Rapid discrimination and quantification analysis of five antineoplastic drugs in aqueous solutions using Raman spectroscopy.
The aim of this study was to assess the ability of Raman spectroscopy to discriminate and quantify five antineoplastic drugs in an aqueous matrix at low concentrations before patient administration. Five antineoplastic drugs were studied at therapeutic concentrations in aqueous 0.9% sodium chloride: 5-fluorouracil (5FU), gemcitabine (GEM), cyclophophamide (CYCLO), ifosfamide (IFOS) and doxorubicin (DOXO). All samples were packaged in glass vials and analyzed using Raman spectrometry from 400 to 4000cm-1. Discriminant analyses were performed using Partial Least Squares Discriminant Analysis (PLS-DA) and quantitative analyses using PLS regression. The best discrimination model was obtained using hierarchical PLS-DA models including three successive models for concentrations higher than the lower limit of quantification (0% of fitting and cross-validation error rate with an excellent accuracy of 100%). According to these hierarchical discriminative models, 90.8% (n=433) of external validation samples were correctly predicted, 2.5% (n=12) were misclassified and 6.7% (n=32) of the external validation set were not assigned. The quantitative analysis was characterized by the RMSEP that ranged from 0.23mg/mL for DOXO to 3.05mg/mL for 5FU. The determination coefficient (R2) was higher than 0.9994 for all drugs evaluated except for 5FU (R2=0.9986). This study provides additional information about the potential value of Raman spectroscopy for real-time quality control of cytotoxic drugs in hospitals. In some situations, this technique therefore constitutes a powerful alternative to usual methods with ultraviolet (UV) detection to ensure the correct drug and the correct dose in solutions before administration to patients and to limit exposure of healthcare workers during the analytical control process.


What goes up must come down! A primary care approach to preventing injuries amongst highflying cheerleaders.
This article provides information regarding the most common nonlife-threatening and catastrophic injuries that occur during cheerleading, and describes the role of the nurse practitioner (NP) in managing patients who participate in cheerleading. Literature review of evidence-based research articles, epidemiological reports, and current guidelines. Cheerleading is one of the most popular sports among adolescent females, and participation has increased rapidly in recent years. Rates of injury have also increased as the difficulty of this activity reaches new heights. Several factors such as body changes during puberty, societal pressures affecting nutrition, and lack of safety regulations place cheerleaders at risk for injury. Sprains/strains are the most common injury, and concussions are the most common traumatic injury. Injuries occur as a result of tumbling, stunting, falling, spotting, and unsafe practice surfaces. The role of the NP in injury prevention is to identify risk factors during preparticipation physicals, initiate conditioning and strength training routines, and implement safety measures during practices and competitions. The NP should also provide education and guidance to cheerleaders, parents, and coaches.


Supplemental protein and postnatal growth of very low birth weight infants: a randomized trial.
Providing adequate nutritional support to promote optimal postnatal growth for very low birth weight (VLBW) infants has been a difficult problem to surmount in the NICU. During the past 4 decades, improvements in neonatal critical care have made it possible for more VLBW infants to survive to discharge from NICUs. The NICHD Neonatal Network reported that while intrauterine growth restriction was present in 22% of VLBW infants at birth, 91% demonstrated postnatal growth restriction by 36 weeks post menstrual age. The persistence of this nearly universal growth deficit is associated with the inadequacy of protein and energy intake, which may account for 45-50% of the postnatal growth restriction. The purpose of this study was to assess whether increasing enteral intake, using supplemental protein, would improve postnatal growth for VLBW infants. Randomized clinical trial. Sixty-four infants were enrolled (34 in control group with 15 infants <1000 g, and 30 in intervention group with 13 infants <1000 g). There were no sustained statistical differences between weekly measurements of weight, length, head circumference, and skinfold thickness between groups. There were no significant differences between laboratory results except blood urea nitrogen at time of peak protein intake for intervention group. Supplemental enteral protein had minimal to no effect on postnatal weight, length, head circumference, body mass, or length of stay. It may be most important to provide consistent sustained nutritional support with protein from birth to reduce postnatal growth restriction, especially for those infants <1000 g at birth.


People's perceptions of HIV/AIDS as portrayed by their labels of the disease: the case of Botswana.
It is typical of societies to come up with their own labels or names to any phenomenon that may befall them in the course of their life time. Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has been no exception to this practice. In Botswana most of these labels are either in Setswana or English whereby an Eglish expression is simply adopted and used to refer to HIV/ AIDS. This study looks at the different labels or names that have been used to refer to HIV/AIDS in Botswana. It is an attempt to provide insights into perceptions of HIV/AIDS by the local communities portrayed through the naming of this disease. The study demonstrates how, through the different labels, the local communities started in denial distancing themselves from this disease and in some cases associating AIDS with ailments already known to them, cultural practices and taboos. Some of these labels further demonstrate the negative attitudes that may have fuelled HIV-related stigma in the country. Based on the informants' responses, the paper further attempts a categorisation of these labels influenced by different attitudes to HIV/AIDS, some of which are self-perpetuating and may continue to be a hindrance to the fight against the disease.


The Relation Between Linguistic Awareness Skills and Spelling in Adults: A Comparison Among Scoring Procedures.
Purpose Spelling is a skill that relies on an individual's linguistic awareness, the ability to overtly manipulate language. The ability to accurately spell is important for academic and career success into adulthood. The spelling skills of adults have received some attention in the literature, but there is limited information regarding which approach for analyzing adults' spelling is optimal for guiding instruction or intervention for those who struggle. Thus, we aimed to examine the concurrent validity of four different scoring methods for measuring adults' spellings (a dichotomous scoring method and three continuous methods) and to determine whether adults' linguistic awareness skills differentially predict spelling outcomes based on the scoring method employed. Method Sixty undergraduate college students who were determined to be average readers as measured by a word reading and contextual word reading task were administered a spelling task as well as morphological, orthographic, phonemic, and syntactic awareness tasks. Results All four scoring methods were highly correlated suggesting high concurrent validity among the measures. Two linguistic awareness skills, morphological awareness and syntactic awareness, predicted spelling performance on both the dichotomous and continuous scoring methods. Contrastively, phonemic awareness and orthographic awareness predicted spelling performance only when spelling was scored using a continuous measure error analysis. Conclusions The results of this study confirm that multiple linguistic awareness skills are important for spelling in adults who are average readers. The results also highlight the need for using continuous measures of spelling when planning intervention or instruction, particularly in the areas of orthographic and phonemic awareness.


Interferon-beta-related DNA is dispersed in the human genome.
Interferon-beta 1 (IFN-beta 1) complementary DNA was used as a hybridization probe to isolate human genomic DNA clones lambda B3 and lambda B4 from a human genomic DNA library. Blot-hybridization procedures and partial nucleotide sequencing revealed that lambda B3 is related to IFN-beta 1 (and more distantly to IFN-alpha 1). Analyses of DNA obtained from a panel of human-rodent somatic cell hybrids that were probed with DNA derived from lambda B3 showed that lambda B3 is on human chromosome 2. Similar experiments indicated that lambda B4 is not on human chromosomes 2, 5, or 9. The finding that DNA related to the IFN-beta 1 gene (and IFN-alpha 1 gene) is dispersed in the human genome raises new questions about the origins of the interferon genes.


Paradoxical effects after microinjection of morphine in the periaqueductal gray matter in the rat.
Paradoxical, concurrent hyper-and hyporeactivity of a profound nature to specific stimuli occurred when 10 micrograms of morphine was microinjected bilaterally into the periaqueductal gray matter of the rat brain. Both effects at this site were dose-dependent. The hyperreactivity (to previously neutral auditory and visual stimuli) was obtained only with intracerebrally injected morphine and never with intraperitoneally injected morphine or with other opiates administered either way. Rapid tolerance to toxic doses of morphine developed at this site, as well as cross tolerance of the hyporeactivity to painful stimuli between routes (intracerebral to intraperitoneal) of morphine administration. Both the hyper- and hyporeactivity were fully reversible by intracerebral injection of naloxone in the periaqueductal gray. Thus, the periaqueductal gray appears to be a major pathway for morphine action.


[Bilateral abducens nerve palsy in nasopharyngeal carcinoma].
We report a case of bilateral abducens palsy as initial finding in nasopharyngeal carcinoma. Possible mode of involvement is discussed. Only one case has been reported in the past.


Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner.
To investigate the role of osteopontin (OPN) and its splice variants in the proliferation of hepatocellular carcinoma (HCC). The expression of OPN variants in HCC cell lines as well as HCC tissue samples and non-tumour tissue was studied using polymerase chain reaction. OPN variant cDNAs were cloned into a mammalian expression vector allowing both transient expression and the production of stable OPN expressing cell lines. OPN expression was studied in these cells using Western blotting, immunofluoresnce and enzyme linked immunosorbent assay. A CD44 blocking antibody and siRNA targeting of CD44 were used to examine the role of this receptor in the OPN stimulated cell growth observed in culture. Huh-7 cells stably expressing either OPN-A, -B or -C were injected subcutaneously into the flanks of nude mice to observe in vivo tumour growth. Expression of OPN mRNA and protein in these tumours was examined using reverse transcription-polymerase chain reaction and immunohistochemistry. OPN is expressed in HCC in 3 forms, the full length OPN-A and 2 splice variants OPN-B and -C. OPN variant expression was noted in HCC tissue as well as cognate surrounding cirrhotic liver tissue. Expression of these OPN variants in the HCC derived cell line Huh-7 resulted in secretion of OPN into the culture medium. Transfer of OPN conditioned media to naïve Huh-7 and HepG2 cells resulted in significant cell growth suggesting that all OPN variants can modulate cell proliferation in a paracrine manner. Furthermore the OPN mediated increase in cellular proliferation was dependent on CD44 as only CD44 positive cell lines responded to OPN conditioned media while siRNA knockdown of CD44 blocked the proliferative effect. OPN expression also increased the proliferation of Huh-7 cells in a subcutaneous nude mouse tumour model, with Huh-7 cells expressing OPN-A showing the greatest proliferative effect. This study demonstrates that OPN plays a significant role in the proliferation of HCC through interaction with the cell surface receptor CD44. Modulation of this interaction could represent a novel strategy for the control of HCC.


