Genome-wide scan of Graves' disease: evidence for linkage on chromosome 5q31 in Chinese Han pedigrees.
Graves' disease (GD), which is a common organ-specific autoimmune disorder, is multifactorial and develops in genetically susceptible individuals. Despite many studies of candidate genes, only associations with human leukocyte antigen and cytotoxic T lymphocyte antigen 4 have been generally detected, and the number of susceptibility genes remains unknown. To identify chromosomal regions contributing to GD, we conducted a genome-wide scan on 322 individuals from 54 Chinese Han multiplex GD pedigrees. Parametric linkage analysis revealed the strongest evidence for linkage at D5S436 on chromosome 5q31, with a maximum two-point LOD score of 2.8 and a maximum multipoint LOD score of 2.3. To further assess the significance of this suggestive finding, we typed four additional markers around D5S436 in this chromosome region, and a maximum two-point LOD score of 4.31 and a maximum multipoint LOD score of 4.12 were obtained for marker D5S2090 (with heterogeneity, = 0.38). Nonparametric multipoint analysis also showed significant excess allele sharing, with a P value as low as 0.001, at the same locus. Our findings provide evidence for a susceptibility locus for GD on chromosome 5q31 and support the existence of genetic heterogeneity in GD.


Enhancing body image in motherhood: A randomised controlled trial of Expand Your Horizon among mothers of young children.
Motherhood can increase vulnerability to body dissatisfaction, but positive body image interventions may mitigate this. Expand Your Horizon (Alleva et al., 2015), an online writing intervention, enhances functionality appreciation, an aspect of positive body image. The intervention's demonstrated efficacy and focus on body functionality indicate its potential use among mothers. However, its original 3-session format may be unfeasible for mothers alongside other commitments. Thus, we tested the impact of a single 15-minute Expand Your Horizon session on state body appreciation and functionality appreciation. Mothers (N = 143) of 0-10-year-olds were randomly allocated to either the intervention group, or an active control group. State body appreciation and functionality appreciation were assessed pre- and post-intervention. Trait self-compassion was tested as a potential moderator. Participants who completed Expand Your Horizon reported greater state body appreciation and functionality appreciation post-intervention than those in the control group. Self-compassion moderated the intervention's effect on state functionality appreciation, with effects strongest for those with lower levels of self-compassion. Overall, findings support the intervention's suitability for mothers, particularly those with low self-compassion. Practical implications include possibly tailoring Expand Your Horizon and similar interventions to benefit all mothers. Future research directions include longitudinal and qualitative designs, and extension to other specific populations.


No persistent effect of intravenous immunoglobulins in patients with narcolepsy with cataplexy.
We report on four patients with narcolepsy with cataplexy (NC), who were treated with high-dose intravenous immunoglobulins (IVIg). Although in some patients transient effects were seen of both objective (multiple sleep latency test and maintenance of wakefulness test) and subjective symptoms (Epworth Sleepiness Scale and frequency of cataplexy), these effects lasted at the most for a few weeks and did not persist. Our report challenges the recent observations of a favorable and persistent effect of IVIg in NC patients.


Complementation between urokinase-producing and receptor-producing cells in extracellular matrix degradation.
The respective roles of urokinase plasminogen activator (u-PA) and the u-PA receptor in extracellular matrix degradation was investigated. Human pro-u-PA and the human u-PA receptor were expressed independently by two different mouse LB6 cell lines. The matrix degradation capacity of these cell lines individually or in coculture was studied. Although pro-u-PA-producing cells alone degrade the matrix in the presence of plasminogen, u-PA-receptor producing cells do not. Cocultivation of a small fraction of pro-u-PA-producing cells with the receptor-producing cells increases the rate of matrix degradation at least threefold. By immunoprecipitation it was shown that cocultivation of the two cell lines increases the conversion of the inactive pro-u-PA to the active two chain u-PA. The enhancement of matrix degradation and of pro-u-PA activation requires actual binding of pro-u-PA to its receptor because it is inhibited by u-PA-receptor antagonists. The u-PA receptor must be cell associated, as binding of pro-u-PA to a receptor solubilized from the cell surface with phosphatidyl-inositol specific phospholipase C did not enhance the activation of pro-u-PA in the presence of plasminogen. The finding that activity of u-PA is enhanced when it is bound to its receptor, even when the receptor is produced by a different cell, might have important implications for the mechanisms of u-PA-induced extracellular proteolysis in vivo.


Effects of a one-year high-intensity versus low-intensity resistance training program on bone mineral density in older women.
The purpose of this study was to determine the effects of a 12-month resistance training program, of two different intensities, on bone mineral density (BMD) in healthy, older women. Twenty-six Caucasian women (aged 65-79 years) completed the study. Subjects were randomly assigned to one of three groups: high-intensity (HI; n = 8), low-intensity (LI; n = 7), and control (CON; n = 11). The active groups performed 10 exercises, 3 days/week under supervision. Exercise intensity was maintained at 80% of one-repetition maximum (1-RM) for the HI groups, and at 40% 1-RM for the LI group. The volume of work was maintained constant between the two groups by assigning the LI group twice as many repetitions for each exercise. Maximal muscular strength and BMD of the lumbar spine and total hip were measured at baseline and at 12 months. Strength was evaluated using the 1-RM method, and BMD was determined by dual-energy X-ray absorptiometry. Exercise session attendance was similar for the two groups (81.0% HI; 76.8% LI). Muscular strength improved in the exercisers compared with the CON group (p < or = 0.05). Percentage change in lumbar spine BMD was 0.7 +/- 1.9%, 0.5 +/- 2.4%, and -0.1 +/- 2.3% for the HI, LI, and CON groups, respectively. Percentage change in total hip BMD was 0.8 +/- 2.3% (HI), 1.0 +/- 1.7% (LI), and 0.9 +/- 1.3% (CON). Group differences in BMD change were not significant (p > 0.05). These findings suggest that high-intensity and low-intensity resistance training regimens effectively increase muscular strength, but not lumbar spine or total hip BMD, in healthy, older women.


Effect of some thiocarbamate compounds on aldehyde dehydrogenase and implications for the disulfiram ethanol reaction.
The effects of S-methyl diethyldithiocarbamate, S-methyl diethylmonothiocarbamate and bis(diethylcarbamoyl) disulphide on sheep liver cytoplasmic aldehyde dehydrogenase were investigated in vitro. The first compound has negligible effect. The second one is a weak inhibitor of the esterase activity of the enzyme and a weaker inhibitor of the dehydrogenase activity. A very low concentration of the third compound, however, acts as a potent inactivator of aldehyde dehydrogenase, similar in this respect to disulfiram, although somewhat slower to react. The possible involvement of these compounds in the physiological phenomenon known as the disulfiram ethanol reaction is discussed.


Do rebreathing manoeuvres for non-invasive measurement of cardiac output during maximum exercise test alter the main cardiopulmonary parameters?
Inert gas rebreathing has been recently described as an emergent reliable non-invasive method for cardiac output determination during exercise, allowing a relevant improvement of cardiopulmonary exercise test clinical relevance. For cardiac output measurements by inert gas rebreathing, specific respiratory manoeuvres are needed which might affect pivotal cardiopulmonary exercise test parameters, such as exercise tolerance, oxygen uptake and ventilation vs carbon dioxide output (VE/VCO2) relationship slope. We retrospectively analysed cardiopulmonary exercise testing of 181 heart failure patients who underwent both cardiopulmonary exercise testing and cardiopulmonary exercise test+cardiac output within two months (average 16 ± 15 days). All patients were in stable clinical conditions (New York Heart Association I-III) and on optimal medical therapy. The majority of patients were in New York Heart Association Class I and II (78.8%), with a mean left ventricular ejection fraction of 31 ± 10%. No difference was found between the two tests in oxygen uptake at peak exercise (1101 (interquartile range 870-1418) ml/min at cardiopulmonary exercise test vs 1103 (844-1389) at cardiopulmonary exercise test-cardiac output) and at anaerobic threshold. However, anaerobic threshold and peak heart rate, peak workload (75 (58-101) watts and 64 (42-90), p < 0.01) and carbon dioxide output were significantly higher at cardiopulmonary exercise testing than at cardiopulmonary exercise test+cardiac output, whereas VE/VCO2 slope was higher at cardiopulmonary exercise test+cardiac output (30 (27-35) vs 33 (28-37), p < 0.01). The similar anaerobic threshold and peak oxygen uptake in the two tests with a lower peak workload and higher VE/VCO2 slope at cardiopulmonary exercise test+cardiac output suggest a higher respiratory work and consequent demand for respiratory muscle blood flow secondary to the ventilatory manoeuvres. Accordingly, VE/VCO2 slope and peak workload must be evaluated with caution during cardiopulmonary exercise test+cardiac output.


Life in the Current: Anatomy and Morphology of Utricularia neottioides.
Rheophytism is extremely rare in the Utricularia genus (there are four strictly rheophytic species out of a total of about 260). Utricularia neottioides is an aquatic rheophytic species exclusively growing attached to bedrocks in the South American streams. Utricularia neottioides was considered to be trap-free by some authors, suggesting that it had given up carnivory due to its specific habitat. Our aim was to compare the anatomy of rheophytic U. neottioides with an aquatic Utricularia species with a typical linear monomorphic shoot from the section Utricularia, U. reflexa, which grows in standing or very slowly streaming African waters. Additionally, we compared the immunodetection of cell wall components of both species. Light microscopy, histochemistry, scanning, and transmission electron microscopy were used to address our aims. In U. neottioides, two organ systems can be distinguished: organs (stolons, inflorescence stalk) which possess sclerenchyma and are thus resistant to water currents, and organs without sclerenchyma (leaf-like shoots), which are submissive to the water streaming/movement. Due to life in the turbulent habitat, U. neottioides evolved specific characters including an anchor system with stolons, which have asymmetric structures, sclerenchyma and they form adhesive trichomes on the ventral side. This anchor stolon system performs additional multiple functions including photosynthesis, nutrient storage, vegetative reproduction. In contrast with typical aquatic Utricularia species from the section Utricularia growing in standing waters, U. neottioides stems have a well-developed sclerenchyma system lacking large gas spaces. Plants produce numerous traps, so they should still be treated as a fully carnivorous plant.


