The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response.
Controlled ovarian hyperstimulation (COH) promotes multifollicular growth, increasing the chance of obtaining euploid embryos that will successfully implant. Whether aneuploidy is increased from COH with exogenous gonadotropins interfering with natural selection of dominant follicles is a concern. This study evaluates the association between gonadotropin exposure and aneuploidy. This is a retrospective cohort study of 828 patients that underwent 1122 IVF cycles involving controlled ovarian stimulation and trophectoderm biopsy for preimplantation genetic screening (PGS), from 2010 to 2015. Polymerase chain reaction (PCR) was used to assess aneuploidy. Kruskal-Wallis tests and logistic regression with generalized estimating equations (GEEs) were used for data analysis. Overall, after controlling for patient age, ovarian reserve, stimulation protocol, days of stimulation, and diagnoses, there was no significant association between cumulative gonadotropin (GND) dose and the odds of aneuploidy (adjusted OR = 1.049, p = 0.232). Similarly, in cycles where patients did not require COH beyond cycle day 12, there was no significant association between cumulative gonadotropin dose and the odds of aneuploidy (adjusted OR = 0.909, p = 0.148). However, in cases where patients were stimulated past cycle day 12, there was a significant increase in the odds of aneuploidy (adjusted OR = 1.20, 95% CI 1.125-1.282, p < 0.0001) with increasing cumulative gonadotropin dose, with a small effect size (Cohen's d = 0.10, 95% CI 0.08-0.12). In this cohort, there was a 16.4% increase in the odds of aneuploidy for each 1000-u increase in cumulative GND exposure (adjusted OR = 1.164, p = 0.002). When the analysis was restricted to low responders (peak estradiol <500 pg/mL or <4 mature follicles achieved; there was no significant association between gonadotropin dose and aneuploidy (adjusted OR = 1.12, 95% CI 0.982-1.28, p = 0.09), regardless of the duration of COH required to reach vaginal oocyte retrieval. The degree of exposure to exogenous gonadotropins did not significantly modify the likelihood of aneuploidy in patients with a normal ovarian response to stimulation (not requiring COH beyond cycle day 12). Patients requiring prolonged COH were demonstrated to have elevated odds of aneuploidy with increasing cumulative gonadotropin dose. This finding may reflect an increased tendency towards oocyte and embryonic aneuploidy in patients with a diminished response to gonadotropin stimulation.


Stereochemical effect revealed in self-assemblies based on archaeal lipid analogues bearing a central five-membered carbocycle: a SAXS study.
The relative stereochemistry (cis or trans) of a 1,3-disubstituted cyclopentane unit in the middle of tetraether archaeal bipolar lipid analogues was found to have a dramatic influence on their supramolecular self-assembly properties. SAXS studies of two synthetic diastereomeric archaeal lipids bearing two lactosyl polar head groups at opposite ends revealed different lyotropic behaviors. The cis isomer led to L(c)-L(α)-Q(II) transitions whereas the trans isomer retained an L(α) phase from 20 to 100 °C. These main differences originate from the conformational equilibrium (pseudorotation) of 1,3-disubstituted cyclopentanes. Indeed, this pseudorotation exhibits quite similar orientations of the two substituents in a trans isomer whereas several orientations of the two alkyl chains are expected in a cis-1,3-dialkyl cyclopentane, thus authorizing more conformational flexibility in the lipid packing.


Artificial intelligence model substantially improves stratum corneum moisture content prediction from visible-light skin images and skin feature factors.
Appropriate skin treatment and care warrants an accurate prediction of skin moisture. However, current diagnostic tools are costly and time-consuming. Stratum corneum moisture content has been measured with moisture content meters or from a near-infrared image. Here, we establish an artificial intelligence (AI) alternative for conventional skin moisture content measurements. Skin feature factors positively or negatively correlated with the skin moisture content were created and selected by using the PolynomialFeatures(3) of scikit-learn. Then, an integrated AI model using, as inputs, a visible-light skin image and the skin feature factors were trained with 914 skin images, the corresponding skin feature factors, and the corresponding skin moisture contents. A regression-type AI model using only a visible-light skin-containing image was insufficiently implemented. To improve the accuracy of the prediction of skin moisture content, we searched for new features through feature engineering ("creation of new factors") correlated with the moisture content from various combinations of the existing skin features, and have found that factors created by combining the brown spot count, the pore count, and/or the visually assessed skin roughness give significant correlation coefficients. Then, an integrated AI deep-learning model using a visible-light skin image and these factors resulted in significantly improved skin moisture content prediction. Skin moisture content interacts with the brown spot count, the pore count, and/or the visually assessed skin roughness so that better inference of stratum corneum moisture content can be provided using a common visible-light skin photo image and skin feature factors.


Increased analgesic tolerance to acute morphine in fosB knock-out mice: a gender study.
The proteins of Fos family are a potential candidate to link molecular mechanisms of morphine action with behavioural effects such as morphine-induced reward, dependence and tolerance. We used both male and female mice lacking fosB gene to study its contribution to morphine effects. Morphine analgesia (tail-flick test) and hypothermia were studied using morphine at cumulative doses in morphine-naive and morphine-tolerant (tolerance induced by 24 h prior 100 mg/kg morphine administration) mice. FosB -/- mice, as compared to fosB +/+ mice, developed enhanced tolerance to morphine-induced analgesia. No effects of genotype or gender on tolerance to morphine-induced hypothermia were observed. These results suggest that fosB may be involved in the development of tolerance to morphine analgesia but not hypothermia. The gender study implicates that lack of FosB proteins in female fosB -/- mice enhanced morphine analgesic potency. In conclusion, we show that fosB gene is important to analgesia but not hypothermia phenotype indicating its role in morphine effects.


Dietary patterns and depressive symptoms in a Taiwanese population aged 53 years and over: Results from the Taiwan Longitudinal Study of Aging.
The present study aimed to examine the associations between dietary patterns and depressive symptoms in a Taiwanese population aged 53 years and over, and evaluate the longitudinal impacts of dietary patterns on depressive symptoms. Data were from the Taiwan Longitudinal Study of Aging. Depressive symptoms were identified in 23% of adults aged ≥53 years. Multivariate logistic regression analysis showed that a Western dietary pattern, which was characterized by frequent consumption of meat/poultry and eggs, with infrequent consumption of fish, beans/legumes, vegetables and fruit, was cross-sectionally associated with a high risk of depressive symptoms (P < 0.05). A traditional dietary pattern, which was characterized by frequent consumption of meat/poultry and eggs with infrequent consumption of fish, increased by 60% the risk of depressive symptoms during the subsequent 8 years (P < 0.05). A healthy dietary pattern, which was characterized by frequent consumption of fish, vegetables and fruits, was not significantly associated with subsequent depressive symptoms. Dietary patterns correlate with depressive symptoms in a Taiwanese population aged 53 years and over. The Western and traditional dietary patterns, characterized by frequent consumption of meat/poultry and eggs, and infrequent consumption of fish, increased the risk of current and subsequent depressive symptoms. Geriatr Gerontol Int 2016; 16: 1289-1295.


Fluorodeoxyglucose positron emission tomography in Richardson's syndrome and progressive supranuclear palsy-parkinsonism.
We hypothesized that postural instability and cognitive decline in patients with Richardson's syndrome could be a consequence of reduced thalamic and frontal metabolism. Severe Parkinsonian signs in patients with progressive supranuclear palsy-parkinsonism may be reflected by alterations in putaminal metabolism. Eleven patients with Richardson's syndrome, 8 patients with progressive supranuclear palsy-parkinsonism, 12 with Parkinson's disease, and 10 controls underwent clinical assessment and fluorodeoxyglucose positron emission tomography (PET). Richardson's syndrome patients showed pronounced thalamic hypometabolism, and patients with progressive supranuclear palsy-parkinsonism pronounced putaminal hypometabolism, compared to all other investigated groups. The putamen/thalamus uptake ratio differentiated progressive supranuclear palsy-parkinsonism from Richardson's syndrome (area under the curve 5 0.86) and from Parkinson's disease (area under the curve 5 0.80) with acceptable accuracy. Frontal hypometabolism was predominantly found in Richardson's syndrome patients. Richardson's syndrome, progressive supranuclear palsy-parkinsonism and Parkinson's disease showed different metabolic patterns in fluorodeoxyglucose PET.


Protease-armed bacteria in the skin.
The skin constitutes a formidable barrier against commensal and pathogenic bacteria, which permanently and transiently colonise the skin, respectively. Commensal and pathogenic species inhabiting skin both express proteases. Whereas proteases secreted by commensals contribute to homeostatic bacterial coexistence on skin, proteases from pathogenic bacteria are used as virulence factors, helping them colonise skin with breached integrity of the epithelial layer. From these initial sites of colonisation, pathogens can disseminate into deeper layers of skin, possibly leading to the spread of infection. Secreted bacterial proteases probably play an important role in this process and in the deterrence of innate defence mechanisms. For example, Staphylococcus aureus proteases are essential for changing the bacterial phenotype from adhesive to invasive by degrading adhesins on the bacterial cell surface. Secreted staphylococcal proteases mediate pathogen penetration by degrading collagen and elastin, essential components of connective tissue in the dermis. The activation of the contact system and kinin generation by Streptococcus pyogenes and S. aureus proteases contributes to an inflammatory reaction manifested by oedema, redness and pain. Kinin-enhanced vascular leakage might help bacteria escape into the circulation thereby causing possible systemic dissemination of the infection. The inflammatory reaction can also be fueled by the activation of protease-activated receptors on keratinocytes. Concomitantly, bacterial proteases are involved in degrading antimicrobial peptides, disarming the complement system and neutrophils and preventing the infiltration of the infected sites with immune cells by inactivation of chemoattractants. Together, this provides protection for colonising and/or invading pathogens from attack by antibacterial forces of the skin.