Predicting local persistence/recurrence after radiation therapy for head and neck cancer from PET/CT using a multi-objective, multi-classifier radiomics model.
Accurate identifying head and neck squamous cell cancer (HNSCC) patients at high risk of local persistence/recurrence (P/R) is of importance for personalized patient management. Here we developed a multi-objective, multi-classifier radiomics model for early HNSCC local P/R prediction based on post-treatment PET/CT scans and clinical data. We retrospectively identified 328 individuals (69 patients have local P/R) with HNSCC treated with definitive radiation therapy at our institution. The median follow-up from treatment completion to the first surveillance PET/CT imaging was 114 days (range: 82-159 days). Post-treatment PET/CT scans were reviewed and contoured for all patients. For each imaging modality, we extracted 257 radiomic features to build a multi-objective radiomics model with sensitivity, specificity, and feature sparsity as objectives for model training. Multiple representative classifiers were combined to construct the predictive model. The output probabilities of models built with features from various modalities were fused together to make the final prediction. We built and evaluated three single-modality models and two multi-modality models. The combination of PET, CT, and clinical data in the multi-objective, multi-classifier radiomics model trended towards the best prediction performance, with a sensitivity of 93%, specificity of 83%, accuracy of 85%, and AUC of 0.94. Our study demonstrates the feasibility of employing a multi-objective, multi-classifier radiomics model with PET/CT radiomic features and clinical data to predict outcomes for patients with HNSCC after radiation therapy. The proposed prediction model shows the potential to detect cancer local P/R early after radiation therapy.


Spatiotemporal expression patterns of anxiety disorder-associated genes.
Anxiety disorders (ADs) are the most common form of mental disorder that affects millions of individuals worldwide. Although physiological studies have revealed the neural circuits related to AD symptoms, how AD-associated genes are spatiotemporally expressed in the human brain still remains unclear. In this study, we integrated genome-wide association studies of four human AD subtypes-generalized anxiety disorder, social anxiety disorder, panic disorder, and obsessive-compulsive disorder-with spatial gene expression patterns. Our investigation uncovered a novel division among AD-associated genes, marked by significant and distinct expression enrichments in the cerebral nuclei, limbic, and midbrain regions. Each gene cluster was associated with specific anxiety-related behaviors, signaling pathways, region-specific gene networks, and cell types. Notably, we observed a significant negative correlation in the temporal expression patterns of these gene clusters during various developmental stages. Moreover, the specific brain regions enriched in each gene group aligned with neural circuits previously associated with negative decision-making and anxious temperament. These results suggest that the two distinct gene clusters may underlie separate neural systems involved in anxiety. As a result, our findings bridge the gap between genes and neural circuitry, shedding light on the mechanisms underlying AD-associated behaviors.


Streptomyces tardus sp. nov.: A Slow-Growing Actinobacterium Producing Candicidin, Isolated From Sediments of the Trondheim Fjord.
Marine environments are home to an extensive number of microorganisms, many of which remain unexplored for taxonomic novelty and functional capabilities. In this study, a slow-growing Streptomyces strain expressing unique genomic and phenotypic characteristics, P38-E01 T , was described using a polyphasic taxonomic approach. This strain is part of a collection of over 8,000 marine Actinobacteria isolates collected in the Trondheim fjord of Norway by SINTEF Industry (Trondheim, Norway) and the Norwegian University of Science and Technology (NTNU, Trondheim, Norway). Strain P38-E01 T was isolated from the sediments of the Trondheim fjord, and phylogenetic analyses affiliated this strain with the genus Streptomyces, but it was not closely affiliated with other described species. The closest related type strains were Streptomyces daliensis YIM 31724 T (98.6%), Streptomyces rimosus subsp. rimosus ATCC 10970 T (98.4%), and Streptomyces sclerotialus NRRL ISP-5269 T (98.3%). Predominant fatty acids were C16:0 iso, C16:0, and Summed Feature 3, and the predominant respiratory quinones were MK-10(H6), MK-10(H4), and MK9(H4). The main polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphoglycolipid. The whole-cell sugars were glucose, ribose, and in minor amounts, mannose. The cell wall peptidoglycan contained LL-diaminopimelic acid. The draft genome has a size of 6.16 Mb, with a %G + C content of 71.4% and is predicted to contain at least 19 biosynthetic gene clusters encoding diverse secondary metabolites. Strain P38-E01 T was found to inhibit the growth of the pathogenic yeast Candida albicans ATCC 90028 and a number of Gram-positive bacterial human and plant pathogens. Metabolites extracted from cultures of P38-E01 T were analyzed by mass spectrometry, and it was found that the isolate produced the antifungal compound candicidin. Phenotypic and chemotaxonomic signatures, along with phylogenetic analyses, distinguished isolate P38-E01 T from its closest neighbors; thus, this isolate represents a novel species of the genus Streptomyces for which the name Streptomyces tardus sp. nov. (P38-E01 T = CCM 9049 T = DSM 111582 T ) is proposed.


Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii.
During chronic infection of mice with Toxoplasma gondii, gene message for IL-12p40, CD86, and the potassium channel Kv1.3 was detected in brain mononuclear cells, suggesting the presence of dendritic cells (DC) in the CNS. Consistently, cells bearing the DC markers CD11c and 33D1 were localized at inflammatory sites in the infected brain. The number of isolated CD11c+ brain cells increased until peak inflammation. The cells exhibited the surface phenotype of myeloid DC by coexpressing 33D1 and F4/80, little DEC-205, and no CD8alpha. These brain DC were mature, as indicated by high-level expression of MHC class II, CD40, CD54, CD80, and CD86. They triggered Ag-specific and primary allogeneic T cell responses at very low APC/T cell ratios. Among mononuclear cells from encephalitic brain, DC were the main producers of IL-12. Evidence for a parasite-dependent development of DC from CNS progenitors was obtained in vitro: after inoculation of primary brain cell culture with T. gondii, IL-12-secreting dendriform cells emerged, and DC marker genes were expressed. Different stimuli elicited the generation and maturation of brain DC: neutralization of parasite-induced GM-CSF prevented outgrowth of dendriform cells and concomitant release of IL-12. IL-12 production was up-regulated by external IFN-gamma but was stopped by inhibiting parasite replication. Consistently, DC isolated from GM-CSF-treated brain cell culture were activated to secrete IL-12 by exposure to parasite lysate. In sum, these results demonstrate T. gondii-induced expansion and functional maturation of DC in the CNS and, thus, highlight a mechanism that may contribute to the chronicity of the host response.


The role of social capital in shaping livelihood for rural Vietnamese households.
This study explores the role of social capital in the livelihoods of rural households in Vietnam, examining both direct and indirect impacts. The author uses a revised sustainable livelihood framework to analyze social capital, focusing on bonding-bridging and linking forms. The study applies quantitative methods to a secondary dataset from a rural household survey, including entropy-weighted indicators, cluster analysis, and SEM models. The findings suggest that social capital has complex and significant impacts on household livelihood strategies. Bridging and linking social capital promotes non-agricultural and wage-based strategies, while bonding social capital drives transfer-based strategies. The study highlights the importance of social capital as a complementary resource to other livelihood capitals, such as financial, human, and physical capital. These results have important implications for policy implementation aimed at supporting rural households and their livelihoods, especially regarding social capital's interaction with other livelihood capitals. By understanding the complex relationship between social capital, other livelihood capitals and livelihood strategies, policymakers can design more effective policies that harness the potential of social connections to support rural households.


Immunoprotection in sheep against Haemonchus contortus using its thiol-purified excretory/secretory proteins.
Excretory/Secretory antigen was prepared by culturing live adult worms of Haemonchus contortus in RPMI 1640 medium at a concentration of 50 worms per mL in a culture-flask at 37 ˚C for 24 hr and the culture supernatant was used as antigen. The E/S antigen was purified by thiol-sepharose affinity chromatography. On western blot analysis, it was demonstrated that thiol-purified antigen showed a single reactive band at 66 kDa. In immunization trial, sheep were administered intramuscularly with 500 µg of thiol-purified excretory/secretory antigen along with montanide as adjuvant on day 0, 30 and 60. On ELISA, it was observed that the mean absorbance values were significantly (p ≤ 0.01) higher up to 20 weeks post immunization in Group-I (purified antigen) compared to Group- II (unimmunized control). Further, the mean EPG values was lower in Group I (200.00 ± 40.82 to 400.00 ± 91.29) than Group II (2200.00 ± 108.01 to 5100.00 ± 169.56) and the percentage reduction in mean fecal egg counts was 88.50%. Similarly, the mean abomasal worm counts was lower in Group I (808.33 ± 78.29) than Group II (3280.00 ± 147.19) and the percentage reduction in mean abomasal worm count was 75.40%.


Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome.
Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired vascular function. GH-releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion. We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS. Eighteen women with PCOS participated in a double-blind, crossover study. They received sitagliptin either 100 mg or placebo daily for 1 month, with crossover treatments separated by an 8-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT) and assessments of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm. During OGTT, sitagliptin increased glucagon-like peptide-1 (P < 0.001), early insulin secretion (from mean [± SD] insulinogenic index 1.9 ± 1.2 to 3.2 ± 3.1; P = 0.02), and decreased peak glucose (mean -17.2 mg/dL [95% CI, -27.7 to -6.6]; P < 0.01). At 1 month, sitagliptin decreased VAT (from 1141.9 ± 700.7 to 1055.1 ± 710.1 g; P = 0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9 ± 3.6 to 17.0 ± 6.8 min, N = 16; P = 0.04) and interpulse interval (from 53.2 ± 20.0 to 77.3 ± 38.2 min, N = 16; P < 0.05) but did not increase mean overnight GH (P = 0.92 vs placebo). Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval. This study was registered at www.clinicaltrials.gov as NCT02122380 prior to enrollment of the first participant.


