Fundamentals of Crystalline Evolution and Properties of Carbon Nanotube-Reinforced Polyether Ether Ketone Nanocomposites in Fused Filament Fabrication.
As fused filament fabrication (FFF) continues to gain popularity, many studies are turning to nanomaterials or optimization of printing parameters to improve the materials' properties; however, many overlook how materials formulation and additive manufacturing (AM) processes cooperatively engineer the evolution of properties across length scales. Evaluating the in-process evolution of the nanocomposite using AM will provide a fundamental understanding of the material's microstructure, which can be tailored to create unique characteristics in functionality and performance. In this study, the crystallinity behavior of polyetheretherketone (PEEK) was studied in the presence of carbon nanotubes (CNTs) as a nucleation aid for improved crystallization during FFF processing. Using various characterization techniques and molecular dynamics simulations, it was discovered that the crystallization behavior of extruded filaments is very different from that of 3D printed roads. Additionally, the printed material exhibited cold crystallization, and the CNT addition increased the crystallization of printed roads, which were amorphous without CNT addition. Tensile strength and modulus were increased by as much as 42 and 51%, respectively, due to higher crystallinity during printing. Detailed knowledge on the morphology of PEEK-CNT used in FFF allows gaining a fundamental understanding of the morphological evolution occurring during the AM process that in turn enables formulating materials for the AM process to achieve tailored mechanical and functional properties, such as crystallinity or conductivity.


Integration of multi-disciplinary geospatial data for delineating agroecosystem uniform management zones.
Understanding agricultural ecosystems and their complex interactions with the environment is important for improving agricultural sustainability and environmental protection. Developing the necessary understanding requires approaches that integrate multi-source geospatial data and interdisciplinary relationships at different spatial scales. In order to identify and delineate landscape units representing relatively homogenous biophysical properties and eco-environmental functions at different spatial scales, a hierarchical system of uniform management zones (UMZ) is proposed. The UMZ hierarchy consists of seven levels of units at different spatial scales, namely site-specific, field, local, regional, country, continent, and globe. Relatively few studies have focused on the identification of the two middle levels of units in the hierarchy, namely the local UMZ (LUMZ) and the regional UMZ (RUMZ), which prevents true eco-environmental studies from being carried out across the full range of scales. This study presents a methodology to delineate LUMZ and RUMZ spatial units using land cover, soil, and remote sensing data. A set of objective criteria were defined and applied to evaluate the within-zone homogeneity and between-zone separation of the delineated zones. The approach was applied in a farming and forestry region in southeastern Ontario, Canada, and the methodology was shown to be objective, flexible, and applicable with commonly available spatial data. The hierarchical delineation of UMZs can be used as a tool to organize the spatial structure of agricultural landscapes, to understand spatial relationships between cropping practices and natural resources, and to target areas for application of specific environmental process models and place-based policy interventions.


Genetic variation in angiotensin-converting enzyme 2 gene is associated with extent of left ventricular hypertrophy in hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy, a common, inherited cardiac muscle disease, is primarily caused by mutations in sarcomeric protein-encoding genes and is characterized by overgrowth of ventricular muscle that is highly variable in extent and location. This variability has been partially attributed to locus and allelic heterogeneity of the disease-causing gene, but other factors, including unknown genetic factors, also modulate the extent of hypertrophy that develops in response to the defective sarcomeric functioning. Components of the renin-angiotensin-aldosterone system are plausible candidate hypertrophy modifiers because of their role in controlling blood pressure and biological effects on cardiomyocyte hypertrophy.


Favorable effects of vitamin D supplementation on pregnancy outcomes in gestational diabetes: a double blind randomized controlled clinical trial.
Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for unfavorable pregnancy outcomes. Prevalence of vitamin D deficiency is highly prevalent among women with GDM. This study was designed to assess the effect of vitamin D supplementation on pregnancy outcomes of pregnant women with GDM who were not on oral hypoglycemic agents. This randomized controlled clinical trial was performed among 45 pregnant women diagnosed with GDM at 24-28 weeks' gestation. Subjects were randomly assigned to consume either vitamin D supplements (cholecalciferol) or placebo. Individuals in the vitamin D group (n=22) received 50 000 IU vitamin D3 pearl 2 times during the study: at study baseline and day 21 of intervention and those in placebo group (n=23) received 2 placebos at the mentioned times. Fasting blood samples were taken at baseline to measure fasting plasma glucose. Participants underwent a 3-h oral glucose tolerance tests (OGTT) and the blood samples were collected at time 60, 120, and 180 min to measure plasma glucose levels. Newborn's weight, height, head circumference, Apgar score, and hyperbilirubinemia were determined. Taking vitamin D supplements, compared with placebo, resulted in improved pregnancy outcomes; such that those in the vitamin D group had no case of polyhydramnios, while 17.4% of subjects in placebo group had this condition (p=0.04). In addition, newborn's hyperbilirubinemia was significantly lower in vitamin D group than that in placebo group (27.3% vs. 60.9%, p=0.02). In conclusion, vitamin D supplementation for 6 weeks among pregnant women with GDM resulted in decreased maternal polyhydramnios and infant hyperbilirubinemia compared with placebo. Clinical trial registration number www.irct.ir:IRCT201305115623N7.


Effects of a Polymorphism of the Neuronal Amino Acid Transporter SLC6A15 Gene on Structural Integrity of White Matter Tracts in Major Depressive Disorder.
The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the pathophysiology of MDD through regulation of glutamate transmission in the brain. However, the involvement of this gene in microstructural changes in white matter (WM) tracts remains unclear. We aimed to investigate the influence of a polymorphism of this gene (rs1545853) on the structural integrity of WM tracts in the cortico-limbic network. Eighty-six patients with MDD and 64 healthy controls underwent T1-weighted structural magnetic resonance imaging, including diffusion tensor imaging (DTI), and genotype analysis. We selected the genu of the corpus callosum, the uncinate fasciculus, cingulum, and fornix as regions of interest, and extracted fractional anisotropy (FA) values using the FMRIB Diffusion Toolbox software. FA values for the left parahippocampal cingulum (PHC) was significantly reduced in the patients with MDD compared to healthy control participants (p = 0.004). We also found that MDD patients with the A allele showed reduced FA values for the left PHC than did healthy controls with the A allele (p = 0.012). There was no significant difference in the FA value of left PHC for the comparison between the G homozygotes of MDD and healthy control group. We observed an association between the risk allele of the SLC6A15 gene rs1545843 and the WM integrity of the PHC in MDD patients, which is known to play an important role in the neural circuit involved in emotion processing.


Quantitative assessment of miR34a as an independent prognostic marker in breast cancer.
Aberrant expression of microRNAs (miRNAs) is associated with cancer progression, initiation and metastasis. MiR34a is a miRNA that has been previously described as a tumour suppressor. Herein, we assess the expression of miR34a in three independent breast cancer cohorts using a quantitative in situ hybridisation assay (qISH) and determined its association with disease-specific death in breast cancer. The qISH method was applied to three independent primary breast cancer cohorts (Cohort 1 with 461, Cohort 2 with 279 and Cohort 3 with 795 patients) using 5' and 3' double DIG-labelled LNA-modified probe against miR34a using the protocol described previously. Level of expression measured as automated quantitative analysis (AQUA) score for miR34a was determined for each patient and assessed for association with risk of disease-specific death. An optimal cutpoint was determined using the X-tile software for disease-specific survival in Cohort 1 and this cutpoint was then applied to the other two cohorts after median normalisation of AQUA scores. Loss of miR34a is associated with poor outcome in three independent breast cancer cohorts (uncorrected log-rank P=0.0188 for Cohort 1, log-rank P=0.0024 for Cohort 2 and log-rank P=0.0455 for Cohort 3). In all three cohorts, loss of miR34a is able to stratify patients with poor disease-specific survival among node-negative patients, but not in node-positive population. Multivariate Cox proportional hazards analysis in Cohort 1 (P=0.0381) and Cohort 2 (P=0.0468) revealed that loss of miR34a is associated with poor outcome, independent of age, node status, receptor status and tumour size. Loss of the tumour suppressor, miR34a, identifies a subgroup of breast cancer patients with poor disease-specific survival. This study is consistent with the well-established preclinical observations for miR34a as a tumour suppressor and suggests that miR34a may have future value as a biomarker in breast cancer.


5-HT radioligands for human brain imaging with PET and SPECT.
The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT(1A), 5-HT(1B), 5-HT(2A), and 5-HT(4) receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging.


Heat-sensitive moxibustion in patients with osteoarthritis of the knee: a three-armed multicentre randomised active control trial.
In China, heat-sensitive moxibustion (HSM) is used for knee osteoarthritis (KOA) to reduce pain and improve physical activity. However, there is little high-quality evidence of its effectiveness. To evaluate the effectiveness of HSM in the treatment of KOA compared with usual care. We performed a multicentre, randomised controlled trial. In total, 432 patients with KOA were randomly assigned to one of three groups (HSM, conventional moxibustion, or conventional injection with sodium hyaluronate). The primary end point was the guiding principle of clinical research on new drugs in the treatment of KOA (GPCRND-KOA). Measurements were obtained at baseline and after 1 and 6 months (month 7) of study. For GPCRND-KOA, there were significant differences among the three groups after treatment at months 1 and 7. Pairwise comparisons showed that HSM was more effective than the conventional drug. There was no difference in any measures between conventional moxibustion and the conventional drug. Compared with conventional moxibustion, HSM resulted in greater improvement in all outcomes. This trial provided some evidence of the superiority of HSM in patients with KOA, suggesting that the observed differences might be due to superiority effects of a heat-sensitive point, although the effect of expectation cannot be ruled out. The trial was registered at Controlled Clinical Trials: ChiCTR-TRC-09000600.