Osteopontin is expressed by adult human osteoarthritic chondrocytes: protein and mRNA analysis of normal and osteoarthritic cartilage.
Osteopontin, a sulfated phosphoprotein with cell binding and matrix binding properties, is expressed in a variety of tissues. In the embryonic growth plate, osteopontin expression was found in bone-forming cells and in hypertrophic chondrocytes. In this study, the expression of osteopontin was analyzed in normal and osteoarthritic human knee cartilage. Immunohistochemistry, using a monoclonal anti-osteopontin antibody was negative on normal cartilage. These results were confirmed in Western blot experiments, using partially purified extracts of normal knee cartilage. No osteopontin gene expression was observed in chondrocytes of adult healthy cartilage, however, in the subchondral bone plate, expression of osteopontin mRNA was detected in the osteoblasts. In cartilage from patients with osteoarthritis, osteopontin could be detected by immunohistochemistry, Western blot analysis, in situ hybridization, and Northern blot analysis. A qualitative analysis indicated that osteopontin protein deposition and mRNA expression increase with the severity of the osteoarthritic lesions and the disintegration of the cartilaginous matrix. Osteopontin expression in the cartilage was limited to the chondrocytes of the upper deep zone, showing cellular and territorial deposition. The strongest osteopontin detection was found in deep zone chondrocytes and in clusters of proliferating chondrocytes from samples with severe osteoarthritic lesions. These data show the expression of osteopontin in adult human osteoarthritic chondrocytes, suggesting that chondrocyte differentiation and the expression of differentiation markers in osteoarthritic cartilage resembles that of epiphyseal growth plate chondrocytes.


Skid row alcoholism--an objective definition for use in detoxification and treatment planning.
Objective criteria were used to separate skid row alcoholics from others in a public detoxification program. The two groups thus formed were found to have different characteristics, which could lead to more individualized and effective treatment planning in such settings.


Emulsion templating: Unexpected morphology of monodisperse macroporous polymers.
We synthesised monodisperse macroporous polymers via polymerisation of water-in-monomer droplet emulsions and obtained non-spherical pores with layered pore walls. We hypothesise that this morphology is caused by surfactant diffusion and phase separation during polymerisation. We varied the surfactant mass fraction of the emulsions and polymerised the templates with a water-soluble initiator. From the resulting macroporous polymers we determined the shape of the pores and thickness of the layers via scanning election microscopy. The response of the monomer/surfactant mixture to polymerisation was studied by a ternary phase diagram that simulated polymerisation. The emergence of non-spherical pores with layered pore walls is indeed caused by surfactant diffusion and phase separation. During polymerisation the surfactant molecules diffuse either to the water/monomer interface or deeper into the continuous monomer phase. The first process results in non-spherical pores, while the second process generates layered pore walls.


MiR-15a attenuates peripheral nerve injury-induced neuropathic pain by targeting AKT3 to regulate autophagy.
Aim of this study was to detect the expression of miR-15a in rats following chronic constriction injury (CCI) and to investigate the regulatory functions of miR-15a during neuropathic pain (NP) development. CCI was performed in adult Sprague-Dawley rats to set up the rat model of neuropathic pain. MiR-15a agomir and scrambled control were delivered into the implanted catheter of rats. The mechanical allodynia and thermal hyperalgesia were assessed in both CCI- and sham-operated groups. Rat lumbar spinal cord tissues were harvested for mRNA and protein analyses. The primary spinal microglia were isolated from adult Sprague-Dawley rats and transfected with miR-15a mimics, scramble miRNA, miR-15a inhibitor or its corresponding negative control. Cell lysates were collected for mRNA and protein analyses. Compared to sham-operated group, the expression of miR-15a in CCI rats was significantly reduced, whereas neuroinflammation in spinal cord tissues was increased. Intrathecal administration of miR-15a agomir significantly attenuated CCI-induced NP and the levels of proinflammatory cytokines, including IL-6, IL-1β, and TNF-α. AKT3 was predicted and confirmed as a miR-15a-regulated gene. We further demonstrated that miR-15a overexpression downregulated the level of AKT3 in primary rat microglia and rat CCI model. Moreover, the upregulation of miR-15a induced the expressions of autophagy-associated proteins, suggesting that the regulation mechanism of miR-15a in NP development involves AKT3-mediated autophagy via inhibiting the expression of AKT3. Our findings indicated that miR-15a might serve as a promising therapeutic target for the management of NP through the stimulation of autophagic process.


Food insecurity and the risk of depression in people living with HIV/AIDS: a systematic review and meta-analysis.
The link between food insecurity and depression in people living with HIV/AIDS (PLWHA) has been explored in numerous studies; however, the existing evidence is inconclusive due to inconsistent results. Therefore, the objective of this systematic review and meta-analysis is to examine the relationship between food insecurity and depression in PLWHA. We systematically searched PubMed, EMBASE, and Scopus to identify relevant studies. A random-effect model was used for conducting the meta-analysis. We assessed the risk of publication bias by funnel plot and Egger's regression asymmetry test. In this review, seven studies were included in the final analysis. Our meta-analysis revealed that food insecurity significantly increased the risk of depression in PLWHA [RR 2.28 (95% CI 1.56-3.32)]. This association remained significant after adjusting for the confounding effects of drug use [RR 1.63 (95% CI 1.27-2.10)], social support [RR 2.21 (95% CI 1.18-4.16)] as well as ART drugs [RR 1.96 (95% CI 1.17-3.28)]. Our subgroup and sensitivity confirmed the robustness of the main analysis. This systematic review and meta-analysis suggest a significant association between food insecurity and increased risk of depression PLWHA. Therefore, early screening and management of food insecurity in PLWHA seem to be necessary.


New religious movement membership and the importance of stable 'others' for the making of selves.
Challenging the view that people join New Religious Movements because they have fallen victim to powerful brainwashing techniques, the analysis of in-depth life history interviews of 23 former members from 11 different Australian 'cults' suggests that membership was personally negotiated and motivated by a desire for stronger social connections, albeit for different reasons. While for some participants, a desire for social connectedness was related to a strong need for guidance and direction from 'stable' others, for others it reflected a desire for self-change or self-enhancement. To make sense of the participant narratives, symbolic interactionist understandings of the self are applied.


Schedule-induced polydipsia and size of water dipper.
Schedule-induced polydipsia as a function of six water dipper sizes was examined in four food-deprived rats under Fixed Time 1- and 2-minute schedules. Increasing dipper size increased session water intake but did not affect the number of intervals containing at least one barpress (i.e., number of bouts), nor the number of barpresses per bout, nor the temporal distribution of barpressing within the interfood interval. Previous research showing polydipsic intake to be impervious to other types of restrictions on water availability have suggested the notion of a volume constancy mechanism. The present research raises questions about the operation of the volume constancy mechanism, questions about how to conceptualize the dipper size manipulation, and questions about variables which affect the temporal locus of drinking.


Use of the thoracodorsal artery perforator flap for bronchial reinforcement in patients with previous posterolateral thoracotomy.
The thoracodorsal artery perforator flap (TDAP flap) allows raising the same cutaneous island as in the classical latissimus dorsi musculocutaneous flap without its muscular part. All patients who underwent a completion pneumonectomy with reinforcement of bronchial stump with a TDAP flap from December 2009 to October 2010 were followed prospectively. The 30-day mortality and the procedure-related morbidity as well as bronchial fistula and TDAP flap were analyzed. The TDAP flap was used in 6 cases without failure or fistula formation. At 1 month, all patients were alive, and there was no morbidity (seroma, hematoma, fistula, or shoulder dysfunction). Computed tomography scans were performed at 1 month and 3 months postoperatively and showed viable nonatrophic flap. This type of flap has been described in the field of plastic surgery, and this is the first description of its use in the chest. Deepithelialized fasciocutaneous TDAP flap is safe and reliable. It is available even if the latissimus dorsi has been previously divided. It is now our first-line option to reinforce the bronchial stump.


Analysis of intact steroid conjugates by secondary ion mass spectrometry (including FABMS) and by gas chromatography.
The analysis of intact steroid conjugates by two different methods is described. One method employed secondary ion mass spectrometry (SIMS) using a Cs+ beam for ionisation, although comparable data were obtained by fast atom bombardment (FAB) using a Xe0 beam. In both of these mass spectrometric techniques the samples were analysed in a liquid matrix (glycerol). Positive and negative ion spectra have been obtained, the latter being most useful for steroid sulphate and glucuronide analysis. The negative ion spectrum of each steroid is dominated by a pseudomolecular ion at m/z [M - H]- (M of free acid) and a lack of marked fragmentation. Mixtures of steroids can be resolved in a single spectrum, providing the individual steroids differ in mass. The second method was gas chromatography. The carboxylic acid moieties of the steroid glucuronides were derivatised with diazomethane and the remaining functional groups in the steroids were thermally protected by methyloxime formation (for carbonyls) and trimethylsilylation (for all steroidal and glucuronic acid hydroxyls). Satisfactory analysis of steroid glucuronides was achieved through the use of glass or fused silica columns stable at high temperature (330 degrees C). Conveniently, trimethylsilylation resulted in exchange of the sulphate in 3 beta-hydroxy-5-ene steroid sulphates for a trimethylsilyl group so these could effectively be analysed as "free" steroids.


Two-Year Clinical Results of Lateral Collagen Meniscus Implant: A Multicenter Study.
To present the 2-year results of the use of the lateral Collagen Meniscus Implant (CMI) for the treatment of irreparable lateral meniscal lesions or partial lateral meniscal defects, to investigate the potential predictors of clinical results, and to monitor device safety. Forty-three patients with a mean age of 30.1 ± 12.0 years were clinically evaluated 24 months after treatment of partial lateral meniscal defects with the CMI (Ivy Sports Medicine, Gräfelfing, Germany). We used the Lysholm score, the Tegner Activity Scale, a visual analog scale for pain (during strenuous activity, during routine activity, and at rest), a functional questionnaire, and a satisfaction questionnaire for the evaluation. All demographic and surgical parameters were used for multiple regression analysis to find outcome predictors. Serious adverse events and reoperations were monitored. All clinical scores significantly improved from preoperatively to final evaluation at 24.2 ± 1.9 months' follow-up. The Lysholm score improved significantly from 64.3 ± 18.4 preoperatively to 93.2 ± 7.2 at final follow-up (P = .0001). Functional improvement was detected from 6 months after surgery, whereas strenuous activities and knee swelling reached optimal results after 12 months. The highest pain ratings experienced during strenuous activity, during routine activity, and at rest significantly improved from 59 ± 29, 29 ± 25, and 20 ± 25, respectively, preoperatively to 14 ± 18, 3 ± 5, and 2 ± 6, respectively, at 2 years' follow-up (P = .0001). At final follow-up, 58% of patients reported activity levels similar to their preinjury values whereas 95% of patients reported that they were satisfied with the procedure. A higher body mass index, the presence of concomitant procedures, and a chronic injury pattern seemed to negatively affect the final outcomes. Serious adverse events with a known or unknown relation to the scaffold, such as pain, swelling, and scaffold resorption, were reported in 6% of patients, leading to CMI explantation, debridement, or synovectomy. The lateral CMI scaffold could be considered a potentially effective and safe procedure to treat both irreparable lateral meniscal tears and post-meniscectomy syndrome in appropriately selected patients. Chronic injury, high body mass index, and concomitant procedures have been shown to negatively affect the short-term results; however, the results appeared to slowly improve through the 24-month follow-up period. Thus patience is needed when evaluating the expectations for and results of the described procedure. Level IV, therapeutic case series.