Quality of Life in Patients With Breast Cancer: The Influence of Family Caregiver's Burden and the Mediation of Patient's Anxiety and Depression.
Previous research showed that family caregiver's perception of burden can influence patient's report on their quality of life (QoL). The present study investigated the relationship between the two variables by considering the role of patient's anxiety and depression. A total of 382 dyads of Chinese breast cancer patients and their family caregivers participated in this study. The results showed that the mediation model fitted the data well (χ = 49.859; df = 16; χ/df = 3.116; RMSEA = 0.05; TLI = 0.928; CFI = 0.959). It indicated that family caregiver's burden influenced patient's QoL negatively, and this relationship was partially mediated by patient's anxiety and depression.


Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice.
Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investigated whether DXM could reduce macrophage production of cytokines and superoxide and the resultant influence on atherosclerosis formation in mice. We used in vitro and in vivo studies to evaluate the DXM inhibitory effect on oxidative stress. Dextromethorphan pretreatment significantly suppressed the production of tumour necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, interleukin-10, and superoxide in macrophage cell culture after stimulation. Indeed, DXM reduced macrophage nicotinamide adenine dinucleotide phosphate oxidase activity by decreasing membrane translocation of p47(phox) and p67(phox) through the inhibition of protein kinase C and extracellular signal-regulated kinase activation. The anti-atherosclerosis effect of DXM was tested using two animal models, apolipoprotein E (apoE)-deficient mice and a mouse carotid ligation model. Dextromethorphan treatment (10-40 mg/kg/day) for 10 weeks in apoE-deficient mice significantly reduced superoxide production in their polymorphonuclear leukocytes and aortas. It significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and decreased carotid neointima formation after ligation in C57BL/6 mice. Our data show that DXM, with its novel effect in reducing oxidative stress, significantly reduces atherosclerosis and neointima formation in mice.


Simultaneous NO and NO(2) DIAL measurement using BBO crystals.
We report a new differential absorption lidar technique for measuring simultaneously the concentrations of NO and NO(2) in the atmosphere. The technique is based on the correlation of the 450-nm absorption band of NO(2) and 227-nm absorption band of NO by frequency doubling. This performance has been allowed by the advent of a new and highly efficient frequency doubling crystal: the beta-BaB(2)O(4). A test experiment on a NO/NO(2) emitter has been performed, demonstrating the efficiency of the technique. The detection limit is estimated to be ~1 ppm .m for NO(2) and 100 ppb.m for NO. The range of measurement is limited to 1 km, due to the strong UV Rayleigh scattering and O(2) absorption.


Specialist versus primary care: not an easy question.
The central focus in the debate to reform our nation's health care system is on cost, quality, and access. There is general agreement that there are too many specialists in the wrong places, which is said to contribute to the rising cost of health care. Physician profiling has supported the concept that some specialists are more costly than primary care physicians, although the severity of illness in patients treated by specialists may often be greater. Increasing the number of primary care providers may be a solution to reduce costs and will clearly improve access. The study reported in this article was carried out to examine the efficiency of primary care physicians and endocrinologists, a specialty that has been cited as one in which resource utilization is high, in caring for hospital inpatients with diabetic ketoacidosis.


Indirect Haemagglutination Test in Comparison with ELISA for Detection of Antibodies against Invasive Amoebiasis.
Diagnosis of amoebiasis is based on combination of tests like microscopy, imaging, serology and molecular methods. In absence of molecular techniques, serology can be used as an alternative aid. Various serological techniques were reported with different sensitivity and specificity. The diagnostic efficiency of these assays mainly depends on the characteristics of antigen that is being used and various conditions of performance. To evaluate the efficiency of recombinant calcium binding domain containing protein by Indirect Haemagglutination Assay (IHA) against a commercial ELISA among amoebic liver abscess cases and control group. The study was carried out during the period of 2011-2015 and blood samples were collected from suspected amoebiasis cases who were attending the clinics of Medicine and Paediatrics department, JIPMER. A total of 200 sera samples which included 100 Amoebic Liver Abscess (ALA), 50 cases of other parasitic infections and liver diseases and 50 presumed healthy controls were examined by IHA and commercial ELISA. In brief, chick cells were stabilized by Double Aldehyde Sensitization (DAS) method. Optimum Sensitizing Dose (OSD) of the antigen was determined. The test was performed in a U-bottomed microtiter plate with recombinant amoebic antigen (12.5μg/ml), incubated at Room Temperature (RT) for 2 hours. RIDASCREEN Entamoeba IgG ELISA kit which is commercially available was used to evaluate the samples as per manufacturer's instruction. The overall sensitivity and specificity of the IHA was 62% and 96%, respectively when compared to ELISA having sensitivity and specificity of 69% and 90%, respectively. The positive predictive value of the IHA was 91% while negative predictive value was 79%. Similarly, the positive predictive value of the ELISA was 87% while negative predictive value was 74%. As serology heavily suffers due to lack of a standardised test system employing the native antigen, there arises need to identify alternative source of recombinant antigen which could effectively improvise the existing lacunae in the current system. Serology acts as an adjunct in clinical decision making if properly interpreted. This is an important consideration in endemic region where health services resources are limited.


Geometrical flexibility of platinum nanoclusters: impacts on catalytic decomposition of ethylene glycol.
Catalytic decomposition of ethylene glycol on the Pt13 cluster was studied as a model system for hydrogen production from a lignocellulosic material. Ethylene glycol was chosen as a starting material because of two reasons, it is the smallest oxygenate with a 1 : 1 carbon to oxygen ratio and it contains the C-H, O-H, C-C, and C-O bonds also present in biomass. Density functional theory calculations were employed for predictions of reaction pathways for C-H, O-H, C-C and C-O cleavages, and Brønsted-Evans-Polanyi relationships were established between the final state and the transition state for all mechanisms. The results show that Pt13 catalyzes the cleavage reactions of ethylene glycol more favourably than a Pt surface. The flexibility of Pt13 clusters during the reactions is the key factor in reducing the activation barrier. Overall, the results demonstrate that ethylene glycol and thus biomass can be efficiently converted into hydrogen using platinum nanoclusters as catalysts.


Boolean modeling: a logic-based dynamic approach for understanding signaling and regulatory networks and for making useful predictions.
The biomolecules inside or near cells form a complex interacting system. Cellular phenotypes and behaviors arise from the totality of interactions among the components of this system. A fruitful way of modeling interacting biomolecular systems is by network-based dynamic models that characterize each component by a state variable, and describe the change in the state variables due to the interactions in the system. Dynamic models can capture the stable state patterns of this interacting system and can connect them to different cell fates or behaviors. A Boolean or logic model characterizes each biomolecule by a binary state variable that relates the abundance of that molecule to a threshold abundance necessary for downstream processes. The regulation of this state variable is described in a parameter free manner, making Boolean modeling a practical choice for systems whose kinetic parameters have not been determined. Boolean models integrate the body of knowledge regarding the components and interactions of biomolecular systems, and capture the system's dynamic repertoire, for example the existence of multiple cell fates. These models were used for a variety of systems and led to important insights and predictions. Boolean models serve as an efficient exploratory model, a guide for follow-up experiments, and as a foundation for more quantitative models.


Advanced Concepts in the Pathophysiology of Obstructive Sleep Apnea.
The primary pathological event in the disorder obstructive sleep apnea (OSA) is the partial or complete closure of the pharyngeal airway during sleep in an individual with a widely patent airway during wakefulness. This yields an apnea or hypopnea with resulting hypoxia and hypercapnia, and most often requires an arousal to terminate the event. These events occur in a repetitive manner during sleep, yielding intermittent hypoxia and sleep fragmentation with their associated adverse effects on the health and quality of life of the afflicted individual. Here, we focus on the events leading up to these apneas and hypopneas, primarily addressing pharyngeal anatomy, upper airway muscle control, the respiratory arousal threshold, and ventilatory control instability in OSA pathophysiology.


Cytoskeletal interactions determine the electrophysiological properties of human EAG potassium channels.
The electrophysiological properties of ether a go-go (EAG) potassium channels are modified during the cell cycle when they are expressed in heterologous systems. In Chinese hamster ovary (CHO) mammalian somatic cells we found that the cell-cycle-dependent modulation of human EAG (hEAG) channels occurs during the M phase. This modulation has three components: reduction in current density, increased sensitivity to block by intracellular sodium, and increased selectivity for potassium ions. In this work, these three properties have been used to define the mitotic phenotype of EAG currents. The signaling pathway leading to such changes of channel properties is unknown. We tested the hypothesis that cytoskeletal interactions might affect the electrophysiological changes observed during the cell cycle. The disruption of actin filaments induces a significant increase in current density, without inducing the cell-cycle-related phenotype. In contrast, disturbance of the microtubules, achieved by pharmacological means or by mechanical excision of the membrane patch, does induce the cell-cycle-related phenotype. Our results demonstrate that hEAG channels establish complex interactions with cytoskeletal elements, and that these interactions strongly influence the properties of the channels. We also conclude that the electrophysiological changes observed during the cell cycle are most likely due to reorganization of the cytoskeleton during the G2/M transition.


