Response of Rat Tibia to Prolonged Unloading Under the Influence of Electrical Stimulation at the Dorsal Root Ganglion.

Abstract:
PURPOSE
Immobilization of weight bearing skeletons or microgravity results in disuse osteoporosis in both human and animals. Our previous study demonstrated that electrical stimulation at the dorsal root ganglion (DRG) with an implantable micro-electrical stimulation system (IMESS) could trigger secretion of bone anabolic calcitonin gene-related peptide (CGRP) and prevent bone loss in a short-term hindlimb unloading rat model. This study was designed to further investigate whether electrical stimulation to the DRG could prevent bone loss due to prolonged unloading.

METHODS
Eighteen adult rats were randomly assigned into three groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with electrical stimulation (HUES). Electrical stimulation was applied via IMESS to the right DRGs at vertebral levels L4-L6 in HUES group for 6 weeks.

RESULTS
Following unloading for 6 weeks, proximal tibia metaphysis was shown 64.0% decrease in bone mineral content (BMC) and 47.0% decrease in bone mineral density (BMD) in HU group while significant reduced bone lose with 2.7% increase in total BMC and only 9.2% decrease in total BMD in HUES group. Diaphyseal BMD decreased significantly in both HU and HUES group as compared with CC group. There was enhancement of CGRP expression in the DRGs in HUES group.

CONCLUSION
This experimental study proved the proposed concept using electrical stimulation at the DRG for prevention of disuse-induced bone loss in a rat hindlimb suspension model.

Yuen-Chi Lau|Roy|R|
Qian|Xing|X|
Po|Kai-Ting|KT|
Li|Lu-Ming|LM|
Guo|Xia|X|

D015898:Tomography Scanners, X-Ray Computed

electrical stimulation
Dorsal root ganglion
immobilization
microgravity
disuse osteoporosis


Assessing temporal dynamics of predation and effectiveness of caterpillar visual defense using sawfly larval color and resting posture as a model.

Abstract: Caterpillars (Lepidoptera and Symphyta larvae) employ diverse visual defensive tactics, and effectiveness of such tactics may be highly dynamic across time due to seasonal changes in the predator assemblages and their preferences. However, this has rarely been studied especially in tropical regions. Here we assessed temporal changes in the defensive value of caterpillar color and shape, using six types of plasticine dummy caterpillars: three colors (green, black, and white) × two shapes (curled and straight). These dummy caterpillars were deployed five times over different seasons in tropical forests of Xishuangbanna (China) and, as a comparison, twice in a temperate forest of Hirosaki (Japan). The colors and shapes of dummy caterpillars simulate visual traits of black sawfly larvae which take the curled resting posture in tropical rainforests of Xishuangbanna, apparently masquerading excrements commonly found on plants, while in Hirosaki there is no black-curled sawfly larvae and few excrements on plants. We found no significant effects of caterpillar colors or shapes on predation in Hirosaki. In contrast, black and curled caterpillars received significantly lower predation by birds in Xishuangbanna constantly across time. However, we were unable to provide evidence that the black-curled sawfly larvae are masquerading as excrements. Shapes of the dummy caterpillars also affected the predation by ants and parasitoid wasps at certain times. This is the first report on ecological function of the curled posture of sawfly larvae, and we demonstrated the importance to assess the temporal dynamics of predation and effectiveness of defensive tactics in tropical forests.

predation
visual defense
sawfly larva
masquerading
Yunnan
artificial sentinel caterpillar


Typicality-based semantic treatment for anomia results in multiple levels of generalisation.

Abstract: This study investigated the effects of typicality-based semantic feature analysis (SFA) treatment on generalisation across three levels: untrained related items, semantic/phonological processing tasks, and measures of global language function. Using a single-subject design with group-level analyses, 27 persons with aphasia (PWA) received typicality-based SFA to improve their naming of atypical and/or typical exemplars. Progress on trained, untrained, and monitored items was measured weekly. Pre- and post-treatment assessments were administered to evaluate semantic/phonological processing and overall language ability. Ten PWA served as controls. For the treatment participants, the likelihood of naming trained items accurately was significantly higher than for monitored items over time. When features of atypical items were trained, the likelihood of naming untrained typical items accurately was significantly higher than for untrained atypical items over time. Significant gains were observed on semantic/phonological processing tasks and standardised assessments after therapy. Different patterns of near and far transfer were seen across treatment response groups. Performance was also compared between responders and controls. Responders demonstrated significantly more improvement on a semantic processing task than controls, but no other significant change score differences were found between groups. In addition to positive treatment effects, typicality-based SFA naming therapy resulted in generalisation across multiple levels.

