13; q32) in 2 samples. Our combination of targeted RNA-sequencing and data analysis workflow can improve the detection of relevant variants, and expression patterns can assist in establishing HM classification.


Oral splints in the management of nociceptive pain and migraines: A scoping review.
Temporomandibular disorders (TMDs) are characterized by numerous pain manifestations. Their treatment often involves the use of an oral splint. Recent research has found a relationship between migraines, nociceptive pain and TMDs. The aim of the present study was to perform a scoping review of studies in order to evaluate the effectiveness of the various types of oral splint in the treatment of migraine or nociceptive pain. Publications were retrieved from seven databases (PubMed, Web of Science, EMBASE, Scopus, ProQuest, SpringerLink and Ovid). Out of the 15 included publications, three studies were before and after studies, with no control group, whereas the other twelve studies were clinical trials, among which two publications were crossover studies. A clear, single distinction of pain was difficult to describe. Therefore, numerous publications focused on a combination of various types of pains, including myofascial, temporomandibular joint, headaches and migraine-like symptoms, all of which mimicked TMD pain. Overall, six studies used the stabilization splint (SS), three explored the comparison between the SS and the nociceptive trigeminal inhibition splint (NTIS) and two the NTIS. The majority of publications reported a positive outcome of splint therapy. Regarding the type of oral splint usage, the most commonly used one was the SS, followed by the NTIS. The definition and assessment of pain were heterogenous in the identified articles. The findings of the current study showed that occlusal splints may help with pain management, and that effective treatment of TMD-related pain at an early stage can enhance the quality of life of patients.


Accelerometry and heart rate as a measure of physical fitness: cross-validation.
We recently reported on a new method to assess physical fitness, based on the combined use of accelerometry and heart rate (HR) registration. This study tested the validity of the prediction formula in a group of healthy young adults. Twenty-six healthy subjects performed a maximal incremental test on a bicycle ergometer to determine VO2max. A triaxial accelerometer and a HR monitor were worn for 7 d under free-living conditions. The prediction formula developed in a previous experimental group (EXP) was applied on the cross-validation group (CV). No difference was found in subjects' characteristics between the EXP and CV groups except for accelerometer output (activity counts). Although measured VO2max could be predicted for 80% (P < 0.0001), a paired t-test showed a significant difference between measured and predicted VO2max (178 mL.min(-1); P = 0.015). Because of the difference in activity between the EXP and the CV groups, all data were combined and sorted according to activity counts, then two new groups were formed. As a result, EXP and CV groups were created that did not significantly differ in activity or any other parameters. The formula developed in the new experimental group (R2 = 0.74; P < 0.0001) explained 72% (P < 0.0001) of the variation in VO2max in the cross-validation group, a paired t-test showed no difference between measured and predicted VO2max, and Bland-Altman plotting showed no systematic bias. Although a good correlation was seen between measured and predicted VO2max in the cross-validation group, care should be taken in applying the prediction formula on groups that differ in physical activity from the current study population.


Neuropsychiatric profiles in dementia.
We compared patterns of neuropsychiatric symptoms across 4 dementia types [Alzheimer disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB), and Parkinson disease dementia], and 2 mixed groups (AD/VAD and AD/DLB) in sample of 2,963 individuals from the National Alzheimer's Coordinating Center Uniform Data Set between September 2005 and June 2008. We used confirmatory factor analysis to compare neuropsychiatric symptom severity ratings made by collateral sources on the Neuropsychiatric Inventory Questionnaire for people with Clinical Dementia Rating scores of 1 or higher. A 3-factor model of psychiatric symptoms (mood, psychotic, and frontal) was shared across all dementia types. Between-group comparisons revealed unique neuropsychiatric profiles by dementia type. The AD group had moderate levels of mood, psychotic, and frontal symptoms whereas VAD exhibited the highest levels and Parkinson disease dementia had the lowest levels. DLB and the mixed dementias had more complex symptom profiles. Depressed mood was the dominant symptom in people with mild diagnoses. Differing psychiatric symptom profiles provide useful information regarding the noncognitive symptoms of dementia.


MeDBA: the Metalloenzyme Data Bank and Analysis platform.
Metalloenzymes are attractive research targets in fields of chemistry, biology, and medicine. Given that metalloenzymes can manifest conservation of metal-coordination and ligand binding modes, the excavation and expansion of metalloenzyme-specific knowledge is of interest in bridging metalloenzyme-related fields. Building on our previous metalloenzyme-ligand association database, MeLAD, we have expanded the scope of metalloenzyme-specific knowledge and services, by forming a versatile platform, termed the Metalloenzyme Data Bank and Analysis (MeDBA). The MeDBA provides: (i) manual curation of metalloenzymes into different categories, that this M-I, M-II and M-III; (ii) comprehensive information on metalloenzyme activities, expression profiles, family and disease links; (iii) structural information on metalloenzymes, in particular metal binding modes; (iv) metalloenzyme substrates and bioactive molecules acting on metalloenzymes; (v) excavated metal-binding pharmacophores and (vi) analysis tools for structure/metal active site comparison and metalloenzyme profiling. The MeDBA is freely available at https://medba.ddtmlab.org.


Genome-scale CRISPR screening reveals that C3aR signaling is critical for rapid capture of fungi by macrophages.
The fungal pathogen Histoplasma capsulatum (Hc) invades, replicates within, and destroys macrophages. To interrogate the molecular mechanisms underlying this interaction, we conducted a host-directed CRISPR-Cas9 screen and identified 361 genes that modify macrophage susceptibility to Hc infection, greatly expanding our understanding of host gene networks targeted by Hc. We identified pathways that have not been previously implicated in Hc interaction with macrophages, including the ragulator complex (involved in nutrient stress sensing), glycosylation enzymes, protein degradation machinery, mitochondrial respiration genes, solute transporters, and the ER membrane complex (EMC). The highest scoring protective hits included the complement C3a receptor (C3aR), a G-protein coupled receptor (GPCR) that recognizes the complement fragment C3a. Although it is known that complement components react with the fungal surface, leading to opsonization and release of small peptide fragments such as C3a, a role for C3aR in macrophage interactions with fungi has not been elucidated. We demonstrated that whereas C3aR is dispensable for macrophage phagocytosis of bacteria and latex beads, it is critical for optimal macrophage capture of pathogenic fungi, including Hc, the ubiquitous fungal pathogen Candida albicans, and the causative agent of Valley Fever Coccidioides posadasii. We showed that C3aR localizes to the early phagosome during Hc infection where it coordinates the formation of actin-rich membrane protrusions that promote Hc capture. We also showed that the EMC promotes surface expression of C3aR, likely explaining its identification in our screen. Taken together, our results provide new insight into host processes that affect Hc-macrophage interactions and uncover a novel and specific role for C3aR in macrophage recognition of fungi.


High perceived social standing is associated with better health in HIV-infected Ugandan adults on highly active antiretroviral therapy.
Perceived social standing (PSS) was evaluated as a determinant of differences in health outcomes among Ugandan HIV-infected adults from Kampala using cross-sectional study design. PSS was defined using the MacArthur scale of subjective social status translated and adapted for the study setting. Socio-demographic and psychosocial correlates of PSS ranking at enrollment were determined using linear regression models. High versus low PSS was defined based on the median PSS score and evaluated as a determinant of body mass index, hemoglobin, quality of life (QOL) and frailty-related phenotype via linear regression. A log-binomial regression model estimated the relative-risk of good, very good or excellent versus fair or poor self-rated health (SRH) in relation to PSS. Older age, increasing social support and material wealth were correlated with high PSS ranking, whereas female sex, experience of multiple stigmas and multiple depressive symptoms were correlated with low PSS ranking. High PSS participants were on average 1.1 kg/m(2) heavier, had 4.7 % lower frailty scores and 3.6 % higher QOL scores compared to low PSS patients (all p < 0.05); they were also more likely to self-classify as high SRH (RR 1.4, 95 % confidence interval 1.1, 1.7) but had comparable hemoglobin levels (p = 0.634). Low PSS correlated with poor physical and psychosocial wellbeing in HIV-positive Ugandan adults. The assessment of PSS as part of clinical management, combined with efforts to reduce stigma and improve social support, may identify and possibly reduce PSS-associated health inequality in Ugandan adults with HIV.


The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation.
Eosinophils are a subset of granulocytes characterized by a high abundance of specific granules in their cytoplasm. To act as effector cells, eosinophils degranulate and form eosinophil extracellular traps (EETs), which contain double-stranded DNA (dsDNA) co-localized with granule proteins. The exact molecular mechanism of EET formation remains unknown. Although the term "EET release" has been used in scientific reports, it is unclear whether EETs are pre-formed in eosinophils and subsequently released. Moreover, although eosinophil degranulation has been extensively studied, a precise time-course of granule protein release has not been reported until now. In this study, we investigated the time-dependent release of eosinophil peroxidase (EPX) and mitochondrial DNA (mtDNA) following activation of both human and mouse eosinophils. Unexpectedly, maximal degranulation was already observed within 1 min with no further change upon complement factor 5 (C5a) stimulation of interleukin-5 (IL-5) or granulocyte/macrophage colony-stimulating factor (GM-CSF)-primed eosinophils. In contrast, bulk mtDNA release in the same eosinophil populations occurred much slower and reached maximal levels between 30 and 60 min. Although no single-cell analyses have been performed, these data suggest that the molecular pathways leading to degranulation and mtDNA release are at least partially different. Moreover, based on these data, it is likely that the association between the mtDNA scaffold and granule proteins in the process of EET formation occurs in the extracellular space.