Subcutaneous inguinal white adipose tissue is responsive to, but dispensable for, the metabolic health benefits of exercise.
Exercise training has robust effects on subcutaneous inguinal white adipose tissue (iWAT), characterized by a shift to a brown adipose tissue (BAT)-like phenotype. Consistent with this, transplantation of exercise-trained iWAT into sedentary rodents activates thermogenesis and improves glucose homeostasis, suggesting that iWAT metabolism may contribute to the beneficial effects of exercise. However, it is yet to be determined if adaptations in iWAT are necessary for the beneficial systemic effects of exercise. To test this, male C57BL/6 mice were provided access to voluntary wheel running (VWR) or remained as a cage control (SED) for 11 nights after iWAT removal via lipectomy (LIPX) or SHAM surgery. We found that SHAM and LIPX mice with access to VWR ran similar distances and had comparable reductions in body mass, increased food intake, and increased respiratory exchange ratio (RER). Further, VWR improved indexes of glucose homeostasis and insulin tolerance in both SHAM and LIPX mice. The lack of effect of LIPX in the response to VWR was not explained by compensatory increases in markers of mitochondrial biogenesis and thermogenesis in skeletal muscle, epididymal white adipose tissue, or interscapular brown adipose tissue. Together, these data demonstrate that mice with and without iWAT have comparable adaptations to VWR, suggesting that iWAT may be dispensable for the metabolic health benefits of exercise.


Temporal pattern of suicide risk in young individuals with early psychosis.
Individuals with a first episode of psychotic illness are known to be at high risk of suicide, yet little is understood about the timing of risk in this critical period. The present study aimed to examine the temporal pattern of suicide risk in patients with early psychosis (EP) and to determine whether discrete periods of significantly elevated risk can be identified up to 24 months after commencing treatment. Suicidality ratings collected each month as part of patient routine assessment at the Early Psychosis Prevention and Intervention Centre (EPPIC) were retrieved from the service database for patients treated between December 2002 and December 2005 (N=696). Time-series analysis was performed on suicide risk estimated from the aggregated data of 94 individuals who met the study inclusion criteria. Suicide risk was highest in the first month of treatment, decreasing rapidly over the next 6 months and declining slightly thereafter. A power function adequately described this curvilinear trend. Fluctuations around the trend were unpredictable, except for a mild tendency to reverse from month to month, and did not reach statistical significance. The findings suggest limited scope for preventative interventions driven by chronology alone. Intensive routine suicide screening across the course of treatment may facilitate identification and early management of EP patients at suicide risk.


Real-time ultrasound-aided central vein cannulation failure rate: establishing a benchmark.
The use of real-time two-dimensional B-mode ultrasound (RTUS)-aided central venous access device (CVAD) insertion has been recommended by health-care agencies, but a realistic failure rate for bedside attempts is unknown. The failure rate of RTUS-aided CVAD insertion is estimated using data from adult inpatients and outpatients referred to a tertiary referral radiology department for a new CVAD insertion during the 2.5-year period ending February 29, 2008. Cannulation failure, complications, and additional fluoroscopic interventions per central vein cannulation attempt and per patient encounter were retrospectively collected and evaluated. Of the 2456 consecutive patient encounters, the index central vein cannulation failure rate using only RTUS and fluoroscopy was 4.8%; ultimate failure rate was 0.3%. The procedural mortality rate was 0.04%. If the index upper-body central vein cannulation failed, an ipsilateral upper-body attempt through a different central vein failed in 63.6%, whereas a contralateral upper-body attempt failed in 26.7% (p = 0.11) and a common femoral vein attempt failed in 11.5% (p = 0.0039). The minimum bedside failure rate of RTUS-aided CVAD insertion is 4.8% for the index central vein cannulated. The ultimate failure rate of 0.3% and the mortality rate of 0.04% are due to RTUS, fluoroscopy, and the additional equipment available in an IR suite. If the upper-body index central vein cannulation fails, cannulation of the common femoral vein is more likely to succeed than additional attempts in other ipsilateral upper-body central veins.


Increased mortality in trauma patients who develop postintubation hypotension.
Postintubation hypotension (PIH) is common and associated with poor outcomes in critically ill patient populations requiring emergency endotracheal intubation (ETI). The importance of PIH in the trauma population remains unclear. The objective of this study was to determine the prevalence of PIH in trauma patients and assess the association of PIH with patient outcomes. Retrospective case series of adult (≥16 years) patients who were intubated on arrival at a tertiary trauma center in Halifax, Nova Scotia, Canada, between 2000 and 2015. Data were collected from the Nova Scotia Trauma Registry and patient chart, and included demographics, comorbidities, trauma characteristics, intubation time, as well as all fluids, medications, adverse events, interventions, and vital signs during the 15 minutes before/after ETI. We evaluated the prevalence of PIH and created a logistic regression model to determine likelihood of mortality in the PIH and non-PIH groups after controlling for patient and provider characteristics. Overall, 477 patients required ETI on assessment by the trauma service, of which 444 patients met eligibility criteria and were included in the analysis. The prevalence of PIH was 36.3% (161 of 444) in our study population. In-hospital mortality occurred in 29.8% (48 of 161) of patients in the PIH group, compared with 15.9% (45 of 283) of patients in the non-PIH group (p = 0.001). Development of PIH was associated with increased mortality in the emergency department (adjusted odds ratio, 3.45; 95% confidence interval, 1.42-8.36) and in-hospital (adjusted odds ratio, 1.83; 95% confidence interval, 1.01-3.31). In our study of trauma patients requiring ETI, development of PIH was common (36.3%) and associated with increased mortality. Intubation practices in critically ill trauma patients is an important patient safety issue that requires further investigation. Prognostic and epidemiological, level III; Level IV, Therapeutic.


Human resources for health: global crisis and international cooperation.
From the 1990s onwards, national economies became connected and globalized. Changes in the demographic and epidemiological profile of the population highlighted the need for further discussions and strategies on Human Resources for Health (HRH). The health workforce crisis is a worldwide phenomenon. It includes: difficulties in attracting and retaining health professionals to work in rural and remote areas, poor distribution and high turnover of health staff particularly physicians, poor training of health workforces in new sanitation and demographic conditions and the production of scientific evidence to support HRH decision making, policy management, programs and interventions. In this scenario, technical cooperation activities may contribute to the development of the countries involved, strengthening relationships and expanding exchanges as well as contributing to the production, dissemination and use of technical scientific knowledge and evidence and the training of workers and institutional strengthening. This article aims to explore this context highlighting the participation of Brazil in the international cooperation arena on HRH and emphasizing the role of the World Health Organization in confronting this crisis that limits the ability of countries and their health systems to improve the health and lives of their populations.


Development of a compendium of energy expenditures for youth.
This paper presents a Compendium of Energy Expenditures for use in scoring physical activity questionnaires and estimating energy expenditure levels in youth. Modeled after the adult Compendium of Physical Activities, the Compendium of Energy Expenditures for Youth contains a list of over 200 activities commonly performed by youth and their associated MET intensity levels. A review of existing data collected on the energy cost of youth performing activities was undertaken and incorporated into the compendium. About 35% of the activity MET levels were derived from energy cost data measured in youth and the remaining MET levels estimated from the adult compendium. The Compendium of Energy Expenditures for Youth is useful to researchers and practitioners interested in identifying physical activity and energy expenditure values in children and adolescents in a variety of settings.


Angioedema.
Urticarial wheals and angioedema are 2 different clinical symptoms. Both belong to various disease entities, and may occur in combination or be isolated. Increased vasodilation and vasopermeability is a common feature. Histamine and bradykinin are well-known mediators. For clinical purposes, 3 groups of diseases can be differentiated: diseases with urticaria and angioedema, diseases with angioedema alone, and diseases with urticarial lesions without angioedema. The article presents an overview of these groups and the role of the main mediators, and the clinical features of urticaria and angioedema.


[Risk factors of cardiovascular disease among young adults].
A precise knowledge of the prevalence and importance of cardiovascular risk factors will facilitate the development of preventive strategies. To study cardiovascular risk factors among healthy young adults. Eight hundred and fifty subjects aged 22 to 28 years, living in two cities in Valparaiso province, were studied. Weight, height and blood pressure were recorded. A fasting blood sample was obtained from 806 individuals (54% female), to measure plasma lipids, glucose and insulin levels, to estimate their homeostasis model assessment scores (HOMA) and to evaluate the occurrence of metabolic syndrome. Five percent of the studied population had high blood pressure, 14% had obesity, 57% smoked, 25% had high total cholesterol levels, 10.5% had high levels of low density lipoprotein cholesterol, 46% had low levels of high density lipoprotein cholesterol, 16% had high triglyceride levels, 36% had insulin resistance, 7% had a metabolic syndrome, 14% were heavy drinkers and 38% were sedentary. Women had a higher prevalence of obesity and metabolic syndrome. In only 24% of the studied subjects, no risk factor was identified. A high prevalence of cardiovascular risk factors was found in this population of young adults.


Lanthanide-transition-metal complexes: from ion pairs to extended arrays.
New lanthanide-transition-metal (Ln-M) compounds were prepared and the structural relationships of the metal combinations were discerned. Numerous compounds derived from divalent or trivalent lanthanides and from transition metals in groups 7-11 were isolated. Three different types of interactions were observed: (1). Ln-M direct bonds, (2). ionic associations, and (3). carbonyl or cyanide linkers between the metals. These assorted Ln-M interactions influence the assembly of the compounds, and discrete molecules or polymeric arrays were encountered. The extended arrays spanning one, two, and three dimensions can function as heterogeneous catalyst precursors. Two classes of systems, Ln-M carbonyls and cyanides, are described.