Idebenone in Friedreich's ataxia.
Friedreich's ataxia is an autosomal recessive neurodegenerative disease where impaired mitochondrial function and excessive production of free radicals play a central pathogenetic role. Idebenone, a synthetic analogue of coenzyme Q, is a powerful antioxidant that was first administrated to Friedreich's ataxia patients less than 10 years ago. The aim of this study was to evaluate the efficacy of idebenone administration and define the optimal dosage. A critical evaluation of all open and double-blinded idebenone trials in Friedreich's ataxia patients was undertaken. Idebenone is well tolerated in paediatric and adult patients. Most trials demonstrated a positive effect on cardiac hypertrophy. The neurological function is in general not modified in adult patients, but a dose-dependent effect was demonstrated in young Friedreich's ataxia patients. Further double-blinded high-dose trials should evaluate idebenone in Friedreich's ataxia early in the disease course.


Associations between Bystanders and Perpetrators of Online Hate: The Moderating Role of Toxic Online Disinhibition.
Hatred directed at members of groups due to their origin, race, gender, religion, or sexual orientation is not new, but it has taken on a new dimension in the online world. To date, very little is known about online hate among adolescents. It is also unknown how online disinhibition might influence the association between being bystanders and being perpetrators of online hate. Thus, the present study focused on examining the associations among being bystanders of online hate, being perpetrators of online hate, and the moderating role of toxic online disinhibition in the relationship between being bystanders and perpetrators of online hate. In total, 1480 students aged between 12 and 17 years old were included in this study. Results revealed positive associations between being online hate bystanders and perpetrators, regardless of whether adolescents had or had not been victims of online hate themselves. The results also showed an association between toxic online disinhibition and online hate perpetration. Further, toxic online disinhibition moderated the relationship between being bystanders of online hate and being perpetrators of online hate. Implications for prevention programs and future research are discussed.


Unveiling the surface epitopes that render tissue inhibitor of metalloproteinase-1 inactive against membrane type 1-matrix metalloproteinase.
Membrane type 1-matrix metalloproteinase (MT1-MMP) is a zinc-dependent, membrane-associated endoproteinase of the metzincin family. The enzyme regulates extracellular matrix remodeling and is capable of cleaving a wide variety of transmembrane proteins. The enzymatic activity of MT1-MMP is regulated by endogenous inhibitors, the tissue inhibitor of metalloproteinases (TIMP). To date, four variants of mammalian TIMP have been identified. Whereas TIMP-2-4 are potent inhibitors against MT1-MMP, TIMP-1 displays negligible inhibitory activity against the enzyme. The rationale for such selectivity is hitherto unknown. Here we identify the surface epitopes that render TIMP-1 inactive against MT1-MMP. We show that TIMP-1 can be transformed into an active inhibitor against MT1-MMP by the mutation of a single residue, namely threonine 98 to leucine (T98L). The resultant mutant displayed inhibitory characteristics of a typical slow, tight binding inhibitor. The potency of the mutant could be further enhanced by the introduction of valine 4 to alanine (V4A) and proline 6 to valine (P6V) mutations. Indeed, the inhibitory profile of the triple mutant (V4A/P6V/T98L) is indistinguishable from those of other TIMPs. Our findings suggest that threonine 98 is critical in initiating MMP binding and complex stabilization. Our findings also provide a potential mechanistic explanation for MMP-TIMP selectivity.


Copper-Catalyzed Asymmetric Allylation of N-Aryl Aldimines.
The copper-catalyzed enantioselective allylation reaction of N-aryl aldimines has been developed using a combination of Cu(OAc)2 and SPINOL-based phosphonamidite. This protocol significantly broadens the substrate scope, such that imines bearing various ortho-substituents on the N-aryl were converted smoothly into homoallylic amines in up to 99% yield and 98% ee. Taking advantage of the diversity of the N-aryl motif, three kinds of N-heterocyclic compounds were constructed, respectively, from the corresponding homoallylic amines in merely one step.


Duration of antidepressant use during pregnancy and risk of major congenital malformations.
Antidepressant use during the gestational period is a controversial topic. To determine whether duration of antidepressant use during the first trimester increases the risk of major congenital malformations in offspring of women diagnosed with psychiatric disorders. A case-control study was performed among women who had been pregnant between January 1998 and December 2002. Data were obtained from a Medication and Pregnancy registry, built by linking three databases from the province of Quebec, and a self-administered questionnaire. Women eligible for this study had to be 15-45 years old at the beginning of pregnancy, have at least one diagnosis of psychiatric disorder before pregnancy, have used antidepressants for > or =30 days in the year prior to pregnancy and have a pregnancy ending with a delivery. Cases were defined as any major congenital malformation diagnosed in the offspring's first year of life. Odds ratios, adjusted for relevant confounders, were estimated using logistic regression. Among the 2329 women meeting the inclusion criteria, 189 (8.1%) infants were born with a major congenital malformation. Duration of antidepressant use during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations: 1-30 days v. 0 day, adjusted OR=1.23 (95% CI 0.77-1.98); 31-60 days v. 0 day, adjusted OR=1.03 (95% CI 0.63-1.69); > or =61 days v. 0 day, adjusted OR=0.92 (95% CI 0.50-1.69). These data do not support an association between duration of antidepressant use during the first trimester of pregnancy and major congenital malformations in the offspring of women with psychiatric disorders. These findings should help clinicians decide whether to continue antidepressant therapy during pregnancy.


Educational needs and challenges in axial spondyloarthritis.
Axial spondyloarthritis (axSpA) affects 0.5-1% of the population in many regions of the world. This review summarizes the challenges in medical education around axSpA with attention to evidence around delayed diagnosis, clinician familiarity with typical axSpA features, such as inflammatory back pain and adherence to accepted management principles. Clinicians who commonly manage patients with chronic back pain or other typical axSpA features are not consistently aware of the concept of inflammatory back pain and common extra-spinal manifestations. Further, clinicians may not be familiar with the nonradiographic spectrum of axSpA. Management of patients with possible axSpA does not consistently follow principles that would establish an axSpA diagnosis, and diagnosis of axSpA remains delayed by 6-7 years on average, with evidence suggesting management disparities on the basis of sex and race in some cases. Referral recommendations have increased the probability of axSpA diagnosis up to about 40% and, may complement educational efforts in axSpA. Educational efforts in axSpA should focus on providing front-line clinicians with a better understanding of inflammatory back pain, the nonradiographic form of axSpA, and accepted principles in axSpA management.


Transformative Learning in Graduate Medical Education: A Scoping Review.
Transformative learning (TL) is an educational theory focused on deep fundamental shifts in an individual's worldview. Such shifts are well known to occur within graduate medical education (GME). However, TL in GME has yet to be formally explored. We performed a scoping review of the literature on TL within GME to identify areas where trainees currently experience or have potential to experience TL, and to explore areas where fostering TL has been used as a pedagogical tool. In January 2020, we searched 7 databases to identify literature on TL in GME. Additional articles were identified by hand-searching the Journal of Graduate Medical Education. A total of 956 articles were identified through database search with 3 unique articles found via hand-searching. Abstracts and manuscripts were screened by 2 authors and disagreements arbitrated by a third, yielding 28 articles for our analysis. The main components of TL (disorienting dilemma, reflection, discourse, action) took various forms. TL was closely linked with professionalism training and professional identity formation. Training programs in primary care fields were most frequently referenced. Often, trainees were experiencing TL without recognition of the theory by their educators. Gaps in the graduate medical education literature exist pertaining to TL in venues such as diversity, equity, and inclusion. Our scoping review uncovered the following themes: TL and professionalism, TL and primary care, and TL by other names. TL is likely occurring but going unrecognized in some settings.


Computer-based technique for cell aggregation analysis and cell aggregation in in vitro chondrogenesis.
No quantitative methods are currently available to measure different aggregation parameters in cell cultures. In this paper we describe a computer-based technique for the automatic and reliable analysis of cellular aggregates, starting from optical microscopy images of living cells grown in suspension. The method allows determination, on the same sample at different time intervals, of quantitative parameters, including aggregation percentage, average number of cells in aggregates, and aggregate size statistical distribution. To determine the number of cells in an aggregate starting from its two-dimensional microscopic profile, a model has been proposed and verified, using sphere packing theory. Algorithms have been tested on chondrocyte suspension cultures, where cell aggregation is a very early and critical event leading to cell differentiation. Using this technique for the analysis of chick embryo chondrocyte cultures, we observed that aggregate size and development kinetics depend on the culture conditions used. The method, with minor adaptations, is of potential use also in other cell systems to evaluate aggregation indexes or to study aggregation kinetics.


Functionalized resorcinarenes effectively disrupt the aggregation of αA66-80 crystallin peptide related to cataracts.
Cataracts, an eye lens clouding disease, are debilitating and while operable, remain without a cure. αA66-80 crystallin peptide abundant in cataracted eye lenses contributes to aggregation of αA-crystallin protein leading to cataracts. Inspired by the versatility of macrocycles and programmable guest selectivity through discrete functionalizations, we report on three water-soluble ionic resorcinarene receptors (A, B, and C) that disrupt the aggregation of αA66-80 crystallin peptide. A and B each possess four anionic sulfonate groups, while C includes four cationic ammonium groups with four flexible extended benzyl groups. Through multiple non-covalent attractions, these receptors successfully disrupt and reverse the aggregation of αA66-80 crystallin peptide, which was studied through spectroscopic, spectrometric, calorimetric, and imaging techniques. The αA66-80·receptor complexes were also explored using molecular dynamics simulation, and binding energies were calculated. Even though each of the three receptors can bind with the peptide, receptor C was characterized by the highest binding energy and affinity for three different domains of the peptide. In effect, the most efficient inhibitor was a cationic receptor C via extended aromatic interactions. These results highlight the potential of versatile and tunable functionalized resorcinarenes as potential therapeutics to reverse the aggregation of α-crystallin dominant in eye cataracts.


Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses.
HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples. Superinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection. In this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals.


Dexmedetomidine, ketamine, and midazolam for oral rehabilitation: a case report.
Intravenous sedation is frequently provided by anesthesiologists for phobic patients undergoing elective dental treatment in outpatient settings. Propofol is one of the most commonly used anesthetic agents that can result in apnea and respiratory depression, thereby posing potential difficulties with perioperative airway management. Dexmedetomidine has been utilized successfully in intravenous sedation for a wide variety of procedures and holds potential as an alternative to propofol in outpatient dental settings. However, as a single agent, it may not provide adequate depth of sedation and analgesia for oral rehabilitation. In this case report we demonstrate an effective alternative intravenous deep-sedation technique for an adult phobic patient undergoing oral rehabilitation utilizing 3 agents in combination: dexmedetomidine, ketamine, and midazolam. This combination of agents may be especially useful for those patients with a history of substance abuse, where administration of opioids may be undesirable or contraindicated.


Early blood lactate area as a prognostic marker in pediatric septic shock.
We attempted to evaluate whether the early lactate area is useful as an early prognostic marker of mortality in pediatric septic shock patients. We performed a retrospective study of pediatric patients with septic shock who were admitted to the pediatric intensive care unit of Asan Medical Center, Seoul, Korea. Serial arterial lactate levels were obtained immediately and then every 6 h after admission for a total of 24 h. The lactate area (mmol/lh) was defined as the sum of the area under the curve (AUC) of serial lactate levels measured during the 24 h following admission. We compared the lactate-associated parameters as a predictor of mortality. A total of 65 patients were included in this study, and the overall 28-day mortality of these patients was 26.2%. Survivors compared with non-survivors had an initial lactate level of 3.13 ± 2.79 vs. 6.16 ± 4.87 mmol/l, a lactate clearance of 32.8 ± 63.4 vs. -30.8 ± 75.6%, and a lactate area of 59.7 ± 56.0 vs. 168.0 ± 107.0 mmol/lh (p < 0.05 for all variables). Receiver operating characteristic curves indicated a strong predictive power for the lactate area (AUC = 0.828), which demonstrated the largest AUC in comparison with the AUCs of the initial lactate level (0.699) or the 24-h lactate clearance (0.719). Using multivariate logistic regression analysis, the lactate area was a significant prognostic factor. The early lactate area is a potentially feasible and clinically useful predictor of mortality in pediatric septic shock patients.


Sleeping well.
In a study by Cruse et al. published in BMC Medicine, patients with severe brain damage who were in the Vegetative or Minimally Conscious States (VS or MCS, respectively) from traumatic and nontraumatic etiologies had assessments of circadian rhythms using an actigraph, a device worn on a limb to evaluate circadian rhythmicity, in this population. This is a novel approach and is being used as a surrogate for polysomnography and other reference standards. Cruse et al. showed more disruption in circadian rhythms in the VS when compared to the MCS. This suggests that more brain injury occurs in the areas that control circadian rhythmicity in VS than in MCS patients. The study provides opportunities for improved prognostication and rehabilitation strategies in this patient population.


In vitro dissolution and mechanical behavior of c-axis preferentially oriented hydroxyapatite thin films fabricated by pulsed laser deposition.
Owing to its resemblance to the major inorganic constituent of bone and tooth, hydroxyapatite is recognized as one of the most biocompatible materials and is widely used in systems for bone replacement and regeneration. In this study the pulsed laser deposition technique was chosen to produce hydroxyapatite with different crystallographic orientations in order to investigate some of the material properties, including its in vitro dissolution behavior, as well as mechanical properties. The crystallographic orientations of hydroxyapatite coatings can be carefully controlled, mainly by varying the energy density of the KrF excimer laser (248 nm) used for deposition. Nanoindentation results showed that highly c-axis oriented hydroxyapatite coatings have higher hardness and Young's modulus values compared with the values of randomly oriented coatings. After 24h immersion in simulated physiological solution the overall surface morphology of the highly oriented coatings was dramatically altered. The porosity was drastically increased and sub-micron pores were formed throughout the coatings, whereas the average size of the grains in the coatings was not significantly changed. The composition of the textured hydroxyapatite coatings remained essentially unchanged. Their c-axis texture, on the other hand, was rather enhanced with an increase in immersion time. The c-axis oriented hydroxyapatite surfaces are likely to promote preferentially oriented growth through a cyclic process of dissolution and reprecipitation, followed by homoepitaxial growth. The remarkable morphological and microstructural changes after dissolution suggest a capability of highly textured hydroxyapatite as a tissue engineering scaffold with an interconnecting porous network that may be beneficial for cellular activity.


[Incidence of primary malignant lesions in clinically benign teratoma: on the problem of adequate surgical procedure].
The Problem of an Adequate Surgical Approach: Frequency of malignant teratomas is, according to the literature, 2%-10%. Examining 194 own cases (1983-1993) it was 1.5%. We found one squamous cell carcinoma (0.5%). Additionally we found 2 immature teratomas (1%). We point out the different biological behaviour of malignant mature teratomas and immature teratomas. We agree with the majority of authors that the method of choice is the intact removal of all teratomas without iatrogen rupture or contamination of the abdominal cavity by contents of the teratoma. This adequate surgical procedure can and should be performed by laparotomy or laparoscopy with endobag. The often practised method of cutting open the cyst during laparoscopy, sucking off the contents or cutting the teratoma into pieces, has been proven to lead to implantation and worsening the prognosis in case of a malignant teratoma. Even the rinsing of the abdominal cavity, usually carried out with this method, could not compensate always for the disadvantage of this "dirty" endoscopical method compared with usual oncological standards. This is pointed out by case reports in the literature and the first analysis of a German survey with early-follow-up of 192 laparoscopically managed ovarian malignancies [11a]. The principle of intact removal of every teratoma should again be kept in mind.


Flavodiiron oxygen reductase from Entamoeba histolytica: modulation of substrate preference by tyrosine 271 and lysine 53.
Flavodiiron proteins (FDPs) are a family of enzymes endowed with bona fide oxygen- and/or nitric-oxide reductase activity, although their substrate specificity determinants remain elusive. After a comprehensive comparison of available three-dimensional structures, particularly of FDPs with a clear preference toward either O2 or NO, two main differences were identified near the diiron active site, which led to the construction of site-directed mutants of Tyr(271) and Lys(53) in the oxygen reducing Entamoeba histolytica EhFdp1. The biochemical and biophysical properties of these mutants were studied by UV-visible and electron paramagnetic resonance (EPR) spectroscopies coupled to potentiometry. Their reactivity with O2 and NO was analyzed by stopped-flow absorption spectroscopy and amperometric methods. These mutations, whereas keeping the overall properties of the redox cofactors, resulted in increased NO reductase activity and faster inactivation of the enzyme in the reaction with O2, pointing to a role of the mutated residues in substrate selectivity.


Carpal tunnel syndrome impairs index finger responses to unpredictable perturbations.
The fine-tuning of digit forces to object properties can be disrupted by carpal tunnel syndrome (CTS). CTS' effects on hand function have mainly been investigated using predictable manipulation tasks; however, unpredictable perturbations are commonly encountered during manual tasks, presenting situations which may be more challenging to CTS patients given their hand impairments. The purpose of this study was to investigate muscle and force responses of the index finger to unpredictable perturbations in patients with CTS. Nine CTS patients and nine asymptomatic controls were instructed to stop the movement of a sliding plate by increasing index finger force following an unexpected perturbation. The electrical activity of the first dorsal interosseous muscle and forces exerted by the index finger were recorded. CTS patients demonstrated 20.9% greater muscle response latency and 12.0% greater force response latency compared to controls (p<0.05). The duration of plate sliding was significantly different between groups (p<0.05); the CTS group's duration was 142.2±5.8ms compared to the control group's duration of 133.1±8.4ms. Although CTS patients had increased muscle and force response durations comparatively, these differences were not statistically significant. Findings from this study suggest CTS-induced sensorimotor deficits interfere with accurate detection, processing and response to unpredictable perturbations. These deficits could be accounted for at multiple levels of the peripheral and central nervous systems. Delayed and decreased responses may indicate inefficient object manipulation by CTS patients and may help to explain why CTS patients tend to drop objects.


Anaesthesia and tympanometry.
Nitrous oxide and intermittent positive pressure respiration prior to intubation raised the middle ear pressure in children with normal ears. In children with secretory otitis media, nitrous oxide was responsible for aeration alone and this was seen only in children with some gas present prior to surgery. Wide range tympanometry accurately predicted the findings at myringotomy.