Unilateral anhidrosis: a rare presentation of atrial myxoma?
A 50-year-old Chinese woman, non-smoker, presented with a 6-month history of increased sweating on the right side of her face, exertional chest tightness and breathlessness. Although the patient presented with increased sweating on the right, further history and examination revealed unilateral, left-sided anhidrosis, left partial ptosis and miosis consistent with Horner's syndrome. The patient was subsequently investigated with thoracic CT to assess for an apical lung mass (Pancoast tumour). A CT chest ruled out a mediastinal tumour, however, it revealed a large 60×41 mm soft tissue mass arising from the left atrium, protruding across the mitral valve into the left ventricle, suspicious of an intracardiac tumour. The patient was referred urgently for cardiothoracic assessment at a tertiary referral centre and successful open resection was performed. Histology confirmed an atrial myxoma. The patient developed postoperative atrial fibrillation but otherwise made a full recovery.


Lysosomal ceramide mediates gemcitabine-induced death of glioma cells.
Acid sphingomyelinase-induced ceramide release has been shown by many studies to induce apoptosis in response to various stimuli. However, the mechanisms of acid sphingomyelinase/ceramide-mediated death signaling following treatment with chemotherapeutic drugs have not been fully elucidated thus far. The present study demonstrates that treatment of glioma cells with clinically achievable doses of gemcitabine results in acid sphingomyelinase activation, lysosomal accumulation of ceramide, cathepsin D activation, Bax insertion into the mitochondria, and cell death. Pharmacological inhibition or genetic deficiency of acid sphingomyelinase prevented these events while overexpression of the enzyme sensitized cells to gemcitabine. Likewise, inhibitors of lysosomal functions also prevent gemcitabine-induced cell death. Our data indicate a critical role of the acid sphingomyelinase/ceramide system for gemcitabine-induced signaling and suggest that lysosomal ceramide accumulation mediates cell death induced by a chemotherapeutic drug.


A comparison of the pressure exerted on soft tissue by 2 myofascial rollers.
Self-myofascial release (SMR) is a technique used to treat myofascial restrictions and restore soft-tissue extensibility. To determine whether the pressure and contact area on the lateral thigh differ between a Multilevel rigid roller (MRR) and a Bio-Foam roller (BFR) for participants performing SMR. Ten healthy young men and women. Participants performed an SMR technique on the lateral thigh using both myofascial rollers. Thin-film pressure sensels recorded pressure and contact area during each SMR trial. Mean sensel pressure exerted on the soft tissue of the lateral thigh by the MRR (51.8 +/- 10.7 kPa) was significantly (P < .001) greater than that of the conventional BFR (33.4 +/- 6.4 kPa). Mean contact area of the MRR (47.0 +/- 16.1 cm2) was significantly (P < .005) less than that of the BFR (68.4 +/- 25.3 cm2). The significantly higher pressure and isolated contact area with the MRR suggest a potential benefit in SMR.


Tetra-ammine-(carbonato-κ(2) O,O')cobalt(III) nitrate: a powder X-ray diffraction study.
Practical chemistry courses at universities very frequently propose the synthesis and characterization of [Co(CO3)(NH3)4]NO3, but this goal is never achieved since students only obtain the hemihydrated form. The anhydrous form can be prepared, however, and its structure is presented here. Similar to the hemihydrate form, the anhydrous phase contains the Co(III) ion in an octahedral O2N4 coordination by a chelating carbonate group and four ammine ligands. The structure reveals an intricate array of N-H⋯O hydrogen bonds involving both the chelating and the non-chelating O atoms of the carbonate ligand as hydrogen-bond acceptors of the amine H atoms, which are also involved in hydrogen-bonding inter-actions with the nitrate O atoms. The structure of the anhydrous form is close to that of the hemihydrate phase, suggesting a probable topotactic reaction with relatively small rotations and translations of the [Co(CO3)(NH3)4](+) and NO3 (-) groups during the dehydration process, which produces an unusual volume increase of 4.3%.


Novel application of dry needling for neuropathic myofascial ankle pain and dysfunction following insidious integumentary infection: A case report.
Dry needling (DN) was effectively applied to a patient whose primary complaint was hyperalgesia and decreased ankle function meeting criteria for neuropathic myofascial pain following an integumentary infection, skin grafting and immobilization. A 33-year-old male serving on active duty in the United States Air Force was referred to physical therapy for decreased ankle range of motion and pain, eight weeks after an integumentary infection on his ankle. The infection was complicated by tissue loss requiring skin grafting for closure. Two months of traditional rehabilitation was unsuccessful and this patient was referred for DN treatment. Clinically relevant improvements were achieved after one treatment. After 48 hours, the patient's reported Pain Quality Assessment Scale (PQAS) dropped from a baseline 67 to 34 and Lower Extremity Functional Scale (LEFS) increased from 44 to 56. Plantarflexion and dorsiflexion improved by 15° and inversion and eversion by five degrees. After one year and 11 DN treatments, function continued to improve as demonstrated by single leg stance time improvement from 4 s to more than 60 seconds, without pain, a final LEFS of 72 and a return to unrestricted full duty. DN is an increasingly utilized treatment option for myofascial pain. This case report represents a unique application of DN to an atypical patient presenting with neuropathic myofascial pain syndrome that demonstrated improvement with DN as the sole intervention. Further research regarding the application of DN as a treatment option for neuropathic myofascial pain syndromes is needed.


Out-of-hospital cardiac arrest survival in international airports.
The highest achievable survival rate following out-of-hospital cardiac arrest is unknown. Data from airports serving international destinations (international airports) provide the opportunity to evaluate the success of pre-hospital resuscitation in a relatively controlled but real-life environment. This retrospective cohort study included all cases of out-of-hospital cardiac arrest at international airports with resuscitation attempted between January 1st, 2013 and December 31st, 2015. Crude incidence, patient, event characteristics and survival to hospital discharge/survival to 30 days (survival) were calculated. Mixed effect logistic regression analyses were performed to identify predictors of survival. Variability in survival between airports/countries was quantified using the median odds ratio. There were 800 cases identified, with an average of 40 per airport. Incidence was 0.024/100,000 passengers per year. Percentage survival for all patients was 32%, and 58% for patients with an initial shockable heart rhythm. In adjusted analyses, initial shockable heart rhythm was the strongest predictor of survival (odds ratio, 36.7; 95% confidence interval [CI], 15.5-87.0). In the bystander-witnessed subgroup, delivery of a defibrillation shock by a bystander was a strong predictor of survival (odds ratio 4.8; 95% CI, 3.0-7.8). Grouping of cases was significant at country level and survival varied between countries. In international airports, 32% of patients survived an out-of-hospital cardiac arrest, substantially more than in the general population. Our analysis suggested similarity between airports within countries, but differences between countries. Systematic data collection and reporting are essential to ensure international airports continually maximise activities to increase survival.


Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli.
The expression of Ia antigen in rat keratinocytes and gut epithelium was found to be inducible by a variety of immunological stimuli. Graft-vs.-host disease (GvHD) was accompanied by the appearance of Ia antigen in both sites, whereas local immunological stimuli, such as a contact-sensitizing agent applied to the skin and Trichinella spiralis infection of the gut, caused the expression of Ia antigen confined to the sites of contact of these stimuli with the tissues involved. Both T helper and T cytotoxic/suppressor subsets of parental lymphocytes, used to produce GvHD in F1 hybrid recipients, induce Ia expression in the skin and gut of these hosts, but simultaneous removal of both subsets from the donor inocula prevented induction. The Ia antigen expression associated with GvHD was shown to be of host origin but was not acquired from bone marrow-derived cells. Attempts to detect Ia antigen in serum or lymph of rats with GvHD gave negative results, and it was shown that Ia+ cells in the lamina propria of the small intestine did not take up detectable amounts of Ia antigen from the Ia+ intestinal epithelium. It appears that the local recognition of antigen by T lymphocytes can result in the induction of Ia antigen in keratinocytes and in the epithelial cells of the intestine. This antigen is synthesized by the cells in which it is found, and the observation that immunological stimuli are responsible for its appearance suggests that its role is an immunological one. Failure to find evidence that the gut epithelium Ia antigen was transferred to lymph or taken up by other Ia+ cells in the intestinal villi supports the view that this Ia (and, by analogy, that found in keratinocytes) serves a local function, and the possibility that it is involved in antigen presentation to T cells is discussed.


MR of neurocutaneous melanosis.
To describe the MR findings of neurocutaneous melanosis in the brain and correlate these with the known pathology and proposed embryologic basis of this disorder. The brain (seven patients) and spine (three patients) MR scans of seven patients with neurocutaneous melanosis were retrospectively reviewed. In two patients, findings were confirmed at surgery. The pattern of central nervous system involvement was also correlated with known pathologic studies regarding frequency and location of melanotic deposits. Five patients had regions of T1 shortening in the cerebellum; three of these also had T2 shortening. Five patients had regions of T1 shortening in the anterior temporal lobes. Other areas of involvement included the pia mater over the cerebellum (two patients), pons (one patient), medulla (one patient), and left parietal lobe (one patient). Only two lesions showed enhancement, edema, or necrosis; both were proved malignant melanomas at biopsy. No pial enhancement was detected. Neurocutaneous melanosis appears to involve the brain in specific locations that can be detected on MR imaging. Knowledge of these locations can aid in differentiating metastases, secondary to malignant degeneration of the large cutaneous nevi, from melanotic deposits that are a part of the disease. Identification of malignant degeneration of the melanotic deposits is difficult; at present, it depends on the identification of growth, edema, or necrosis of the deposits.


Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants.
The management of venous thromboembolism (VTE) requires an initial treatment with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), followed by oral anticoagulants (OA) for at least 3 months. OA treatment however, requires laboratory monitoring of anticoagulation, carries a definite risk of bleeding, and may be contraindicated in some patients. As an alternative to vitamin K antagonists, subcutaneous LMWH has been proposed and evaluated in randomized clinical trials, but they are all small studies that lack the power to establish if these two treatment modalities are equivalent in efficacy or safety. The objective of this review was to evaluate the efficacy (VTE recurrence) and safety (bleeds and deaths) of long-term treatment of VTE with LMWH compared with OA. A secondary endpoint was to evaluate the effect of LMWH on cancer mortality. Computerized searches of MedLine and EmBase were performed. In addition, randomized clinical trials were located through personal communication with colleagues, and through the manual scanning of meeting proceedings and reference lists of relevant studies. When necessary, the authors of the selected papers were called to obtain additional information. Two reviewers (AI and FG) reviewed and extracted data independently using a standard form. The primary analysis was performed for efficacy and safety endpoints on an intention-to-treat basis for the study period of randomized treatment. A meta-regression analysis was used to investigate the relationship between daily dose and clinical outcome. Seven studies that fulfillled our predefined criteria were identified, for a total of 1379 patients. When all studies were combined, a statistically non-significant reduction in the risk of VTE (OR 0.66; 95% confidence interval [CI] 0.41, 1.07) and in the risk of major bleeding (OR 0.45; 95% CI 0.18, 1.11) in favor of LMWH treatment was found. No difference in total mortality (OR 1.19; 95% CI 0.78, 1.83) or in cancer-related mortality was observed between the LMWH and the OA treatment. The results of this meta-analysis indicate that a 3-month course of LMWH is as effective and safe as a corresponding period of OA treatment, and may thus be considered as a valuable alternative option for patients in whom OA treatment appears contraindicated or problematic.


Spreading chromatin into chemical biology.
Epigenetics, broadly defined as the inheritance of non-Mendelian phenotypic traits, can be more narrowly defined as heritable alterations in states of gene expression ("on" versus "off") that are not linked to changes in DNA sequence. Moreover, these alterations can persist in the absence of the signals that initiate them, thus suggesting some kind of "memory" to epigenetic forms of regulation. How, for example, during early female mammalian development, is one X chromosome selected to be kept in an active state, while the genetically identical sister X chromosome is "marked" to be inactive, even though they reside in the same nucleus, exposed to the same collection of shared trans-factors? Once X inactivation occurs, how are these contrasting chromatin states maintained and inherited faithfully through subsequent cell divisions? Chromatin states, whether active (euchromatic) or silent (heterochromatic) are established, maintained, and propagated with remarkable precision during normal development and differentiation. However, mistakes made in establishing and maintaining these chromatin states, often executed by a variety of chromatin-remodeling activities, can lead to mis-expression or mis-silencing of critical downstream gene targets with far-reaching implications for human biology and disease, notably cancer. Though chromatin biologists have identified many of the "inputs" that are important for controlling chromatin states, the detailed mechanisms by which these processes work remain largely opaque, in part due to the staggering complexity of the chromatin polymer, the physiologically relevant form of our genome. The primary objective of this article is to serve as a "call to arms" for chemists to contribute to the development of the precision tools needed to answer pressing molecular problems in this rapidly moving field.


Excitability changes induced in the human auditory cortex by transcranial direct current stimulation: direct electrophysiological evidence.
Transcranial direct current stimulation (tDCS) can systematically modify behavior by inducing changes in the underlying brain function. Objective electrophysiological evidence for tDCS-induced excitability changes has been demonstrated for the visual and somatosensory cortex, while evidence for excitability changes in the auditory cortex is lacking. In the present study, we applied tDCS over the left temporal as well as the left temporo-parietal cortex and investigated tDCS-induced effects on auditory evoked potentials after anodal, cathodal, and sham stimulation. Results show that anodal and cathodal tDCS can modify auditory cortex reactivity. Moreover, auditory evoked potentials were differentially modulated as a function of site of stimulation. While anodal tDCS over the temporal cortex increased auditory P50 amplitudes, cathodal tDCS over the temporo-parietal cortex induced larger N1 amplitudes. The results directly demonstrate excitability changes in the auditory cortex induced by active tDCS over the temporal and temporo-parietal cortex and might contribute to the understanding of mechanisms involved in the successful treatment of auditory disorders like tinnitus via tDCS.


Evaluation of novel reactive MgO activated slag binder for the immobilisation of lead and zinc.
Although Portland cement is the most widely used binder in the stabilisation/solidification (S/S) processes, slag-based binders have gained significant attention recently due to their economic and environmental merits. In the present study, a novel binder, reactive MgO activated slag, is compared with hydrated lime activated slag in the immobilisation of lead and zinc. A series of lead or zinc-doped pastes and mortars were prepared with metal to binder ratio from 0.25% to 1%. The hydration products and microstructure were studied by X-ray diffraction, thermogravimetric analysis and scanning electron microscopy. The major hydration products were calcium silicate hydrate and hydrotalcite-like phases. The unconfined compressive strength was measured up to 160 d. Findings show that lead had a slight influence on the strength of MgO-slag paste while zinc reduced the strength significantly as its concentration increased. Leachate results using the TCLP tests revealed that the immobilisation degree was dependent on the pH and reactive MgO activated slag showed an increased pH buffering capacity, and thus improved the immobilisation efficiency compared to lime activated slag. It was proposed that zinc was mainly immobilised within the structure of the hydrotalcite-like phases or in the form of calcium zincate, while lead was primarily precipitated as the hydroxide. It is concluded, therefore, that reactive MgO activated slag can serve as clinker-free alternative binder in the S/S process.


Farnesol and cyclic AMP signaling effects on the hypha-to-yeast transition in Candida albicans.
Candida albicans, a fungal pathogen of humans, regulates its morphology in response to many environmental cues and this morphological plasticity contributes to virulence. Farnesol, an autoregulatory molecule produced by C. albicans, inhibits the induction of hyphal growth by inhibiting adenylate cyclase (Cyr1). The role of farnesol and Cyr1 in controlling the maintenance of hyphal growth has been less clear. Here, we demonstrate that preformed hyphae transition to growth as yeast in response to farnesol and that strains with increased cyclic AMP (cAMP) signaling exhibit more resistance to farnesol. Exogenous farnesol did not induce the hypha-to-yeast transition in mutants lacking the Tup1 or Nrg1 transcriptional repressors in embedded conditions. Although body temperature is not required for embedded hyphal growth, we found that the effect of farnesol on the hypha-to-yeast transition varies inversely with temperature. Our model of Cyr1 activity being required for filamentation is also supported by our liquid assay data, which show increased yeast formation when preformed filaments are treated with farnesol. Together, these data suggest that farnesol can modulate morphology in preformed hyphal cells and that the repression of hyphal growth maintenance likely occurs through the inhibition of cAMP signaling.


Detection of N. meningitidis group B antigens by MB-Dot-ELISA in patients with meningitis.
Infection with Neisseria meningitidis group B has been difficult to detect, partly because this bacterial group's polysaccharide is a weak immunogen. This article describes work carried out to test a new procedure (MB-Dot-ELISA) employing a high-titered horse antiserum for detection of N. meningitidis group B antigens. The study assayed cerebrospinal fluid samples from 585 subjects, 574 with suspected meningitis cases and 11 with neurologic disorders. The results of the assay indicated a sensitivity of 0.991 and a specificity of 0.826. These results were superior to those obtained with latex agglutination and in substantial agreement with the results of counterimmunoelectrophoresis and bacteriologic methods. Overall, the MB-Dot-ELISA was found to be sensitive, inexpensive, and suitable for public health laboratory investigations.


Efficacy and safety of selegiline for the treatment of Parkinson's disease: A systematic review and meta-analysis.
Drug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time. PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes. Among the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: -3.56 (-6.67, -0.45); 3 months: -3.32 (-3.75, -2.89); 6 months: -7.46 (-12.60, -2.32); 12 months: -5.07 (-6.74, -3.41); 48 months: -8.78 (-13.75, -3.80); 60 months: -11.06 (-16.19, -5.94)]. A similar trend was also found from the point estimates in UPDRS I, II, III, HAMD and WRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found. Selegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system. https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42021233145.


Changes in smoking, drinking, overweight and physical inactivity in young Australian women 1996-2013.
Issue addressed Smoking, risky drinking, overweight and obesity, and physical inactivity are health-risk factors (HRFs) that contribute significantly to morbidity worldwide. Several initiatives have been introduced over the past two decades to reduce these HRFs. This paper examines changes in the prevalence of HRFs in young women (aged 18-23 years) between 1996 and 2013, overall and within demographic groups. Methods Data from two cohorts of the Australian Longitudinal Study on Women's Health, born in 1973-78 (n=14247) and 1989-95 (n=17012) were weighted to provide national estimates. Prevalence ratios were used to compare HRFs in 2013 relative to 1996. Results In 1996, 32% were current smokers, 38% were risky drinkers, 22% were overweight or obese and 7% were physically inactive. In 2013, corresponding estimates were 19%, 35%, 33% and 6%. Between 1996 and 2013, overall smoking prevalence decreased, but remained over 43% among least educated women. Overweight and obesity increased in all demographic groups. Conclusions The findings suggest that only smoking, which has been the subject of changes in taxation, legislation and regulation, declined significantly, in all except the least educated women. In contrast, the prevalence of overweight and obesity, which has largely been addressed through awareness campaigns and voluntary actions by the food industry, increased markedly in all demographic sub-groups. So what? The findings show that comprehensive health promotion interventions, such as those for tobacco control, are successful (but may still be ineffective among less educated women). In contrast the measures to control population weight gain among young women have been futile so far.