X-linked form of Emery-Dreifuss muscular dystrophy.
Emery-Dreifuss muscular dystrophy (EDMD) is an inherited muscular disorder clinically characterized by slowly progressive weakness affecting humero-peroneal muscles, early joint contractures and cardiomyopathy with conduction defects. Autosomal dominant and recessive forms are caused by mutations in lamin A/C gene. Lamin A/C is a major component of nuclear lamina, and its gene mutations cause several human disorders including muscular dystrophy, cardiomyopathy, lipodystrophy, neuropathy, and progeria syndrome. X-linked recessive form of EDMD is caused by mutation in EMD (or STA) gene encoding an integral protein of the inner nuclear membrane. Emerin expresses ubiquitously, but its deficiency affects only limited tissues of skeletal and cardiac muscles and joints. In this paper, I will focus on clinical and pathological aspects of X-EDMD and possible functions of emerin.


Effects of Intentionally Treated Water on Growth of Arabidopsis thaliana Seeds with Cryptochrome Mutations.
A previous experiment suggested that consumption of intentionally treated tea influenced subjective mood under double-blind, controlled conditions. To investigate that effect objectively, again under double-blind, controlled conditions, we studied whether Arabidopsis thaliana seeds hydrated with intentionally treated vs. untreated water would show differences in hypocotyl length, anthocyanin, and chlorophyll. Three Buddhist monks focused their intention on commercially bottled water with the goal of improving the growth of seeds; bottled water from the same source served as an untreated control. Seeds with the following three variations of cryptochrome (CRY) were used: the wild type Arabidopsis (Columbia-4), a gain-of-function mutation (His-CRY2), and a loss-of function mutation (cry1/2), where "gain" and "loss" refer to enhanced and reduced sensitivity to blue light, respectively. Seeds were hydrated with treated or untreated water under blinded conditions, and then placed in random positions in an incubator. The germination process was repeated three times in each experiment, each time using new seeds, and then the entire experiment was repeated four times. Data combined across the four experiments showed a significant decrease in hypocotyl length in the His-CRY2 seedlings (treated mean 1.31 ± 0.01mm, untreated mean 1.43 ± 0.01mm, P < 10-13), a significant increase in anthocyanin with all three forms of cry, particularly His-CRY2 (treated mean 17.0 ± 0.31mg, untreated mean 14.5 ± 0.31mg, P < 10-4), and a modest increase in chlorophyll in His-CRY2 (treated mean 247.6 ± 5.63mg, untreated mean 230.6 ± 5.63mg, P = .05). These outcomes conformed to the monks' intentions because a decrease in hypocotyl length and increase in anthocyanin and chlorophyll are associated with enhanced photomorphogenic growth. These experiments suggest that the His-CRY2 mutation of Arabidopsis may be an especially robust "detector" of intention.


Determination of serum bile acids in fasting dogs with hepatobiliary disease.
The diagnostic value of determining total conjugated serum bile acid (SBA) concentrations was evaluated in fasting dogs with spontaneous liver disease. Conjugated primary SBA values were determined by radioimmunoassay in 12 healthy dogs, 64 dogs with hepatobiliary disease, and 9 dogs with intestinal disorders unassociated with clinical or biochemical evidence of liver disease. Reference values for SBA concentrations ranged from 0 to 5 mumol/L and were not significantly different from those determined in dogs with intestinal disease (P less than 0.05). Mean SBA concentrations determined in dogs with portosystemic shunts, glucocorticoid-induced hepatopathy, hepatic neoplasia, hepatitis, cholestasis, and cirrhosis were significantly greater than reference values (P less than 0.05). The mean SBA concentration in dogs with glucocorticoid-induced hepatopathy was significantly (P less than 0.05) lower than that in all other clinical groups of dogs with liver disease, except in dogs with cholestasis. Although these 2 groups were statistically indistinguishable, dogs with glucocorticoid-induced hepatopathy generally had lower SBA values (2 to 37 mumol/L) than did the group with cholestasis (2 to 562 mumol/L). The SBA concentrations in fasting dogs were weakly correlated with histologic evidence of hepatic damage, as determined by a total biopsy score (r = 0.28, P less than 0.02). Because total SBA concentrations were increased in 89% of all dogs with hepatobiliary disease, the determination of SBA appears to be a sensitive test of hepatic dysfunction.


Microdialysis monitoring of methylphenidate in blood and brain correlated with changes in dopamine and rat activity.
Methylphenidate (MPD), also called Ritalin, changes the extracellular levels of dopamine (DA) in the brain. This study coupled multiple-site microdialysis sampling with appropriate analytical methods to simultaneously profile the MPD concentration in blood and brain, while monitoring changes in the extracellular level of DA in the striatum of awake and freely moving rats. The animals' activity was also recorded. The maximum concentration of MPD in the blood and brain occurred during the first 20 min of sampling. The maximum DA concentration was reached in the first 20 min and gradually returned to the basal level after 3 h. The activity peak correlated well with the MPD and DA peaks and remained elevated for about 2.5 h. The ability to obtain and correlate data in this manner has the potential to reduce the number of animals required for a given study and to minimize interanimal variation.


A placebo-controlled study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia.
To evaluate the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in men with and without erectile dysfunction (ED). This was a multicentre, double-blind, placebo- and active-controlled, parallel-group study conducted across 45 centres in North and South America, Europe, and Australia. In all, 418 men aged ≥ 40 years with a clinical diagnosis of BPH, an International Prostate Symptom Score (IPSS) of ≥ 13, and maximum urinary flow rate (Q(max) ) of 5-15 mL/s for a voided volume of > 150 mL were stratified into two groups (with and without ED) and randomized to one of seven treatment groups, i.e. UK-369,003 at 10, 25, 50 or 100 mg modified release (MR), UK-369,003 40 mg immediate release (IR), tamsulosin 0.4 mg prolonged release, or placebo, for 12 weeks. The primary study endpoint was the change in total IPSS after 12 weeks of treatment. Secondary efficacy measures were IPSS storage and voiding subscores, Q(max) , International Index of Erectile Function-Erectile Function domain, questions 5 and 6 of the Quality of Erection Questionnaire, the International Consultation on Incontinence Questionnaire-Male LUTS, the patient-reported treatment-impact questionnaire, and a bladder diary in which patients recorded the number of voluntary urinary voids, volume of urine voided per micturition, leaks, and urgency episodes. The mean change in the IPSS from baseline at week 12 for UK-369,003 100 mg MR and 40 mg IR was -2.91 and -2.50 better than placebo, respectively. There was increasing efficacy with increasing dose of the MR formulation. For UK-369,003 100 mg MR, Q(max) improved by 2.10 mL/s compared with 0.84 mL/s in the placebo group. UK-369,003 had clinically meaningful efficacy and was well tolerated in men with LUTS associated with BPH. The Bayesian statistical analysis gave high posterior probabilities for true differences between UK-369,003 100 mg MR and placebo. There was greater preference, satisfaction and willingness to use UK-369,003 again for all treatment groups compared with placebo.


A pilot study of escape, avoidance, and approach behaviors in treated alcohol-dependent males.
Alcohol-dependent individuals are often reported to use behavioral strategies both to escape from and avoid negative affective states, and also to approach positive affective states. However, there has been little examination of how these individuals acquire and express these types of behaviors. In this study, male adults meeting the International Classification of Diseases-10th Revision (ICD-10) criteria for alcohol dependence recruited from an outpatient treatment clinic and healthy male controls were given a computer-based task to assess learning and performance of escape, avoidance, and approach behaviors. In this task, participants control a spaceship and can either gain points by shooting an enemy spaceship or hide in safe areas to escape or avoid on-screen aversive events. We found that patients with alcohol dependence exhibited greater escape and approach behaviors, tended to show greater avoidance behavior, and achieved higher total score on the computer task than healthy controls. This is the first demonstration of such behavioral differences in this population, supporting the overactivation of both positive and negative reinforcement systems in alcohol dependence, and suggesting that such behavioral biases are not limited to alcohol-related cues. The contribution of this work to behavioral assessment and therapeutic approaches, as well as possible future directions, are discussed.


Tuberculosis cases with post-mortem notification in Brazil, 2014: a descriptive study based on surveillance data.
To characterize tuberculosis cases notified at post-mortem in Brazil in 2014. This is a descriptive study of tuberculosis cases notified at post-mortem. Data resulted from linkage of the Notifiable Health Conditions Information System-TB (SINAN-TB) and the Mortality Information System (SIM), and were described according to underlying cause of death: tuberculosis, AIDS and other. In the 2,703 tuberculosis cases notified at post-mortem, a higher proportion was found of people of the male sex (73.5%), aged over 39 (80.8%), <8 years of schooling (66.5%), of Black and brown race/skin color (62.8%), with the pulmonary clinical form of tuberculosis (75.2%); there was also a higher proportion of cases notified by the public health service (57.6%) and in municipalities with HDI-M >0.7 (66.6%). The characteristics described of people with post-mortem notification and the magnitude of this outcome suggest weaknesses in tuberculosis care and surveillance services.


Urethral bulking agents versus other surgical procedures for the treatment of female stress urinary incontinence: a systematic review and meta-analysis.
Bulking agents provide an alternative option in the management of women with stress urinary incontinence and they seem to have an important role in the management flow chart of SUI. However, evidence on this issue is scanty. The most important aspect is to understand whether bulking agents are comparable with the other first-line anti-incontinence surgical procedure (MUS, Burch colposuspension and pubovaginal slings). Hence, the primary aim of the current review was to assess the objective and subjective outcomes of bulking agents in comparison with the other surgical procedures for the treatment of SUI. PubMed and Medline were systematically searched and we included studies evaluating the use of bulking agents in comparison with other surgical approaches for either primary or recurrent treatment of female SUI. Three studies meeting the inclusion criteria were identified. Two of these studies were RCTs evaluating the use of bulking agents versus other surgical procedures for the treatment of primary female SUI; the remnant article was a retrospective cohort study that compared the effectiveness and safety of repeat midurethral sling with urethral bulking after failed midurethral sling. The combined results of all analyses showed that the objective recurrence rate of peri- or trans-urethral injections is significantly higher in comparison with the other surgical procedures. Similar findings were observed when considering separately the treatment for primary or recurrent SUI. Furthermore, lower subjective recurrence rate was observed among patients undergoing other surgical treatment in comparison with those undergoing bulking agents; however, this trend was not statistically significant. Moreover, patients undergoing injection of bulking agents experienced a lower rate of voiding dysfunctions in comparison to the control group. According to current evidence, bulking agents should not be proposed as first-line treatment in those women seeking permanent cure for both primary and recurrent SUI. However, the effectiveness of a procedure should be balanced with its invasiveness and patients' expectations. Bulking agents are a minimally invasive approach to treat SUI and their use should be considered as an alternative strategy particularly in special conditions: patients who are fragile, in those who do not wish to have surgery, or in whom surgical options are restricted (postoperatively, after irradiation).