Utilization of a tobacco quit line prior to and after a tobacco tax increase.
To evaluate the utilization of a tobacco quit line prior to and after an increase in tobacco taxes. Intake data were utilized to assess the number of callers to the quit line between May 2004 and April 2006. The characteristics of callers were also compared over three time periods; the 5 months prior to a voter initiative to increase the tax (May-September 2004), the 3 months just prior to the tax increase (October-December 2004), and the 5 months after the tax became effective (January-May 2005). The mean number of intake calls to the quit line between May 2004 and April 2006 was 388 per month (range = 200-1 088). The number of calls per month increased just prior to and just after the tax increase (3-month moving average = 691-731 calls). Persons completing an intake between October to December 2004 and January to May 2005 were more likely to be younger than 45 years, woman, White, smoke one or more packs of cigarettes per day, and were less likely to have tried to quit using tobacco in the past year than did persons calling between May and September 2004. Organizations supporting quit lines should anticipate an increase in the utilization of these services and changes in the characteristics of callers prior to and following an increase in tobacco taxes.


Sex differences in alcohol self-administration and relapse-like behavior in Long-Evans rats.
Alcohol use disorders are a costly public health dilemma. Complicating this issue is the general lack of basic research assessing sex differences in many aspects of alcohol seeking and taking behaviors. The current experiments sought to decrease this gap in our understanding of sex differences in alcohol use disorders by assessing both male and female Long-Evans rats in parallel on alcohol self-administration, relapse-like behavior following abstinence and extinction, and motivation to respond for the standard alcohol solution and a quinine-adulterated alcohol solution. Here, we show that while males tend to have greater alcohol-reinforced responses throughout self-administration training, females show similar or greater alcohol intake (g/kg). Additionally, when tested for reinstatement of alcohol seeking and self-administration, following abstinence or extinction, males consistently showed greater reinstatement responding than females, which may be related to their training history. However, when assessed using the progressive ratio, there were no sex differences in motivation to respond for alcohol. Further, the consistent patterns of responding across months of self-administration training in both males and females, lend support for the feasibility of conducting these studies in male and female rats in parallel without concerns about daily variability. Our data also suggest that males and females should not be pooled as differences in alcohol lever responses and differences in reinstatement, as observed in the current experiments, could affect the overall outcome and possibly confound data interpretation. These studies demonstrate the importance of assessing males and females in parallel and advance the body of preclinical research on sex differences in alcohol self-administration and relapse.


Comorbidities Associated with Obstructive Sleep Apnea: a Retrospective Study.
Introduction Obstructive sleep apnea (OSA) is characterized by partial or complete recurrent upper airway obstruction during sleep. OSA brings many adverse consequences, such as hypertension, obesity, diabetes mellitus, cardiac and encephalic alterations, behavioral, among others, resulting in a significant source of public health care by generating a high financial and social impact. The importance of this assessment proves to be useful, because the incidence of patients with comorbidities associated with AOS has been increasing consistently and presents significant influence in natural disease history. Objective The objective of this study is to assess major comorbidities associated with obstructive sleep apnea (OSA) and prevalence in a group of patients diagnosed clinically and polysomnographically with OSA. Methods This is a retrospective study of 100 charts from patients previously diagnosed with OSA in our service between October 2010 and January 2013. Results We evaluated 100 patients with OSA (84 men and 16 women) with a mean age of 50.05 years (range 19-75 years). The prevalence of comorbidities were hypertension (39%), obesity (34%), depression (19%), gastroesophageal reflux disease (GERD) (18%), diabetes mellitus (15%), hypercholesterolemia (10%), asthma (4%), and no comorbidities (33%). Comorbidities occurred in 56.2% patients diagnosed with mild OSA, 67.6% with moderate OSA, and 70% of patients with severe OSA. Conclusion According to the current literature data and the values obtained in our paper, we can correlate through expressive values obesity with OSA and their apnea hypopnea index (AHI) values. However, despite significant prevalence of OSA with other comorbidities, our study could not render expressive significance values able to justify their correlations.


Psychological implications of infertility in women with polycystic ovary syndrome.
In polycystic ovary syndrome (PCOS), one of the main features is chronic anovulation associated with lower pregnancy rates. Little is known regarding the psychological aspects associated with infertility in these patients. Therefore, we examined the influence of an unfulfilled wish to conceive on various aspects of psychological functioning in PCOS women. Standardized questionnaires assessing quality-of-life (36-item short-form health survey, SF-36), depressiveness (Beck Depression Inventory), emotional distress (Symptom Check List 90, SCL-90-R), sexual satisfaction and self-worth (visual analogue scales), and a questionnaire on the desire for a child (FKW) were administered at the outpatient endocrine clinic to consecutive PCOS patients. Questionnaires from 115 PCOS patients were analysed. The majority (76.1%) worried about remaining childless in the future, and 51.3% reported a current wish to conceive. 23.9% of patients had scores indicating mild to moderate depression, and 25.2% had scores indicating clinically relevant depression. Furthermore, all quality-of-life scores were significantly lower compared with normative data (P < 0.001). Unexpectedly, comparisons of patients with a current unfulfilled desire to conceive to those with no present wish for a child revealed no discernable impact on depressive symptoms, quality-of-life or emotional distress. Reduced sexual satisfaction and self-worth were largely determined by partnership status and not infertility. However for PCOS patients who wished to conceive, the wish for a child was a significantly greater priority when compared with normative data from infertile patients. PCOS represents a major risk factor for psychosocial and emotional problems, but at least in this sample of PCOS patients, infertility does not appear to constitute a primary determinant of psychological problems.


Fasting plasma peptide YY concentrations are increased in patients with major depression who associate weight loss.
Many patients with major depression refer a decreased appetite and weight loss among their symptoms. Peptide YY (PYY) and ghrelin belong to the family of peptides of the gut-brain axis implicated in the regulation of appetite and energy metabolism. PYY stimulates a powerful central satiety response and ghrelin increases food intake and weight gain. Brain-derived neurotrophic factor (BDNF) also contributes to the central control of food intake as an anorexigenic factor. To study fasting plasma total and acylated ghrelin, plasma PYY and serum BDNF levels in patients with major depression with weight loss as one of their symptoms and compare them with matched healthy controls. Fifteen adult patients, 9 male and 6 female, with recent diagnosis of major depression, and 16 healthy adult subjects, matched by age and anthropometric parameters were studied. All depressed patients referred weight loss and were not under antidepressant therapy. Fasting total PYY, total ghrelin and acylated ghrelin and BDNF were determined. Fasting total PYY was higher in patients than controls (2.01±0.09 vs 1.29±0.16 pmol/l). There were no differences in fasting total ghrelin, acylated ghrelin or BDNF levels. Major depressed patients, with weight loss at diagnosis, showed higher fasting plasma PYY levels that could contribute to their reduced appetite.


[Analysis of the patients who missed their appointments at the neurology clinic of the Marina Alta].
To analyze the frequency, reasons and characteristics of patients who missed their appointments (NP) at the Neurology Clinic (CEN). To compare the characteristics of the NP with the patients who did not miss their appointment. Suggest measures to reduce avoidable causes of NP. During the period 1/10/99 to 30/4/2000 the cases of NP were prospectively recorded and compared with a sample of patients who attended the CEN during the same period. We analyze the data on age, sex, distance of home from CEN, diagnosis, type of consultation and date of last consultation. The NP were contacted by phone and asked why they had not gone for their appointments. The reasons given were then classified as avoidable or unavoidable. Of the 1,842 consultations scheduled, 19% were NP. When the NP and the patients who did attend were compared we found statistically significant differences regarding the distance home/CEN. According to the diagnosis, the NP had more 'symptoms/signs' and other MIA, whilst those who attended the clinic had more 'neuropathies' and 'awaiting diagnosis'. The commonest avoidable reasons (55.8%) for NP were forgetting, administrative error and communication failure, and for unavoidable reasons (44.2%) physical disability, other priorities and improvement. There is a large proportion of NP in the CEN of the Marina Alta. The distance from home to CEN (over 25 km) was the main factor affecting the rate of NP. Since 56% of the NP were due to avoidable causes, strategies could be designed to reduce this percentage. In the NP group, the main causes were forgetting, administrative errors and communication failure.


What Do We Know Now About Autologous Fat Grafting?
Autologous fat grafting has remained part of the plastic surgeon's armamentarium. Although there have been numerous articles written on this topic, its scientific basis has recently come under some scrutiny with authors questioning what we really know about fat grafting. This article reviews the various fat grafting techniques used today based on the volume and specific need of the patient. Moreover, this review acts as a guideline to the plastic and reconstructive surgeon to choose the fat grafting technique tailored to the specific goal of the procedure. Once volume of fat and the final goal of the procedure is determined, fat grafting becomes a more individualized approach for our patients. While fat grafting is not a cookie-cutter procedure, it can be defined by the volume needed and divided into 3 categories of small, mega or large, and nanofat grafting techniques. A discussion of these 3 main categories of fat grafting techniques will be presented, along with a discussion of the mechanisms of adipocyte survival after transplant based on the graft survival and graft replacement theories. Finally, the role of adipose-derived stem cells in fat grafting based on clinical studies will be delineated. It is our hope to provide the most updated information on what do we know now about autologous fat grafting.