Trastuzumab emtansine: first global approval.
Genentech and ImmunoGen are collaborating on the development of trastuzumab emtansine, a HER2 antibody-drug conjugate that comprises Genentech's trastuzumab antibody linked to ImmunoGen's anti-mitotic agent, mertansine (a maytansine derivative; also known as DM1). The conjugate combines two strategies: the anti-HER2 activity of trastuzumab, and the targeted intracellular delivery of mertansine, a tubulin polymerisation inhibitor which interferes with mitosis and promotes apoptosis. The linker in trastuzumab emtansine is a non-reducible thioether linker, N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC, designated MCC after conjugation). Trastuzumab emtansine (Kadcyla™) has been launched in the USA as second-line monotherapy for HER2-positive metastatic breast cancer, and has been filed for approval in the EU and Japan in this indication. Trastuzumab emtansine is in phase III development as first-line combination therapy or monotherapy for metastatic HER2-positive breast cancer, and as third-line monotherapy for metastatic HER2-positive breast cancer. Phase II development is underway for early-stage breast cancer and phase II/III development is underway in patients with HER2-positive gastric cancer. This article summarizes the milestones in the development of trastuzumab emtansine leading to this first approval for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.


Analyzing cell-cell interactions in 3-dimensional adhesion assays.
The organization of cells is key to the proper formation and function of tissues and it appears to be dependent upon various intracellular and extracellular signals. These signals come from cell-cell interactions, as well as interactions with the surrounding extracellular milieu. In order to investigate these properties and interactions among cells, our lab utilizes and has developed several techniques that provide a 3-dimensional, in vivo-like environment for in vitro cell culture. In this chapter, we describe several techniques for isolating primary cardiac cells, including myocytes, endothelial cells, and fibroblasts. In addition, we discuss and outline an adhesion assay and an aggregation assay that can be used for numerous cell types, as well as a collagen gel assay for examination of cell-cell and cell-matrix interactions.


The binding of CO2 to human hemoglobin.
CO2-dissociation curves of concentrated human deoxy- and carbonmonoxyhemoglobin at 37 degrees, pH 7.6 to 7.0, PCO2 equal to 10 to 160 mm Hg, have been obtained by a rapid mixing and ion exchange technique. The CO2-dissociation curves for deoxyhemogloblin can only be fitted by assuming two classes of binding sites for carbon dioxide. The simplest way to account for the experimental data is to assume that the alpha-amino groups of the alpha and beta chains react with carbon dioxide with affinities that differ by at least a factor of 3. No difference in reactivity with CO2 was found among the four terminal alpha-amino groups of carbonmonoxyhemoglobin.


Body image, strategies to change muscles and weight, and puberty: do they impact on positive and negative affect among adolescent boys and girls?
The purpose of this study was to examine the impact of strategies to both decrease weight and increase muscle tone on negative (depression, anxiety) and positive affect among adolescent males and females. The respondents were 1185 adolescents (587 males, 598 females) who were enrolled in grades 7 and 9 (mean age for males=13.22 years; mean age for females=13.21 years). Respondents completed the Body Image and Body Change Inventory that assessed body image satisfaction, body image importance, body change strategies to decrease weight, body change strategies to increase muscle tone, and food supplements. Respondents also completed the Pubertal Development Scale, the depression and anxiety scales of the Depression Anxiety and Stress Scale, and the positive affect items from the Positive and Negative Affect Scale. Structural equation modelling was used to determine how body satisfaction and importance, body change strategies, and puberty impacted on depression, anxiety, and positive affect. The results demonstrated that for both boys and girls, there was a strong association between body change strategies and negative affect. For boys, body dissatisfaction did not predict negative affect, although this was a strong predictor for girls. Body change strategies did not strongly predict positive affect for either boys or girls, although body image satisfaction was a strong predictor for both genders. The implications of these findings for obtaining a better understanding of the role of pubertal development, body image, and body change strategies in predicting positive and negative affect among adolescent males and females are discussed.


An improved genome assembly and annotation of the Antarctic copepod Tigriopus kingsejongensis and comparison of fatty acid metabolism between T. kingsejongensis and the temperate copepod T. japonicus.
Copepods in the genus Tigriopus are widely distributed in the intertidal zone worldwide. To assess differences in fatty acid (FA) metabolism among congeneric species in this genus inhabiting polar and temperate environments, we analyzed and compared FA profiles of the Antarctic copepod Tigriopus kingsejongensis and the temperate copepod T. japonicus. Higher amounts of total FAs were found in the Antarctic copepod T. kingsejongensis than the temperate copepod T. japonicus under administration of the identical amount of Tetraselmis suecica. To determine the genomic basis for this, we identified fatty acid metabolism-related genes in an improved genome of T. kingsejongensis. The total length of the assembled genome was approximately 338 Mb with N50 = 1.473 Mb, 938 scaffolds, and a complete Benchmarking Universal Single-Copy Orthologs value of 95.8%. A total of 25,470 genes were annotated using newly established pipeline. We identified eight elongation of very long-chain fatty acid protein (Elovl) genes and nine fatty acid desaturase (Fad) genes in the genome of T. kingsejongensis. In addition, fatty acid profiling suggested that the duplicated Δ5/6 desaturase gene in T. kingsejongensis is likely to play an essential role in synthesis of different FAs in T. kingsejongensis to those in T. japonicus. However, further experimental research is required to validate our in silico findings. This study provides a better understanding of fatty acid metabolism in the Antarctic copepod T. kingsejongensis.


Ambiguous loss in organ donor families: A constructivist grounded theory.
Explore families' experiences when being approached for organ donation authorisation after brainstem death. The complexities of potential organ donor families' experiences include challenges related to emotional distress, coping with the loss and the organ donation decision-making process, and support needed. A lack of conceptual clarity was found concerning families' experiences when being approached for organ donation authorisation, which guided the study. Constructivist grounded theory. Seventy-one participants, including healthcare professionals and families, were recruited from two large hospitals in Chile between 2017 and 2019. Field notes, documents (n = 80), interviews (n = 27) and focus groups (n = 14) were collected and analysed following Charmaz's constructivist grounded theory principles and practices until theoretical saturation was reached. The study is reported using the COREQ checklist. A third type of ambiguous loss of bereaved families' experience was developed as a fourfold process: (1) impending loss, (2) confirming loss, (3) ambiguous loss and organ donation decision-making and (4) organ donation as a third type of ambiguous loss. This grounded theory expands the concepts of ambiguous loss by Boss, dying by Glaser and Strauss and grief by Brinkmann, enabling explanation of families' experiences. Families of potential organ donors develop a highly complex grieving process, which may play a significant role in the organ donation decision-making process. Ambiguity is embedded in how donor families reframe the existence of the donor through the act of giving life. The findings shed light on families' experiences on the organ donation process after brainstem death. The study can be used in nursing practice, education and to inform policy nationally and globally, mainly due to the current focus on quantitative measures and legislative changes fostering individual decision-making. Families contributed through their first-hand experiences of the organ donation process.


Age specific fecundity and size of offspring in the prosobranch snail, Viviparus ater.
Age specific fecundity and size of offspring were compared in two populations of Viviparus ater, one from Lake Zürich (Switzerland) and one from Lake Maggiore (Italy). Females were caged and their offspring sampled at weekly intervals. Average fecundity per female over one year was 19.6 and 14.7 offspring in Lake Zürich and Lake Maggiore, respectively. Average shell widths of offspring at birth in the two lakes were 8.5 mm and 7.4 mm. Fecundity did not change with age in Lake Zürich but decreased with increasing age of the snails in Lake Maggiore. Fecundity and offspring size were positively correlated with the size of the females in both lakes, but fecundity was higher and offspring were larger in Lake Zürich than in Lake Maggiore irrespective of the size of the females. An analysis of covariance, correcting for differences between the two lakes in the total fresh weight of the offspring produced annually, showed that females from the two lakes distributed their reproductive investment differently. Females in Lake Zürich produced relatively fewer but larger offspring than females in Lake Maggiore. This trade-off was hidden because females in Lake Zürich produced twice as much offspring biomass as females in Lake Maggiore. The possibility that different selection regimes might account for the observed differences is discussed.


Olesoxime accelerates myelination and promotes repair in models of demyelination.
Multiple sclerosis is a neurodegenerative disease characterized by episodes of immune attack of oligodendrocytes leading to demyelination and progressive functional deficit. One therapeutic strategy to address disease progression could consist in stimulating the spontaneous regenerative process observed in some patients. Myelin regeneration requires endogenous oligodendrocyte progenitor migration and activation of the myelination program at the lesion site. In this study, we have tested the ability of olesoxime, a neuroprotective and neuroregenerative agent, to promote remyelination in the rodent central nervous system in vivo. The effect of olesoxime on oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis was tested directly in organotypic slice cultures and OPC-neuron cocultures. Using naive animals and different mouse models of demyelination, we morphologically and functionally assessed the effect of the compound on myelination in vivo. Olesoxime accelerated oligodendrocyte maturation and enhanced myelination in vitro and in vivo in naive animals during development and also in the adult brain without affecting oligodendrocyte survival or proliferation. In mouse models of demyelination and remyelination, olesoxime favored the repair process, promoting myelin formation with consequent functional improvement. Our observations support the strategy of promoting oligodendrocyte maturation and myelin synthesis to enhance myelin repair and functional recovery. We also provide proof of concept that olesoxime could be useful for the treatment of demyelinating diseases.