Assessment of fluctuation between grandiose and vulnerable narcissism: Development and initial validation of the FLUX scales.
There is a growing interest in the distinction between grandiose and vulnerable narcissism, along with a hypothesis of a fluctuation between grandiose and vulnerable narcissism within individuals. There are several well-validated measures of both grandiose and vulnerable narcissism, but research has generally found that they are relatively distinct in their relations with their nomological networks. Further, the existing measures of narcissism do not actually assess for a possible fluctuation. The present study developed three scales of narcissistic fluctuation: fluctuation between indifference and anger, grandiosity and shame, and assertiveness and insecurity. Consistent with expectations, the FLUX scales correlated with both grandiose and vulnerable narcissism, displayed convergent and discriminant validity with factor derived-narcissism scales and the five-factor model, and correlated at moderate-to-large effect sizes with measures of affective lability. The three FLUX scales were also reduced to one unidimensional nine-item scale of narcissistic fluctuation (the g-FLUX) that retained the correlational properties for the more specific scales and had incremental validity over the Five-Factor Narcissism Inventory and Pathological Narcissism Inventory grandiose and vulnerable scales in accounting for affective lability. Results from the present study suggest that the FLUX scales may provide an informative assessment of a fluctuation between grandiose and vulnerable narcissism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Point-of-care laboratory of pathogen diagnosis in rural Senegal.
In tropical Africa, where the spectrum of the bacterial pathogens that cause fevers is poorly understood and molecular-based diagnostic laboratories are rare, the time lag between test results and patient care is a critical point for treatment of disease. We implemented POC laboratory in rural Senegal to resolve the time lag between test results and patient care. During the first year of the study (February 2011 to January 2012), 440 blood specimens from febrile patients were collected in Dielmo and Ndiop villages. All samples were screened for malaria, dengue fever, Borrelia spp., Coxiella burnetii, Tropheryma whipplei, Rickettsia conorii, R. africae, R. felis, and Bartonella spp. We identified DNA from at least one pathogenic bacterium in 80/440 (18.2%) of the samples from febrile patients. B. crocidurae was identified in 35 cases (9.5%), and R. felis DNA was found in 30 cases (6.8%). The DNA of Bartonella spp. was identified in 23/440 cases (4.3%), and DNA of C. burnetii was identified in 2 cases (0.5%). T. whipplei (0.2%) was diagnosed in one patient. No DNA of R. africae or R. conorii was identified. Among the 7 patients co-infected by two different bacteria, we found R. felis and B. crocidurae in 4 cases, B. crocidurae and Bartonella spp. in 2 cases, and B. crocidurae and C. burnetii in 1 case. Malaria was diagnosed in 54 cases. In total, at least one pathogen (bacterium or protozoa) was identified in 127/440 (28.9%) of studied samples. Here, the authors report the proof of concept of POC in rural tropical Africa. Discovering that 18.2% of acute infections can be successfully treated with doxycycline should change the treatment strategy for acute fevers in West Africa.


Carcass characteristics, meat quality, sensory palatability and chemical composition of Thai native cattle grazing in lowland and Phu Phan mountain forest.
The aim of this study was to assess the effect of Thai native cattle grazing in the lowland or mountain forest on carcass characteristics, meat quality, sensory palatability, and chemical composition. Twelve male Thai native cattle with an average weight of 110 ± 10 kg are allowed to be grazing in the lowland or Phu Phan mountain forest during the rainy season in northeastern Thailand. The carcass characteristics, meat pH, and meat color were unaffected by treatment (p>0.05). The boiling loss was lower in the cattle grazing on the mountain forest (p=0.027). The cattle grazing in the mountain forest had increased shear force (p=0.039), tenderness (p=0.011) and flavor intensity (p=0.003). The protein and fat were higher (p<0.001 and p=0.035, respectively) in cattle grazing in the mountain forest. The different grazing systems of the cattle had no effect (p>0.05) fatty acids in meat, except for capric acid (C10:0) and lauric acid (C12:0), which were higher (p=0.046 and p=0.049, respectively) when the cattle were grazing in the mountain forest. The different grazing systems did not influence (p>0.05) the unsaturated fatty acids (UFA) in meat. Thai native cattle grazing in the Phu Phan mountain forest in the rainy season improves meat quality, sensory evaluation, and chemical composition.


[New class III antiarrhythmic drugs for treatment of atrial fibrillation].
Last two decades have been dedicated to intensive search for new class III antiarrhythmic drugs, especially for atrial fibrillation. Here we present a review of the status this problem. Influence on transmembranous ion currents and mechanisms of antiarrhythmic action are described. Results of experimental and clinical studies are reviewed. Possible perspectives of newest atrial-selective medications are discussed. Russia's class III antiarrhythmic drugs are of special interest of the article. First data on efficacy and safety of newest agent niferidil are presented. This drug undergoes clinical testing at present time.


Effects of short-term hormone replacement therapies on low-density lipoprotein metabolism in cynomologus monkeys.
Estrogen replacement therapy reduces the risk of coronary heart disease in women and decreases the extent of atherosclerosis in monkeys. In our previous studies, estrogen treatment decreased arterial LDL degradation and accumulation, thus indicating one mechanism by which estrogen inhibits the progression of atherosclerosis. The influence of progestins on these processes remains nuclear. The objective of this study was to determine the effects of oral estrogen (conjugated equine estrogens) and progestin (medroxyprogesterone acetate) alone or in combination on arterial LDL metabolism after 12 weeks of atherogenic stimulus. This relatively short period of treatment was chosen to determine effects on arterial LDL metabolism before substantial subendothelial macrophage accumulation. In contrast to previous studies (16 to 18 weeks of treatment), when macrophages were present in the intima, neither estrogen nor progestin (nor their combination) had any effect on any index of arterial LDL metabolism. These results suggest that estrogen may preferentially reduce LDL metabolism in macrophages with little effect on cells of the normal artery. In contrast to arterial LDL metabolism, hepatic LDL uptake was significantly increased in animals treated with estrogen or estrogen plus progestin. Despite the increased LDL uptake by the liver, hepatic lipid content was significantly decreased by approximately 50% in both estrogen and estrogen-plus-progestin treatment compared with control and progestin-treated animals. The decrease in hepatic cholesterol content in hypothesized to be due to increased biliary secretion of cholesterol.


Geometry of Bermuda Calcareous Dune Cross-Bedding.
Bermuda wind-blown limesands are lobate-shaped bodies composed internally of leeward foreset strata which dip at 30 to 35 degrees and windward strata which dip at 10 to 15 degrees in an opposite direction. The foreset beds are convex upward. This convex upward cross-stratification is preserved because of the early stabilization of the eolian calcareous sand due to surface cementation by percolating rain water.


Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.
Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.


The impact of resveratrol on skin wound healing, scarring, and aging.
Resveratrol is a well-known antioxidant that harbours many health beneficial properties. Multiple studies associated the antioxidant, anti-inflammatory, and cell protective effects of resveratrol. These diverse effects of resveratrol are also potentially involved in cutaneous wound healing, scarring, and (photo-)aging of the skin. Hence, this review highlighted the most relevant studies involving resveratrol in wound healing, scarring, and photo-aging of the skin. A systematic review was performed and the database PubMed was searched for suitable publications. Only original articles in English that investigated the effects of resveratrol in wound healing, scarring, and (photo-)aging of the skin were analysed. The literature search yielded a total of 826 studies, but only 41 studies met the inclusion criteria. The included studies showed promising results that resveratrol might be a feasible treatment approach to support wound healing, counteract excessive scarring, and even prevent photo-aging of the skin. Resveratrol represents an interesting and promising novel therapy regime but to confirm resveratrol-associated effects, more evidence based in vitro and in vivo studies are needed.


Glycerol for acute stroke.
Brain oedema is a major cause of early death after stroke. A 10% solution of glycerol is a hyperosmolar agent that is claimed to reduce brain oedema. To determine whether I.V. glycerol treatment in acute stroke, either ischaemic or haemorrhagic, influences death rates and functional outcome in the short or long term and whether the treatment is safe. The Cochrane Stroke Group Trials Register was searched, conference proceedings were screened and some trialists were personally contacted. All completed, randomised and quasi-randomized, controlled, published and unpublished comparisons, evaluating clinical outcome in which intravenous (I.V.) glycerol treatment was initiated within the first days after stroke onset. Two reviewers independently applied the inclusion criteria, assessed the trial quality and extracted data and this was checked with all co-reviewers. Death from all causes, functional outcome and adverse effects were analysed. Eleven completed, randomised trials comparing I.V. glycerol and control were considered. Analysis of death during the scheduled treatment period for acute ischaemic and/or haemorrhagic stroke was possible in ten trials where 482 glycerol treated patients were compared with 463 control patients. Glycerol was associated with a non-significant reduction in the odds of death within the scheduled treatment period (OR 0.78, 95% Confidence Intervals 0.58 - 1.06). Among patients with definite or probable ischaemic stroke, glycerol was associated with a significant reduction in the odds of death during the scheduled treatment period (odds ratio 0.65, 95% CI 0.44-0.97). However, at the end of the scheduled follow up period, there was no significant difference in the odds of death (odds ratio 0.98, 95% CI 0.73-1.31). Functional outcome was reported in only two studies but there were non-significantly more patients who had a good outcome at the end of scheduled follow up (odds ratio 0.73, 95% CI 0.37-1.42). Haemolysis seems to be the only relevant adverse effect of glycerol treatment. This systematic review suggests a favourable effect of glycerol treatment on short term survival in patients with probable or definite ischaemic stroke but the magnitude of the treatment effect may be minimal (as low as a 3% reduction in odds). Due to the relatively small number of patients and that the trials have been performed in the pre-CT era, the results must be interpreted cautiously. The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke.


Treatment of 'Diabesity': Beyond Pharmacotherapy.
Obesity is a prominent risk factor for type 2 diabetes. Management of type 2 diabetes requires weight management in addition to glycemic parameters. For obese type 2 diabetes patients, metformin, Sodium-glucose co-transporter-2 inhibitors or Glucagon-Like Peptide-1 Receptor Agonists should be prescribed as the first priority for controlling both hyperglycemia and body weight or fat distribution. The combination of these drugs with sulfonylureas, thiazolidinediones, and insulin may also be required in chronic cases. These drugs cause weight gain. Fortunately, many phytochemicals having a beneficial effect on diabetes and obesity, have minimum side-effects as compared to synthetic drugs. This review discusses the treatment strategies for controlling glycemia and weight management, with the focus on anti-diabetic drugs and phytochemicals. Glucagonostatic role, activation of Adenosine monophosphate-activated protein kinase and adipocyte targeting potential of anti-diabetic drugs and phytochemicals are also discussed.