The content validity of the ANMS GCSI-DD in patients with idiopathic or diabetic gastroparesis.
The American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary (ANMS GCSI-DD) was developed to meet Food and Drug Administration (FDA) recommendations for patient-reported outcome (PRO) endpoints in gastroparesis studies, including therapeutic trials. The current version of the ANMS GCSI-DD contains five items pertaining to nausea, early satiety, post-prandial fullness, upper abdominal pain, and vomiting. The specific aims of this study were to determine if the appropriate symptoms are included in the ANMS GCSI-DD and to assess the content validity in patients with idiopathic (IG) and diabetic gastroparesis (DG). Patients diagnosed with IG or DG were recruited by five clinical sites in the United States for a cross-sectional, qualitative study involving one-on-one in-person concept elicitation and cognitive debriefing interviews. Concept elicitation included open-ended questions to elicit patients' symptoms and impacts of gastroparesis, while cognitive debriefing was designed to assess the comprehensiveness of the ANMS GCSI-DD and clarity of the instructions, items, and response scales. The interviews were audio-recorded and transcribed. Transcripts were analyzed using a content analysis approach with ATLAS.ti. Of 25 patients interviewed, 15 (60%) had IG and 10 (40%) DG. Mean age of the sample was 42.3 years (range: 20-70 years), and most patients were female (n = 19, 76%) and white (n = 19, 76%). During concept elicitation, patients endorsed the following signs and symptoms as relevant and important to their condition: early satiety (n = 25, 100%), post-prandial fullness (n = 25, 100%), nausea (n = 22, 88%), upper abdominal pain (n = 18, 72%), vomiting (n = 15, 60%), and bloating (n = 11, 44%). Many patients (n = 20, 80%) experienced day-to-day symptom change. During cognitive debriefing, patients confirmed the ANMS GCSI-DD content was comprehensive and reflective of their gastroparesis experience. Patients could easily select a response option and describe how they arrived at their answers. Overall, patients found the instrument's instructions, recall period, items, and response options clear and understandable. The ANMS GCSI-DD was easily understood, found to contain the most important symptoms for patients with IG and DG, and no changes were recommended. Results support the content validity of the ANMS GCSI-DD for clinical trials and clinical care among IG or DG patients.


Imaging and invasive techniques for diagnosis and treatment of surgical infections.
Advances in imaging techniques have caused a radical change in the radiologic approach to the diagnosis and treatment of surgical infections. Review of the pertinent English-language literature. Ultrasonography (US) is a useful modality for the initial evaluation of intra-abdominal infection, whereas computed tomography (CT) often represents the modality of choice for definitive identification of the cause and extent of the infection. Both US and CT can be used to guide diagnostic fluid aspiration or drainage catheter placement. Fluoroscopy may be useful for diagnostic and interventional procedures in the biliary and urinary tracts, whereas magnetic resonance imaging plays a leading role in evaluating bone and soft tissue structures and the pancreatobiliary tree. The choice of imaging study must be individualized to the particular circumstances of the clinical situation, particularly whether image-guided therapy may be required in addition to diagnosis. Computed tomography is the most versatile for most clinical circumstances.


Modelling of zero-inflation improves inference of metagenomic gene count data.
Metagenomics enables the study of gene abundances in complex mixtures of microorganisms and has become a standard methodology for the analysis of the human microbiome. However, gene abundance data is inherently noisy and contains high levels of biological and technical variability as well as an excess of zeros due to non-detected genes. This makes the statistical analysis challenging. In this study, we present a new hierarchical Bayesian model for inference of metagenomic gene abundance data. The model uses a zero-inflated overdispersed Poisson distribution which is able to simultaneously capture the high gene-specific variability as well as zero observations in the data. By analysis of three comprehensive datasets, we show that zero-inflation is common in metagenomic data from the human gut and, if not correctly modelled, it can lead to substantial reductions in statistical power. We also show, by using resampled metagenomic data, that our model has, compared to other methods, a higher and more stable performance for detecting differentially abundant genes. We conclude that proper modelling of the gene-specific variability, including the excess of zeros, is necessary to accurately describe gene abundances in metagenomic data. The proposed model will thus pave the way for new biological insights into the structure of microbial communities.


Asbestos bodies in bronchoalveolar lavage in the 21st century: a time-trend analysis in a clinical population.
Asbestos bodies (AB) in bronchoalveolar lavage (BAL) can be detected by light microscopy and their concentration is indicative of past cumulative asbestos exposure. We assessed clinical and exposure characteristics, as well as possible time trends, among patients in whom AB had been quantified in BAL. BAL samples obtained from 578 participants between January 1997 and December 2014 were available for analysis. The processing of samples and the microscopic analysis were performed by a single expert and 76% of samples came from a single tertiary care hospital, allowing clinical and exposure data to be extracted from patient files. The study population (95% males) had a mean age of 62.5 (±12.4) years. AB were detected in 55.2% of the samples, giving a median concentration of 0.5 AB/mL (95th centile: 23.6 AB/mL; highest value: 164.5 AB/mL). The AB concentration exceeded 1 AB/mL in 39.4% and 5 AB/mL in 17.8%. A significant decrease from a geometric mean of 0.93 AB/mL in 1997 to 0.2 AB/mL in 2014 was apparent. High AB concentrations generally corresponded with occupations with (presumed) high asbestos exposure. AB concentrations were higher among patients with asbestosis and pleural plaques, when compared with other disease groups. Nevertheless, a substantial proportion of participants with likely exposure to asbestos did not exhibit high AB counts. This retrospective study of a large clinical population supports the value of counting AB in BAL as a complementary approach to assess past exposure to asbestos.


Development of a medical module for disaster information systems.
This study aims to improve a medical module which provides a real-time medical information flow about pre-hospital processes that gives health care in disasters; transferring, storing and processing the records that are in electronic media and over internet as a part of disaster information systems. In this study which is handled within the frame of providing information flow among professionals in a disaster case, to supply the coordination of healthcare team and transferring complete information to specified people at real time, Microsoft Access database and SQL query language were used to inform database applications. System was prepared on Microsoft .Net platform using C# language. Disaster information system-medical module was designed to be used in disaster area, field hospital, nearby hospitals, temporary inhabiting areas like tent city, vehicles that are used for dispatch, and providing information flow between medical officials and data centres. For fast recording of the disaster victim data, accessing to database which was used by health care professionals was provided (or granted) among analysing process steps and creating minimal datasets. Database fields were created in the manner of giving opportunity to enter new data and search old data which is recorded before disaster. Web application which provides access such as data entry to the database and searching towards the designed interfaces according to the login credentials access level. In this study, homepage and users' interfaces which were built on database in consequence of system analyses were provided with www.afmedinfo.com web site to the user access. With this study, a recommendation was made about how to use disaster-based information systems in the field of health. Awareness has been developed about the fact that disaster information system should not be perceived only as an early warning system. Contents and the differences of the health care practices of disaster information systems were revealed. A web application was developed supplying a link between the user and the database to make date entry and data query practices by the help of the developed interfaces.


Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification.
Autoantibodies against post-translationally modified proteins (anti-modified protein antibodies or AMPAs) are a hallmark of rheumatoid arthritis (RA). A variety of classes of AMPAs against different modifications on proteins, such as citrullination, carbamylation and acetylation, have now been described in RA. At present, there is no conceptual framework explaining the concurrent presence or mutual relationship of different AMPA responses in RA. Here, we aimed to gain understanding of the co-occurrence of AMPA by postulating that the AMPA response shares a common 'background' that can evolve into different classes of AMPAs. Mice were immunised with modified antigens and analysed for AMPA responses. In addition, reactivity of AMPA purified from patients with RA towards differently modified antigens was determined. Immunisation with carbamylated proteins induced AMPAs recognising carbamylated proteins and also acetylated proteins. Similarly, acetylated proteins generated (autoreactive) AMPAs against other modifications as well. Analysis of anti-citrullinated protein antibodies from patients with RA revealed that these also display reactivity to acetylated and carbamylated antigens. Similarly, anti-carbamylated protein antibodies showed cross-reactivity against all three post-translational modifications. Different AMPA responses can emerge from exposure to only a single type of modified protein. These findings indicate that different AMPA responses can originate from a common B-cell response that diversifies into multiple distinct AMPA responses and explain the presence of multiple AMPAs in RA, one of the hallmarks of the disease.


[Comparative study of the effectiveness of acycloguanosine and phosphonoacetic acid in herpetic infection in cell cultures].
A comparative study of cytotoxicity and antiherpes activity of acycloguanosine (Acg) of the Soviet and American manufacture and a Soviet preparation of phosphonoacetic acid (PAA) for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) was carried out in primary and continuous cell cultures. The Acg preparation was shown not to be inferior in maximal tolerated concentration, minimal inhibiting concentration, and chemotherapeutic index (CTI) to American drug. Zovirax (Zvr), in relation to both herpes simplex virus types in primary and continuous cell lines. The CTI of Acg and Zvr was 25-30-fold higher than that of PAA for HSV-1 (Vero cells) and 80-fold higher in chick embryo fibroblast cultures (CEF), and 25-fold higher for HSV-2 in CEF.