Tissue blood flow and distribution of cardiac output in cats: changes caused by intravenous infusions of histamine and histamine receptor agonists.
1 The effects of infusions of histamine on blood pressure, cardiac output, heart rate, total peripheral resistance, stroke volume and tissue blood flow have been determined in anaesthetized cats using radio-active microspheres to measure cardiac output and tissue blood flow.2 Histamine caused dose-dependent falls in blood pressure and total peripheral resistance over the dose-range 1 x 10(-8) to 3.3 x 10(-7) mol kg(-1) min(-1). Histamine had no effect on cardiac output, heart rate or stroke volume.3 Histamine caused vasodilatation in the heart and stomach, with increased blood flow through these organs, and in the small and large intestine where blood flow was maintained despite the falls in arterial blood pressure. Blood flow to the brain, kidneys, liver, adrenal glands, skeletal muscle, spleen and skin was reduced when arterial blood pressure fell. Vascular resistance increased in the skin and spleen, presumably due to reflex vasoconstriction when blood pressure fell.4 The selective H(1)-receptor agonist 2-(2-aminoethyl)pyridine lowered blood pressure and decreased total peripheral resistance but did not change cardiac output, heart rate or stroke volume. 2-(2-Aminoethyl)pyridine caused vasodilatation in the heart, small and large intestine and kidneys. Vascular resistance was increased in the spleen and skin.5 The selective H(2)-receptor agonist 4-methylhistamine also lowered blood pressure and decreased total peripheral resistance but did not change cardiac output, heart rate or stroke volume. 4-Methylhistamine caused vasodilatation in the heart, stomach, small and large intestines and skeletal muscle. Vascular resistance was increased in the skin.


The teaching of neurology in the degree course in dentistry.
The problem of neurology teaching in the degree course in dentistry is addressed in the light of data gathered from teachers of the course. The first part of the paper deals with the teachers and the organization of the course, the second with the teaching objectives and relations with other disciplines and the third with the reform hypothesis of Table XVIII bis and the role of neurology in the curriculum of the dentistry school. The last part examines the assessment of teachers by students and the repercussions of improved teaching on attendance and attainment.


β-cell function, incretin response, and insulin sensitivity of glucose and fat metabolism in obese youth: Relationship to OGTT-time-to-glucose-peak.
In adults, the time-to-glucose-peak at or after 30 minutes during an oral glucose tolerance test (OGTT) identifies physiologically distinct groups with differences in insulin sensitivity, β-cell function and risk for type 2 diabetes. In obese non-diabetic adolescents, we investigated if the OGTT-time-to-glucose-peak also reflects incretin and free fatty acid (FFA) responses besides insulin sensitivity and β-cell function, measured by the clamp. Obese adolescents (n = 278) were categorized according to their OGTT-time-to-glucose-peak by Early-peak (at 30 minutes) vs Late-peak (>30 minutes) groups. Body composition, visceral adipose tissue, oral disposition index and OGTT-area under the curve (AUC) were examined. A subset of 102 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β-cell function relative to insulin sensitivity. Compared with the Early-peak group, the Late-peak group had impaired β-cell function relative to insulin sensitivity, lower glucose-dependent insulinotropic polypeptide-AUC, and higher FFA-AUC despite higher insulin- and C-peptide-AUC. They also had lower hepatic and peripheral insulin sensitivity despite similar percent body fat and visceral adipose tissue, and had higher prevalence of impaired glucose tolerance (all P < .05). In obese non-diabetic youth, those with a Late-peak vs an Early-peak glucose during an OGTT showed diminished β-cell function, blunted incretin secretion, and lower insulin sensitivity of glucose and FFA metabolism. It remains to be determined if Late-peak glucose predicts the future development of type 2 diabetes in these high-risk youth.


Corticotropin-releasing hormone (CRH) stimulates cocaine- and amphetamine-regulated transcript gene (CART1) expression through CRH type 1 receptor (CRHR1) in chicken anterior pituitary.
Cocaine- and amphetamine-regulated transcript (CART) peptide(s) is generally viewed as neuropeptide(s) and can control food intake in vertebrates, however, our recent study revealed that CART1 peptide is predominantly expressed in chicken anterior pituitary, suggesting that cCART1 peptide is a novel pituitary hormone in chickens and its expression is likely controlled by hypothalamic factor(s). To test this hypothesis, in this study, we examined the spatial expression of CART1 in chicken anterior pituitary and investigated the effect of hypothalamic corticotropin-releasing hormone (CRH) on pituitary cCART1 expression. The results showed that: 1) CART1 is expressed in both caudal and cephalic lobes of chicken anterior pituitary, revealed by quantitative real-time PCR (qPCR), western blot and immuno-histochemical staining; 2) CRH potently stimulates cCART1 mRNA expression in cultured chick pituitary cells, as examined by qPCR, and this effect is blocked by CP154526 (and not K41498), an antagonist specific for chicken CRH type I receptor (cCRHR1), suggesting that cCRHR1 expressed on corticotrophs mediates this action; 3) the stimulatory effect of CRH on pituitary cCART1 expression is inhibited by pharmacological drugs targeting the intracellular AC/cAMP/PKA, PLC/IP3/Ca(2+), and MEK/ERK signaling pathways. This finding, together with the functional coupling of these signaling pathways to cCRHR1 expressed in CHO cells demonstrated by luciferase reporter assay systems, indicates that these intracellular signaling pathways coupled to cCRHR1 can mediate CRH action. Collectively, our present study offers the first substantial evidence that hypothalamic CRH can stimulate pituitary CART1 expression via activation of CRHR1 in a vertebrate species.


Absorbance of amniotic fluid at 650 nm as a fetal lung maturity test: a comparison with the lecithin/sphingomyelin ratio and tests for disaturated phosphatidylcholine and phosphatidylglycerol.
We compared absorbance of amniotic fluid at 650 nm (A650) against the lecithin/sphingomyelin ratio, the quantity of disaturated phosphatidylcholine, and the presence or absence of phosphatidylglycerol in 374 uncontaminated amniotic fluid samples. In addition, we studied these measures of fetal lung maturity in 80 pregnancies where neonatal outcomes were known. Statistical analysis revealed a significant association between increasing absorbance and biochemical indices of lung maturation. Our results indicate that A650 of amniotic fluid is useful as a measure of lung maturity but that the greatest utility may be for samples with either low absorbance (less than 0.10) or high absorbance (greater than 0.20). Because of large false positive and false negative values between these two absorbances, other lung maturity estimates should be used when absorbances fall within this range. Therefore, A650 may be most useful as a screen or as part of a battery of lung maturity estimates. We are exploring these possibilities as a means of providing better fetal lung maturity estimates.


Steroid 5-alpha reductase type 2 activity in biopsies from malignant and normal prostatic tissues.
The conversion of testosterone (T) to the more potent metabolite dihydrotestosterone (DHT) by prostate-specific steroid 5 alpha-reductase isoenzymes is a key mechanism in the action of androgens in the prostate and it is important in the promotion and progression of prostate diseases. We described an adaptation of a sensitive method for evaluation of the 5 alpha-reductase type 2 (5 alpha-R2) activity using a small quantity of protein. We used 29 human prostate transrectal ultrasound-guided core biopsies obtained from patients (median age 70, range 55-86 y) undergoing this procedure for diagnostic purposes. 4-[(14)C]testosterone and NADPH were incubated with biopsy homogenate. Reaction products were extracted, separated by thin layer chromatography and revealed by autoradiography. Areas correspondent to T and DHT were scraped into vials and their radioactivity determined. The 5 alpha-R2 activity was expressed as ln (natural logarithm). The assay was validated according to the protein concentration and incubation time linearities. The 5 alpha-R2 activity showed a significant difference between normal and neoplastic tissues with significance level set at P<0.05, mainly in the left prostate lobe. This was independent from the PSA levels. Determination of 5 alpha-R2 activity, using the conditions reported herein, could be utilized as an efficient biochemical parameter of prostate neoplastic processes.


Soil core microbiota drive community resistance to mercury stress and maintain functional stability.
Soil microbial communities have resistance to environmental stresses and thus can maintain ecosystem functions such as decomposition, nutrient provisioning, and plant pathogen control. However, predominant factors driving community resistance of soil microbiome to heavy metal pollution stresses and ecosystem functional stability are still unclear, limiting our ability to forecast how soil pollution might affect ecosystem sustainability. Here, we conducted microcosm experiments to estimate the importance of soil microbiome in predicting community resistance to heavy metal mercury (Hg) stress in paired paddy and upland fields. We found that community resistance of soil microbiome was strongly correlated with ecosystem functional stability, so were the individual groups of organisms such as bacteria, saprotrophic fungi, and phototrophic protists. The core phylotypes within soil microbiome had a major contribution to community resistance, which was essential for the maintenance of functional stability. Co-occurrence network further confirmed that community resistances of main ecological clusters were positively correlated with ecosystem functional stability. Together, our results provide new insights into the link between community resistance and functional stability, and highlight the importance of core microbiota in driving community resistance to environmental stresses and maintain functional stability.


Environmental restraints and life strategies: a habitat templet matrix.
Four basic environmental restraints on life are deduced from the requirements of life's inherent order laws. Possible life strategies to contend with these restraints are listed. The various combinations of the restraints are subsequently investigated, and appropriate combinations of life strategies are fitted. This model is finally tested against insect case histories in various environments, and is demonstrated to explain some combinations of characteristics of insects in ecosystems not covered by the r-K or r-K-A continua. The role of heterochrony in achieving appropriate life strategies is briefly discussed.


Perfluorinated aromatic spacers for sensitizing europium(III) centers in dinuclear oligomers: better than the best by chemical design?
Transfer news: the use of a simple method allows the various sensitization steps in Eu(III) -containing complexes to be deciphered. Incorporation of an increasing number of electron-withdrawing fluorine atoms on the rigid and electronically tunable phenyl spacer between two tridentate binding units (see picture, red O, dark blue N) affects the quantum yield, intersystem crossing, and energy-transfer processes in a rational way.


[Diplopia: An important symptom in internal medicine!]
Diplopia is defined as "double vision" when looking at a single object. Monocular diplopia is related to an ocular disorder and must be differentiated from binocular diplopia which is secondary to ocular misalignment. The examination of the patient with binocular diplopia is often challenging for non-specialists. However, a careful and systematic clinical examination followed by targeted ancillary testing allows the clinician to localize the lesion along the oculomotor pathways. The lesion may involve the brainstem, the ocular motor nerves III, IV or VI, the neuromuscular junction, the extraocular ocular muscles, or the orbit. Causes of binocular diplopia are numerous and often include disorders typically managed by internal medicine such as inflammatory, infectious, neoplastic, endocrine, and metabolic disorders. In addition to treating the underlying disease, it is important not to leave diplopia uncorrected. Temporary occlusion of one eye by applying tape on one lens or patching one eye relieves the diplopia until more specific treatments are offered should the diplopia not fully resolve.