Perceptions of HIV Risk and Explanations of Sexual Risk Behavior Offered by Heterosexual Black Male Barbershop Patrons in Brooklyn, NY.
To describe HIV risk factors among adult heterosexual Black men recruited from four barbershops located in high HIV seroprevalent neighborhoods of Brooklyn, NY. Data on HIV-risk related behaviors and other characteristics were collected from barbershop clients. All participants (n=60) completed brief risk assessments; and a subset (n=22) also completed focus groups and/or individual interviews. Of the subset of 22 men, 68% were US born, 59% had been in jail/prison, 32% were unemployed; and during the 3 months before the interviews, 68% reported at least two partners and 45% reported unprotected vaginal or anal sex with two or more women. Emergent themes included: 1) the psychological function of multiple partnerships; 2) calculated risk taking regarding condom use; 3) the role of emotional attachment and partner trust in condom use; 4) low perceived HIV risk and community awareness; and 5) lack of relationship between HIV testing and safer sex practices. Interventions among heterosexual Black men should focus not only on increasing HIV awareness and reducing sexual risk, but also on contextual and interpersonal factors that influence sexual risk.


CCR6 promotes steady-state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance.
The intestinal lamina propria (LP) contains antigen-presenting cells with features of dendritic cells and macrophages, collectively referred to as mononuclear phagocytes (MNPs). Association of MNPs with the epithelium is thought to play an important role in multiple facets of intestinal immunity including imprinting MNPs with the ability to induce IgA production, inducing the expression of gut homing molecules on T cells, facilitating the capture of luminal antigens and microbes, and subsequent immune responses in the mesenteric lymph node (MLN). However, the factors promoting this process in the steady state are largely unknown, and in vivo models to test and confirm the importance of LP-MNP association with the epithelium for these outcomes are unexplored. Evaluation of epithelial expression of chemoattractants in mice where MNP-epithelial associations were impaired suggested CCL20 as a candidate promoting epithelial association. Expression of CCR6, the only known receptor for CCL20, was required for MNPs to associate with the epithelium. LP-MNPs from CCR6-/- mice did not display defects in acquiring antigen and stimulating T-cell responses in ex vivo assays or in responses to antigen administered systemically. However, LP-MNPs from CCR6-deficient mice were impaired at acquiring luminal and epithelial antigens, inducing IgA production in B cells, inducing immune responses in the MLN, and capturing and trafficking luminal commensal bacteria to the MLN. These findings identify a crucial role for CCR6 in promoting LP-MNPs to associate with the intestinal epithelium in the steady state to perform multiple functions promoting gut immune homeostasis.


Microwave-Generated Steam Decontamination of N95 Respirators Utilizing Universally Accessible Materials.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a severe, international shortage of N95 respirators, which are essential to protect health care providers from infection. Given the contemporary limitations of the supply chain, it is imperative to identify effective means of decontaminating, reusing, and thereby conserving N95 respirator stockpiles. To be effective, decontamination must result in sterilization of the N95 respirator without impairment of respirator filtration or user fit. Although numerous methods of N95 decontamination exist, none are universally accessible. In this work, we describe a microwave-generated steam decontamination protocol for N95 respirators for use in health care systems of all sizes, geographies, and means. Using widely available glass containers, mesh from commercial produce bags, a rubber band, and a 1,100-W commercially available microwave, we constructed an effective, standardized, and reproducible means of decontaminating N95 respirators. Employing this methodology against MS2 phage, a highly conservative surrogate for SARS-CoV-2 contamination, we report an average 6-log10 plaque-forming unit (PFU) (99.9999%) and a minimum 5-log10 PFU (99.999%) reduction after a single 3-min microwave treatment. Notably, quantified respirator fit and function were preserved, even after 20 sequential cycles of microwave steam decontamination. This method provides a valuable means of effective decontamination and reuse of N95 respirators by frontline providers facing urgent need.IMPORTANCE Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an increasing shortage of protective gear necessary to keep health care providers safe from infection. As of 9 April 2020, the CDC reported 9,282 cumulative cases of COVID-19 among U.S. health care workers (CDC COVID-19 Response Team, MMWR Morb Mortal Wkly Rep 69:477-481, 2020, https://doi.org/10.15585/mmwr.mm6915e6). N95 respirators are recommended by the CDC as the ideal method of protection from COVID-19. Although N95 respirators are traditionally single use, the shortages have necessitated the need for reuse. Effective methods of N95 decontamination that do not affect the fit or filtration ability of N95 respirators are essential. Numerous methods of N95 decontamination exist; however, none are universally accessible. In this study, we describe an effective, standardized, and reproducible means of decontaminating N95 respirators using widely available materials. The N95 decontamination method described in this work will provide a valuable resource for hospitals, health care centers, and outpatient practices that are experiencing increasing shortages of N95 respirators due to the COVID-19 pandemic.


CT-revealed choroidal effusions as a sign of carotid cavernous fistula.
Choroidal effusions may appear as subtle abnormalities on CT scans. Recognition of choroidal effusions, however, is critical because they may be an early sign of ocular pathologic abnormality. After detection, the various causes of choroidal effusions, such as carotid cavernous fistulas, ocular hypotony, tumors, and inflammatory conditions, should be considered.


Calponin homology domain containing kinesin, KIS1, regulates chloroplast stromule formation and immunity.
Chloroplast morphology changes during immunity, giving rise to tubule-like structures known as stromules. Stromules extend along microtubules and anchor to actin filaments along nuclei to promote perinuclear chloroplast clustering. This facilitates the transport of defense molecules/proteins from chloroplasts to the nucleus. Evidence for a direct role for stromules in immunity is lacking since, currently, there are no known genes that regulate stromule biogenesis. We show that a calponin homology (CH) domain containing kinesin, KIS1 (kinesin required for inducing stromules 1), is required for stromule formation during TNL [TIR (Toll/Interleukin-1 receptor)-type nucleotide-binding leucine-rich repeat]-immune receptor-mediated immunity. Furthermore, KIS1 is required for TNL-mediated immunity to bacterial and viral pathogens. The microtubule-binding motor domain of KIS1 is required for stromule formation while the actin-binding, CH domain is required for perinuclear chloroplast clustering. We show that KIS1 functions through early immune signaling components, EDS1 and PAD4, with salicylic acid-induced stromules requiring KIS1. Thus, KIS1 represents a player in stromule biogenesis.


The central morphology of the giant interneurons and their spatial relationship with the thoracic motorneurons in the cockroach, Periplaneta americana (Insecta).
Three groups of giant fibers are found in the cockroach ventral nerve cord. A latero-dorsal group (dorsal GIs), a latero-ventral group (ventral GIs) and a medio-ventral group. The morphology of all three groups of fibers within the thoracic ganglia is described. The morphology of the dorsal and ventral GI pathways in the abdominal and suboesophageal ganglia is also described. The projection patterns of the neurons in each ganglion are remarkably similar which suggests a common function. When motorneurons 5rl (depressor) and 6Br4 (levator) are stained simultaneously with the dorsal and ventral GI groups, some branches from both motor and giant neurons converge. The branching of the remaining medio-ventral group of fibers and their proximity to areas receiving motorneuronal input suggests that these are the small diameter axons described by Dagan and Parnas (1970).


Cytomegalovirus (CMV) retinitis immune restoration disease occurs during highly active antiretroviral therapy-induced restoration of CMV-specific immune responses within a predominant Th2 cytokine environment.
Plasma levels of cytomegalovirus (CMV)-specific immunoglobulin G (IgG), soluble (s) CD30, sCD26 (dipeptidyl peptidase IV [DPP IV]) enzyme activity, and tumor necrosis factor receptor-I (TNFR-I) were assessed in human immunodeficiency virus (HIV)-infected patients who experienced CMV retinitis (CMVR) as an immune restoration disease (IRD) during their first 6 months of highly active antiretroviral therapy (HAART) and in CMV-seropositive, HIV-infected patients with similar baseline CD4(+) T cell counts who had uneventful immune reconstitution. Patients who experienced CMVR IRD had a significant increase in CMV-specific IgG during their first 12 months of HAART, indicating restored CMV-specific immune responses. They also had significantly higher levels of sCD30 both before HAART and for up to 12 months after start of treatment. sCD30 levels remained elevated during 48 months of HAART, suggesting persistence of a predominant Th2 cytokine environment. Levels of sCD26 (DPP IV) enzyme activity and TNFR-I did not differ significantly between the 2 groups at any time point.


Effect of aging on gallbladder contraction and release of cholecystokinin-33 in humans.
The objective of this study was to examine the effect of aging on gallbladder contraction and cholecystokinin (CCK) release, as well as on the correlation between the two in humans who are free of gallbladder disease. Twenty-nine human volunteers were divided into a young group of 14 individuals (ages 22 to 42 years, median age 32 years) and an older group of 15 individuals (ages 60 to 84 years, median age 66 years). In the study each person in both groups was given corn oil (Lipomul), 1.5 ml/kg, by mouth after an overnight fast. Blood was collected for measurement of CCK-33 by radioimmunoassay before and at intervals after ingestion of Lipomul. Simultaneous measurements of gallbladder volume were obtained by real-time varian ultrasonography. Both fasting and fat-stimulated concentrations of CCK in plasma were significantly higher in the older individuals than in the younger volunteers. The 60-minute integrated measurement of CCK release was significantly increased in the older people as compared with the young. Both fasting and maximally contracted gallbladder volumes were equal in the older and younger groups. The rate of emptying of the gallbladder was equal in both age groups, but the gallbladders of older people appeared to show an earlier initiation of contraction. The highly significant correlation of gallbladder contraction with levels of CCK was similar in both age groups, but the sensitivity of the gallbladder to CCK in the older people was significantly decreased. In conclusion, both fasting and fat-stimulated plasma levels of CCK increase with aging. The sensitivity of the gallbladder muscle to stimulation by CCK is diminished with age, but this appears, teleologically, to be matched by the increased release of CCK, so the kinetics of gallbladder emptying are little different in the aged.