Pathology of the pleura: what the pulmonologists need to know.
Primary and metastatic pleural neoplasms, and non-neoplastic pleural diseases, can have similar clinical, radiographic and gross features. However, treatments and prognoses of these diverse pleural conditions vary greatly. Accurate diagnosis of pleural disease is therefore extremely important, and histological interpretation of pleural biopsies is vital to rendering an accurate diagnosis. Smaller biopsies contribute to the difficulties in accurately characterizing pleural lesions, and immunostains are frequently employed in their assessment. Diffuse malignant mesothelioma, the most common primary pulmonary neoplasm, is rare; however, other less common primary pleural neoplasms, including solitary fibrous tumour, the most common benign primary pleural neoplasm, occur. These neoplasms are discussed. Also, non-neoplastic pleural diseases, including granulomatous pleuritis, eosinophilic pleuritis and fibrous and fibrinous pleuritis, among other diseases, are discussed.


Purification and analysis with monoclonal antibodies of P2, the major outer membrane protein of nontypable Haemophilus influenzae.
The protein P2 comprises a large proportion of the outer membrane of nontypable Haemophilus influenzae and functions as a porin. In view of the importance of the protein as a surface antigen, the present study was designed to purify and analyze P2 with particular emphasis on detection of antigenic determinants expressed on the bacterial surface and identification of bactericidal targets on P2. The P2 protein was purified by using detergent solubility, anion-exchange chromatography, and gel-filtration chromatography sequentially. Two monoclonal antibodies to P2 were developed. One antibody (2E6) recognized a determinant expressed on the bacterial surface, whereas the other antibody (3F3) recognized an internal epitope. The surface-exposed 2E6 determinant was present on 12% of strains from a nationwide collection. P2 is a bactericidal target for antibody 2E6. Cyanogen bromide cleavage of P2 resulted in two fragments, as in type b strains. Both monoclonal antibodies recognized epitopes on the larger fragment. These observations have potentially important implications regarding the development of vaccines to prevent H. influenzae infections and the development of a serotyping system for epidemiologic studies.


Relative age effects in Australian Football League National Draftees.
This study examined the birth distribution for adolescent (i.e. <20 years) and mature age players (i.e. ≥20 years) selected in the Australian Football League (AFL) National Draft between 2001 and 2012. Birth-date information was accessed for all first time AFL national draftees and players were then classified as either adolescent (N = 736) or mature age (N = 70) draftees. Chi-squared analysis showed a clear bias in the birth distribution of adolescent draftees towards players born in the first part of the classification period for both quartile (P < 0.001) and half-year (P < 0.001) compared to the Australian national population. There was a reverse relative age effect (RAE) for mature age draftees, with a significant bias towards players born in the latter part of the selection period for both quartile (P = 0.047) and half-year (P = 0.028) compared to the Australian national population. The selection bias towards relatively older players in adolescent AFL draftees may be related to advanced physical and psychological maturity, and exposure to higher-level coaching compared to their younger counterparts. The reverse RAE in mature age draftees is a novel finding and supports the need for strategies to encourage continued participation pathways for talented Australian football players born later in the selection year.


The effects of actual and perceived body weight on unhealthy weight control behaviors and depressed mood among adult women in Seoul, Korea.
This study was conducted to examine the mediating function of body weight perception (BWP) on the relationship between body mass index (BMI) and unhealthy weight control behaviors (UWCB: e.g., fasting, or taking diet pills or laxatives) and between BMI and depressed mood, and to explore the effect of distorted BWP on UWCB and depressed mood among adult women. A regionally representative sample of 8,581 women aged 20-64 years residing in Seoul, the capital of Korea, completed the 2001 Seoul Citizens Health Indicator Survey which provides self-reported information about height, weight, BWP, UWCB, depressed mood, demographic/ socioeconomic characteristics, and health-related behaviors. Data were analyzed using bivariate and multivariate logistic regression. BMI was significantly associated both with UWCB and depressed mood, even controlling for all covariates. However, the magnitude and significance of each association was considerably attenuated when BWP was taken into account, indicating that BWP functioned, in part, as a mediator between BMI and UWCB and between BMI and depressed mood, respectively. Among the combinations of BMI and BWP, women who perceived themselves to be heavier than their actual BMIs appeared more likely to use UWCB, whereas women who had a distorted BWP, either underestimation or overestimation as compared with their BMIs, tended to be at greater risk for depressed mood than those who had an undistorted BWP. These findings suggest that how women perceive their body weight may be an important predictor and/or mediator of UWCB and depressed mood among adult Korean women.


A Novel Platform for Evaluating Dose Rate Effects on Oxidative Damage to Peptides: Toward a High-Throughput Method to Characterize the Mechanisms Underlying the FLASH Effect.
High dose rate radiation has gained considerable interest recently as a possible avenue for increasing the therapeutic window in cancer radiation treatment. The sparing of healthy tissue at high dose rates relative to conventional dose rates, while maintaining tumor control, has been termed the FLASH effect. Although the effect has been validated in animal models using multiple radiation sources, it is not yet well understood. Here, we demonstrate a new experimental platform for quantifying oxidative damage to protein sidechains in solution as a function of radiation dose rate and oxygen availability using liquid chromatography mass spectrometry. Using this reductionist approach, we show that for both X-ray and electron sources, isolated peptides in solution are oxidatively modified to different extents as a function of both dose rate and oxygen availability. Our method provides an experimental platform for exploring the parameter space of the dose rate effect on oxidative changes to proteins in solution.


Obstetric Anesthesia for a Pregnant Woman With Brainstem Cavernous Malformations: A Case Report.
There are no well-defined guidelines for obstetric and anesthetic management of pregnant patients with cerebral cavernous malformations (CMs). We need to pay careful attention to the attendant risks of both general and neuraxial anesthesia in this population. Here, we describe the anesthetic management of a pregnant woman with brainstem CMs who underwent cesarean delivery. We selected a general anesthetic technique because of concerns of undesirable effects of neuraxial anesthesia in the presence of cerebral CMs.


Role of heme oxygenase-1 in the antidepressant-like effect of ursolic acid in the tail suspension test.
This study investigated the involvement of heme oxygenase-1 (HO-1) in the antidepressant-like effects of ursolic acid (UA), a plant-derived compound with neuroprotective and antidepressant-like properties. Mice received intracerebroventricular injections of zinc protoporphyrin IX (ZnPP) or cobalt protoporphyrin IX (CoPP) to inhibit or induce HO-1, respectively, together with effective (0.1 mg/kg, p.o.) or sub-effective (0.01 mg/kg, p.o.) doses of UA or fluoxetine (10 mg/kg, p.o.). Immobility time was assessed using the tail suspension test (TST) and the ambulatory behaviour with the open field test. HO-1 immunocontent was evaluated in mice hippocampus and prefrontal cortex. ZnPP prevented the anti-immobility effects of UA and fluoxetine. Combined treatment with a sub-effective dose of CoPP and UA synergistically exerted antidepressant-like effects in the TST. Acute administration of UA or CoPP, but not fluoxetine, increased the HO-1 immunocontent in the hippocampus. None of the treatments altered the HO-1 immunocontent in the prefrontal cortex. In conclusion, this work shows that increased hippocampal HO-1 content and activity mediate the antidepressant-like effect of UA in the TST.


Comprehensive analysis of HLA-DR- and HLA-DP4-restricted CD4+ T cell response specific for the tumor-shared antigen survivin in healthy donors and cancer patients.
Because of the wide distribution of the survivin Ag in a variety of tumors, we have investigated the survivin-specific CD4+ T cell response in healthy donors and cancer patients. Screening of the entire sequence of survivin for HLA class II binding led to the identification of seven HLA-DR promiscuous peptides, including four HLA-DP4 peptides. All of the peptides were able to prime in vitro CD4+ T cells of eight different healthy donors. The peptide-specific T cell lines were stimulated by dendritic cells loaded with the recombinant protein or with the lysates of tumor cells. The high frequency of responders (i.e., immunoprevalence) was provided by a wide reactivity of multiple peptides. Six peptides were T cell stimulating in at least half of the donors and were close to CD8+ T cell epitopes. HLA-DR molecules were more frequently involved in T cell stimulation than were HLA-DP4 molecules, and hence immunoprevalence relies mainly on HLA-DR promiscuity in the survivin Ag. In two cancer patients a spontaneous CD4+ T cell response specific for one of these peptides was also observed. Based on these observations, the tumor-shared survivin does not appear to be the target of immune tolerance in healthy donors and cancer patients and is a relevant candidate for cancer vaccine.