Electrophysiologic characteristics of tibial and sciatic nerves in the hen.
The peripheral nerve of the hen has become an increasingly important animal model in studies of peripheral neuropathy, especially that induced by organophosphorus agent exposure. However, few electrophysiologic studies have been performed, and few data on normal peripheral nerve function exist. The purpose in the present study was to measure the characteristics of the compound action potential of peripheral nerves of the healthy hen. The results showed that conduction velocities of the tibial and the sciatic nerves were 41 m/s and 60 m/s, respectively. The relative refractory period was slightly shorter in the sciatic nerve. The tibial nerve exhibited a lower threshold for stimulation and a significantly shorter chronaxie (19 microseconds) than did the sciatic nerve (25 microseconds). Variability between animals was relatively small. These data should provide useful reference points on studies in which peripheral neuropathy is induced or suspected.


Orbital fibrous histiocytoma mimicking cavernous hemangioma on dynamic contrast-enhanced MRA imaging.
Orbital lesions include a broad spectrum of tumors, vascular abnormalities, and inflammatory conditions. High-resolution imaging has become an invaluable tool toward formulating an accurate diagnosis, and facilitates proper counseling regarding appropriate interventions. Imaging may guide whether partial excision to minimize damage to orbital structures, or en bloc removal to prevent potential recurrence, as seen in mesenchymal tumors, is indicated., Recently, dynamic contrast-enhanced magnetic resonance angiography (MRA) has demonstrated use in helping differentiate orbital vascular lesions. This imaging modality uses rapid MRI acquisition to provide noninvasive, dynamic flow information with high spatial resolution. However, even with modern imaging, reaching a diagnosis prior to histopathological analysis can be challenging. We present a case of orbital fibrous histiocytoma that appeared nearly identical to cavernous hemangioma on dynamic contrast-enhanced MRA.


The forensic analysis of office paper using oxygen isotope ratio mass spectrometry. Part 1: Understanding the background population and homogeneity of paper for the comparison and discrimination of samples.
Isotope ratio mass spectrometry (IRMS) using carbon isotopes has previously been shown to be a robust and discriminating technique for the comparison of document papers. This study aims to examine the inter and intra sample variability for oxygen isotopes measured in standard 80gsm white document papers, to inform the comparison of document papers in forensic casework. 123 paper samples collected from Australia and New Zealand over a 24-month period were measured for their bulk oxygen isotopic abundance and were found to sit within a range of 15‰. A homogeneity study was undertaken which included examining the variability of samples at the sheet, ream and brand source levels. The results of this study were used to construct guidelines for sample comparison and as such, 95% confidence intervals were observed to be inappropriate for use given the high intra sample variability. Instead, a 1.4‰ discrimination range (0.7‰ either side of the measured value) was defined for use as a benchmark for discrimination when samples were measured in the same sequence. Utilising this value, 82% of the samples could be discriminated using a paired comparison, demonstrating a strong potential for use within forensic casework.


Evaluation of the peritoneal carcinomatosis index with CT and MRI.
The aim was to determine the incremental value of MRI compared with CT in the preoperative estimation of the peritoneal carcinomatosis index (PCI). CT and MRI examinations of patients with peritoneal carcinomatosis were evaluated. CT images were first analysed by two observers who determined a first PCI (PCICT ). Then, the two observers reviewed MRI examinations in combination with CT and determined a second PCI (PCICT+MRI ). The sensitivity and negative predictive value of the two imaging sets were determined using surgery as a reference standard (PCIRef ). CT plus MRI was more accurate in predicting the surgical PCI than CT alone. The absolute difference between PCICT+MRI and PCIRef was lower than that between PCICT and PCIRef (mean(s.d.) 3·96(4·10) versus 4·89(4·73); P = 0·010). The number of true-positive findings increased from 106 to 125 for reader 1 and from 117 to 132 for reader 2 with the adjunct of MRI. For both readers, an increased sensitivity was obtained when both MRI and CT were used (from 63 to 81 per cent for reader 1; from 44 to 81 per cent for reader 2). The increase in sensitivity was greater for patients with a moderate volume of disease. The combination of CT and MRI improved the preoperative estimation of PCI compared with CT alone.


Expression of animal anti-apoptotic gene Ced-9 enhances tolerance during Glycine max L.-Bradyrhizobium japonicum interaction under saline stress but reduces nodule formation.
The mechanisms by which the expression of animal cell death suppressors in economically important plants conferred enhanced stress tolerance are not fully understood. In the present work, the effect of expression of animal antiapoptotic gene Ced-9 in soybean hairy roots was evaluated under root hairs and hairy roots death-inducing stress conditions given by i) Bradyrhizobium japonicum inoculation in presence of 50 mM NaCl, and ii) severe salt stress (150 mM NaCl), for 30 min and 3 h, respectively. We have determined that root hairs death induced by inoculation in presence of 50 mM NaCl showed characteristics of ordered process, with increased ROS generation, MDA and ATP levels, whereas the cell death induced by 150 mM NaCl treatment showed non-ordered or necrotic-like characteristics. The expression of Ced-9 inhibited or at least delayed root hairs death under these treatments. Hairy roots expressing Ced-9 had better homeostasis maintenance, preventing potassium release; increasing the ATP levels and controlling the oxidative damage avoiding the increase of reactive oxygen species production. Even when our results demonstrate a positive effect of animal cell death suppressors in plant cell ionic and redox homeostasis under cell death-inducing conditions, its expression, contrary to expectations, drastically inhibited nodule formation even under control conditions.


Intelligent Nanoplatform Integrating Macrophage and Cancer Cell Membrane for Synergistic Chemodynamic/Immunotherapy/Photothermal Therapy of Breast Cancer.
Cell membrane-coated nanoplatforms for drug delivery have garnered significant attention due to their inherent cellular properties, such as immune evasion and homing abilities, making them a subject of widespread interest. The coating of mixed membranes from different cell types onto the surface of nanoparticles offers a way to harness natural cell functions, enhancing biocompatibility and improving therapeutic efficacy. In this study, we merged membranes from murine-derived 4T1 breast cancer cells with RAW264.7 (RAW) membranes, creating a hybrid biomimetic coating referred to as TRM. Subsequently, we fabricated hybrid TRM-coated Fe3O4 nanoparticles loaded with indocyanine green (ICG) and imiquimod (R837) for combination therapy in breast cancer. Comprehensive characterization of the RIFe@TRM nanoplatform revealed the inherent properties of both cell types. Compared to bare Fe3O4 nanoparticles, RIFe@TRM nanoparticles exhibited remarkable cell-specific self-recognition for 4T1 cells in vitro, leading to significantly prolonged circulation life span and enhanced in vivo targeting capabilities. Furthermore, the biomimetic RIFe@TRM nanoplatform induced tumor necrosis through the Fenton reaction and photothermal effects, while R837 facilitated enhanced uptake of tumor-associated antigens, further activating CD8+ cytotoxic T cells to strengthen antitumor immunotherapy. Hence, RIFe@TRM nanoplatform demonstrated outstanding synergy in chemodynamic/immunotherapy/photothermal therapies, displaying significant inhibition of breast tumor growth. In summary, this study presents a promising biomimetic nanoplatform for effective treatment of breast cancer.


C4-C5 segment finite element model development, validation, and load-sharing investigation.
Detailed cervical spine models are necessary to better understand cervical spine response to loading, improve our understanding of injury mechanisms, and specifically for predicting occupant response and injury in auto crash scenarios. The focus of this study was to develop a C4-C5 finite element model with accurate representations of each tissue within the segment. This model incorporates more than double the number of elements of existing models, required for accurate prediction of response. The most advanced material data available were then incorporated using appropriate nonlinear constitutive models to provide accurate predictions of response at physiological levels of loading. This tissue-scale segment model was validated against a wide variety of experimental data including different modes of loading (axial rotation, flexion, extension, lateral bending, and translation), and different load levels. In general, the predicted response of the model was within the single standard deviation response corridors for both low and high load levels. Importantly, this model demonstrates that appropriate refinement of the finite element mesh, representation at the tissue level, and sufficiently detailed material properties and constitutive models provide excellent response predictions without calibration of the model to experimental data. Load sharing between the disc, ligaments, and facet joints was investigated for various modes of loading, and the dominant load-bearing structure was found to correlate with typical anatomical injury sites for these modes of loading. The C4-C5 model forms the basis for the development of a full cervical spine model. Future studies will focus on tissue-level injury prediction and dynamic response.


Semi-automatic, octave-spanning optical frequency counter.
This work presents and demonstrates a semi-automatic optical frequency counter with octave-spanning counting capability using two fiber laser combs operated at different repetition rates. Monochromators are utilized to provide an approximate frequency of the laser under measurement to determine the mode number difference between the two laser combs. The exact mode number of the beating comb line is obtained from the mode number difference and the measured beat frequencies. The entire measurement process, except the frequency stabilization of the laser combs and the optimization of the beat signal-to-noise ratio, is controlled by a computer running a semi-automatic optical frequency counter.