Three-dimensional shape-controllable focal spot array created by focusing vortex beams modulated by multi-value pure-phase grating.
We propose a method for creating a three-dimensional (3D) shape-controllable focal spot array by combination of a two-dimensional (2D) pure-phase modulation grating and an additional axial shifting pure-phase modulation composed of four-quadrant phase distribution unit at the back aperture of a high numerical aperture (NA) objective. It is demonstrated that the one-dimensional (1D) grating designed by optimized algorithm of selected number of equally spaced arbitrary phase value in a single period could produce desired number of equally spaced diffraction spot with identical intensity. It is also shown that the 2D pure-phase grating designed with this method could generate 2D diffraction spot array. The number of the spots in the array along each of two dimensions depends solely on the number of divided area with different phase values of the dimension. We also show that, by combining the axial translation phase modulation at the back aperture, we can create 3D focal spot array at the focal volume of the high NA objective. Furthermore, the shape or intensity distribution of each focal spot in the 3D focal array can be manipulated by introducing spatially shifted multi vortex beams as the incident beam. These kinds of 3D shape-controllable focal spot array could be utilized in the fabrication of artificial metamaterials, in parallel optical micromanipulation and multifocal multiphoton microscopic imaging.


CatSper and the relationship of hyperactivated motility to intracellular calcium and pH kinetics in equine sperm.
In vitro fertilization does not occur readily in the horse. This may be related to failure of equine sperm to initiate hyperactivated motility, as treating with procaine to induce hyperactivation increases fertilization rates. In mice, hyperactivated motility requires a sperm-specific pH-gated calcium channel (CatSper); therefore, we investigated this channel in equine sperm. Motility was assessed by computer-assisted sperm motility analysis and changes in intracellular pH and calcium were assessed using fluorescent probes. Increasing intracellular pH induced a rise in intracellular calcium, which was inhibited by the known CatSper blocker mibefradil, supporting the presence of a pH-gated calcium channel, presumably CatSper. Hyperactivation was associated with moderately increased intracellular pH, but appeared inversely related to increases in intracellular calcium. In calcium-deficient medium, high-pH treatment induced motility loss, consistent with influx of sodium through open CatSper channels in the absence of environmental calcium. However, sperm treated with procaine in calcium-deficient medium both maintained motility and underwent hyperactivation, suggesting that procaine did not act via opening of the CatSper channel. CATSPER1 mRNA was identified in equine sperm by PCR, and CATSPER1 protein was localized to the principal piece on immunocytochemistry. Analysis of the predicted equine CATSPER1 protein revealed species-specific differences in structure in the pH-sensor region. We conclude that the CatSper channel is present in equine sperm but that the relationship of hyperactivated motility to calcium influx is weak. Procaine does not appear to act via CatSper in equine sperm, and its initial hyperactivating action is not dependent upon external calcium influx.


Sorting of large-diameter semiconducting carbon nanotube and printed flexible driving circuit for organic light emitting diode (OLED).
A novel approach was developed to sort a large-diameter semiconducting single-walled carbon nanotube (sc-SWCNT) based on copolyfluorene derivative with high yield. High purity sc-SWCNTs inks were obtained by wrapping arc-discharge SWCNTs with poly[2,7-(9,9-dioctylfluorene)-alt-4,7-bis(thiophen-2-yl)benzo-2,1,3-thiadiazole] (PFO-DBT) aided by sonication and centrifugation in tetrahydrofuran (THF). The sorted sc-SWCNT inks and nanosilver inks were used to print top-gated thin-film transistors (TFTs) on flexible substrates with an aerosol jet printer. The printed TFTs demonstrated low operating voltage, small hysteresis, high on-state current (up to 10(-3) A), high mobility and on-off ratio. An organic light emitting diode (OLED) driving circuit was constructed based on the printed TFTs, which exhibited high on-off ratio up to 10(4) and output current up to 3.5 × 10(-4) A at V(scan) = -4.5 V and Vdd = 0.8 V. A single OLED was switched on with the driving circuit, showing the potential as backplanes for active matrix OLED applications.


Neuropsychological deficits in long-term frequent cannabis users.
The authors examined neuropsychological functioning in 20 long-term (LT), 20 shorter term (ST) heavy frequent cannabis users, and 24 controls after abstinence for > or =24 hours prior to testing. LT users performed significantly worse on verbal memory and psychomotor speed. LT and ST users had a higher proportion of deficits on verbal fluency, verbal memory, attention, and psychomotor speed. Specific cognitive domains appear to deteriorate with increasing years of heavy frequent cannabis use.


Chaos mirror for free-space links.
We propose a novel reflector, called a chaos mirror, designed by use of the principles of chaotic reflection. A feature of the reflector is that it converts a one-dimensional spread of incident rays into a two-dimensional spread of reflected rays. This can be useful for making free-space optical beam links by sweeping a transmission beam in only one dimension.


Different patterns of transcription from the two Antennapedia promoters during Drosophila embryogenesis.
The homeotic genes of Drosophila control the differentiation of segments during development. Mutations in these genes cause one or more segments to develop structures normally found elsewhere in the organism. Several studies have shown that the spatial patterns of homeotic gene transcription are highly complex, and that these precise patterns of transcription are critical to normal development. The homeotic gene Antennapedia (Antp), a member of the Antennapedia Complex, is required for the correct differentiation of thoracic segments in both embryos and adults. The patterns of total Antp transcript and protein accumulation have been described in detail, but the contribution of each promoter to the overall pattern in embryos has not been reported. We have examined in detail the spatial distribution of transcripts from each of the Antp promoters in both embryo sections and whole embryos by in situ hybridization using promoter-specific probes. We show that the transcripts from each of the two promoters accumulate in distinct, but overlapping patterns during embryogenesis. The results demonstrate that the two Antp promoters are differentially regulated in embryos and provide a basis for examining the regulation of the two promoters and characterizing more fully the function of Antp during embryogenesis. In addition, we have examined the regulation of each of the Antp promoters by genes of the bithorax complex (BX-C). We show that in BX-C- embryos both promoters are derepressed in the abdomen.


Do Single Experiences of Childhood Abuse Increase Psychopathology Symptoms in Adulthood?
Experiencing emotional, physical, and/or sexual abuse in childhood increases the risk (compared with baseline) of developing psychopathological symptoms in adulthood. In the present study, we explored the effects of experiencing only a single abusive event on adulthood psychopathology, and compared this with the risk in individuals with no abusive experiences and with the risk in individuals with several abusive experiences. We used a Finnish population-based sample of 10,980 adult participants (3,766 male and 7,214 female twins and their siblings). The participants reported abuse experiences using the Childhood Trauma Questionnaire (CTQ) and current psychopathology symptoms using the depression and anxiety scales of the Brief Symptom Inventory-18 (BSI-18). We found that in both men and women even single experiences of emotional and sexual abuse were associated with increased psychopathology symptoms compared with no abuse experiences. Single experiences of physical abuse did not, however, increase the risk in either women or men. As expected, experiences of repeated abuse (of all abuse types) increased the risk of psychopathology symptoms compared with experiences of single abuse. When we isolated individuals who only had a single experience of any type of abuse (i.e., emotional, physical, or sexual) to control for possible co-morbidity, no increased risk was found. This study shows that individuals who report experiencing single events of abuse of a specific abuse type have an increased risk of displaying psychopathology symptoms in adulthood. This increase is, however, mainly due to co-morbidity of abuse types.


Is meconium useful to predict fetal exposure to organochlorines and hydroxylated PCBs?
The objective of this study is to compare meconium and maternal serum as biomarkers of fetal exposure to organochlorines (OCs). A subset of 40 meconium samples and complementary maternal sera from the Northern Norway Mother-and-Child Contaminant Cohort Study (MISA) were selected. Meconium samples were collected at the earliest opportunity (median 9.0 hours postpartum, range 0-61) and maternal serum in the 2nd trimester (median 19.0 gestational weeks, range 13-34) and analysed for OC contaminants selected from the Arctic Monitoring and Assessment Programme's (AMAP) suite of OCs and selected hydroxylated metabolites. Eight compounds with detection frequencies ≥70% in both media (criterion for inclusion) were included in the statistical analyses. Median concentration ratios for p,p'-DDE, HCB, trans-nonachlor and cis-nonachlor favoured meconium, and PCB 138 and 153 and OH-PCB 146 and 172 were higher in maternal serum. All inter-media correlations were significant (Spearman's rho) for wet-weight concentrations and improved when concentrations in a small subset of 15 meconium and serum samples were both lipid-adjusted; only OH-PCB 146 slightly favoured maternal serum. Multivariable linear regression modelling confirmed that maternal serum was the most consistent predictor of meconium concentrations, with gestational age and time of meconium sampling improving the models. Although more challenging to analyse, the lipid-adjusted OC concentration in meconium is viewed as a sensitive and informative fetal exposure index when taking into account the gestational age and its postpartum sampling time.