Buried disc drusen have hypo-reflective appearance on SD-OCT.
Buried disc drusen are an important differential diagnosis for papilledema. Spectral domain optical coherence tomography (SD-OCT) affords clinicians with new non-invasive opportunities to probe below the surface of the optic nerve. Clinicians may use the knowledge of this appearance to rule out buried disc drusen in patients with irregular optic nerve borders or a bulging, hyperemic appearance. SD-OCTs were obtained in a patient with one surfacing disc druse, identifying the nature of the appearance of this disc druse and others in this and the contralateral eye when imaged with this technology. B-scan ultrasonography was used to confirm the presence of disc drusen. Additional scans in multiple patients with confirmed buried drusen were obtained for comparison. Drusen appear as rounded hyporeflectant areas on SD-OCT, similar in appearance to blood vessels. They share the appearance of cysts but show a fine hyperreflective border anteriorly. These same discrete hyporeflective areas were found at various depths within optic nerve heads with confirmed buried disc drusen. The hyporeflective appearance may not be anticipated by clinicians, as B-scans show calcified drusen as hyperreflective on echo. It is hypothesized that the hyporeflectant appearance of drusen is due to a constancy in refractive index through the druse, as OCT detects changes in optical reflectivity. Thus, drusen are likely dense and homogenous. SD-OCT may be more useful in those patients with buried disc drusen which are not calcified as B-scan often contributes little in such cases.


A new hypothesis for the origin of Amazonian Dark Earths.
Amazonian Dark Earths (ADEs) are unusually fertile soils characterised by elevated concentrations of microscopic charcoal particles, which confer their distinctive colouration. Frequent occurrences of pre-Columbian artefacts at ADE sites led to their ubiquitous classification as Anthrosols (soils of anthropic origin). However, it remains unclear how indigenous peoples created areas of high fertility in one of the most nutrient-impoverished environments on Earth. Here, we report new data from a well-studied ADE site in the Brazilian Amazon, which compel us to reconsider its anthropic origin. The amounts of phosphorus and calcium-two of the least abundant macronutrients in the region-are orders of magnitude higher in ADE profiles than in the surrounding soil. The elevated levels of phosphorus and calcium, which are often interpreted as evidence of human activity at other sites, correlate spatially with trace elements that indicate exogenous mineral sources rather than in situ deposition. Stable isotope ratios of neodymium, strontium, and radiocarbon activity of microcharcoal particles also indicate exogenous inputs from alluvial deposition of carbon and mineral elements to ADE profiles, beginning several thousands of years before the earliest evidence of soil management for plant cultivation in the region. Our data suggest that indigenous peoples harnessed natural processes of landscape formation, which led to the unique properties of ADEs, but were not responsible for their genesis. If corroborated elsewhere, this hypothesis would transform our understanding of human influence in Amazonia, opening new frontiers for the sustainable use of tropical landscapes going forward.


Detection of rheumatoid arthritis bone erosions by two different dedicated extremity MRI units and conventional radiography.
To compare the ability of two different dedicated extremity MRI (E-MRI) units and conventional radiography (CR) for identifying bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) and wrist joints. CR and two MRI examinations (using 0.2 T Esaote Artoscan and 0.2 T portable MagneVu MV1000 units) of 418 bones in the dominant wrist and second to fifth MCP joints of 15 patients with RA and 4 healthy controls were performed and evaluated blindly for bones being visible and for erosions. In MCP joints, MagneVu visualised 18.5% of bones entirely and 71.1% were 67-99% visualised. In wrists, MagneVu visualised 1.5% of bones entirely, 39.8% were 67-99% visualised and 19% were not visualised at all. Artoscan and CR visualised all bones entirely. Artoscan, MagneVu and CR found 22, 19 and 15 bones with erosions in MCP joints and 66, 40 and 13 bones with erosions in wrist joints, respectively. With the previously validated Artoscan unit as standard reference, MagneVu and CR had sensitivities of 0.82 and 0.55, respectively, in MCP joint bones and 0.41 and 0.14 in wrist bones. Specificities of CR and MagneVu were comparable (0.82-0.99). The MagneVu unit was particularly more sensitive than CR for metacarpal heads and carpal bones. MagneVu MRI and CR detected 100% and 89%, respectively, of large erosions (Outcome Measures in Rheumatoid Arthritis Clinical Trials-Rheumatoid Arthritis MRI Scoring System (OMERACT-RAMRIS) score >1 on Artoscan) in MCP joints and 69% and 15.8% of large erosions in wrists. Both E-MRI units detected more erosions than CR, in particular due to a higher sensitivity in metacarpal heads and carpal bones. The MagneVu unit detected fewer erosions than the Artoscan unit due to a lower average image quality and a smaller proportion of bones being visualised.


Whole cell biocatalysts for the preparation of nucleosides and their derivatives.
Nucleosides constitute an extensive group of natural and chemically modified compounds that display a wide range of structures and activities. Different biocatalysts have been developed for their preparation, but the choice of commercially available enzymes is limited. Therefore, the search of new biocatalysts is particularly attractive. In this sense, microorganisms are a vast source of enzymatic diversity that can be directly used as a whole cell biocatalysts providing a potential cheaper and suitable route for industrial applications. This work makes particular emphasis on the following methods: the biocatalyzed whole cell synthesis of nucleosides mediated by phosphorylases, key biocatalyzed steps involved in other chemoenzymatic routes to prepare nucleoside analogues and the transformation of nucleosides in derivatives with particular properties. The literature covered in this work confirms that biocatalytic procedures that make use of whole cell systems can be successfully applied to obtain a wide variety of nucleoside analogues and their derivatives, providing alternative and complementary routes to traditional chemistry. The direct use of microbial whole cells as biocatalysts affords competitive results since it avoids the cumbersome procedures involved in enzyme isolation and facilitates multienzymatic processes. These biocatalysts also maintain the enzymes in their natural environment, protecting their activities from reaction conditions. Although the information presented herein shows that these methodologies have reached a high degree of development, it is expected that future contributions of protein engineering and nucleoside metabolism knowledge, among other disciplines, will expand the already wide range of applications in nucleoside chemistry of whole cell biocatalysis.


Multiwalled carbon nanotube@a-C@Co9S8 nanocomposites: a high-capacity and long-life anode material for advanced lithium ion batteries.
A one-dimensional MWCNT@a-C@Co9S8 nanocomposite has been prepared via a facile solvothermal reaction followed by a calcination process. The amorphous carbon layer between Co9S8 and MWCNT acts as a linker to increase the loading of sulfides on MWCNT. When evaluated as anode materials for lithium ion batteries, the MWCNT@a-C@Co9S8 nanocomposite shows the advantages of high capacity and long life, superior to Co9S8 nanoparticles and MWCNT@Co9S8 nanocomposites. The reversible capacity could be retained at 662 mA h g(-1) after 120 cycles at 1 A g(-1). The efficient synthesis and excellent performances of this nanocomposite offer numerous opportunities for other sulfides as a new anode for lithium ion batteries.


Hyperactivity in the ventral cochlear nucleus after cochlear trauma.
The emergence of hyperactivity in the form of elevated spontaneous firing rates after cochlear trauma has been well documented in a number of central auditory structures, including the auditory cortex, inferior colliculus, and dorsal subdivision of the cochlear nucleus. This hyperactivity is of interest as a possible neural substrate of tinnitus. Whether the ventral subdivision of the cochlear nucleus shows hyperactivity has never been investigated despite the fact that, like the dorsal division, it also receives direct input from the damaged cochlea and supplies major ascending inputs to brainstem and midbrain auditory centers. We investigated spontaneous neuronal firing rates in the ventral cochlear nucleus in a guinea pig model of cochlear trauma in which we have shown that hyperactivity consistently develops in the inferior colliculus (Mulders and Robertson, 2009). The mean spontaneous firing rates of ventral cochlear nucleus neurons was significantly elevated compared to sham controls. This hyperactivity was more evident in primary-like and onset categories of neurons. Hyperactivity in the ventral subdivision of cochlear nucleus therefore needs to be considered in relation to neural models of the genesis of tinnitus.


A decade-long surveillance of nasopharyngeal colonisation with Streptococcus pneumoniae among children attending day-care centres in south-eastern France: 1999-2008.
The antimicrobial resistance and serotype distribution of Streptococcus pneumoniae (SP) among children attending day-care centres in south-eastern France were monitored from 1999 to 2008, before and after interventions promoting prudent antibiotic use initiated in 2000 and the availability of pneumococcal conjugate vaccine in 2003. Antibiotic susceptibility and serotypes of SP isolates were determined on nasopharyngeal samples of children aged 3-40 months attending day-care centres, from January to March 1999, 2002, 2004, 2006 and 2008. SP carriage fell from 54% to 45%, and SP with diminished susceptibility to penicillin (PDSP) fell from 34% to 19%. Antibiotic prescriptions dropped from 63% to 38% of children, but third-generation cephalosporins were increasingly prescribed. The overall antibiotic susceptibility increased. Over 90% of the children had received at least one vaccine dose in 2008. Vaccine serotypes 6B, 9V, 19F and 23F (76%) in 1999 were replaced by non-vaccine types (95%) in 2008, among which were 15 (20%), 19A (15%), 23A/B (10%) and 6A (9%). Serotypes 6A, 19A and 15 accounted for over 50% of PDSP strains in 2008 versus 6% in 1999. Children now mostly harbour non-vaccine types; however, PDSP isolates are mainly recruited among these. Vaccine-related benefits may be threatened by combined vaccine- and antibiotic-driven selective pressure.