The mechanisms by which infectious agents may contribute to atherosclerosis and its clinical manifestations.
Three infectious agents have recently gained considerable interest as potential pathogens in atherosclerosis and in its clinical manifestations: herpes simplex virus, cytomegalovirus, and Chlamydia pneumoniae. Chronic and often asymptomatic infections with these agents occur widely in the general population. These pathogens may affect atherosclerosis either directly or indirectly. Direct effects on vascular wall cells might include cell lysis, transformation, lipid accumulation, proinflammatory changes, and augmentation of procoagulant activity. Indirect systemic effects may involve induction of acute-phase proteins, establishment of a prothrombotic state, hemodynamic stress caused by tachycardia, increased cardiac output, or a regional inflammatory activation in response to systemic endotoxemia and cytokinemia. The effects of microbial infection, usually in combination with other risk factors (for example, smoking, hyperlipidemia, family history), might promote atherogenesis and eventually trigger acute coronary events.


Traditional uses, phytochemistry, and pharmacology of Persicaria orientalis (L.) Spach - A review.
Persicaria orientalis (L.) Spach (internationally accepted and only valid name; synonym: Polygonum orientale L.; family: Polygonaceae), which is named Hongcao in China, is a Chinese herbal medicine that has a wide range of pharmacological effects including treatment to rheumatoid arthritis, coronary heart disease, hernia, carbuncle sore, enhance immunity, antimicrobial, osteogenic and dilated bronchiectasis. This review aims to provide systematically organized information on traditional uses of Persicaria orientalis (L.) Spach (P. orientalis) and to critically analyze evidences in phytotherapeutic, botanical, and pharmacological literatures that support its therapeutic potential in treatment to human diseases. Isolation of additional compounds and detailed pharmacological investigations are key areas to investigate. Relevant information on P. orientalis was collected through published scientific materials (including PubMed, ScienceDirect, Wiley, ACS, CNKI, Scifinder, Springer, Taylor & Francis, Web of Science, Google Scholar, and Baidu Scholar) and other literature sources (e.g., Chinese Pharmacopoeia, 2015 edition, Chinese herbal classic books and PhD and MSc thesis, etc.). Traditional uses were compiled in this review, including classic prescriptions and historical applications. Approximately 70 compounds, mainly including flavonoids, phenolics, lignans, limonoids and steroids, have been isolated and identified from P. orientalis. Among them, flavonoids were main components. Crude extracts and pure compounds isolated from P. orientalis exhibited various pharmacological activities, such as protection against ischemia and hypoxia-induced myocardial cells and hypoxia/reoxygenation cardiomyocyte, increase the blood flow in myocardium, expanding bronchus, anti-inflammatory and analgesic, and antithrombotic effects and so on. P. orientalis is a valuable source with therapeutic potential on a wide range of diseases especially cardiovascular-system disorders. Though most traditional uses of P. orientalis are supported by in vitro/vivo pharmacological studies, however, there is still a lack of researches on active pharmacodynamic ingredients as well as in-depth and in-vivo mechanistic studies. Therefore, isolation and identification of more active compounds (especially flavonoids), their structure-activity relationship and studies on pharmacodynamic mechanisms by more elaborative in-vivo studies on P. orientalis may be focused on in order to confirm efficacy of reported therapeutic effects of P. orientalis and help explore it's therapeutic potentials. Furthermore, research designs of pharmacological studies based on traditional uses of anti-rheumatoid arthritis through cell lines and animal models should also be considered as key research topics.


Long noncoding RNA CASC11 suppresses sorafenib-triggered ferroptosis via stabilizing SLC7A11 mRNA in hepatocellular carcinoma cells.
As a frontline treatment for patients with advanced hepatocellular carcinoma (HCC), sorafenib is an effective drug approved by the Food and Drug Administration (FDA). Ferroptosis, a newly defined programmed cell death process with the hallmark of the accumulation of iron-dependent lipid peroxides, can be induced by sorafenib treatment. Our previous study identified oncogenic roles of long noncoding RNA (lncRNA) Cancer susceptibility candidate 11 (CASC11) in HCC progression. However, the relationship between CASC11 and sorafenib-induced ferroptosis in HCC remains unclear. In the present study, we aim to investigate the role of CASC11 in sorafenib-induced ferroptosis in HCC cell lines and determine the involved molecular mechanisms. Here, we demonstrated that sorafenib decreased CASCL11 expression. Knockdown of CASC11 enhanced sorafenib-induced ferroptosis, while overexpression of CASC11 exerted the opposite effect in HCC cells. Moreover, CASC11 led to the accumulation of intracellular malondialdehyde (MDA), lipid reactive oxygen species (ROS) and Fe2+ while depleting glutathione (GSH), thereby suppressing sorafenib-induced ferroptosis and cell death. Ferrostatin-1 (Ferr-1), a ferroptosis inhibitor, reversed the enhanced anticancer effect of sorafenib caused by the silence of CASC11 in HCC cells. Mechanistically, CASC11 upregulated the expression of solute carrier family 7 member 11 (SLC7A11) which is critical for ferroptosis inhibition. CASC11 associated with and stabilized SLC7A11 mRNA. In summary, our data revealed, for the first time, that CASC11 inhibits the sorafenib-induced ferroptosis in HCC cells via regulating SLC7A11, providing a new basis for clinical therapeutic strategies for patients with HCC.


Comparative study of HbA1c and fasting plasma glucose vs the oral glucose tolerance test for diagnosis of diabetes in people with tuberculosis.
To compare HbA1c and fasting plasma glucose assessment, with the 2-h oral glucose tolerance test as reference, in screening for diabetes in people with turberculosis. Individuals (N=268) with newly diagnosed smear-positive tuberculosis were screened for diabetes at a tertiary hospital in Lahore, Pakistan. Diabetes diagnosis was based on WHO criteria: thresholds were ≥48 mmol/mol (≥6.5%) for HbA1c and ≥7.0mmol/l for fasting plasma glucose. The proportion of participants diagnosed with diabetes was 4.9% (n =13) by oral glucose tolerance test, while 11.9% (n =32) and 14.6% (n =39) were diagnosed with diabetes using HbA1c and fasting plasma glucose criteria, respectively. The area under the receiver-operating characteristic curve was 0.79 (95% CI 0.64 to 0.94) for HbA1c and 0.61 (95% CI 0.50 to 0.73) for fasting plasma glucose, with a borderline significant difference between the two tests (P=0.07). HbA1c and fasting plasma glucose performed equally in terms of diagnosing new diabetes cases in individuals with tuberculosis, but the proportion of participants falsely classified as positive was higher for fasting plasma glucose. This may be explained by acute blood glucose fluctuations when using fasting plasma glucose. HbA1c may be a more reliable test in individuals with transient hyperglycaemia.


PLA2G6-associated late-onset parkinsonism in a Sudanese family.
The phospholipase A2 group VI gene (PLA2G6) encodes an enzyme that catalyzes the hydrolytic release of fatty acids from phospholipids. Four neurological disorders with infantile, juvenile, or early adult-onset are associated with PLA2G6 genetic alterations, namely infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia-parkinsonism (DP), and autosomal recessive early-onset parkinsonism (AREP). Few studies in Africa reported PLA2G6-associated disorders and none with parkinsonism of late adult onset. The patients were clinically assessed following UK Brain Bank diagnostic criteria and International Parkinson and Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Brain MRI without contrast was performed. Genetic testing was done using a custom-made Twist panel, screening 34 known genes, 27 risk factors, and 8 candidate genes associated with parkinsonism. Filtered variants were PCR-amplified and validated using Sanger sequencing and also tested in additional family members to study their segregation. Two siblings born to consanguineous parents developed parkinsonism at the age of 58 and 60 years, respectively. MRI showed an enlarged right hippocampus in patient 2, but no overt abnormalities indicative of INAD or iron deposits. We found two heterozygous variants in PLA2G6, an in-frame deletion NM_003560:c.2070_2072del (p.Val691del) and a missense variant NM_003560:c.956C>T (p.Thr319Met). Both variants were classified as pathogenic. This is the first case in which PLA2G6 is associated with late-onset parkinsonism. Functional analysis is needed to confirm the dual effect of both variants on the structure and function of iPLA2β.


Clinical experience of use of percutaneous peripheral arterial cannulation in sick neonates in a developing country.
Continuous invasive arterial monitoring is necessary in sick neonates needing hemodynamic and ventilatory support. The primary objective of our study was to describe clinical experience with percutaneous peripheral arterial cannulation (PAC) in sick neonates. Neonates needing PAC were prospectively enrolled in the study. Inclusion criteria were: neonates needing respiratory support (invasive or non-invasive), neonates requiring vasoactive medications or neonate likely to need more than 5 sampling pricks in 24 h. One hundred eight neonates (93.1%) needed cannulation of one arterial site while 8 (6.9%) needed cannulation of 2 arterial sites, thus giving a total of 124 cannulations. Out of the 124 cannulations, 102 (82%) were performed in first attempt, while 22 (18%) cannulations needed 2 or more attempts. Serious complications like discolouration of digits, blanching of skin or bleeding were seen in 6 (4.9%) cannulations. These resolved after removal of arterial line and no long term consequences were noted. On comparing neonates having radial arterial cannulation(n = 108) with posterior tibial arterial cannulation (n = 16) there was no difference in duration of arterial line between radial artery group (mean, SD 53.30 ± 22.56) and posterior tibial artery group (mean, SD 48.25 ± 27.39). However, more attempts were needed to cannulate post tibial artery (mean, SD 2.25 ± 1.32) as compared to radial artery (mean 1.22 ± 0.789) and this difference was statistically significant (MD -1.02, 95% CI - 1.75 to - 0.30). There was no difference in incidence of serious complications between the radial artery group (3.7%, n = 4) as compared to posterior tibial group (5.5%, n = 1, OR 0.57, 95% CI 0.06-5.51, p = 0.63). Peripheral arterial cannulation is a safe method for hemodynamic monitoring and blood sampling in sick neonates. Complications can be minimized by diligent monitoring and proactive removal of line if there is damping of tracing.


Limb salvage in the elderly.
Sixty-eight lower extremity bypass procedures for severe lower limb ischemia were undertaken on 53 patients of 75 years of age and over. The operative mortality was 4.4%. At two years cumulative limb salvage, patient survival, graft patency and survival with an intact limb were 77%, 72%, 44%, and 56%, respectively. Of all patients who died, 66% had an intact limb at the time of death. Based on these results we continue to offer reconstructive surgery to elderly patients.