Validity and Reliability of Dermoscopic Criteria Used to Differentiate Nevi From Melanoma: A Web-Based International Dermoscopy Society Study.
The comparative diagnostic performance of dermoscopic algorithms and their individual criteria are not well studied. To analyze the discriminatory power and reliability of dermoscopic criteria used in melanoma detection and compare the diagnostic accuracy of existing algorithms. This was a retrospective, observational study of 477 lesions (119 melanomas [24.9%] and 358 nevi [75.1%]), which were divided into 12 image sets that consisted of 39 or 40 images per set. A link on the International Dermoscopy Society website from January 1, 2011, through December 31, 2011, directed participants to the study website. Data analysis was performed from June 1, 2013, through May 31, 2015. Participants included physicians, residents, and medical students, and there were no specialty-type or experience-level restrictions. Participants were randomly assigned to evaluate 1 of the 12 image sets. Associations with melanoma and intraclass correlation coefficients (ICCs) were evaluated for the presence of dermoscopic criteria. Diagnostic accuracy measures were estimated for the following algorithms: the ABCD rule, the Menzies method, the 7-point checklist, the 3-point checklist, chaos and clues, and CASH (color, architecture, symmetry, and homogeneity). A total of 240 participants registered, and 103 (42.9%) evaluated all images. The 110 participants (45.8%) who evaluated fewer than 20 lesions were excluded, resulting in data from 130 participants (54.2%), 121 (93.1%) of whom were regular dermoscopy users. Criteria associated with melanoma included marked architectural disorder (odds ratio [OR], 6.6; 95% CI, 5.6-7.8), pattern asymmetry (OR, 4.9; 95% CI, 4.1-5.8), nonorganized pattern (OR, 3.3; 95% CI, 2.9-3.7), border score of 6 (OR, 3.3; 95% CI, 2.5-4.3), and contour asymmetry (OR, 3.2; 95% CI, 2.7-3.7) (P < .001 for all). Most dermoscopic criteria had poor to fair interobserver agreement. Criteria that reached moderate levels of agreement included comma vessels (ICC, 0.44; 95% CI, 0.40-0.49), absence of vessels (ICC, 0.46; 95% CI, 0.42-0.51), dark brown color (ICC, 0.40; 95% CI, 0.35-0.44), and architectural disorder (ICC, 0.43; 95% CI, 0.39-0.48). The Menzies method had the highest sensitivity for melanoma diagnosis (95.1%) but the lowest specificity (24.8%) compared with any other method (P < .001). The ABCD rule had the highest specificity (59.4%). All methods had similar areas under the receiver operating characteristic curves. Important dermoscopic criteria for melanoma recognition were revalidated by participants with varied experience. Six algorithms tested had similar but modest levels of diagnostic accuracy, and the interobserver agreement of most individual criteria was poor.


Investigation of physical properties of a polycaprolactone dermal filler when mixed with lidocaine and lidocaine/epinephrine.
In esthetic treatments with dermal fillers, increasing numbers of physicians are using the technique of mixing an anesthetic agent into the dermal filler before treatment to increase the comfort of the patients. This study aimed at evaluating the effects on the physical properties of a polycaprolactone (PCL)-based dermal filler after mixing with lidocaine. A range of 2.0% lidocaine and 2.0% lidocaine/epinephrine concentrations was mixed with the PCL dermal filler to evaluate the changes in dynamic viscosity and elasticity, extrusion force, pH, and needle jam rates. The number of passes back to forth for optimal homogeneity of lidocaine and PCL dermal filler was determined. With 15 mixing strokes the lidocaine solution can effectively be mixed into dermal filler resulting in a homogenous blend. The viscosity, elasticity, and the extrusion force decrease with increasing lidocaine volume. The viscosity and elasticity of the dermal filler is sufficient to keep the PCL microspheres in suspension. There were no needle jams. The pH of the PCL dermal filler mixed with lidocaine solution is equivalent to that of the original dermal filler. It is concluded that mixing of lidocaine into the PCL-based dermal filler can safely be performed without harmful changes in the physical properties of the original dermal filler.


IgG4-related diseases: state of the art on clinical practice guidelines.
Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing-remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids. In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD. With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centres.


Unconventional myosins in inner-ear sensory epithelia.
To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined the distribution of four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes. Of the four isozymes, each from a different class, three are expressed in the hair cells of amphibia and mammals. In stereocilia, constructed of cross-linked F-actin filaments, myosin-Ibeta is found mostly near stereociliary tips, myosin-VI is largely absent, and myosin-VIIa colocalizes with crosslinks that connect adjacent stereocilia. In the cuticular plate, a meshwork of actin filaments, myosin-Ibeta is excluded, myosin-VI is concentrated, and modest amounts of myosin-VIIa are present. These three myosin isozymes are excluded from other actin-rich domains, including the circumferential actin belt and the cortical actin network. A member of a fourth class, myosin-V, is not expressed in hair cells but is present at high levels in afferent nerve cells that innervate hair cells. Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt. Our localization results suggest specific functions for three hair-cell myosin isozymes. As suggested previously, myosin-Ibeta probably plays a role in adaptation; concentration of myosin-VI in cuticular plates and association with stereociliary rootlets suggest that this isozyme participates in rigidly anchoring stereocilia; and finally, colocalization with cross-links between adjacent stereocilia indicates that myosin-VIIa is required for the structural integrity of hair bundles.


A Model to Estimate the Amount of Primary Inoculum of Elsinoë ampelina.
In Eastern Canada, anthracnose, caused by the fungus Elsinoë ampelina, is a serious disease on susceptible grape cultivars. In the absence of management tools, anthracnose management relies almost exclusively on fungicide applications programmed at fixed intervals. Therefore, a better understanding of the factors affecting primary inoculum release and abundance would help in the timing of the first fungicide applications. The temporal dynamics of airborne primary inoculum released from cane cankers were investigated from 2007 to 2010. One to three times per week, starting in the first week of April, six 12-cmlong cane pieces were randomly selected from diseased canes that had overwintered on a vineyard floor. The concentration of E. ampelina conidia was expressed as the number of conidia per square millimeter of canker. In total, 27, 32, 33, and 118 samplings were conducted in 2007, 2008, 2009, and 2010, respectively, with the 118 samplings conducted on three sites at 49, 35, and 34 samplings for site 1, 2, and 3, respectively. Each year, the number of conidia per square millimeter of canker was expressed as the proportion of seasonal inoculum (PSI) at the same site and analyzed as a function of degree-days (DD; base temperature = 0°C) accumulated since 1 April (cumulative degreedays [CDD]). The nonlinear sigmoid model in the form PSI = 1.003/(1 + e-((CDD - 566.133)/139.204)) provided adequate fit to the observed data (P < 0.0001, R2 = 0.97). When the model was validated against independent data, the model adequately predicted PSI; however, reliability was improved by adding a "dry days" threshold of 6 days during which accumulation of DD is stopped. This study shows that primary inoculum of grape anthracnose is available early in the season before bud break; meaning that emerging leaves could be infected provided that weather conditions are favorable. The results also show that there is an overlap in the availability of primary and secondary inoculum, mainly during the period of rapid leaf growth, a situation that may explain the explosive nature of the disease. The results suggest that, on susceptible cultivars and when there is a history of anthracnose in the vineyard, a fungicide spray program should be initiated early in the season, as soon as leaves are present.


Serum Lipids in Association With Type 2 Diabetes Risk and Prevalence in a Chinese Population.
We previously reported an association between lysophosphatidylinositol (LPI) (16:1) and risk for type 2 diabetes in a Chinese population using an untargeted analysis. To examine the overall associations of LPIs and their related metabolites, such as nonesterified fatty acids (NEFAs) and acylcarnitines, with incident and prevalent type 2 diabetes using a targeted approach. A case-control study was nested within the Singapore Chinese Health Study. Cases and controls were individually matched by age, sex, and date of blood collection. We used both liquid and gas chromatography tandem mass spectrometry to measure serum metabolite levels at baseline, including 8 LPIs, 19 NEFAs, and 34 acylcarnitines. Conditional logistic regression models were used to estimate the associations between metabolites and diabetes risk. Participants included 160 incident and 144 prevalent cases with type 2 diabetes and 304 controls. Incident and prevalent type 2 diabetes. On the basis of a false discovery rate <0.1, we identified 37 metabolites associated with prevalent type 2 diabetes, including 7 LPIs, 18 NEFAs, and 12 acylcarnitines, and 11 metabolites associated with incident type 2 diabetes, including 2 LPIs and 9 NEFAs. Two metabolites, LPI (16:1) and dihomo-γ-linolenic acid, showed independent associations with incident type 2 diabetes and significantly enhanced the risk prediction. We found several LPIs and NEFAs that were associated with risk for type 2 diabetes and may improve our understanding of the pathogenesis. The findings suggest that lipid profiles could aid in diabetes risk assessment in Chinese populations.


Reducing Patient Uncertainty: Implementation of a Shared Decision-Making Process Enhances Treatment Quality and Provider Communication.
Patients with cancer can experience uncertainty when making treatment decisions. When unaddressed, patient uncertainty can result in decisional conflict and decisional regret. Providers can assist in decreasing these factors by involving patients in the decision-making process. Patients who agree to participate should be informed about their diagnosis, prognosis, and treatment options, including the benefits, the risks and harms, or the option of no treatment. Providers also can help patients to clarify their values, which reveal patient preferences and inform tailoring of care for each patient. When an informed patient's personal preferences align with care decisions, decisional quality is achieved.


Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review
Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.


Hearing: cortical activation does matter.
Lesion studies have suggested that the auditory cortex may not be involved in many aspects of hearing. A recent report casts doubt on this long-held view by showing that reversible inactivation of the auditory cortex leads to a transient impairment in tone detection and frequency discrimination.


Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics.
A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK(-/-)) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (V(max)) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK(-/-) mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK(-/-) mice, but ejection fraction (EF) remained normal. V(max), however, was significantly reduced in the CK(-/-) mice [wild-type, 2.32 +/- 0.09 vs. CK(-/-), 1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK(-/-) MI, 1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK(-/-) mice (wild-type, 6.68 +/- 0.27 vs. CK(-/-), 4.12 +/- 0.63 ml/g.min, P < 0.05; and wild-type MI, 3.97 +/- 0.65 vs. CK(-/-) MI, 3.71 +/- 0.57 ml/g.min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK(-/-) phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.


Enhancing public health and safety by diagnosing and treating obstructive sleep apnea in the transportation industry: an American Academy of Sleep Medicine position statement.
Obstructive sleep apnea (OSA) may lead to serious health, safety, and financial implications-including sleepiness-related crashes and incidents-in workers who perform safety-sensitive functions in the transportation industry. Evidence and expert consensus support its identification and treatment in high-risk commercial operators. An Advanced Notice of Proposed Rulemaking regarding the diagnosis and treatment of OSA in commercial truck and rail operators was issued by the Federal Motor Carrier Safety Administration and Federal Railroad Administration, but it was later withdrawn. This reversal has led to questions about whether efforts to identify and treat OSA are warranted. In the absence of clear directives, we urge key stakeholders, including clinicians and patients, to engage in a collaborative approach to address OSA by following, at a minimum, the 2016 guidelines issued by a Medical Review Board of the Federal Motor Carrier Safety Administration, alone or in combination with 2006 guidance by a joint task force. The current standard of care demands action to mitigate the serious health and safety risks of OSA. Das AM, Chang JL, Berneking M, et al. Enhancing public health and safety by diagnosing and treating obstructive sleep apnea in the transportation industry: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2022;18(10):2467-2470.


Guidance of collective cell migration by substrate geometry.
Collective behavior refers to the emergence of complex migration patterns over scales larger than those of the individual elements constituting a system. It plays a pivotal role in biological systems in regulating various processes such as gastrulation, morphogenesis and tissue organization. Here, by combining experimental approaches and numerical modeling, we explore the role of cell density ('crowding'), strength of intercellular adhesion ('cohesion') and boundary conditions imposed by extracellular matrix (ECM) proteins ('constraints') in regulating the emergence of collective behavior within epithelial cell sheets. Our results show that the geometrical confinement of cells into well-defined circles induces a persistent, coordinated and synchronized rotation of cells that depends on cell density. The speed of such rotating large-scale movements slows down as the density increases. Furthermore, such collective rotation behavior depends on the size of the micropatterned circles: we observe a rotating motion of the overall cell population in the same direction for sizes of up to 200 μm. The rotating cells move as a solid body, with a uniform angular velocity. Interestingly, this upper limit leads to length scales that are similar to the natural correlation length observed for unconfined epithelial cell sheets. This behavior is strongly altered in cells that present a downregulation of adherens junctions and in cancerous cell types. We anticipate that our system provides a simple and easy approach to investigate collective cell behavior in a well-controlled and systematic manner.


Psychotherapy and bulimia nervosa. Longer-term effects of interpersonal psychotherapy, behavior therapy, and cognitive behavior therapy.
To determine whether cognitive behavior therapy (CBT) for bulimia nervosa has a specific therapeutic effect and determine whether a simplified behavioral treatment (BT) of CBT is as effective as the full treatment. Randomized controlled trial involving three psychological treatments. Two planned comparisons, CBT with interpersonal psychotherapy (IPT), and CBT with BT. Closed 12-month follow-up period. Independent assessors. Secondary referral center. Seventy-five consecutively referred patients with bulimia nervosa. Patients with concurrent anorexia nervosa were excluded. Cognitive behavior therapy, IPT, BT conducted on an individual outpatient basis. There were nineteen sessions over 18 weeks. Six experienced therapists administered all three treatments. There was no concurrent treatment. Frequency of binge eating and purging. High rate (48%) of attrition and withdrawal among the patients who received BT. Over follow-up, few patients undergoing BT met criteria for a good outcome (cessation of all forms of binge eating and purging). Patients in the CBT and IPT treatments made equivalent, substantial, and lasting changes across all areas of symptoms, although there were clear temporal differences in the pattern of response, with IPT taking longer to achieve its effects. Bulimia nervosa may be treated successfully without focusing directly on the patient's eating habits and attitudes to shape and weight. Cognitive behavior therapy and IPT achieved equivalent effects through the operation of apparently different mediating mechanisms. A further comparison of CBT and IPT is warranted. The behavioral version of CBT was markedly less effective than the full treatment.


The role of ultrasound biomicroscopy in ocular trauma.
To demonstrate the usefulness of ultrasound biomicroscopy (UBM) in detecting and localizing small ocular foreign bodies. This is a retrospective study of the records of 555 consecutive patients evaluated by UBM by the Visual Physiology Unit of the Wills Eye Hospital from August 1994 to November 1997. In 9 patients, a foreign body was identified. In 6 patients, the history suggested the presence of a foreign body, but one could not be detected by clinical examination. In 2 patients, the referring physicians requested UBM to determine whether or how deep a known foreign body had penetrated the globe. In 1 patient, the foreign body was not suspected clinically. In regard to other diagnostic techniques, CT failed to identify the foreign body in 1 patient. In another, contact B-scan ultrasonography failed. In a third, both CT and contact B-scan ultrasonography failed. The foreign body was intracorneal in 2 eyes, subconjunctival in 2, intrascleral in 3, and intraocular in 2. Six were nonmetallic. Two were metallic. In one case, the foreign body was lost and its composition is unknown. In 5 cases, the UBM findings altered the patient's management. UBM is a valuable adjunct in the evaluation of small, anteriorly located foreign body that may not be detectable by other methods. UBM may be especially useful for finding nonmetallic foreign bodies.


bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS.
Cell death is a common feature of neural development in all vertebrates. The bcl-2 proto-oncogene has been shown to protect a variety of cell types from programmed cell death. We have examined the distribution of bcl-2 protein in the developing and adult nervous systems. bcl-2 protein is widespread during embryonic development. Proliferating neuroepithelial cells of ventricular zones as well as the postmitotic cells of the cortical plate, cerebellum, hippocampus and spinal cord express bcl-2. Postnatally, bcl-2 is principally retained in the granule cells of the cerebellum and dentate gyrus of the hippocampus. bcl-2 expression in the CNS declines with aging. In the peripheral nervous system, neurons and supporting cells of sympathetic and sensory ganglia retain substantial bcl-2 protein throughout life. The widespread expression of bcl-2 in CNS and PNS neurons during embryonic development and its selective retention in the adult PNS is consistent with a role for bcl-2 in regulating neuronal survival. In addition, the expression of bcl-2 in some neuronal populations beyond the recognized period of cell death is suggestive of a role for bcl-2 beyond simply protecting neurons from developmental cell death.


Prevalence of extended-spectrum beta-lactamase-producing enterobacterial urinary infections and associated risk factors in small children of Garoua, Northern Cameroon.
the emergence of extended-spectrum beta-lactamase-producing Entero bacteriaceae (E-ESBLs) is currently a major public health problem in the world and, in particular, in developing countries. In Cameroon, data on E-ESBLs are rare, especially in Garoua and in the northern region of the country. The objective of this study is to document the epidemiology of E-ESBL infections in small children and to explore their associations with possible risk factors. this was a cross-sectional, descriptive study conducted from June 14 to September 30, 2018, including small children with suspected urinary tract infections (UTI) attending the outpatient pediatric departments of two health facilities in the city of Garoua. Urine samples were analyzed at the Bacteriology Laboratory of the Pasteur Center of Cameroon, Annex Garoua. Bacterial culture was carried out on Bio-Rad UriSelect® chromogenic agar and the identification was confirmed by bioMérieux API 20E. The antibiotic susceptibility was determined using the bioMérieux ATB UR gallery and the ESBL phenotype was detected by the double disk synergy method according to the CA-SFM 2013 recommendations. The data was analyzed with the R Statistical Software version 2.15.2. a total of 57 urine samples were collected from children aged from one month to two years, 37 boys and 20 girls. Bacteria were detected by culture in 20 samples: Escherichia coliwas the most frequently (75 %) isolated species followed by Klebsiella pneumoniae(25%). More than half of the infected samples (55%) contained E-ESBL. The presence of an ESBL was significantly associated with previous antibiotic intake up to 3 months prior current UTI (p=0.01664). The E-ESBL strains showed co-resistance to different antibiotics. this study reveals the important dissemination of E-ESBLs among small children in the community and a high rate of co-resistance to the different antibiotic families commonly used.