Nondispersing wave packets.
We have formed nondispersing wave packets from atomic Li Rydberg eigenstates by adding a small microwave field approximately resonant with the Deltan=1 transition. The orbital motion of the Rydberg electron in states of 70<or=n<or=78 becomes phase locked to a 17.5 GHz microwave field and remains so for 900 ns, roughly 15 000 orbits of the Rydberg electron. A Floquet approach provides a reasonable quantum-mechanical description.


[Sources of thalamocortical afferentation of the area of forelimb representation in the first somatosensory zone of the cerebral cortex in the cat].
Retrogradely labelled thalamic neurons--the sources of afferentation in the focus of maximal activity evoked by stimulation of n. radialis--were studied in adult cats by means of microiontophoretic injections of horseradish peroxidase into the first somatosensory zone of the cerebral cortex. The labelled cells were predominantly found in the thalamic nucleus ventralis posterolateralis; some cells (a minor part) were also found in the nucleus ventralis posteromedialis. The labelled neurons in these nuclei were distributed in groups whose composition according to many morphological characteristics was heterogeneous.


Parity, time since last live birth and long-term functional outcome: a study of women participating in the Norfolk Arthritis Register.
To investigate the relationship between pre-symptom onset live births and functional outcome in women with inflammatory polyarthritis (IP). 1872 women with no subsequent pregnancies were registered with the Norfolk Arthritis Register between 1990 and 2004 and followed-up for a median of 5 years. Functional disability over time was assessed by Health Assessment Questionnaire (HAQ). The number and calendar year of past live births were recorded. Differences in HAQ score over time by parity and time since last live birth (latency), adjusted for age and symptom duration, were examined using linear random effects models. The results were then adjusted for a number of potential confounders. 1553 women (83%) had ≥1 live births before symptom onset. The median latency was 26 years (IQR 16-35). Parous women had significantly lower HAQ scores over time than nulliparous women (-0.19, 95% CI -0.32 to -0.06). Increasing latency was associated with increasing HAQ score; the mean HAQ score of women with a latency of approximately 32 years was the same as for nulliparous women. This was independent of autoantibody status, socioeconomic status, smoking history and comorbidity. Parous women who develop IP have better functional outcome over time than nulliparous women who develop IP. The beneficial effect of parity diminishes with time.


Mendelian disorders of the epigenetic machinery: postnatal malleability and therapeutic prospects.
The epigenetic machinery in conjunction with the transcriptional machinery is responsible for maintaining genome-wide chromatin states and dynamically regulating gene expression. Mendelian disorders of the epigenetic machinery (MDEMs) are genetic disorders resulting from mutations in components of the epigenetic apparatus. Though individually rare, MDEMs have emerged as a collectively common etiology for intellectual disability (ID) and growth disruption. Studies in model organisms and humans have demonstrated dosage sensitivity of this gene group with haploinsufficiency as a predominant disease mechanism. The epigenetic machinery consists of three enzymatic components (writers, erasers and chromatin remodelers) as well as one non-enzymatic group (readers). A tally of the entire census of such factors revealed that although multiple enzymatic activities never coexist within a single component, individual enzymatic activities often coexist with a reader domain. This group of disorders disrupts both the chromatin and transcription states of target genes downstream of the given component but also DNA methylation on a global scale. Elucidation of these global epigenetic changes may inform our understanding of disease pathogenesis and have diagnostic utility. Moreover, many therapies targeting epigenetic marks already exist, and some have proven successful in treating cancer. This, along with the recent observation that neurological dysfunction in these disorders may in fact be treatable in postnatal life, suggests that the scientific community should prioritize this group as a potentially treatable cause of ID. Here we summarize the recent expansion and major characteristics of MDEMs, as well as the unique therapeutic prospects for this group of disorders.


The worksite component of variance: design effects and the Healthy Worker Project.
Variance estimates in worksite health promotion studies depend partly on the intraclass correlation coefficient (ICC). ICC quantifies homogeneity of a variable within worksites. ICC would be zero for randomly formed worksites, but is generally positive because employees tend to share personal characteristics. The ratio comparing the variance estimated from worksite means with that estimated from individuals under simple random sampling is the design effect (DEFF). A DEFF of 1.0 indicates no excess variance due to worksite. The Healthy Worker Project (HWP) was a 32 worksite cross-sectional and longitudinal study of a weight and smoking intervention program. ICCs in cross-sectional surveys for health-related outcome variables ranged from 0.006 to 0.009, DEFFs from 2.0 to 2.6 ICCs/DEFF's in longitudinal analysis were smaller; ICCs ranged from -0.002 to 0.003, DEFFs from 0.7 to 1.5. Positive ICCs substantially increased variance estimates at a single measurement, yet variance of longitudinal analysis was less subject to worksite dependence. It is concluded the worksite component of variance is real and should not be ignored, although the worksite component of variance is small in these longitudinal analyses. This observation should be replicated before it is used in other worksite health promotion research.


Making interprofessional education work: the strategic roles of the academy.
Faculties (i.e., schools) of medicine along with their sister health discipline faculties can be important organizational vehicles to promote, cultivate, and direct interprofessional education (IPE). The authors present information they gathered in 2007 about five Canadian IPE programs to identify key factors facilitating transformational change within institutional settings toward successful IPE, including (1) how successful programs start, (2) the ways successful programs influence academia to bias toward change, and (3) the ways academia supports and perpetuates the success of programs. Initially, they examine evidence regarding key factors that facilitate IPE implementation, which include (1) common vision, values, and goal sharing, (2) opportunities for collaborative work in practice and learning, (3) professional development of faculty members, (4) individuals who are champions of IPE in practice and in organizational leadership, and (5) attention to sustainability. Subsequently, they review literature-based insights regarding barriers and challenges in IPE that must be addressed for success, including barriers and challenges (1) between professional practices, (2) between academia and the professions, and (3) between individuals and faculty members; they also discuss the social context of the participants and institutions. The authors conclude by recommending what is needed for institutions to entrench IPE into core education at three levels: micro (what individuals in the faculty can do); meso (what a faculty can promote); and macro (how academic institutions can exert its influence in the health education and practice system).


A matrix-assisted laser desorption/ionization tandem mass spectrometry method for direct screening of small molecule mixtures against an aminoglycoside kinase.
Aminoglycoside phosphotransferase 3'IIIa (APH3'IIIa) is a bacterial enzyme involved in antibiotic resistance through phosphorylation of aminoglycosides, which can potentially be overcome by co-administration of an APH3'IIIa inhibitor with the antibiotic. Current assay methods for discovery of APH3'IIIa inhibitors suffer from low specificity and high false positive/negative hit rates. Here, we describe a method for screening APH3'IIIa inhibitors based on direct detection of kanamycin A phosphorylation using MALDI-MS/MS, which is more rapid than conventional assays and does not require secondary assays or sample cleanup. The MALDI-MS/MS assay operates at an ionic strength of 45 mM and co-factors can be utilized at near-physiological levels for optimal enzyme activity. Detection via MALDI-MS/MS allowed for improved reproducibility when compared to ESI-MS/MS. Furthermore, the use of MS/MS provided better signal-to-noise ratios relative to MS alone on the MALDI instrument. The assay was validated via generation of Z'-factors, with values of 0.78 and 0.56 in the absence and presence of 0.2% DMSO, respectively. The assay was used to screen a kinase directed library of >200 compounds, assayed as 21 mixtures of 10 compounds each. Five novel synthetic inhibitors were identified following mixture deconvolution. Inhibition constants were obtained for the aforementioned inhibitors using the MALDI-MS/MS assay, revealing several low to mid micromolar "hits", and highlighting the quantitative nature of the assay.


TGF-β signaling in liver metastasis.
The presence of liver metastases drastically worsens the prognosis of cancer patients. The liver is the second most prevalent metastatic site in cancer patients, but systemic therapeutic opportunities that target liver metastases are still limited. To aid the discovery of novel treatment options for metastatic liver disease, we provide insight into the cellular and molecular steps required for liver colonization. For successful colonization in the liver, adaptation of tumor cells and surrounding stroma is essential. This includes the formation of a pre-metastatic niche, the creation of a fibrotic and immune suppressive environment, angiogenesis, and adaptation of tumor cells. We illustrate that transforming growth factor β (TGF-β) is a central cytokine in all these processes. At last, we devise that future research should focus on TGF-β inhibitory strategies, especially in combination with immunotherapy. This promising systemic treatment strategy has potential to eliminate distant metastases as the efficacy of immunotherapy will be enhanced.


Novel dispersive and focusing device configuration based on curved waveguide grating (CWG).
Configuration of a novel compact dispersive and focusing device based on a Curved Waveguide Grating (CWG) is presented, which is essentially an integrated optic wavelength demultiplexer consisting of a curved stripe waveguide with tilted grating, a slab waveguide adjacent to it, and a set of output waveguides locate on focal line of the curved waveguide. Underlying wavelength demultiplexing mechanism of CWG is theoretically illustrated by employing the Fourier optics approach. Analysis shows that device based on CWG possesses fine wavelength resolution, compact configuration, and potentially low cost as well, which make it a promising wavelength demultiplexer, or a network performance monitor, in DWDM optical networks.