Vasorelaxant properties of isolated human radial arteries: comparison with internal mammary arteries.
Radial arteries, used in revascularisation surgery, are prone to spasm. We have examined the ability of nitrovasodilators, calcium channel blockers, and K(ATP) channel openers to cause vasodilation, and to attenuate contractions due to depolarisation and receptor activation in radial and mammary arteries used in coronary artery bypass graft surgery. Two to three millimetre rings of artery obtained from patients at surgery were studied in organ baths in vitro. Constriction to KC1 and phenylephrine was examined before and again after treatment of the rings with drug or vehicle. Calcium channel blockers were the only compounds to inhibit contractions to both KC1 and phenylephrine. Sodium nitroprusside attenuated constriction to phenylephrine but not KC1 in both vessels. K(ATP) channel openers similarly attenuated constriction to phenylephrine in radial arteries but were much less effective in mammary arteries. These studies support the continued use of calcium blockers after revascularisation with radial artery but suggest that other classes of drug may be as effective at minimising spasm due to receptor mediated constriction.


Reproducibility of sphero-cylindrical prescriptions.
To investigate the reproducibility of the sphero-cylindrical prescriptions provided by 40 optometrists. Forty registered optometrists were randomly selected from the cities of Oxford and Westminster in the UK to perform a sphero-cylindrical refraction on an asymptomatic 29-year-old male subject. The 95% limits of reproducibility for each component of refraction were assessed and are presented together with scatterplots, distribution ellipsoids and polar profiles of dioptric power. The mean stigmatic (spherical equivalent) refraction for the right eye was -0.83 D (S.D. = 0.28 D) with 95% limits of agreement -1.38 and -0.28 D. The 95% reproducibility limits for stigmatic data [1.96(square root of 2) (S.D.)] was 0.78 D. The average inter-ocular difference in the stigmatic components of refraction was -0.044 D (S.D. = 0.20 D) but estimates ranged from -0.50 to +0.50 D. Mean ortho- and oblique antistigmatic refractions were -0.23 D (S.D. = 0.084 D) and -0.14 D (S.D. = 0.086 D) respectively. The findings of this paper suggest that refractions performed by multiple optometrists on a single eye will differ in their stigmatic component by over 0.78 D on average not more than once in 20 refractions. The reproducibility of refractions reported here, approximately twice as variable as those reported under repeatability conditions, has profound implications for the analysis of refractive data collected by multiple optometrists over the course of replication, longitudinal and epidemiological studies.


Immunosuppression by embryonic stem cells.
Embryonic stem cells or their progeny inevitably differ genetically from those who might receive the cells as transplants. We tested the barriers to engraftment of embryonic stem cells and the mechanisms that determine those barriers. Using formation of teratomas as a measure of engraftment, we found that semiallogeneic and fully allogeneic embryonic stem cells engraft successfully in mice, provided a sufficient number of cells are delivered. Successfully engrafted cells did not generate immunological memory; unsuccessfully engrafted cells did. Embryonic stem cells reversibly, and in a dose-dependent manner, inhibited T-cell proliferation to various stimuli and the maturation of antigen-presenting cells induced by lipopolysaccharide. Inhibition of both was owed at least in part to production of transforming growth factor-beta by the embryonic stem cells. Thus, murine embryonic stem cells exert "immunosuppression" locally, enabling engraftment across allogeneic barriers.


Simultaneous determination of nine major active compounds in Dracocephalum rupestre by HPLC.
A new method was developed for the simultaneous determination of nine major constituents in Dracocephalum rupestre, including 5,7-dihydroxychromone (1), eriodictyol-7-O-beta-d-glucoside (2), luteolin-7-O-beta-d-glucoside (3), naringenin-7-O-beta-d-glucoside (4), apigenin-7-O-beta-d-glucoside (5), eriodictyol (6), luteolin (7), naringenin (8) and apigenin (9). The quantitative determination was conducted by reversed phase high-performance liquid chromatography with photodiode array detector (LC-PDA). Separation was performed on an Agilent Eclipse XDB-C(18) column (150 mm x 4.6 mm i.d., 5 microm) with gradient elution of acetonitrile and 0.5% aqueous acetic acid. The components were identified by retention time, ultraviolet (UV) spectra and quantified by LC-PDA at 260 nm. All calibration curves showed good linearity (r(2)>0.999) within test ranges. The reproducibility was evaluated by intra- and inter-day assays and R.S.D. values were less than 3.0%. The recoveries were between 95.15 and 104.45%. The limits of detection (LOD) ranged from 0.002 to 0.422 microg/ml and limits of quantification (LOQ) ranged from 0.005 to 1.208 microg/ml, respectively. The identity of the peaks was further confirmed by high-performance liquid chromatography with triple-quadrupole mass spectrometry system coupled with electrospray ionization (ESI) interface. The developed method was applied to the determination of nine constituents in 14 samples of D. rupestre collected at various harvesting times. Most compounds accumulated at much higher amounts in about June-July. The satisfactory results indicated that the developed method was readily utilized as a quality control method for D. rupestre.


Short vein grafts: a superior option for arterial reconstructions to poor or compromised outflow tracts?
To determine whether vein graft length is a factor that influences infrapopliteal bypass patency, we reviewed 237 consecutive reversed saphenous vein bypasses performed because of critical ischemia during a 5-year period. One hundred seventeen long vein grafts (LVGs) were longer than 40 cm (42 to 92 cm, mean 60.9 +/- 9 cm) and 120 short vein grafts (SVGs) were 40 cm or shorter (6 to 40 cm, mean 24.7 +/- 8 cm). Ninety-three percent of the LVGs originated from or were proximal to the superficial femoral artery (SFA) whereas all of the SVGs originated at or distal to the SFA. The cumulative patency rate for LVGs at 3 years was 45% and for SVGs was 63% (p less than 0.025). In the absence of an intact pedal arch, 3-year patency rates for LVGs (51 cases) and SVGs (78 cases) were 22% and 53%, respectively (p less than 0.01). High intraoperative outflow resistance measurements (greater than 0.7 mm Hg/ml/min) were encountered in 25 cases. Of these, occlusion within 6 months occurred in six of seven cases with LVGs and in only 8 of 18 cases with SVGs (p less than 0.05). Wound complications at vein harvest sites occurred in 17% of LVGs and in only 6% of SVGs (p less than 0.01). Of 16 additional cases in which a proximal patch angioplasty or percutaneous transluminal angioplasty was performed tandem with a short distal vein graft, four occluded (less than 6 months) and 12 remained patent from 3 to 43 months (mean 12.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)


Risk of cardiovascular events leading to hospitalisation after Streptococcus pneumoniae infection: a retrospective cohort LIFE Study.
To elucidate the risk of cardiovascular event occurrence following Streptococcus pneumoniae infection. Retrospective cohort study using a LIFE Study database. Three municipalities in Japan. Municipality residents who were enrolled in either National Health Insurance or the Latter-Stage Elderly Healthcare System from April 2014 to March 2020. Occurrence of S. pneumoniae infection. Occurrence of one of the following cardiovascular events that led to hospitalisation after S. pneumoniae infection: (1) coronary heart disease (CHD), (2) heart failure (HF), (3) stroke or (4) atrial fibrillation (AF). S. pneumoniae-infected patients were matched with non-infected patients for each cardiovascular event. We matched 209 infected patients and 43 499 non-infected patients for CHD, 179 infected patients and 44 148 non-infected patients for HF, 221 infected patients and 44 768 non-infected patients for stroke, and 241 infected patients and 39 568 non-infected patients for AF. During follow-up, the incidence rates for the matched infected and non-infected patients were, respectively, 38.6 (95% CI 19.9 to 67.3) and 30.4 (29.1 to 31.8) per 1000 person-years for CHD; 69.6 (41.9 to 108.8) and 50.5 (48.9 to 52.2) per 1000 person-years for HF; 75.4 (48.3 to 112.2) and 35.5 (34.1 to 36.9) per 1000 person-years for stroke; and 34.7 (17.9 to 60.6) and 11.2 (10.4 to 12.0) per 1000 person-years for AF. Infected patients were significantly more likely to develop stroke (adjusted HR: 2.05, 95% CI 1.22 to 3.47; adjusted subdistribution HR: 1.94, 95% CI 1.15 to 3.26) and AF (3.29, 1.49 to 7.26; 2.74, 1.24 to 6.05) than their non-infected counterparts. S. pneumoniae infections elevate the risk of subsequent stroke and AF occurrence. These findings indicate that pneumococcal infections have short-term effects on patients' health and increase their midterm to long-term susceptibility to serious cardiovascular events.


Identification and initial characterization of transforming growth factor-like mitogen(s) in human anterior pituitary.
Transforming growth factor (TGFs) are a family of peptide(s) defined by their ability to induce anchorage-independent growth of non-neoplastic indicator cells in soft agar. We found that acid-ethanol extracts of human anterior pituitary tissues were able to stimulate colony growth of normal rat kidney fibroblasts in soft agar. When subjected to gel-filtration on a column of Bio-Gel P-60 in 1 M acetic acid, the majority of TGF activity eluted in fractions corresponding to an apparent mol wt 15,000. The activity was heat- and acid-stable, but was inactivated by treatment with trypsin and dithiothreitol. Pituitary TGF-like materials did not compete with epidermal growth factor (EGF) for receptor binding and did not require EGF for colony-forming activity. Thus, human pituitary TGF was not like type alpha or type beta TGF.


Phylogenetic Analysis of MERS-CoV in a Camel Abattoir, Saudi Arabia, 2016-2018.
We detected Middle East respiratory syndrome coronavirus (MERS-CoV) RNA in 305/1,131 (27%) camels tested at an abattoir in Al Hasa, Eastern Province, Saudi Arabia, during January 2016-March 2018. We characterized 48 full-length MERS-CoV genomes and noted the viruses clustered in MERS-CoV lineage 5 clade B.


Passion in hiking guides affects their group management skills and functional psychobiosocial experiences.
Using the individual zones of optimal functioning model as a conceptual framework, the purpose of this study was to examine the interplay between passion, perceived group management skills, and functional emotion-related (psychobiosocial) experiences in hiking guides. The participants were 60 Italian hiking guides, 47 men and 13 women, aged 32-74 years (M = 57.25, SD = 10.49). They were asked to fill in an online questionnaire containing measures of harmonious and obsessive passion, perceived group management skills, and psychobiosocial experiences. Path analysis results showed positive indirect effects of both harmonious passion and obsessive passion on psychobiosocial experiences via group management skills. Additional results from moderated moderation suggest that high levels of obsessive passion, combined with low levels of both harmonious passion and perceived group management skills, are associated with lower intensity levels of psychobiosocial experiences. The findings contribute to increasing our understanding of the overall experience of hiking guides, and the important role they play in motivating people to engage in physical activity in a natural environment.