Implantable cardioverter/defibrillator interventions in primary prevention: do current implantation criteria really predict ICD interventions?
Randomized controlled trials have proven the efficacy of implantable cardioverter/defibrillators (ICDs) to prevent sudden cardiac death (SCD) in primary prevention. However,long-term data on the incidence of appropriate and inappropriate interventions in real life and on the predictive value of commonly used clinical variables to guide patient selection are scarce. We retrospectively studied 101 patients who received an ICD for primary prophylaxis of SCD: 63.4% with ischaemic heart disease (IHD) and 36.6% with idiopathic dilated cardiomyopathy (IDCM). The mean follow-up period was 26.2 (+/- 14.8; median 27.8; range 5.6-70.5) months. Age, left ventricular ejection fraction (LVEF), QRS duration, NYHA class and electrophysiological study (EPS) outcome were evaluated as predictors of ICD intervention. At 2 years the cumulative incidence of appropriate (17.5% in IHD; 28% in IDCM; P= 0.63) and inappropriate (12.8% in IHD, 15.4% in IDCM; P = 0.62) interventions was similar in both groups. Atrial fibrillation was the most common cause of inappropriate interventions in the IHD group, sinus tachycardia in the IDCM group. Advanced age was associated with less inappropriate interventions (HR: 0.96 (95% confidence interval (CI) 0.94-0.98); P < 0.01), and a better LVEF with less appropriate interventions (HR: 0.97 (95% Cl 0.94-0.99); P < 0.01). This amounted in a significant absolute difference in the number of appropriate interventions between the group with a LVEF < 25% and 25-34% after 3 years of follow-up of 42% in IHD (48% vs 6%). A prolonged QRS duration was associated with a slightly elevated risk for appropriate interventions only in the IHD group (HR: 1.01 (95% CI 1.00-1.03); P = 0.04). On the other hand, increased NYHA class was only associated with increased risk for appropriate interventions in the IDCM group (HR: 5.24 (95% CI1.11-24.74); P= 0.04). No significant statistical association was found between a positive EPS and appropriate or inappropriate interventions. In primary prevention, during a mean follow-up of 2 years, one in five patients had a possibly live-saving appropriate intervention. However, the incidence of inappropriate interventions was substantial. Predictors for appropriate interventions were: (i) LVEF in the total study group, (ii) NYHA class in the IDCM group and (iii) QRS duration in the IHD group.


Cloaking the underlying long-range order of randomly perturbed lattices.
Random, uncorrelated displacements of particles on a lattice preserve the hyperuniformity of the original lattice, that is, normalized density fluctuations vanish in the limit of infinite wavelengths. In addition to a diffuse contribution, the scattering intensity from the the resulting point pattern typically inherits the Bragg peaks (long-range order) of the original lattice. Here we demonstrate how these Bragg peaks can be hidden in the effective diffraction pattern of independent and identically distributed perturbations. All Bragg peaks vanish if and only if the sum of all probability densities of the positions of the shifted lattice points is a constant at all positions. The underlying long-range order is then "cloaked" in the sense that it cannot be reconstructed from the pair correlation function alone. On the one hand, density fluctuations increase monotonically with the strength of perturbations a, as measured by the hyperuniformity order metric Λ[over ¯]. On the other hand, the disappearance and reemergence of long-range order, depending on whether the system is cloaked as the perturbation strength increases, is manifestly captured by the τ order metric. Therefore, while the perturbation strength a may seem to be a natural choice for an order metric of perturbed lattices, the τ order metric is a superior choice. It is noteworthy that cloaked perturbed lattices allow one to easily simulate very large samples (with at least 10^{6} particles) of disordered hyperuniform point patterns without Bragg peaks.


Refining the cheatgrass-fire cycle in the Great Basin: Precipitation timing and fine fuel composition predict wildfire trends.
Larger, more frequent wildfires in arid and semi-arid ecosystems have been associated with invasion by non-native annual grasses, yet a complete understanding of fine fuel development and subsequent wildfire trends is lacking. We investigated the complex relationships among weather, fine fuels, and fire in the Great Basin, USA. We first modeled the annual and time-lagged effects of precipitation and temperature on herbaceous vegetation cover and litter accumulation over a 26-year period in the northern Great Basin. We then modeled how these fine fuels and weather patterns influence subsequent wildfires. We found that cheatgrass cover increased in years with higher precipitation and especially when one of the previous 3 years also was particularly wet. Cover of non-native forbs and native herbs also increased in wet years, but only after several dry years. The area burned by wildfire in a given year was mostly associated with native herb and non-native forb cover, whereas cheatgrass mainly influenced area burned in the form of litter derived from previous years' growth. Consequently, multiyear weather patterns, including precipitation in the previous 1-3 years, was a strong predictor of wildfire in a given year because of the time needed to develop these fine fuel loads. The strong relationship between precipitation and wildfire allowed us to expand our inference to 10,162 wildfires across the entire Great Basin over a 35-year period from 1980 to 2014. Our results suggest that the region's precipitation pattern of consecutive wet years followed by consecutive dry years results in a cycle of fuel accumulation followed by weather conditions that increase the probability of wildfire events in the year when the cycle transitions from wet to dry. These patterns varied regionally but were strong enough to allow us to model annual wildfire risk across the Great Basin based on precipitation alone.


Awareness Mentality and Strategic Behavior in Science.
Acknowledgement of scientific achievements was and is essentially achieved through the citation of a publication. Increasingly, however, it is no longer just the publication itself that plays an important role, but also the degree of attention that a scientist achieves with this very publication. Thus, the importance of strategic behavior in science is progressing and an awareness mentality is spreading. In this paper, the causes and backgrounds of this development are discussed, identifying the use of reductionist, quantitative systems in science management and research funding, the loss of critical judgment and technocratic dominance, quantitative assessments used for decision making, altmetrics and the like as alternative views, the use of perception scores in reference databases and universities as well as ambitions of journals as main drivers. Besides, different forms of strategic behavior in science and the resulting consequences and impacts are being highlighted.


The experience of sexuality during breastfeeding among primiparous women.
The purpose of this study was to describe various aspects of sexuality for primiparous breastfeeding women. The conceptual framework used for the study was Bernhard's theory of women's integrated sexuality which describes female sexuality as a multidimensional, biopsychosocial phenomenon. The investigators used a descriptive design, analyzing data from the 576 primiparous breastfeeding women who, as part of a larger study, completed the Breastfeeding and Sexuality Tool at the time of complete weaning. The women were from a large, private hospital in urban Minnesota. Subjects completed initial questionnaires during the postpartum hospitalization. Follow-up data were collected by phone at 1, 3, 6, and 12 months postpartum. Those who had not weaned by 12 months were followed every 3 months until complete weaning was reported. Overall, women perceived that breastfeeding had a slightly negative impact on the physiologic aspects of sexuality, but did not greatly affect the woman's sexual relationship with her partner. In addition, breastfeeding mothers perceived their partners' attitudes towards breastfeeding and sexuality as slightly positive, and did not worry that sexual activity would harm their milk supply or their ability to nurse. Overall, breastfeeding had a slightly negative impact on sexuality. However, a wide range of responses were reported by the women. Health care providers should be familiar with the whole range of possible responses to sexuality while breastfeeding in order to appropriately counsel women about what is normal and what to expect during this time.


Personalized genetic testing and norovirus susceptibility.
The availability of direct-to-consumer personalized genetic testing has enabled the public to access and interpret their own genetic information. Various genetic traits can be determined including resistance to norovirus through a nonsense mutation (G428A) in the FUT2 gene. Although this trait is believed to confer resistance to the most dominant norovirus genotype (GII.4), the spectrum of resistance to other norovirus strains is unknown. The present report describes a cluster of symptomatic norovirus GI.6 infection in a family identified to have norovirus resistance through personalized genetic testing. In January 2013, four members of a family determined by a direct-to-consumer genetic test to be homozygous for the norovirus resistance trait (A/A genotype for single nucleotide polymorphism rs601338) developed symptoms consistent with acute viral gastroenteritis. Stool and vomitus samples were submitted for enteric viral pathogen testing. Samples were positive for norovirus GI.6 in three of the four cases. The present report is the first to describe norovirus GI.6 infection in patients with the G428A nonsense mutation in FUT2; this cluster of cases suggests that the G428A mutation in FUT2 may not confer resistance to norovirus GI.6. Direct-to-consumer genetic testing is empowering members of the public to identify novel associations with their genetic traits. Expert consultation is important for the interpretation of personalized genetic test results, and follow-up laboratory testing can confirm any potentially novel associations.


Role of electrocardiography and echocardiography in prevention and predicting outcome of subjects at increased risk of heart failure.
Asymptomatic left ventricular dysfunction (ALVD) is relatively common in both community and high-risk populations. Early pharmacological intervention can improve clinical outcomes in subjects with this condition. This multicentre study consists on electrocardiographic and echocardiographic examination of stage A and B heart failure (HF) asymptomatic subjects with one or more cardiovascular risk factors, to assess the prognostic value of cardiovascular risk factors per se, clinical history, and electrocardiographic and echocardiographic parameters in prediction of progression of HF and/or in development of cardiovascular primary or secondary events. A total of 2142 asymptomatic subjects (mean age 63 years, 1162 males) performed an electrocardiographic and echocardiographic examination. Electrocardiogram (ECG) pathological signs according to Minnesota code and left ventricular dysfunction both systolic and diastolic by echocardiography were evaluated. There were 2002 subjects who were followed up for 26 ± 11 months, observing their primary and secondary end points. At follow up, the study population presented 111 primary end points (5.2%) and 441 secondary end points (20.6%). ECG criteria of LV hypertrophy and signs of ischaemia or previous myocardial infarction (p < 0.0001) were highly significantly related to primary end points. Both ECG and echocardiography (systolic function) are able at Kaplan-Meier cumulative survival curves to predict primary end points (p < 0.0001). Presence or absence of left ventricular systolic and /or diastolic dysfunction has an incremental value in comparison to cardiovascular risk factors, clinical history, and ECG findings to predict both the evolution towards a more severe HF stage (stage C) and also the occurrence of cardiovascular events.