Influence of collars on the primary stability of cementless femoral stems: A finite element study using a diverse patient cohort.
For cementless femoral stems, there is debate as to whether a collar enhances primary stability and load transfer compared to collarless designs. Finite Element (FE) analysis has the potential to compare stem designs within the same cohort, allowing for subtle performance differences to be identified, if present. Subject-specific FE models of intact and implanted femora were run for a diverse cohort (21 males, 20 females; BMI 16.4-41.2 kg/m2 , age 50-80 yrs). Collared and collarless versions of Corail® (DePuy Synthes, Warsaw, IN) were sized and positioned using an automated algorithm that aligns the femoral/stem axes, preserves the head-center location, and maximizes metaphyseal fit. Joint contact and muscle forces simulating peak forces in level gait and stair climbing and were scaled to the body mass and applied to each subject. Three failure scenarios were assessed: Potential for peri-prosthetic fibrous tissue formation (stem micromotion), potential for peri-prosthetic bone damage (equivalent strains), and calcar bone remodeling (changes in strain-energy density). Comparisons were performed using paired t-tests. Only subtle differences were found (mean 90th percentile micromotion: Collared = 86 µm, collarless = 92.5 µm, mean 90th percentile interface strains: Collared = 733 µϵ, collarless = 767 µϵ, and similar remodeling stimuli were predicted). The slight differences observed were small in comparison with the inter-patient variability. Statement of clinical significance: Our results suggest that the presence/absence of a collar is unlikely to substantially alter the bone-implant biomechanics nor the initial mechanical environment. Hence, a collar is likely to have minimal clinical impact. Analysis using different femoral stem designs is recommended before generalising these findings. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1185-1195, 2018.


Impaired executive control of emotional information in social anhedonia.
We examined the executive control of emotional information and its relationship to social functioning in individuals at risk for schizophrenia, defined by high social anhedonia (SA). Using the same structure as the Attentional Network Test (ANT), we developed a measure of executive control of emotional information (ANT-Emotion) in which subjects identify the direction of an arrow flanked by irrelevant angry or neutral faces. Subjects completed the ANT, ANT-Emotion, and the Social Adjustment Scale, Self-Report (SAS-SR), a measure of social functioning. While there were no group differences in the alerting, orienting, and executive control networks assessed by the ANT, high SA individuals exhibited a specific impairment in the executive control of emotional information. High SA individuals also reported poorer social functioning. However, executive control of emotional information did not mediate the relationship between SA and social functioning. These findings indicate that, in high-risk populations, the impaired ability to inhibit emotional information allows negative affective stimuli to exert inappropriate influence on cognitive processes. These results are consistent with studies indicating similar findings in schizophrenia patients, suggesting that impaired inhibition of negative emotion may be part of the liability for the disorder.


Ecosystem regime shifts disrupt trophic structure.
Regime shifts between alternative stable ecosystem states are becoming commonplace due to the combined effects of local stressors and global climate change. Alternative states are characterized as substantially different in form and function from pre-disturbance states, disrupting the delivery of ecosystem services and functions. On coral reefs, regime shifts are typically characterized by a change in the benthic composition from coral to macroalgal dominance. Such fundamental shifts in the benthos are anticipated to impact associated fish communities that are reliant on the reef for food and shelter, yet there is limited understanding of how regime shifts propagate through the fish community over time, relative to initial or recovery conditions. This study addresses this knowledge gap using long-term data of coral reef regime shifts and recovery on Seychelles reefs following the 1998 mass bleaching event. It shows how trophic structure of the reef fish community becomes increasingly dissimilar between alternative reef ecosystem states (regime-shifted vs. recovering) with time since disturbance. Regime-shifted reefs developed a concave trophic structure, with increased biomass in base trophic levels as herbivorous species benefitted from increased algal resources. Mid trophic level species, including specialists such as corallivores, declined with loss of coral habitat, while biomass was retained in upper trophic levels by large-bodied, generalist invertivores. Recovering reefs also experienced an initial decline in mid trophic level biomass, but moved toward a bottom-heavy pyramid shape, with a wide range of feeding groups (e.g., planktivores, corallivores, omnivores) represented at mid trophic levels. Given the importance of coral reef fishes in maintaining the ecological function of coral reef ecosystems and their associated fisheries, understanding the effects of regime shifts on these communities is essential to inform decisions that enhance ecological resilience and economic sustainability.


[Continuous thoracic epidural fentanyl in postoperative pain control--a comparison of two different dosages].
We evaluate the postoperative pain relief using continuous epidural fentanyl infusion in two different dosages for thoracic and upper abdominal surgeries. A total of 21 ASA class III patients were studied. A thoracic epidural catheter was placed before surgery but pain control was begun when the patients became fully awake and complained of pain in the recovery room. Patients were divided into group A (n = 9) and group B (n = 12). Those in group A were given fentanyl 1.5 micrograms/kg in saline solution as initial dose followed by continuous infusion at a rate of 1 microgram/kg/h for 23 hours. In group B the initial dose and the maintenance dose were respectively 1.0 microgram/kg and 0.5 micrograms/kg/h. Following the initial dose, the intensity of pain was assessed hourly for a total of 24 hours using a visual analogue pain scale with scores from 0 to 10. In group A, the pain scale fell from the baseline level of 7.7 +/- 2.6 to 2.3 +/- 2.0 at the first hour while in group B it fell from 8.9 +/- 1.4 to 4.3 +/- 2.1. The pain scores following continuous infusion in groups A and B were respectively 1.3 +/- 1.5 and 2.9 +/- 1.7. Although the analgesic effect appeared to be better in group A, pain relief was satisfactory in both groups (p less than 0.01). Regarding respiratory depression, there was a greater degree of rise in PaCO2 in group A and some of the patients even had a PaCO2 value above 50 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)


Successful treatment of hand and foot psoriasis with infliximab.
Hand and foot psoriasis is a disabling condition associated with significant quality-of-life issues. It is characterized by hyperkeratosis and/or the development of recurrent crops of sterile pustules with associated erythema, fissuring, and scaling symmetrically localized on palm and soles. Systemic conventional therapies include retinoids, psoralen-UVA (PUVA), methotrexate, and cyclosporine. So far, only limited evidence supports the use of TNF-alfa blockers. Because there are reports of paradoxical induction of pustular psoriasis following the use or withdrawal of infliximab as well as other TNF inhibitors, the use of these agents in palmoplantar psoriasis has been cautioned. The authors describe the clinical characteristics and evolution of 4 adult patients with severe palmoplantar psoriasis who were treated successfully with infliximab. Patient data is available for a minimum of 10 months and as many as 16. One of them with concomitant HCV infection showed no increased viral replication or progression of liver disease for a follow-up of 10 months; afterwards infliximab was stopped because of an infusion-related urticaria. All other patients displayed a good clinical response (> or =PPPASI 50) and were still receiving this regimen at last observation. This report provides preliminary evidence to support a cautious use of infliximab in patients with palmoplantar psoriasis.


Cancer incidence and mortality among Aboriginal people living on reserves and northern villages in Quebec, 1988-2004.
Little information is available on the incidence and mortality of cancer among the Aboriginal population in the Province of Québec, Canada. Cancer was likely rare in this population historically, but recent life-style changes suggest that this may no longer be the case. The purpose of this study was to estimate incidence and mortality rates among Aboriginal people living on reserves and in northern villages in Québec during the period 1988-2004, and to compare these estimates with those of the general population. Incidence and mortality data were extracted respectively from the provincial tumour registry and death file. Aboriginal people were identified based on geographic residence codes. Population data were taken from the Canadian census of 1991, 1996 and 2001. Incidence and mortality rates were calculated and age-standardized according to the World Standard Population. The Aboriginal incidence and mortality rates for cancer, all sites combined, was 321.8 per 100,000 (95% confidence interval 304.5-339.2) and 160.3 per 100,000 (95% CI 147.8-172.8), respectively. These rates are not significantly different from those of the general population of Québec. However, there are differences according to cancer site and sex. Aboriginal men had a higher risk for liver, lung and kidney cancers and a lower risk for prostate, bladder, leukemia and non-Hodgkin's lymphoma cancers, whereas Aboriginal women had a higher risk for colorectal, lung, cervix and kidney cancers, and a lower risk for breast, uterus, bladder, brain, leukemia, stomach and pancreas cancers. Aboriginal people in Québec now experience an overall cancer risk comparable to the general population. The observed differences in specific sites suggest exposure to unique environmental risk factors. Basic surveillance specific to this population is necessary for the planning and evaluation of cancer preventive and curative services.


Anthropological contributions to the understanding of age-related cognitive impairment.
Medical anthropology has not only helped us to understand the social, political, and ethical foundations of modern biomedicine, but also improved the identification and treatment of patients in various geographic, sociological, and medical contexts. In this article, we present an anthropological perspective on the understanding, diagnosis, and treatment of age-related cognitive impairment. The ubiquity of cognitive changes in the growing number of elderly people around the world, and the many diverse responses that human communities have taken to such challenges, require biocultural approaches. Anthropology can serve as an ally in accomplishing the goal of improving the quality of life of those with cognitive impairment by highlighting the role of sociocultural processes that influence the development, meaning, and experience of dementia. So too can it serve as a framework for criticism of biomedical research, theory, and practice.