Registered report: Discovery and preclinical validation of drug indications using compendia of public gene expression data.
The Science Translational Medicine in 2011 (Sirota et al., 2011). The key experiments being replicated include Figure 4C and D and Supplemental Figure 1. In these figures, Sirota and colleagues. tested a proof of concept experiment validating their prediction that cimetidine, a histamine-2 (H2) receptor agonist commonly used to treat peptic ulcers (Kubecova et al., 2011), would be effective against lung adenocarcinoma (Figure 4C and D). As a control they also tested the effects of cimetidine against renal carcinoma, for which it was not predicted to be efficacious (Supplemental Figure 1). The Reproducibility Project: Cancer Biology is a collaboration between the eLife.


In vitro evaluation of liposomes containing bio-enhancers for the oral delivery of macromolecules.
The aim of this work was to develop a new type of liposomes containing bio-enhancers for oral delivery of hydrophilic macromolecules. The study focused on EPC/cholesterol-based formulations combined with TPGS 1000 and 400, cholylsarcosine (CS), cetylpyridinium chloride (CpCl) and stearylamine (SA) covering a broad range of different types of enhancers. Most of the tested liposomal formulations and enhancers showed neither influence on cell viability in the Alamar Blue® assay nor an increase in lactate dehydrogenase LDH release. But, at a concentration of 1 mM, CpCl exhibited a strong toxicity after 2 h, TPGS 1000 reduced the cell viability at the same concentration after 8h significantly. Only one liposomal formulation with 25% CpCl led to a decrease in viability to 60.0% after 8h at a total lipid concentration of 5 mM. In the Caco-2 Transwell® model, one formulation with 5% TPGS 400 improved the permeation of FITC-dextran 70 kDa 3.34 ± 0.62-fold, one with 10% CpCl 3.69 ± 0.67 and one with 10% CS and 2.5% SA 3.41 ± 0.51-fold without influencing the TER. Liposomes with 10% SA or 25% CpCl increased the permeation of FITC-dextran 29.02 ± 5.84, respectively 39.28 ± 2.10-fold, but led also to a strong reduction in the TER. Especially, the three formulations which enhanced the permeation of FITC-dextran around 3.5-fold without showing any cell toxicity or decrease in TER should be safe and effective candidates for the development of an oral delivery system for hydrophilic macromolecules.


Analyzing matrices of meta-analytic correlations: current practices and recommendations.
Researchers have become increasingly interested in conducting analyses on meta-analytic correlation matrices. Methodologists have provided guidance and recommended practices for the application of this technique. The purpose of this article is to review current practices regarding analyzing meta-analytic correlation matrices, to identify the gaps between current and best practices, and to offer a comprehensive set of recommendations regarding the planning, collection, analysis, and interpretation of studies that utilize meta-analytic correlation matrices. Copyright © 2016 John Wiley & Sons, Ltd.


Direct thrombin inhibitors are not equally effective in vivo against arterial thrombosis: in vivo evaluation of DuP714 and argatroban in a porcine angioplasty model and comparison to r-hirudin.
Qualitative differences in antithrombotic efficacy between thrombin inhibitors may be explained by the affinity for which they bind thrombin. This affinity is inversely proportional to the inhibitory constant for the agent (Ki). Thrombin inhibitors, DuP714 (Ki=10(-11)) and argatroban (Ki=10(-8)), were compared to our previous studies with r-hirudin (Ki=10(-13)). Prior to balloon angioplasty, thirty pigs randomly received DuP714 (0.1 mg/kg bolus and 0.6 mg/kg/h infusion; n=8), argatroban (0.2 mg/kg/min. continuous infusion; n=9), or saline (n=17). Injured arterial segments were measured for (111)In-platelet and 125I-fibrin(ogen) deposition and the incidence of macroscopic thrombus. In DuP714-treated animals, platelet and fibrin(ogen) deposition were significantly lower than controls in both carotid (10+/-2 vs. 62+/-18 and 20+/-4 vs. 74+/-6) and coronary (10+/-4 vs. 160+/-63 and 17+/-3 vs. 86+/-22) arteries (p<0.005). In contrast, platelet and fibrin(ogen) deposition were similar when comparing argatroban to saline in carotid (41+/-20 vs. 40+/-9 and 71+/-5 vs. 49+/-7) and coronary (92+/-33 vs. 151+/-45 and 114+/-37 vs. 89+/-38) arteries (p=0.82 and 0.38, respectively). Compared to argatroban, fibrin(ogen) (p<0.001) and coronary platelet deposition (p<0.05) were significantly reduced in animals treated with DuP714 with no significant difference in carotid platelet deposition (p=0.10). Neither inhibitor prevented macroscopic thrombosis. In previous studies with r-hirudin in this model, platelet deposition was limited to a monolayer with complete inhibition of macroscopic thrombus. Direct thrombin inhibitors do not equally prevent arterial thrombosis. Qualitative differences may be explained in part by the affinity for which they bind thrombin.


Excitation of carotid body chemoreceptors by neuropeptide-Y.
Neuropeptide-Y (NPY) is a peptide co-localised with noradrenaline in many sympathetic nerves. Recently, it has been found in postganglionic sympathetic nerves running to blood vessels in the carotid body. When NPY is administered to cats by infusion into the arterial blood close to the carotid bodies, breathing is stimulated. This effect is abolished when the carotid sinus nerves are cut. Similar intra-carotid infusions of NPY can be demonstrated to increase the frequency of firing of chemoreceptor afferent nerves. However, NPY introduced into the blood vessels of the carotid body immediately prior to halting its blood flow does not modify the development of chemoreceptor discharge in response to developing asphyxia. The findings are consistent with NPY causing excitation of chemoreceptors by causing local vasoconstriction and stagnant asphyxia.


Fetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free fetal DNA in maternal plasma.
When a pregnant woman has an antibody with the potential to cause hemolytic disease of the fetus and newborn, it is beneficial to determine whether her fetus has the corresponding antigen to assess risk. In many countries this is now done routinely for RhD, by testing cell-free fetal DNA in the maternal plasma. Similar tests for K, C, c, and E are reported. Real-time quantitative polymerase chain reaction incorporating an allele-specific primer was developed for detecting the K allele of KEL and the C, c, and E alleles of RHCE. These methods were used to test DNA isolated from plasma of pregnant women with antibodies to K, C, c, or E. Accuracy of the tests was determined by comparing results with serologic tests performed on cord red blood cells (RBCs) after delivery or by molecular genotyping on DNA obtained from fetal cells. The K test incorporated an allele-specific primer with two locked nucleic acids and a mismatch. In 70 tests, including 27 K+ fetuses, only one false-negative and no false-positive results were obtained. The C, c, and E tests, performed on 13, 44, and 46 samples, respectively, gave rise to no false results. Reliable methods have been developed for predicting fetal K, C, c, and E phenotypes, by testing fetal DNA in the plasma samples of pregnant women whose RBCs lack the corresponding antigens. These methods are now being used routinely in a diagnostic service in the United Kingdom.


[Study of local changes in the structure of phage DNA by electron microscopy].
DNA of defective bacteriophage PBSX was studied by electron microscopy. The presence and distribution of sites containing local structure changes were revealed using antibodies specific for the DNA molecules modified in situ. These structural changes are related to the capsid geometry, but not to the DNA primary sequence.


[Do flame retardants increase the risk of non-Hodgkin lymphoma? The levels of polybrominated diphenyl ethers are increasing in the environment].
Adipose tissue levels of tetra-BDE (2,2',4,4' tetra-brominated diphenyl ether) were measured in 42 male or female cancer patients [19 with non-Hodgkin's lymphoma (NHL), 23 with malignant melanoma (MM)], and in 27 controls without a diagnosis of cancer. As compared with tetra-BDE concentrations in controls, those in the MM subgroup did not differ, but those in the NHL subgroup were higher. Subgrouping of the cancer patients by occupational categories showed professional car, bus and truck drivers (at possible risk of exposure to PBDEs used as flame retardants in vehicle manufacture) to have higher tetra-BDE levels than controls, but not computer operators (at possible risk of exposure to PBDEs used in VDUs). Due to the small size of the series, however, the results may solely be regarded as hypothesis-generating, and further studies are needed.


CRH-R1 and CRH-R2 differentially modulate dendritic outgrowth of hippocampal neurons.
Corticotropin-releasing hormone (CRH) has been implicated to be involved in the development of dendrites in brain. In the present study, we examined the effect of CRH on dendrite outgrowth in primary cultured hippocampal neurons and defined the specific CRH receptor subtype involved. Treatment of neurons with increasing concentration of CRH resulted in an increase in the total dendritic branch length (TDBL) of neurons compared with untreated neurons over 2-4 days period of treatment. These effects can be reversed by the specific CRH-R1 antagonist antalarmin but not by the CRH-R2 antagonist astressin 2B. Treatment of neurons with urocortin II, the exclusive CRH-R2 agonist, significantly decreased TDBL of the cultured neurons. These effects can be reversed by the CRH-R2 antagonist astressin 2B. Our results suggest that CRH-R1 and CRH-R2 differentially modulate the dendritic growth of hippocampal neurons in culture.


Exploring Mental Health and Psychosocial Well-Being in Recovered Jordanian Individuals With COVID-19: A Phenomenological Study.
COVID-19-related healthcare services focus primarily on medical and physical treatments. Related treatments for psychosocial and mental health needs have not been a priority for healthcare professionals. Understanding the process by which individuals who have recovered from COVID-19 adapt psychologically will allow better planning for mental healthcare and healthcare outcomes. The purpose of this study was to explore how recovered individuals with COVID-19 adapted to related psychological and social stressors during the infection period. A descriptive phenomenological approach was used to investigate a purposive sample of 13 individuals in Jordan who had recovered from COVID-19. Data were collected using semistructured interviews. Perceptions related to being diagnosed with COVID-19 were distinguished into four major themes: conscious awareness (acceptance, victimization, and normalizing), uncertainty (apprehension and poor communication), sources of psychosocial support (caring family, healthcare professionals' support, and self-grieving), and resilience (optimism, positive thinking, and spirituality). The findings of this study indicate the need to integrate psychosocial and mental healthcare services into healthcare plans provided to individuals with COVID-19 and similar pandemic infections.