Generalisation Aphasia Typicality Rehabilitation


An update on the pathogenesis of hidradenitis suppurativa: implications for therapy.

Abstract: Hidradenitis suppurativa is a chronic, inflammatory disease characterized by painful nodules, abscesses, and sinuses in the intertriginous areas, with significant associated comorbidities. The pathogenesis remains unclear, although advances have been made in understanding the disease process. Management of the disease is challenging, with a wide range of treatment options available with variable clinical response. Areas covered: This review discusses the most updated studies on the complex pathogenic mechanisms of hidradenitis suppurativa and the relevant literature on the current treatment options for this condition. Expert commentary: There is increasing evidence supporting the role of Th17 cells and enhanced expression of IL-17 and IL-1β, which represent potential targets for therapy. Bacteria and biofilms are likely contributory but secondary drivers of inflammation. There is also evolving evidence to suggest the presence of systemic comorbidities associated with HS, which underlie the importance of better understanding the pathogenesis and treatment of this disease.


Measurement of Arterial Stiffness: A Novel Tool of Risk Stratification in Hypertension.

Abstract: Cardiovascular diseases are the leading causes of morbidity and mortality in industrialized countries worldwide, despite highly effective preventive treatments available. As a difference continues to exist between the estimated and true number of events, further improvement of risk stratification is an essential part of cardiovascular research.Among hypertensive patients measurement of arterial stiffness parameters, like carotid-femoral pulse wave velocity (cfPWV) or brachial-ankle pulse wave velocity (baPWV) can contribute to the identification of high-risk subpopulation of patients. This is a hot topic of vascular research including the possibility of the non-invasive measurement of central hemodynamics, wave reflections and recently, 24-h arterial stiffness monitoring as well. This chapter discusses the past and the present of this area including the scientific achievements with cfPWV, baPWV and other measures, provides a short overview of methodologies and the representation of arterial stiffness parameters in guidelines.

Arterial stiffness
Hypertension
Pulse wave velocity
Guidelines


Effect of pH on phosphorus (P) dissolution and recovery from polyaluminum chlorides (PAC) sludge.

Abstract: Phosphorus (P) dissolution from polyaluminum chlorides (PAC) sludge was investigated for sustainable P recovery. P dissolution followed 1st order kinetics with the rate constants of 3.8 × 10-2, 0.8 × 10-2, 1.3 × 10-2 and 1.9 × 10-2 min-1 at pH 1, 2.5, 10.5 and 12, respectively. Strong acidic and alkaline conditions dissolved about 82 (pH 1) and 88% (pH 12) of the total P by adding 0.214 g HCl and 0.357 g NaOH per gram P dissolved, respectively. Chemical P fractionation showed that more than 96% of the total P of the PAC sludge was AlP and it was reduced to 11.3 (pH 12) and 12.6% (pH 1.0) after the acid and alkali treatment. ATR-FTIR showed that AlPO4 in the PAC sludge was transformed to Mg3(PO4)2∙4H2O and CaHPO4∙2H2O after alkali treatment and H3PO4 and Na/MgP after acid treatment. Dissolved P can be recovered by precipitation with Ca and Mg.

pH
Polyaluminum chlorides
ATR-FTIR
Dissolution kinetics
Phosphorus dissolution
Phosphorus fractionation


Intuitive physics ability in systemizers relies on differential use of the internalizing system and long-term spatial representations.

Abstract: According to the Empathizing-Systemizing theory (E-S Theory), individual differences in how people understand the physical world (systemizing) and the social world (empathizing), are two continuums in the general population with several implications, from vocational interests to skills in the social and physical domains. The underlying mechanisms of intuitive physics performance among individuals with strong systemizing and weak empathizing (systemizers) are, however, unknown. Our results affirm higher intuitive physics skills in healthy adult systemizers (N=36), and further reveal the brain mechanisms that are characteristic for those individuals in carrying out such tasks. When the participants performed intuitive physics tasks during functional magnetic resonance imaging, combined higher systemizing and lower empathizing was associated with stronger activations in parts of the default mode network (DMN, cuneus and posterior cingulate gyrus), middle occipital gyrus, and parahippocampal region. The posterior cingulate gyrus and parahippocampal gyrus were specifically associated with systemizing "brain type" even after controlling for task performance, while especially in the parietal cortex, the activation changes were simply explained by higher task performance. We therefore suggest that utilization of DMN-parahippocampal complex, suggested to play a role in internalizing and activating long-term spatial memory representations, is the factor that distinguishes systemizers from empathizers with the opposite "brain type" in intuitive physics tasks.