[Long-term proton pump inhibitor therapy and osteoporosis. Is there a real danger?].
Proton pump inhibitors are widely used in the treatment of acid-related diseases because they are considered to be effective and safe. In the past 10 years the use of proton pump inhibitors increased by over three folds, which is not associated with the increased prevalence of acid-related diseases obviously. However, like any other drugs, they have potential side effects. In recent years many studies have been published about the correlation between long-term proton pump inhibitor therapy and the increase of bone fractures. Most studies showed that long-term proton pump inhibitor therapy moderately increased fracture risk. The underlying mechanisms of increased number of bone fractures are not clarified yet. However, chronic acid suppression caused by long-term proton pump inhibitor therapy may play a crucial role in decreased absorption of calcium and vitamin B12 and, therefore, indirectly affecting the bones resulting in a decrease of bone mineral density. The available data suggest that proton pump inhibitors should be used with caution in patients with increased risk of osteoporosis.


Farnesyl transferase inhibitors in myeloid disorders.
Farnesyl transferase inhibitors (FTIs), a novel class of anticancer agents that competitively inhibit farnesyl protein transferase, are currently being developed and tested across a wide range of human cancers. Myeloid malignancies are reasonable disease targets in that they likely overexpress relevant biologic targets, such as Ras, mitogen-activated protein kinase (MAPK), or AKT. Several phase I clinical trials using FTIs in myeloid malignancies have been performed, demonstrating enzyme target inhibition, low toxicity, and anticancer activity. Many phase II trials are now under way, aiming to assess the response rate and to identify the actual downstream signal transduction targets that may be modified by these agents. It is expected that results from these trials will optimize the role of FTIs in patients with myeloid disorders by identifying patient and disease characteristics that will predict for response, facilitating their incorporation into current therapeutic strategies and providing insight into effective methods of combining FTIs with other antineoplastics.


[Radiation exposure in x-ray mammography].
When discussing the radiation risk of X-ray mammography, the magnitude of the dose applied has decisive importance. The radiation exposure of the breast is the predominant factor in risk considerations, since it contributes more than 98% to the effective dose of this examination. At present, it is generally assumed that, with regard to cancer induction by ionizing radiation, the glandular tissue is the most vulnerable part in the breast. Therefore, the average glandular dose, i.e., the mean value of the absorbed dose in the glandular tissue, is used for a description of the radiation risk. The average glandular dose cannot be measured directly, but is calculated under certain assumptions from the experimentally determined entrance surface air kerma or entrance surface dose by the use of a so-called conversion factors. During the seventies, i.e., in the era of the industrial type X-ray film, the mean value of the average glandular dose per exposure for a larger sample of patients (n > 100) was about 20 mGy. Due to the progress in radiographic technique such as, for example, the use of sensitive film-screen systems, optimized radiation qualities and modern automatic exposure control units this value has now decreased to about 1 mGy. Further dose reductions seem possible by the introduction of digital image receptors.


Sex differences in serum trace elements and minerals levels in unmedicated patients with major depressive episode: The role of suicidal ideation.
We aimed to examine the influence of gender on serum trace elements and minerals levels in depression, as well as the impact of suicidal ideation (SI) on these gender dimorphisms. A total of 260 unmedicated patients with a current major depressive episode were enrolled. The Beck Scale for Suicide Ideation was utilized to evaluate SI. The serum levels of copper, zinc, iron, calcium, phosphorus, and magnesium were quantified. Within the non-SI (NSI) group, females exhibited higher levels of copper (p = 0.001) and phosphorus (p = 0.008), and lower levels of zinc (p = 0.022) and calcium (p = 0.008) compared to males. Conversely, no discernible gender disparities were observed in the SI group (all p > 0.05). Also, no group differences in these trace elements/minerals were observed between the SI and NSI groups (all p > 0.05). Notably, serum iron levels exhibited a significant group-by-sex interaction effect (p = 0.024). Further analysis revealed that iron levels were higher in the SI group than in the NSI group among females (p = 0.048), but lower in females than in males within the NSI group (p < 0.001). Moreover, a positive association between the fourth quantile of serum iron and SI was detected in females (odds ratio [OR] = 2.88, 95 % confidence interval [CI]: 1.08-8.11). Gender effects on serum trace element/mineral levels were different in depressed patients with and without SI. Female patients were susceptible to SI when serum iron was at the upper end of normal.


Use of stem cells and growth factors in rotator cuff tendon repair.
The management of rotator cuff tears continues to prove challenging for orthopaedic surgeons. Such tears affect most age groups and can lead to significant morbidity in patients. The aetiology of these tears is likely to be multifactorial; however, an understanding of the mechanisms involved is still under review. Despite advancements in surgical operative techniques and the materials used, post-operative recurrence rates after surgical repair remain high. A growing area of research surrounds biological adjuncts used to improve the healing potential of the repaired tissues. This review of recent publications focuses on the strengths and limitations of using stem cells and growth factors in rotator cuff repair.


2D Transformations of Energy Signals for Energy Disaggregation.
The aim of Non-Intrusive Load Monitoring is to estimate the energy consumption of individual electrical appliances by disaggregating the overall power consumption that has been sampled from a smart meter at a house or commercial/industrial building. Last decade's developments in deep learning and the utilization of Convolutional Neural Networks have improved disaggregation accuracy significantly, especially when utilizing two-dimensional signal representations. However, converting time series' to two-dimensional representations is still an open challenge, and it is not clear how it influences the performance of the energy disaggregation. Therefore, in this article, six different two-dimensional representation techniques are compared in terms of performance, runtime, influence on sampling frequency, and robustness towards Gaussian white noise. The evaluation results show an advantage of two-dimensional imaging techniques over univariate and multivariate features. In detail, the evaluation results show that: first, the active and reactive power-based signatures double Fourier based signatures, as well as outperforming most of the other approaches for low levels of noise. Second, while current and voltage signatures are outperformed at low levels of noise, they perform best under high noise conditions and show the smallest decrease in performance with increasing noise levels. Third, the effect of the sampling frequency on the energy disaggregation performance for time series imaging is most prominent up to 1.2 kHz, while, above 1.2 kHz, no significant improvements in terms of performance could be observed.


Isolated and solitary splenic metastasis detected by positron emission tomography in a patient with malignant melanoma: case report and review of the literature.
Splenic metastasis from malignant melanoma is an extremely rare occurrence and is most often reported during autopsy. As in other solid tumors, splenic metastasis is usually part of multiple organ metastases in melanoma and is rarely an isolated or solitary mass. As the use of positron emission tomography /computed tomography and imaging techniques become more common, splenic metastases are seen more often than before. Even though it is a commonly known fact that positron emission tomography/computed tomography is no help during primary staging and patient relations in malignant melanoma, several studies and meta-analyses have proven that it is more specific, sensitive and accurate to identify metastases than raditional methods. Therefore, using techniques with high specificity and accuracy rates such as positron emission tomography/computed tomography in the diagnosis of splenic metastasis in patients with malignant melanoma will increase the survival rate with an earlier splenectomy. We report the case of a 35-year-old male patient with cutaneous malignant melanoma whose splenic metastasis was detected with positron emission tomography/computed tomography. This article describes, with reference to the literature, a malignant melanoma case, which presented with splenomegaly and solitary mass lesion and was diagnosed as metastasis by splenectomy after positron emission tomography/computed tomography.


Exploring Fear of Falling and Exercise Self-Efficacy in Older Women With Vertebral Fractures.
Fear of falling is a common issue among older adults, which decreases quality of life and leads to an avoidance of activities they are still able to do. The goal of this secondary data analysis was to explore the relationship between fear of falling and exercise self-efficacy in 141 women with at least one nontraumatic Genant Grade 2 vertebral fracture. Fear of falling, exercise self-efficacy, history of falling, the number of falls, the use of assisting devices, and pain at rest or during movement were obtained using medical history and health status questionnaires. There was a negative association between fear of falling and exercise self-efficacy (pseudo R2 = .253; p = .004), which persisted when the analysis was adjusted for history and number of falls, use of assistive devices, and pain at rest (pseudo R2 = .329; p < .0001) or during movement (pseudo R2 = .321; p < .0001). Fear of falling may be negatively associated with exercise self-efficacy in older women with vertebral fracture.


Review of interventions for the prevention and control of folate and vitamin B12 deficiencies.
Folate and vitamin B12 deficiencies represent important and evolving global health challenges that contribute to the global burden of anemia, neurologic conditions, neurodevelopmental disorders, and birth defects. We present a review of population-based programs designed to increase consumption of folates and vitamin B12. A folic acid supplementation program targeting couples prior to marriage in China has led to optimal consumption of supplements containing folic acid and a significant reduction of neural tube defects (NTD). Supplementation programs that use mass community education show some promise, but have not been shown to be as effective as targeted education. The success of supplementation programs hinges on a strong and persistent educational component and access to the supplements. Fortification with folic acid has been shown to reduce the prevalence of NTD in the countries where it has been implemented. Challenges to fortification programs include identifying the appropriate delivery vehicles, setting the optimal fortification level, sustaining the quality assurance of the fortification level, and addressing regulatory challenges and trade barriers of commercially fortified flours. Supplementation and fortification are cost-effective and viable approaches to reducing the burden of NTD, anemia, and other conditions resulting from folate deficiency. The experience with interventions involving folic acid could provide a model for the subsequent development of supplementation and fortification programs involving vitamin B12.