Cutaneous stimulation at the ankle: a differential effect on proprioceptive postural control according to the participants' preferred sensory strategy.
Ankle movements can be partially encoded by cutaneous afferents. However, little is known about the central integration of these cutaneous signals, and whether individual differences exist in this integration. The aim of this study was to determine whether the effect of cutaneous stimulation at the ankle would differ depending on the participants' preferred sensory strategy appraised by relative proprioceptive weighting (RPw). Forty-seven active young individuals free of lower-limb injury stood on a force platform either barefoot or wearing a custom-designed bootee. Vibrations (60 Hz, 0.5 mm) were applied either to the peroneal tendons or to the lumbar paraspinal muscles. The barefoot RPw was strongly negatively correlated to the absolute change in RPw measured in the bootee condition (r = -0.81, P < 0.001). Participants were then grouped depending on their barefoot RPw value. The RPw was significantly higher in the bootee condition than in the barefoot condition only for participants with low barefoot RPw. The external cutaneous stimulation given by the bootee increased the weight of ankle proprioceptive signals only for participants with low barefoot RPw. This result confirmed that optimization of the ankle proprioceptive signals provided by cutaneous afferent stimulation has a differential effect depending on the participants' preferred sensory strategy.


NAPS Fusion: A framework to overcome experimental data limitations to predict human performance and cognitive task outcomes.
In the area of human performance and cognitive research, machine learning (ML) problems become increasingly complex due to limitations in the experimental design, resulting in the development of poor predictive models. More specifically, experimental study designs produce very few data instances, have large class imbalances and conflicting ground truth labels, and generate wide data sets due to the diverse amount of sensors. From an ML perspective these problems are further exacerbated in anomaly detection cases where class imbalances occur and there are almost always more features than samples. Typically, dimensionality reduction methods (e.g., PCA, autoencoders) are utilized to handle these issues from wide data sets. However, these dimensionality reduction methods do not always map to a lower dimensional space appropriately, and they capture noise or irrelevant information. In addition, when new sensor modalities are incorporated, the entire ML paradigm has to be remodeled because of new dependencies introduced by the new information. Remodeling these ML paradigms is time-consuming and costly due to lack of modularity in the paradigm design, which is not ideal. Furthermore, human performance research experiments, at times, creates ambiguous class labels because the ground truth data cannot be agreed upon by subject-matter experts annotations, making ML paradigm nearly impossible to model. This work pulls insights from Dempster-Shafer theory (DST), stacking of ML models, and bagging to address uncertainty and ignorance for multi-classification ML problems caused by ambiguous ground truth, low samples, subject-to-subject variability, class imbalances, and wide data sets. Based on these insights, we propose a probabilistic model fusion approach, Naive Adaptive Probabilistic Sensor (NAPS), which combines ML paradigms built around bagging algorithms to overcome these experimental data concerns while maintaining a modular design for future sensor (new feature integration) and conflicting ground truth data. We demonstrate significant overall performance improvements using NAPS (an accuracy of 95.29%) in detecting human task errors (a four class problem) caused by impaired cognitive states and a negligible drop in performance with the case of ambiguous ground truth labels (an accuracy of 93.93%), when compared to other methodologies (an accuracy of 64.91%). This work potentially sets the foundation for other human-centric modeling systems that rely on human state prediction modeling.


Inflammation and type 2 diabetes.
Low-grade inflammation is a common feature in subjects with type 2 diabetes (T2D). Heart disease, the metabolic syndrome and T2D all have in common the increased concentration of circulatory cytokines as a result of inflammation. Inflammatory cytokines are produced by different cell types and secreted into the circulation, where they regulate different tissues through their local, central and peripheral actions. This review focuses on C-reactive protein (CRP), a well-established marker of the development of inflammation, on tumour necrosis factor (TNF)-α, an inflammatory marker strongly associated with diabetes, and on adiponectin, a cytokine produced by adipose tissue and associated with insulin sensitivity. While it is clear from the literature that these cytokines play a major role in the development of T2D or, in the case of adiponectin, its prevention, the best strategy for favourably altering the inflammatory response is still a matter of debate.


Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison.
Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions. In contrast, four of the five clear cell adenocarcinomas contained prominent areas with clear cells. Nephrogenic adenomas generally showed only mild cytologic atypia, whereas four of the five clear cell adenocarcinomas showed severe atypia. A single mitotic figure was identified in only two of the nephrogenic adenomas, whereas the mitotic rate in the clear cell adenocarcinomas ranged from 2 to 14 per 10 high-power fields. None of the nephrogenic adenomas showed evidence of necrosis, but focal necrosis was noted in four of the five clear cell adenocarcinomas. In general, the nephrogenic adenomas and clear cell adenocarcinomas showed negative to weak staining with CK903 but strong staining with AE1, AE3, and Cam 5.2. Variable staining was observed with Brst-3 and antibodies to S-100, CEA (monoclonal and polyclonal), LeuM-1, and CA19.9. Nephrogenic adenomas and clear cell adenocarcinomas were all negative for prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and estrogen and progesterone receptors (except for two nephrogenic adenomas, which showed only focal weak staining for estrogen receptor). Neither bcl-2 nor c-erbB-2 staining was able to discriminate between the tumors. However, strong staining for p53 was noted in each clear cell adenocarcinoma and in none of the nephrogenic adenomas. MIB-1 positivity in nephrogenic adenomas ranged from 0 to 13 (average of 5.5) per 200 cells, whereas the positive range for clear cell adenocarcinomas was 33 to 70 (average of 47) per 200 cells. In summary, histopathologic features that favor clear cell adenocarcinoma over nephrogenic adenoma include a predominance of clear cells, severe cytological atypia, high mitotic rate, necrosis, high MIB-1 positivity, and strong staining for p53.


Effects of intermittent versus continuous dieting on weight and body composition in obese and overweight people: a systematic review and meta-analysis of randomized controlled trials.
Intermittent dieting may be an alternative to continuous dieting for weight reduction. To evaluate the effect of intermittent dieting versus continuous dieting on weight and body composition in overweight or obese adults. A systematic review and meta-analysis of randomized controlled trials (RCTs). Five databases were searched until February 2018 for RCTs comparing intermittent versus continuous dieting. Intermittent dieting consisted of two types: regular intermittent was caloric restriction interspersed with days of weight maintenance or ad libitum eating; intensified intermittent was caloric restriction interspersed with days of even lower caloric restriction. Continuous was continual caloric restriction. Primary outcomes were weight, body fat, lean mass, waist circumference, hip circumference, and energy expenditure. Data were pooled by the inverse variance method using random-effects models and expressed as mean differences (MD) and their 95% confidence intervals (CI). Nine trials met the inclusion criteria (n = 782), six comparing regular intermittent vs continuous (n = 553), and three comparing intensified intermittent vs continuous (n = 229). Populations were heterogeneous: obese only in five studies, and overweight or obese (mixed) in four studies. Lean mass was significantly lower in regular intermittent vs continuous (MD -0.86 kg; 95% CI -1.62 to -0.10; p = 0.03). No differences were found for the remaining outcomes for both comparisons (regular intermittent or intensified intermittent vs continuous). There was low heterogeneity of effects across trials. Subgroup effects by time to follow-up, gender, per-protocol versus intention-to-treat, enforced exercise, and diabetes were similar to main analyses. This systematic review in obese and overweight individuals showed that regular intermittent dieting decreased lean mass compared to continuous dieting. There were no differences in effects for either intermittent vs continuous interventions across all other outcomes. In contrast to previous systematic reviews, this study suggested that lean mass is better preserved in continuous dieting compared to regular intermittent dieting.


Performance of enhanced anaerobic digestion with different pyrolysis biochars and microbial communities.
Anaerobic digestion (AD) is commonly used to treat biowastes, however, there are challenges in AD such as low methane yield, intermediate inhibition, and system instability. In this study, the effects of typical biochars on methane yield and microbial variation for AD with straw and cow manure were explored. The results indicated that cumulative methane yield with coconut shell biochar was higher than that without a biochar (319.44 vs. 282.77 mL/g VS). Interestingly, AD with biochars had a secondary methane yield peak, whereas control groups did not show this phenomenon. A suitable dosage (e.g., straw biochar of 2%) improved cumulative methane yield, but excessive addition (4%) could inhibit AD. AD system with biochar was more helpful for the growth of acetoclastic methanogens rather than hydrogenotrophic methanogens. The study demonstrated biochar can indeed enhance AD performance, and microbial community analyses could supply valuable information to elucidate the mechanism of enhancement.


In cervical arthroplasty, only prosthesis with flexible biomechanical properties should be used for achieving a near-physiological motion pattern.
In cervical arthroplasty, qualitative motion analysis generally investigates the position of the center of rotation (COR) before and after surgery. But is the pre-op COR suitable as reference? We believe that only a comparison against healthy individuals can answer whether a physiological motion pattern has been achieved. The aim of our study was to examine how the COR for flexion/extension after insertion of 3 biomechanically completely different types of disc prostheses compares to healthy volunteers, and whether and how prosthesis design contributes to a more natural or maybe even worse motion pattern. In 15 healthy volunteers, MRI in flexion and in extension was taken, and the coordinates for the CORs (COR-HV) from C3 to C7 were determined. Then pre- and post-op flexion/extension x-rays from 30 patients with a one-level disc prosthesis underwent analysis for determination of COR from C3 to C7; 10 patients who received a Bryan, a Prestige STLP, or a Discover prosthesis were chosen, respectively. Change of post-op COR position was investigated in relation to the COR-HV. The pre-operative COR is not congruent with the COR found in healthy subjects and therefore cannot be used as reference for investigation whether a disc prosthesis resembles natural motion. However, the comparison with healthy individuals shows that prosthesis insertion can change the coordinates of the COR to any direction in all levels from C3/4 to C6/7 regardless of the operated segment. Prostheses with flexible biomechanical properties can contribute to shift the COR toward normal, but devices with unphysiological biomechanical design, like fixed ball socket designs, for instance, can make the motion pattern even worse. Even if the small cohorts in our study do not allow strong conclusions, it seems that in cervical arthroplasty, the biomechanical concept of the prosthesis has a significant impact whether a near-physiological motion pattern can be achieved or not. As it is a rumor but not scientifically proven that prosthesis design has no influence on clinical outcome, surgeons should only choose devices with flexible biomechanical properties for disc replacement.