[Is optimal anticoagulation possible in ambulatory practice? Report on a retrospective 5-year study of a cardiology practice].
In a 5-year retrospective study (1982-1978) in a well defined population of 332 patients (representing greater than or equal to 2140 anticoagulation years) from a heart specialist's practice, the question was studied whether optimum anticoagulation (Quick test between 18-29%, INR 4.0-2.75, Geigy thromboplastin, capillary blood method) with minimum complications could be achieved. In the qualitative study it was found that 75% of Quick determinations were in the optimum range for phenprocoumon, 71.6% for clorindion, 62% for acenocoumarol and 72% for all anticoagulants. 77% of phenprocoumon patients were optimally anticoagulated for more than 3 years. With phenprocoumon there was no difference in intensity of anticoagulation between the oldest and youngest patient groups, as all mean Quick values ranged over 20% (means Q% 1982-1978 = 25, INR = 3.0). It was also shown that after 6 months' anticoagulant therapy it is clearly recognizable whether optimum anticoagulation is feasible or not: at that moment the criteria for halting or continuing anticoagulant therapy can and should be reviewed.


Creative foraging: An experimental paradigm for studying exploration and discovery.
Creative exploration is central to science, art and cognitive development. However, research on creative exploration is limited by a lack of high-resolution automated paradigms. To address this, we present such an automated paradigm, the creative foraging game, in which people search for novel and valuable solutions in a large and well-defined space made of all possible shapes made of ten connected squares. Players discovered shape categories such as digits, letters, and airplanes as well as more abstract categories. They exploited each category, then dropped it to explore once again, and so on. Aligned with a prediction of optimal foraging theory (OFT), during exploration phases, people moved along meandering paths that are about three times longer than the shortest paths between shapes; when exploiting a category of related shapes, they moved along the shortest paths. The moment of discovery of a new category was usually done at a non-prototypical and ambiguous shape, which can serve as an experimental proxy for creative leaps. People showed individual differences in their search patterns, along a continuum between two strategies: a mercurial quick-to-discover/quick-to-drop strategy and a thorough slow-to-discover/slow-to-drop strategy. Contrary to optimal foraging theory, players leave exploitation to explore again far before categories are depleted. This paradigm opens the way for automated high-resolution study of creative exploration.


On the mechanisms of phenothiazine-induced mitochondrial permeability transition: Thiol oxidation, strict Ca2+ dependence, and cyt c release.
Phenothiazines (PTZ) are drugs widely used in the treatment of schizophrenia. Trifluoperazine, a piperazinic PTZ derivative, has been described as inhibitor of the mitochondrial permeability transition (MPT). We reported previously the antioxidant activity of thioridazine at relatively low concentrations associated to the inhibition of the MPT (Brit. J. Pharmacol., 2002;136:136-142). In this study, it was investigated the induction of MPT by PTZ derivatives at concentrations higher than 10 microM focusing on the molecular mechanism involved. PTZ promoted a dose-response mitochondrial swelling accompanied by mitochondrial transmembrane potential dissipation and calcium release, being thioridazine the most potent derivative. PTZ-induced MPT was partially inhibited by CsA or Mg(2+) and completely abolished by the abstraction of calcium. The oxidation of reduced thiol group of mitochondrial membrane proteins by PTZ was upstream the PTP opening and it was not sufficient to promote the opening of PTP that only occurred when calcium was present in the mitochondrial matrix. EPR experiments using DMPO as spin trapping excluded the participation of reactive oxygen species on the PTZ-induced MPT. Since PTZ give rise to cation radicals chemically by the action of peroxidases and cyanide inhibited the PTZ-induced swelling, we propose that PTZ bury in the inner mitochondrial membrane and the chemically generated PTZ cation radicals modify specific thiol groups that in the presence of Ca(2+) result in MPT associated to cytochrome c release. These findings contribute for the understanding of mechanisms of MPT induction and may have implications for the cell death induced by PTZ.


Observations concerning the pathogenesis of epithelioid hemangioma (angiolymphoid hyperplasia).
Epithelioid hemangioma (EH) is a benign vascular lesion that is characterized by well-formed, capillary-sized vessels lined by histiocytoid or epithelioid endothelial cells and often accompanied by a secondary inflammatory infiltrate. Whether or not these lesions are reactive or neoplastic has been debated and is reflected in the various designations, such as angiolymphoid hyperplasia with eosinophilia (ALHE), pseudopyogenic granuloma, and inflammatory angiomatous nodules. In order to study the pathogenesis of this lesion, 96 examples of EH of superficial and deep soft tissue origin were reviewed, noting the frequency with which these lesions arose adjacent to a damaged vessel and the incidence of antecedent trauma. In 60 cases (63%), an artery or vein was associated with the mass and, in the majority (52 cases), the vessel was damaged, as evidenced by the presence of fibrointimal proliferation, discontinuity of the internal elastic lamina, and/or mural disruption. No evidence of active arteritis was seen in any case. Antecedent trauma was documented in 12 cases and, in one of these, the subsequent formation of an arteriovenous malformation and development of the EH were noted. EH associated with damaged vessels or those in which a preceding history of trauma was available did not differ histologically from cases in which these variables were absent. Our findings suggest that a significant percentage of EH of soft tissue are not neoplastic, but arise on a reactive basis probably secondary to damage and repair of an artery or vein.


Surgical Treatment of Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.


IMPACT OF BARIATRIC SURGERY ON THE INFLAMMATORY STATE BASED ON CPR VALUE.
PCR (C-reactive protein), produced in the liver after stimuli of inflammatory mediators, is determined as a marker of inflammatory activity (adipocytokines) and is present within adipocyte cells; besides being an inflammatory product, many studies have shown to be a predictor of complications. To determine if the inflammatory state of the obese patient decreases after bariatric surgery, based on pre and post-operative PCR. A prospective, observational study in patients undergoing Roux-en-Y gastric by-pass surgery followed up for three months after surgery, with serum preoperative CRP in 30, 60 and 90 days after surgery. A total of 19 patients, who had a mean CRP value before the surgical procedure of 0.80(±0.54) mg/dl, were followed, and when compared to the CRP with 30 days of surgery, they presented a significant increase to 2.68 mg/dl (p=0.012). When compared with the PCR of 60 days after the surgical procedure, it was also higher with the value of 3.32 mg/dl (p=0.27). However, at three months after surgery, the CRP showed a decrease when compared to the preoperative mark, with value of 0.45 mg/dl (p=0.0042). Roux-en-Y gastric bypass was able to decrease the chronic inflammation status of these patients, based on the value of CRP, with three months of surgery.


Pituitary atypical teratoid rhabdoid tumor in a patient with prolactinoma: A unique description.
Atypical teratoid rhabdoid tumor (ATRT) is an aggressive tumor of the CNS and characteristically occurs in the pediatric age. In adulthood, ATRT is rare and it is mainly localized in the cerebral hemispheres. Only 16 cases of ATRT have been described in the sellar region up to now. Interestingly, all sellar ATRTs occurred in adult female patients. Herein we report a novel case of sellar ATRT in a patient with previous history of lactotroph adenoma. Similar to other sellar ATRTs, this case occurred in a female adult patient. At histological examination, it was characterized by a small number of rhabdoid cells. In addition, it did not have homozygous deletion of SMARCB1 gene, but it rather showed a frameshift mutation at exon 4 of SMARCB1 which had not been previously found in ATRT. Clinico-pathological and molecular findings observed in this case confirm previous evidence that sellar ATRT seems to be a distinct entity. Association with previous prolactin-secreting pituitary adenoma is discussed.


All-Organic Battery Based on Deep Eutectic Solvent and Redox-Active Polymers.
Sustainable battery concepts are of great importance for the energy storage demands of the future. Organic batteries based on redox-active polymers are one class of promising storage systems to meet these demands, in particular when combined with environmentally friendly and safe electrolytes. Deep Eutectic Solvents (DESs) represent a class of electrolytes that can be produced from sustainable sources and exhibit in most cases no or only a small environmental impact. Because of their non-flammability, DESs are safe, while providing an electrochemical stability window almost comparable to established battery electrolytes and much broader than typical aqueous electrolytes. Here, we report the first all-organic battery cell based on a DES electrolyte, which in this case is composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) and N-methylacetamide (NMA) alongside the electrode active materials poly(2,2,6,6-tetramethylpiperidin-1-yl-oxyl methacrylate) (PTMA) and crosslinked poly(vinylbenzylviologen) (X-PVBV2+ ). The resulting cell shows two voltage plateaus at 1.07 V and 1.58 V and achieves Coulombic efficiencies of 98 %. Surprisingly, the X-PVBV/X-PVBV+ redox couple turned out to be much more stable in NaTFSI : NMA 1 : 6 than the X-PVBV+ /X-PVBV2+ couple, leading to asymmetric capacity fading during cycling tests.


The emergency medicine approach to transplant complications.
Organ transplantation provides improved quality of life and longevity in patients with end-organ disease. These patients have significant physiological and anatomical modifications, and with new immunosuppressive agents, many of these patients will present to the emergency department with complications. The objective was to provide emergency physicians with a review of transplant complications, including infection, rejection, medication adverse effects, and specific complications related to the transplant. Transplant patients present significant challenges due to a large spectrum of complications that may arise. Infection is the most common complication and can be separated into different periods. The first month after transplant is associated with nosocomial and surgical infections, 1 month to 6 months after transplant with opportunistic infection, and greater than 6 months acquired infection. Rejection occurs in the hyperacute, acute, and chronic phases, with symptoms dependent on the specific organ. Medication adverse effects due to immunosuppressive agents are common and include renal dysfunction, anemia, metabolic syndrome, and gastrointestinal effects. Renal transplant dysfunction includes vascular complications, hematoma, obstruction, and lymphocele. Liver transplant complications include vascular defects, biliary tract malfunctions, and fluid collections. Heart transplant complications manifest with vasculopathy and dysrhythmia. Lung transplant complications include airway dysfunction, phrenic nerve dysfunction, and pleural fluid collections. All transplant patients in the emergency department require close communication with the transplant physician and emergency provider. Transplant patients can present significant challenges to the emergency provider. Knowledge of these complications may improve patient care. All cases require contact with the transplant physician.