Polyunsaturated fatty acids and reduced odds of MCI: the Mayo Clinic Study of Aging.
Mono- and polyunsaturated fatty acids (MUFA, PUFA) have been associated with a reduced risk of dementia. The association of these fatty acids with mild cognitive impairment (MCI) is not fully established. The objective of the study was to investigate the cross-sectional association of dietary fatty acids with MCI in a population-based sample. Participants aged >or= 70 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale (participant and informant), a neurological evaluation, and neuropsychological testing. A panel of nurses, physicians, and neuropsychologists reviewed the data for each participant in order to establish a diagnosis of MCI, normal cognition, or dementia by consensus. Participants also completed a 128-item food-frequency questionnaire. Among 1,233 non-demented subjects, 163 (13.2%) had MCI. The odds ratio (OR) of MCI decreased with increasing PUFA and MUFA intake. Compared to the lowest tertile, the OR (95% confidence interval) for the upper tertiles were 0.44 (0.29-0.66; p for trend = 0.0004) for total PUFA; 0.44 (0.30-0.67; p for trend = 0.0004) for omega-6 fatty acids; 0.62 (0.42-0.91; p for trend = 0.012) for omega-3 fatty acids; and 0.56 (0.38-0.83; p for trend = 0.01) for (MUFA+PUFA):saturated fatty acid ratio after adjustment for age, sex, number of years of education, and caloric intake. In this study, higher intake of PUFA and MUFA was associated with a reduced likelihood of MCI among elderly persons in the population-based setting.


The conceptualisation of forgiveness among Turkish children and adolescents.
This study examined (a) how Turkish children and adolescents define forgiveness, (b) the association between self-reported forgiveness and the concepts participants hold and (c) the association between self-reported forgiveness and age. Three hundred and sixty-seven Turkish children in primary (N = 220) and secondary schools (N = 147) were involved in the study. Participants were asked to define forgiveness, and the study used the Enright Forgiveness Inventory for Children (EFI-C). Participants' conceptions of forgiveness were categorised into four groups: conditional forgiveness, reconciliation, ignoring the hurtful event and affective reactions. Half of all the participants in the study were found to be in the conditional forgiveness category. Turkish children were found to be mostly in the category of conditional forgiveness, reconciliation and affective reactions compared with adolescents. Adolescents were mainly found to be in the ignoring the hurtful event category. The highest self-reported forgiveness mean was in the affective reactions category. Participants were commonly offended by friends, siblings, teachers and fathers. No correlation was found between self-reported forgiveness and age. The present results expand the literature of forgiveness by presenting evidence that Turkish children's and adolescents' understanding of forgiveness moderately relates to theoretical definitions.


Effect of different adhesives combined with two resin composite cements on shear bond strength to polymeric CAD/CAM materials.
This study tested the impact of different adhesives and resin composite cements on shear bond strength (SBS) to polymethyl methacrylate (PMMA)- and composite-based CAD/CAM materials. SBS specimens were fabricated and divided into five main groups (n=30/group) subject to conditioning: 1. Monobond Plus/Heliobond (MH), 2. Visio.link (VL), 3. Ambarino P60 (AM), 4. exp. VP connect (VP), and 5. no conditioning-control group (CG). All cemented specimens using a. Clearfil SA Cement and b. Variolink II were stored in distilled water for 24 h at 37 °C. Additionally, one half of the specimens were thermocycled for 5,000 cycles (5 °C/55 °C, dwell time 20 s). SBS was measured; data were analyzed using descriptive statistics, four- and one-way ANOVA, unpaired two-sample t-test and Chi(2)-test. CAD/CAM materials without additional adhesives showed no bond to resin composite cements. Highest SBS showed VL with Variolink II on composite-based material, before and after thermocycling.


Lack of activation of the unfolded protein response in mouse and cellular models of Niemann-Pick type C disease.
Niemann-Pick type C (NPC) disease is a fatal lysosomal storage disease related to progressive neurodegeneration secondary to abnormal intracellular accumulation of cholesterol. Signs of endoplasmic reticulum (ER) stress have been reported in other lipidoses. Adaptation to ER stress is mediated by the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates stress or triggers apoptosis of irreversibly damaged cells. To investigate the possible engagement of ER stress responses in NPC models. We used NPC1 deficient mice and an NPC cell-based model by knocking down the expression of NPC1 to measure several UPR markers through different approaches. Despite expectations that the UPR will be activated in NPC, our results indicate a lack of ER stress reactions in the cerebellum of symptomatic mice. Similarly, knocking down NPC1 in Neuro2a cells leads to clear cholesterol accumulation without evidence of UPR activation. Our results suggest that cholesterol overload and neuronal dysfunction in NPC is not associated with ER stress, which contrasts with recent reports suggesting the activation of the UPR in other lysosomal storage diseases.


Photoexcited charge carrier dynamics of interconnected TiO2 nanoparticles: evidence of enhancement of charge separation at anatase-rutile particle interfaces.
The charge carrier kinetics of hydrothermally treated TiO2 nanoparticles, consisting of interconnected anatase and rutile crystallographic forms, was investigated using a heterodyne transient grating technique to obtain direct evidence of the enhancement of charge separation efficiency. We found that surface recombination arising from trapped electrons was retarded, compared with that of P25 TiO2 nanoparticles, with the aid of an increase of particle interfaces. This means that the charge separation efficiency of hydrothermally treated TiO2 nanoparticles is higher than that of P25 TiO2 nanoparticles, to which the enhanced photocatalytic performance of the hydrothermally treated TiO2 nanoparticles could be attributed.


Development of a scanning, solar-blind, water Raman lidar.
The need for an instrument capable of measuring water-vapor fluxes over mixed canopy and large areas has long been recognized. Such a device would greatly enhance the study of evapotranspiration processes and has great practical value for water management. To address this problem, a scanning water Raman lidar has been designed and constructed. Analytical methods have also been developed to take advantage of the type of information that this lidar can generate. The lidar is able to measure the absolute water content and calculate the evaporative flux quickly over relatively large areas. This capability provides new opportunities for the study of microscale atmospheric processes. The variogram data indicate that the spatial sampling size must be of the order of 10 m if fluxes and scalars are to be properly represented. Examples of data are presented.


Scanning tunneling luminescence of individual CdSe nanowires.
The local luminescence properties of individual CdSe nanowires composed of segments of zinc blende and wurtzite crystal structures are investigated by low-temperature scanning tunneling luminescence spectroscopy. Light emission from the wires is achieved by the direct injection of holes and electrons, without the need for coupling to tip-induced plasmons in the underlying metal substrate. The photon energy is found to increase with decreasing wire diameter due to exciton confinement. The bulk bandgap extrapolated from the energy versus diameter dependence is consistent with photon emission from the zinc blende-type CdSe sections.


Low entropic barrier to the hydrophobic collapse of the prion protein: effects of intermediate states and conformational flexibility.
A simple kinetic model is applied to study the folding reaction of the C-terminal domain of the murine prion protein, mPrP(121-231). The model provides an equation linking a protein's folding rate with its native topology and the conformational entropic cost of folding. The model predicts that the average conformational entropic cost per residue associated with the folding transition of mPrP(121-231) is smaller than the average for a broad sample of two-state folding proteins. The results are consistent with the native state of mPrP(121-231) being more flexible than the average protein, but the behavior could also arise from the presence of early intermediate states. The findings are in agreement with experimental and theoretical results on the prion protein conformational flexibility. The model is fully analytical and provides a simple way to obtain a quantitative measure of conformational flexibility in two-state proteins from kinetic and structural experimental data.


Requirement for protein kinase C activation in basic fibroblast growth factor-induced human endothelial cell proliferation.
The intracellular signaling mechanisms that mediate basic fibroblast growth factor (bFGF)-induced angiogenesis have not been fully identified. In particular, whether activation of the intracellular enzyme protein kinase C (PKC) is necessary or sufficient for bFGF-induced mitogenesis of human endothelial cells is not clear. Accordingly, the effect of bFGF stimulation on the Ca2+ increase and PKC activity of normal human endothelial cells (HEC) was studied, as was the effect of inhibition of PKC and the distribution of PKC isoenzymes in these cells. The addition of bFGF to cultured HEC increased overall PKC activity in the absence of an increase in intracellular Ca2+ and markedly stimulated their proliferation, as did the addition of PKC-activating phorbol esters. bFGF-induced proliferation was prevented by the PKC inhibitors chelerythrine and H-7 and by downregulation of PKC after prolonged incubation with phorbol esters. In contrast, these inhibitors did not prevent HEC proliferation induced by epidermal growth factor. Because of the failure of bFGF to increase Ca2+, we determined whether bFGF-induced proliferation could be mediated by novel or atypical PKC isoenzymes (which are not regulated by Ca2+). Investigation of the isoenzyme distribution of confluent and subconfluent HEC by immunoblotting, Northern transfer analysis, and polymerase chain reaction of reverse-transcribed RNA revealed the presence of several novel and atypical isoenzymes (PKC-delta, -eta, -theta, and -zeta) as well as small amounts of the conventional (Ca(2+)-regulated) isoenzymes PKC-alpha and -beta. Activation of PKC by bFGF, in the absence of an increase in intracellular Ca2+, suggests that one or more of these Ca(2+)-independent PKC isoenzymes are both necessary and sufficient for HEC proliferation after bFGF.


Effects of a nutritional intervention in obese postmenopausal women on atypical antipsychotics.
To investigate the effects of a nutritional intervention on the body weight, body composition, blood glucose and lipid levels of obese postmenopausal women taking atypical antipsychotics in Greece. In a case-control design, 25 obese postmenopausal women treated with antipsychotic medications and 28 obese healthy comparisons were followed for 3 months. A nutritional program was individually designed for each participant. At baseline and at 3 months of the study, anthropometric, body composition, blood glucose and lipid measurements were performed. Significant reductions in body weight, body mass index (BMI), fat and waist circumference were found both in the patients and their healthy comparisons from baseline to 3 months (P<0.05). Patients reduced significantly less their BMI (P=0.044) and body fat percentage compared to the healthy women (P=0.023). Waist circumference was significantly reduced in both subject groups, with no significant difference found between them (P=0.07). Glucose and lipid levels were not altered during the intervention in the patients' group, while significant changes were observed in the healthy women in total cholesterol (P=0.016), low density lipoprotein cholesterol (P=0.022) and triglycerides (P=0.042). Obese postmenopausal women on atypical antipsychotic medication appear to respond favorably to a nutritional program. The improvements seen in BMI and body fat are attenuated in the patients compared to their healthy counterparts; moreover no change in lipid levels was found in the patients' group. These findings suggest that atypical antipsychotics may play an adverse role in fat loss and lipid metabolism in this population.