Development of a combined OCT-Raman probe for the prospective in vivo clinical melanoma skin cancer screening.
A combined optical coherence tomography (OCT)-Raman probe was designed and built into a spectral domain OCT head, and its performance was evaluated and compared to the most common Raman probe setups, based on a fiber bundle and confocal free space optics. Due to the use of the full field of view of an OCT scanning lens, the combined probe has a superior performance within maximum permissible exposure limits, compared to the other two probes. Skin Raman spectra, recorded in vivo, further prove the feasibility of the OCT-Raman probe for the future in vivo clinical applications in skin cancer screening.


Transcriptomic Analysis of Quinoa Reveals a Group of Germin-Like Proteins Induced by Trichoderma.
Symbiotic strains of fungi in the genus Trichoderma affect growth and pathogen resistance of many plant species, but the interaction is not known in molecular detail. Here we describe the transcriptomic response of two cultivars of the crop Chenopodium quinoa to axenic co-cultivation with Trichoderma harzianum BOL-12 and Trichoderma afroharzianum T22. The response of C. quinoa roots to BOL-12 and T22 in the early phases of interaction was studied by RNA sequencing and RT-qPCR verification. Interaction with the two fungal strains induced partially overlapping gene expression responses. Comparing the two plant genotypes, a broad spectrum of putative quinoa defense genes were found activated in the cultivar Kurmi but not in the Real cultivar. In cultivar Kurmi, relatively small effects were observed for classical pathogen response pathways but instead a C. quinoa-specific clade of germin-like genes were activated. Germin-like genes were found to be more rapidly induced in cultivar Kurmi as compared to Real. The same germin-like genes were found to also be upregulated systemically in the leaves. No strong correlation was observed between any of the known hormone-mediated defense response pathways and any of the quinoa-Trichoderma interactions. The differences in responses are relevant for the capabilities of applying Trichoderma agents for crop protection of different cultivars of C. quinoa.


Power losses in deformed graded-index polymer optical fibers.
We investigate the power losses in bent and elongated graded-index polymer optical fibers (GI POFs). The variations of power losses in deformed GI POFs for various radii of curvature and elongations are measured. A simple tensile test result is used to calculate the average plastic energy density (APED) in a deformed GI POF at various elongations. The results indicate that the APED accumulated in a deformed GI POF can be considered as a key index to study the power loss in POF. Based on the experimental results, a curve-fitted equation is proposed to estimate the power loss using the APED for various radii of curvature. The maximum difference between the proposed equation and the experimental results is less than 3% for the deformed GI POFs.


Ultrastructural changes in human gingival fibroblasts after exposure to 2-hydroxy-ethyl methacrylate.
Polymerized resin-based materials are successfully utilized in medical applications. One draw- back is the release of monomers from the matrix due to an incomplete polymerization or degradation processes. Released monomers can diffuse in the systemic circulation and induceadverse effects to biological tissues. Although there are many hypotheses about the induction of cell death by resin monomers, the underlying mechanisms are still under discussion. The aim of the study was to investigate the morphological modifications in human gingival fibroblasts exposed to 2-hydroxy-ethyl methacrylate (HEMA) to better elucidate the mechanism of cell death induced by resin monomers. Primary cultures of gingival fibroblasts were exposed to 3mM HEMA for 24 h, 72 h, 96 h. Morphological investigations were performed by scanning and transmission electron microscopy, while western blot for caspase-3 was carried out to ver- ify apoptosis. Electron microscopy images showed deep changes in the cell surface and cyto- plasm after 72 h and 96 h of HEMA treatment. Autophagic vesicles were easily observed just after 24 h. Cleaved caspase-3 was detected after 72 h of treatment. These findings suggest that resin based materials induced cell death by the cooperation of apoptosis and autophagy mecha- nisms. The understanding of these mechanisms will lead to the development of smart biomate- rials without or with low adverse effects.


Ryanodine as a probe for the functional state of the skeletal muscle sarcoplasmic reticulum calcium release channel.
In this paper, we study the modulation of the rabbit fast twitch skeletal muscle calcium release channel by assaying the kinetics of [3H]ryanodine binding, 45Ca2+ flux, and single-channel activity. The effects of modulators of the Ca2+ release channel (confirmed here with both flux and single-channel data) were examined for effects on [3H]ryanodine binding to terminal cisternae vesicles. We find that activators of the release channel, such as adenine nucleotides (1 mM) and caffeine (1 mM), enhance the rate of association of [3H]ryanodine, whereas inhibitors, such as Mg2+ (1 mM) and ruthenium red (100 nM), decrease the rate of association. High concentrations of either ryanodine or ruthenium red, which close the channel, slow the dissociation of [3H]ryanodine, suggesting that at these concentrations the inhibitory effects of both ryanodine and ruthenium red occur as the result of binding at a site distinct from but interacting cooperatively with the high affinity site. Our data are consistent with a model in which the high affinity ryanodine binding site is within a conformationally sensitive area of the channel, such that conditions that open the channel (ATP, caffeine, etc.) enhance the rate at which [3H]ryanodine reaches its binding site and other conditions that close the channel (the binding of ryanodine and ruthenium red to a low affinity site) slow the dissociation of [3H]ryanodine from the high affinity site. Some conditions that inhibit channel activity (high concentrations of Mg2+ and Ca2+) slow association but do not affect dissociation of bound [3H]ryanodine, suggesting a completely different state of the channel from that which is inactive in the presence of high concentrations of ryanodine or ruthenium red. In summary, the functional state of the fast twitch skeletal muscle calcium release channel can be characterized by the changes in the kinetics of [3H]ryanodine binding. Different modulators (activators/inhibitors) affect different aspects of ryanodine binding (association/dissociation).


Impact of alcohol marketing on drinkers with Alcohol use disorders seeking treatment: a mixed-method study protocol.
The marketing of alcohol influences patterns of alcohol consumption. Existing studies have focused, for the most part, on adolescents and the links between exposure to marketing and alcohol initiation. In France, the Evin law, a French exception, was set up in 1991 with the aim of regulating this exposure to marketing, but since 2009 it has been severely compromised. Alcohol consumption causes severe damage, which may be seenfrom 1 standard unit per day and mostly among adults who are regular users of alcohol. In this at-risk population, studies analysing the impact of marketing are sparse. The specific objectives include (i) the evaluation of the perception of alcohol marketing by patients with an AUD (ii) gaining understanding of the links between alcohol marketing and patients with AUD behaviours (iii) the development of alcohol demarketing strategy in patients receiving AUD coaching. Our main objective isto evaluate the impact of marketing on a population with an AUD. The methodology was in 4 steps: step 1 is a pre-test (N = 100) selecting type of alcohol consumed and type of marketing stimuli identified by patients aged 18 + with an AUD. Step 2 is a qualitative study (N = 20), with in-depth interview, to understand links between alcohol marketing and patients with AUD behaviours. Step 3 is a quantitative study(N = 600) to confirm these links and the impact of alcohol marketing on patients with AUD behaviours. Step 4 is an interventional step, including and testing the impact of demarketing intervention on patients with AUD while using the results of the three first steps (N = 120). This study will contribute to a better definition of the impact of alcohol marketing on patients with AUD and will enable identification of the determinants of this impact. These data will inform the development of interventions that take into account demarketingstrategies on patients under AUD management. The Trial registrationregistration number is NCT03876132, and it was registered on the 15th march 2019.


Lung ultrasound and computed tomography to monitor COVID-19 pneumonia in critically ill patients: a two-center prospective cohort study.
Lung ultrasound can adequately monitor disease severity in pneumonia and acute respiratory distress syndrome. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia in critically ill patients. Adult patients with COVID-19 pneumonia admitted to the intensive care unit of two academic hospitals who underwent a 12-zone lung ultrasound and a chest CT examination were included. Baseline characteristics, and outcomes including composite endpoint death or ICU stay > 30 days were recorded. Lung ultrasound and CT images were quantified as a lung ultrasound score involvement index (LUSI) and CT severity involvement index (CTSI). Primary outcome was the correlation, agreement, and concordance between LUSI and CTSI. Secondary outcome was the association of LUSI and CTSI with the composite endpoints. We included 55 ultrasound examinations in 34 patients, which were 88% were male, with a mean age of 63 years and mean P/F ratio of 151. The correlation between LUSI and CTSI was strong (r = 0.795), with an overall 15% bias, and limits of agreement ranging - 40 to 9.7. Concordance between changes in sequentially measured LUSI and CTSI was 81%. In the univariate model, high involvement on LUSI and CTSI were associated with a composite endpoint. In the multivariate model, LUSI was the only remaining independent predictor. Lung ultrasound can be used as an alternative for chest CT in monitoring COVID-19 pneumonia in critically ill patients as it can quantify pulmonary involvement, register changes over the course of the disease, and predict death or ICU stay > 30 days. NTR, NL8584. Registered 01 May 2020-retrospectively registered, https://www.trialregister.nl/trial/8584.


What Is New in Prenatal Skeletal Dysplasias?
The purpose of this article is to discuss advances in imaging and diagnosis of skeletal dysplasias. Skeletal dysplasias are a heterogeneous group of disorders affecting bone and cartilage and characterized by abnormal shape, growth, and integrity of the skeleton. These disorders may be inherited in a multitude of genetic patterns-autosomal dominant, autosomal recessive, somatic mosaic, imprinting errors of metabolism, X-linked, and teratogenic exposure. Most are monogenic diseases. The prenatal diagnosis is challenging; the findings are first seen during routine ultrasound.