Belgian Recommendations for Analytical Verification and Validation of Immunohistochemical Tests in Laboratories of Anatomic Pathology.
Analytical verification and validation of immunohistochemical (IHC) tests and their equipment are common practices for today's anatomic pathology laboratories. Few references or guidelines are available on how this should be performed. The study of Sciensano (the Belgian national competent authority regarding licensing of medical laboratories) performed in 2016, demonstrated a significant interlaboratory variation in validation procedures of IHC tests among Belgian laboratories. These results suggest the unavailability of practical information on the approach to the verification and validation of these tests. The existing Belgian Practice Guideline for the implementation of a quality management system in anatomic pathology laboratories has been reviewed to meet this demand and, in addition, to prepare the laboratories for the EU-IVD revised regulations (IVDR). This paper describes Belgian recommendations for the verification and validation of IHC tests before implementation, for ongoing validation, and for revalidation. For each type of test (according to the IVDR classification and the origin) and its intended use (purpose), it addresses how to perform analytical verification/validation by recommending: (1) the number of cases in the validation set, (2) the performance characteristics to be evaluated, (3) the objective acceptance criteria, (4) the evaluation method for the obtained results, and (5) how and when to revalidate. A literature study and a risk analysis taking into account the majority of variables regarding verification/validation of methods have been performed, resulting in an expert consensus recommendation that is a compromise among achievability, affordability, and patient safety. This new consensus recommendation has been incorporated in the aforementioned ISO 15189:2012-based Practice Guideline.


Vitamin K antagonists and risk of subdural hematoma: meta-analysis of randomized clinical trials.
Subdural hematomas are an important bleeding complication of anticoagulation. We quantify the risk of subdural hematoma associated with anticoagulation with vitamin K antagonists (VKAs) compared with other oral antithrombotic therapies. Randomized trials were identified from the Cochrane Central Register of Controlled Trials and were included if published since 1980 and compared oral VKAs with antiplatelet therapy or with direct-acting oral anticoagulants. Two reviewers independently extracted data with differences resolved by joint review. Nineteen randomized trials were included that involved 92 156 patients and 275 subdural hematomas. By meta-analysis, VKAs were associated with a significantly increased risk of subdural hematoma (odds ratios, 3.0; 95% confidence interval, 1.5-6.1) compared with antiplatelet therapy (9 trials, 11 603 participants). The risk of subdural hematoma was also significantly higher with VKAs versus factor Xa inhibitors (meta-analysis odds ratios, 2.9; 95% confidence interval, 2.1-4.1; 5 trials, 49 687 patients) and direct thrombin inhibitors (meta-analysis odds ratios, 1.8; 95% confidence interval, 1.2-2.7; 5 trials, 30 866 patients) versus VKAs. The absolute rate of subdural hematoma among 24 485 patients with atrial fibrillation treated with VKAs pooled from 6 trials testing direct-acting oral anticoagulants was 2.9 (95% confidence interval, 2.5-3.5) per 1000 patient-years. VKA use significantly increases the risk of subdural hematoma by ≈3-fold relative to antiplatelet therapy. Direct-acting oral anticoagulants are associated with a significantly reduced risk of subdural hematomas versus VKAs. Based on indirect comparisons to VKAs, the risks of subdural hematoma are similar with antiplatelet monotherapies and factor Xa inhibitors.


Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: randomized withdrawal design.
To evaluate lisdexamfetamine dimesylate maintenance of efficacy in adults with attention-deficit/hyperactivity disorder (ADHD). Adults (aged 18-55 years) who had ADHD meeting DSM-IV-TR criteria, baseline ADHD Rating Scale-IV (ADHD-RS-IV) with adult prompts total scores of < 22, and Clinical Global Impressions-Severity of Illness (CGI-S) ratings of 1, 2, or 3 were enrolled. After previously receiving commercially available lisdexamfetamine dimesylate (30, 50, or 70 mg/d) for ≥ 6 months with acceptable tolerability and maintaining response during a 3-week open-label phase at a stable lisdexamfetamine dimesylate dose, the participants entered a 6-week double-blind randomized withdrawal phase on treatment with lisdexamfetamine dimesylate (same dose) or placebo. Data were collected from April 2009 to July 2010. The primary outcome was the proportion of participants having symptom relapse (≥ 50% increase in ADHD-RS-IV score and ≥ 2 rating-point increase in CGI-S score). A total of 116 participants were randomized (lisdexamfetamine dimesylate n = 56; placebo n = 60). At the randomized withdrawal phase baseline, mean (SD) ADHD-RS-IV scores for lisdexamfetamine dimesylate and placebo were 10.6 (4.96) and 10.6 (4.82), respectively. At endpoint, 8.9% (5/56) of adults taking lisdexamfetamine dimesylate and 75.0% (45/60) taking placebo (P < .0001) showed symptom relapse; most showed relapse after 1 and 2 weeks of the randomized withdrawal phase (4 and 0 adults taking lisdexamfetamine dimesylate, 26 and 10 taking placebo, respectively). During the randomized withdrawal phase, treatment-emergent adverse events were reported in 48.2% and 30.0% of participants in the lisdexamfetamine dimesylate and placebo groups, respectively. Treatment-emergent adverse events with incidence ≥ 5% in the lisdexamfetamine dimesylate and placebo groups were headache (14.3% and 5.0%), insomnia (5.4% and 5.0%), and upper respiratory tract infection (8.9% and 0%). In adults with ADHD on medium- to long-term treatment, lisdexamfetamine dimesylate demonstrated maintenance of efficacy vs placebo upon randomized withdrawal. A majority of patients given placebo showed symptom relapse by 2 weeks. The safety profile of lisdexamfetamine dimesylate was generally consistent with previous lisdexamfetamine dimesylate studies. ClinicalTrials.gov identifier: NCT00877487.


Swiss general internal medicine board examination: quantitative effects of publicly available and unavailable questions on question difficulty and test performance.
Formerly, a substantial number of the 120 multiple-choice questions of the Swiss Society of General Internal Medicine (SSGIM) board examination were derived from publicly available MKSAP questions (Medical Knowledge Self-Assessment Program®). The possibility to memorise publicly available questions may unduly influence the candidates' examination performance. Therefore, the examination board raised concerns that the examination did not meet the objective of evaluating the application of knowledge. The society decided to develop new, "Helvetic" questions to improve the examination. The aim of the present study was to quantitatively assess the degree of difficulty of the Helvetic questions (HQ) compared with publicly available and unavailable MKSAP questions and to investigate whether the degree of difficulty of MKSAP questions changed over time as their status changed from publicly available to unavailable. The November 2019 examination consisted of 40 Helvetic questions, 40 publicly available questions from MKSAP edition 17 (MKSAP-17) and 40 questions from MKSAP-15/16, which were no longer publicly available at the time of the examination. An one factorial univariate analysis of variance (ANOVA) examined question difficulty (lower values mean higher difficulty) between these three question sets. A repeated ANOVA compared the difficulty of MKSAP-15/16 questions in the November 2019 examination with the difficulty of the exact same questions from former examinations, when these questions belonged to the publicly available MKSAP edition. The publicly available MKSAP-17 and the publicly unavailable Helvetic questions served as control. The analysis of the November 2019 exam showed a significant difference in average item difficulty between Helvetic and MKSAP-17 questions (71% vs 86%, p <0.001) and between MKSAP-15/16 and MKSAP-17 questions (70% vs 86%, p <0.001). There was no significant difference in item difficulty between Helvetic and MKSAP-15/16 questions (71% vs 70%, p = 0.993). The repeated measures ANOVA on question use and the three question categories showed a significant interaction (p <0.001, partial eta-squared = 0.422). The change in the availability of MKSAP-15/16 questions had a strong effect on difficulty. Questions became on average 21.9% more difficult when they were no longer publicly available. In contrast, the difficulty of the MKSAP-17 and Helvetic questions did not change significantly across administrations. This study provides the quantitative evidence that the public availability of questions has a decisive influence on question difficulty and thus on SSGIM board examination performance. Reducing the number of publicly available questions in the examination by introducing confidential, high-quality Helvetic questions contributes to the validity of the board examination by addressing higher order cognitive skills and making rote-learning strategies less effective.


The Effect of Ibuprofen on Cytokine Production by Mononuclear Cells from Schizophrenic Patients.
The existence of a restrained inflammatory state in schizophrenic individuals posed the question whether anti-inflammatory drugs may exert antipsychotic effects. Therefore, the effect of ibuprofen (IB) on cytokine production by human peripheral blood mononuclear cells (PBMC) from schizophrenic patients was examined and compared to that of healthy subjects. PBMC from 25 schizophrenic patients and 24 healthy volunteers were incubated for 24 h with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IB. The levels of IL-1β, IL-6, TNF-α, IL-10 and IL-1ra in the supernatants were tested applying ELISA kits. The secretion of TNF-α by cells from schizophrenic patients was significantly lower compared with controls. IB caused stimulation of TNF-α and IL-6 production by cells of the two groups and enhanced IL-1β secretion by cells from schizophrenic patients. IB inhibited IL-1ra and IL-10 generation by cells from the two groups. Without IB, IL-1ra secretion was negatively correlated with the disease severity, while 200 μg/ml of IB positively correlated with the PANSS total score. IL-10 production was positively correlated with the PANSS positive subscale score both in the absence or presence of IB. The findings suggest that the effect of IB on the production of inflammatory cytokines may benefit the health of schizophrenic patients.