Structure and function of a spectrin-like regulator of bacterial cytokinesis.
Bacterial cell division is facilitated by a molecular machine--the divisome--that assembles at mid-cell in dividing cells. The formation of the cytokinetic Z-ring by the tubulin homologue FtsZ is regulated by several factors, including the divisome component EzrA. Here we describe the structure of the 60-kDa cytoplasmic domain of EzrA, which comprises five linear repeats of an unusual triple helical bundle. The EzrA structure is bent into a semicircle, providing the protein with the potential to interact at both N- and C-termini with adjacent membrane-bound divisome components. We also identify at least two binding sites for FtsZ on EzrA and map regions of EzrA that are responsible for regulating FtsZ assembly. The individual repeats, and their linear organization, are homologous to the spectrin proteins that connect actin filaments to the membrane in eukaryotes, and we thus propose that EzrA is the founding member of the bacterial spectrin family.


Structural insights into calicivirus attachment and uncoating.
The Caliciviridae family comprises positive-sense RNA viruses of medical and veterinary significance. In humans, caliciviruses are a major cause of acute gastroenteritis, while in animals respiratory illness, conjunctivitis, stomatitis, and hemorrhagic disease are documented. Investigation of virus-host interactions is limited by a lack of culture systems for many viruses in this family. Feline calicivirus (FCV), a member of the Vesivirus genus, provides a tractable model, since it may be propagated in cell culture. Feline junctional adhesion molecule 1 (fJAM-1) was recently identified as a functional receptor for FCV. We have analyzed the structure of this virus-receptor complex by cryo-electron microscopy and three-dimensional image reconstruction, combined with fitting of homology modeled high-resolution coordinates. We show that domain 1 of fJAM-1 binds to the outer face of the P2 domain of the FCV capsid protein VP1, inducing conformational changes in the viral capsid. This study provides the first structural view of a native calicivirus-protein receptor complex and insights into the mechanisms of virus attachment and uncoating.


Genetic Bases of Fungal White Rot Wood Decay Predicted by Phylogenomic Analysis of Correlated Gene-Phenotype Evolution.
Fungal decomposition of plant cell walls (PCW) is a complex process that has diverse industrial applications and huge impacts on the carbon cycle. White rot (WR) is a powerful mode of PCW decay in which lignin and carbohydrates are both degraded. Mechanistic studies of decay coupled with comparative genomic analyses have provided clues to the enzymatic components of WR systems and their evolutionary origins, but the complete suite of genes necessary for WR remains undetermined. Here, we use phylogenomic comparative methods, which we validate through simulations, to identify shifts in gene family diversification rates that are correlated with evolution of WR, using data from 62 fungal genomes. We detected 409 gene families that appear to be evolutionarily correlated with WR. The identified gene families encode well-characterized decay enzymes, e.g., fungal class II peroxidases and cellobiohydrolases, and enzymes involved in import and detoxification pathways, as well as 73 gene families that have no functional annotation. About 310 of the 409 identified gene families are present in the genome of the model WR fungus Phanerochaete chrysosporium and 192 of these (62%) have been shown to be upregulated under ligninolytic culture conditions, which corroborates the phylogeny-based functional inferences. These results illuminate the complexity of WR and suggest that its evolution has involved a general elaboration of the decay apparatus, including numerous gene families with as-yet unknown exact functions.


Analysis of the size distributions of fetal and maternal cell-free DNA by paired-end sequencing.
Noninvasive prenatal diagnosis with cell-free DNA in maternal plasma is challenging because only a small portion of the DNA sample is derived from the fetus. A few previous studies provided size-range estimates of maternal and fetal DNA, but direct measurement of the size distributions is difficult because of the small quantity of cell-free DNA. We used high-throughput paired-end sequencing to directly measure the size distributions of maternal and fetal DNA in cell-free maternal plasma collected from 3 typical diploid and 4 aneuploid male pregnancies. As a control, restriction fragments of lambda DNA were also sequenced. Cell-free DNA had a dominant peak at approximately 162 bp and a minor peak at approximately 340 bp. Chromosome Y sequences were rarely longer than 250 bp but were present in sizes of <150 bp at a larger proportion compared with the rest of the sequences. Selective analysis of the shortest fragments generally increased the fetal DNA fraction but did not necessarily increase the sensitivity of aneuploidy detection, owing to the reduction in the number of DNA molecules being counted. Restriction fragments of lambda DNA with sizes between 60 bp and 120 bp were preferentially sequenced, indicating that the shotgun sequencing work flow introduced a bias toward shorter fragments. Our results confirm that fetal DNA is shorter than maternal DNA. The enrichment of fetal DNA by size selection, however, may not provide a dramatic increase in sensitivity for assays that rely on length measurement in situ because of a trade-off between the fetal DNA fraction and the number of molecules being counted.


Ventromedial arcuate nucleus communicates peripheral metabolic information to the suprachiasmatic nucleus.
The arcuate nucleus (ARC) is crucial for the maintenance of energy homeostasis as an integrator of long- and short-term hunger and satiety signals. The expression of receptors for metabolic hormones, such as insulin, leptin, and ghrelin, allows ARC to sense information from the periphery and signal it to the central nervous system. The ventromedial ARC (vmARC) mainly comprises orexigenic neuropeptide agouti-related peptide and neuropeptide Y neurons, which are sensitive to circulating signals. To investigate neural connections of vmARC within the central nervous system, we injected the neuronal tracer cholera toxin B into vmARC. Due to variation of injection sites, tracer was also injected into the subependymal layer of the median eminence (seME), which showed similar projection patterns as the vmARC. We propose that the vmARC forms a complex with the seME, their reciprocal connections with viscerosensory areas in brain stem, and other circumventricular organs, suggesting the exchange of metabolic and circulating information. For the first time, the vmARC-seME was shown to have reciprocal interaction with the suprachiasmatic nucleus (SCN). Activation of vmARC neurons by systemic administration of the ghrelin mimetic GH-releasing peptide-6 combined with SCN tracing showed vmARC neurons to transmit feeding related signals to the SCN. The functionality of this pathway was demonstrated by systemic injection of GH-releasing peptide-6, which induced Fos in the vmARC and resulted in a reduction of about 40% of early daytime Fos immunoreactivity in the SCN. This observation suggests an anatomical and functional pathway for peripheral hormonal feedback to the hypothalamus, which may serve to modulate the activity of the SCN.


Dynamic kinematic responses of female volunteers in rear impacts and comparison to previous male volunteer tests.
The objective was to quantify dynamic responses of 50th percentile females in rear impacts and compare to those from similar tests with males. The results will serve as a basis for future work with models, criteria, and safety systems. A rear impact sled test series with 8 female volunteers was performed at velocity changes of 5 and 7 km/h. The following dynamic response corridors were generated for the head, T1 (first thoracic vertebra) and head relative to T1: (1) accelerations in posterior-anterior direction, (2) horizontal and vertical displacements, (3) angular displacements for 6 females close to the 50th percentile in size. Additionally, the head-to-head restraint distance and contact time and neck injury criterion (NIC) were extracted from the data set. These data were compared to results from previously performed male volunteer tests, representing the 50th percentile male, in equivalent test conditions. T-tests were performed with the statistical significance level of .05 to quantify the significance of the parameter value differences for the males and females. At 7 km/h, the females showed 29 percent earlier head-to-head restraint contact time (p = .0072); 27 percent shorter horizontal rearward head displacement (p = .0017); 36 percent narrower head extension angle (p = .0281); and 52 percent lower NIC value (p = .0239) than the males in previous tests. This was mainly due to 35 percent shorter initial head-to-head restraint distance for the females (p = .0125). The peak head acceleration in the posterior-anterior direction was higher and occurred earlier for the females. The overall result indicated differences in the dynamic response for the female and male volunteers. The results could be used in developing and evaluating a mechanical and/or mathematical average-sized female dummy model for rear impact safety assessment. These models can be used as a tool in the design of protective systems and for further development and evaluation of injury criteria.


Iliosacral screw insertion using computer-assisted CT image guidance: a laboratory study.
Procedures were performed to evaluate the efficacy of using a computer-assisted image-guided system to improve the accuracy of inserting iliosacral screws for posterior pelvic ring injuries. The fluoroscopic method currently in use has shortcomings that do not eliminate the risk to the L5 and sacral nerve roots and iliac vessels. The procedure was performed on embalmed cadaver pelvis specimens with intact soft tissues. Iliosacral screws were inserted across each sacroiliac joint after registering the opposite ilium to simulate a clinical situation. Two trials were performed. The first was necessary to become familiar with the system and test the basic methods of registration. In the second trial, deficiencies were corrected by using spherical-headed fiducial screws for fiducials and a better reference frame clamp, and by better spacing of more fiducials. Results were evaluated by inlet and outlet X-ray views and dissection. All eight S-1 iliosacral 7.0-mm cannulated screws were entirely inside bone. Of the eight S-2 screws, five were inside bone, two infringed upon an S-1 foramen, and one had threads out of the sacral body anteriorly and intruding into an S-1 foramen. This system was felt to be effective and sufficiently safe to warrant clinical trials.