Association between the PDE4D gene and ischaemic stroke in the Chinese Han population.
Recent findings suggests that PDE4D (gene encoding phosphodiesterase 4D) is a stroke-related gene in the Icelandic population, but it is still very controversial as to whether it is a susceptible gene for stroke in other populations. In the present study, we attempted to explore the role of the gene in the pathogenesis of stroke in the Chinese Han population of eastern China. A total of 649 ischaemic stroke patients and 761 unrelated control individuals with no history of stroke or transient ischaemic attack were examined in a case-control study. Four SNPs (single nucleotide polymorphisms) rs152312 (C/T), SNP56 (A/T), SNP83 (C/T) and SNP87 (C/T) with a minor allele frequency over 5% were genotyped and the corresponding haplotypes were constructed. In an analysis of the combined cardiogenic and carotid stroke group, both the allele (P=0.0060) and genotype (P=0.0160) frequencies between cases and controls at SNP83 showed significant differences. However, no difference in haplotype frequencies was observed between cases and controls at rs152312 and SNP56. In the analysis of the small-artery-occlusive stroke group, no difference in allele or genotype frequencies was observed at any marker between cases and controls; the global haplotype frequency in rs152312 and SNP56 had a significant difference between cases and controls (P=0.0162); the frequency of haplotype C-A was higher in cases than in controls (P=0.0122). In conclusion, our present findings show that polymorphisms in the PDE4D gene are associated with an increased risk of ischaemic stroke in the Chinese Han population. The present study adds further support to the role of PDE4D in stroke.


Fluorometric Method to Assess Lipase Inhibition Activity.
Obesity and excess weight have become serious health problems in our developed societies today. Increased blood pressure, blood glucose levels and abnormal blood lipids are frequent consequences. Inhibition of digestive enzymes by pharmacological or nutritional intervention are one avenue to be considered to treat this population. In the present study a robust assay to screen biologically active materials for their ability to inhibit pancreatic lipase, the most important enzyme in fat digestion, has been developed. Methyl-umbelliferyl butyrate was used as an artificial substrate, enabling assessment of lipase activity via specific fluorescence emission. Applicability of the assay was shown by assessment of lipase inhibition activity of wild plants from Switzerland and France. Testing showed some plants to have a high inhibition rate of about 70%. In further projects, this lipase inhibition assay could be used for a scientific proof of biological activity of raw materials with the intention to develop functional foods for weight reduction.


Induction of defense responses by extracts of spent mushroom substrates in rice.
We investigated the effect of treatment with hot water extracts from the spent mushroom substrates (SMSs) of Lentinula edodes and Hypsizygus marmoreus on the resistance of rice leaves to Pyricularia oryzae infection. The spraying of the SMS extracts clearly suppressed the development of lesions caused by Py. oryzae infection. The accumulation of phytoalexins momilactones A and B, oryzalexin A, and sakuranetin was markedly induced by the spraying of extracts. The enhanced expression of defense related genes PR1b and PBZ was also found in leaves sprayed with the extracts. Treatments with the extracts also affected phytohormone levels. The levels of N 6-(Δ2-isopentenyl)adenine and trans-zeatin markedly increased in response to treatment, whereas the levels of salicylic and jasmonic acids were largely unchanged.


Comparison of the effects of topical fusidic acid and rifamycin on wound healing in rats.
Wound healing is an active and dynamic process that begins from the moment of injury. Any delay in the initiation of the response to injury can prolong the healing process. The aim of this study was to investigate the effects of topically applied fusidic acid and rifamycin on wound healing in a full-thickness wound model. Ten female Sprague-Dawley rats, aged 4 months and weighing 200-250 g, were used. Four rifamycin (R), four fusidic acid (F) and four control (K) areas were generated on their backs by using a 5-mm punch biopsy pen. On the 4th, 7th, 14th and 21st days, biopsies were taken from each wound area of all the rats. Fusidic acid group demonstrated a statistically significant increase of collagen and intensity of fibroblast proliferation on the 21st day of wound healing, whereas in the rifamycin group, healing time was, as expected, similar to physiological wound-healing phases. Despite the limited number of subjects, topical fusidic acid was found to delay wound healing by prolonging fibroblast proliferation.


Connectionist neuropsychology: uncovering ultimate causes of acquired dyslexia.
Acquired dyslexia offers a unique window on to the nature of the cognitive and neural architecture supporting skilled reading. This paper provides an integrative overview of recent empirical and computational work on acquired dyslexia within the context of the primary systems framework as implemented in connectionist neuropsychological models. This view proposes that damage to general visual, phonological or semantic processing abilities are the root causes of different forms of acquired dyslexia. Recent case-series behavioural evidence concerning pure alexia, phonological dyslexia and surface dyslexia that supports this perspective is presented. Lesion simulations of these findings within connectionist models of reading demonstrate the viability of this approach. The commitment of such models to learnt representations allows them to capture key aspects of performance in each type of acquired dyslexia, particularly the associated non-reading deficits, the role of relearning and the influence of individual differences in the premorbid state of the reading system. Identification of these factors not only advances our understanding of acquired dyslexia and the mechanisms of normal reading but they are also relevant to the complex interactions underpinning developmental reading disorders.


Development of Nuclear Microsatellite Loci and Mitochondrial Single Nucleotide Polymorphisms for the Natterjack Toad, Bufo (Epidalea) calamita (Bufonidae), Using Next Generation Sequencing and Competitive Allele Specific PCR (KASPar).
Amphibians are undergoing a major decline worldwide and the steady increase in the number of threatened species in this particular taxa highlights the need for conservation genetics studies using high-quality molecular markers. The natterjack toad, Bufo (Epidalea) calamita, is a vulnerable pioneering species confined to specialized habitats in Western Europe. To provide efficient and cost-effective genetic resources for conservation biologists, we developed and characterized 22 new nuclear microsatellite markers using next-generation sequencing. We also used sequence data acquired from Sanger sequencing to develop the first mitochondrial markers for KASPar assay genotyping. Genetic polymorphism was then analyzed for 95 toads sampled from 5 populations in France. For polymorphic microsatellite loci, number of alleles and expected heterozygosity ranged from 2 to 14 and from 0.035 to 0.720, respectively. No significant departures from panmixia were observed (mean multilocus F IS = -0.015) and population differentiation was substantial (mean multilocus F ST = 0.222, P < 0.001). From a set of 18 mitochondrial SNPs located in the 16S and D-loop region, we further developed a fast and cost-effective SNP genotyping method based on competitive allele-specific PCR amplification (KASPar). The combination of allelic states for these mitochondrial DNA SNP markers yielded 10 different haplotypes, ranging from 2 to 5 within populations. Populations were highly differentiated (G ST = 0.407, P < 0.001). These new genetic resources will facilitate future parentage, population genetics and phylogeographical studies and will be useful for both evolutionary and conservation concerns, especially for the set-up of management strategies and the definition of distinct evolutionary significant units.


Enhancing Compression Level for More Efficient Compressed Sensing and Other Lessons from NMR Spectroscopy.
Modern nuclear magnetic resonance spectroscopy (NMR) is based on two- and higher-dimensional experiments that allow the solving of molecular structures, i.e., determine the relative positions of single atoms very precisely. However, rich chemical information comes at the price of long data acquisition times (up to several days). This problem can be alleviated by compressed sensing (CS)-a method that revolutionized many fields of technology. It is known that CS performs the most efficiently when measured objects feature a high level of compressibility, which in the case of NMR signal means that its frequency domain representation (spectrum) has a low number of significant points. However, many NMR spectroscopists are not aware of the fact that various well-known signal acquisition procedures enhance compressibility and thus should be used prior to CS reconstruction. In this study, we discuss such procedures and show to what extent they are complementary to CS approaches. We believe that the survey will be useful not only for NMR spectroscopists but also to inspire the broader signal processing community.


Inequalities in awareness and availability of bereavement services in North-East England.
National guidance recommends equality in access to bereavement services; despite this, awareness and availability appears inconsistent. The aim of this study was to explore availability and accessibility of bereavement services across the North-East of England and to highlight issues potentially applicable across the UK, at a time of unprecedented need due to the impact of COVID-19. Phase 1: an eight item, web-based survey was produced. A survey link was cascaded to all GP practices (General Practitioners) in the region. Phase 2: an email was sent to all services identified in phase 1, requesting details such as referral criteria and waiting times. All 392 GP practices in the region were invited to participate. The response rate was 22% (85/392). Twenty-one per cent (18/85) of respondents reported that they do not refer patients, comments included 'not aware of any services locally'. A total of 36 services were contacted with 72% responding with further information. Most bereavement specific support was reliant on charity-funded services including hospices, this sometimes required a pre-existing link with the hospice. Waiting times were up to 4 months. Although multiple different, usually charity-funded services were identified, awareness and accessibility were variable. This survey was conducted prior to the COVID-19 pandemic, where complex situations surrounding death is likely to impact on the usual grieving process and increase the need for bereavement support. Meanwhile, charities providing this support are under severe financial strain. There is an urgent need to bridge the gap between need and access to bereavement services.


Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage.
To test the hypothesis that terminal differentiation of chondrocytes in human osteoarthritic cartilage might lead to the failure of repair mechanisms and might cause progressive loss of structure and function of articular cartilage. Markers for terminally differentiated chondrocytes, such as alkaline phosphatase, annexin II, annexin V and type X collagen, were detected by immunohistochemical analysis of human normal and osteoarthritic knee cartilage from medial and lateral femoral condyles. Apoptosis in these specimens was detected using the TUNEL labeling. Mineralization and matrix vesicles were detected by alizarin red S staining and electron microscopic analysis. Alkaline phosphatase, annexin II, annexin V and type X collagen were expressed by chondrocytes in the upper zone of early stage and late stage human osteoarthritic cartilage. However, these proteins, which are typically expressed in hypertrophic and calcifying growth plate cartilage, were not detectable in the upper, middle and deep zones of healthy human articular cartilage. TUNEL labeling of normal and osteoarthritic human cartilage sections provided evidence that chondrocytes in the upper zone of late stage osteoarthritic cartilage undergo apoptotic changes. In addition, mineral deposits were detected in the upper zone of late stage osteoarthritic cartilage. Needle-like mineral crystals were often associated with matrix vesicles in these areas, as seen in calcifying growth plate cartilage. Human osteoarthritic chondrocytes adjacent to the joint space undergo terminal differentiation, release alkaline phosphatase-, annexin II- and annexin V-containing matrix vesicles, which initiate mineral formation, and eventually die by apoptosis. Thus, these cells resume phenotypic changes similar to terminal differentiation of chondrocytes in growth plate cartilage culminating in the destruction of articular cartilage in osteoarthritis.