Riekki|Tapani|T|
Salmi|Juha|J|
Svedholm-Häkkinen|Annika M|AM|
Lindeman|Marjaana|M|

Intuitive physics
Systemizing
Empathizing-systemizing theory
Empathizing
fMRI


Using the Auditory Brainstem Response (ABR) to Determine Sensitivity of Hearing in Mutant Mice.

Abstract: Measurements of auditory evoked potentials can be used to determine reliably an audiometric representation of hearing sensitivity in mice. In a high-throughput phenotyping screen of mice carrying targeted mutations of single genes, the auditory brainstem response (ABR) is used to gain an estimate of hearing threshold for broadband click stimuli and pure tone frequencies ranging from 6 to 30 kHz. Comparison of thresholds obtained in mutant and wild-type mice give a means to determine mild, moderate, and severe hearing impairment. This gives a clear advantage over using a "clickbox" test to assess hearing by observations of the Preyer reflex. The ABR screen has identified several mutant lines with mild and moderate hearing loss, which appear to demonstrate normal Preyer responses. The ABR technique also allows frequency-selective hearing loss to be identified. Curr. Protoc. Mouse Biol. 1:279-287 © 2011 by John Wiley & Sons, Inc.

Ingham|Neil J|NJ|
Pearson|Selina|S|
Steel|Karen P|KP|

hearing
evoked potential
electrophysiology
high-throughput screening


Urban Disadvantage, Obesity, and Underweight in 31 Lower-Income Countries.

Abstract: Although some studies have shown that obesity and other non-communicable diseases are more common in more disadvantaged areas, no publications to date have examined the interaction of obesity with urban and rural disadvantage in lower-income countries. This study analyzed the rates of obesity and underweight in disadvantaged urban women and disadvantaged rural women in 31 lower-income countries, and calculated the age-adjusted odds ratios of urban vs. rural obesity and underweight. The odds of obesity were significantly (p<0.05) higher for urban populations in 16 of the 31 countries and in all aggregated regions; the evidence that underweight is also associated more with urban populations was mixed. Because obesity is a rapidly-growing threat to the public health and financial strength of lower-income countries, and urban disadvantage is associated with more obesity than rural disadvantage, policymakers should work to understand, predict, and prevent obesity in urban populations specifically.

Sheets|Lincoln R|LR|
Woldu|Henok G|HG|
Swart|Rina|R|
Simoes|Eduardo|E|

Geographic Factors
Healthcare Disparities
Obesity Epidemiology


A map of tumor-host interactions in glioma at single-cell resolution.

Abstract:
BACKGROUND
Single-cell RNA sequencing is the reference technique for characterizing the heterogeneity of the tumor microenvironment. The composition of the various cell types making up the microenvironment can significantly affect the way in which the immune system activates cancer rejection mechanisms. Understanding the cross-talk signals between immune cells and cancer cells is of fundamental importance for the identification of immuno-oncology therapeutic targets.

RESULTS
We present a novel method, single-cell Tumor-Host Interaction tool (scTHI), to identify significantly activated ligand-receptor interactions across clusters of cells from single-cell RNA sequencing data. We apply our approach to uncover the ligand-receptor interactions in glioma using 6 publicly available human glioma datasets encompassing 57,060 gene expression profiles from 71 patients. By leveraging this large-scale collection we show that unexpected cross-talk partners are highly conserved across different datasets in the majority of the tumor samples. This suggests that shared cross-talk mechanisms exist in glioma.

CONCLUSIONS
Our results provide a complete map of the active tumor-host interaction pairs in glioma that can be therapeutically exploited to reduce the immunosuppressive action of the microenvironment in brain tumor.

Caruso|Francesca Pia|FP|
Garofano|Luciano|L|
D'Angelo|Fulvio|F|
Yu|Kai|K|
Tang|Fuchou|F|
Yuan|Jinzhou|J|
Zhang|Jing|J|
Cerulo|Luigi|L|
Pagnotta|Stefano M|SM|
Bedognetti|Davide|D|
Sims|Peter A|PA|
Suvà|Mario|M|
Su|Xiao-Dong|XD|
Lasorella|Anna|A|
Iavarone|Antonio|A|
Ceccarelli|Michele|M|

D001932:Brain Neoplasms
D002450:Cell Communication
D005910:Glioma
D006801:Humans
D017423:Sequence Analysis, RNA
D059016:Tumor Microenvironment

Tumor Microenvironment
Brain Tumors
Ligand-receptor signalling
Single Cells


Imaging of Cystic and Cyst-like Lesions of the Mediastinum with Pathologic Correlation.

Abstract: Cystic masses of the mediastinum are a heterogenous group of asymptomatic or symptomatic, congenital, infectious, or neoplastic lesions. For early and correct diagnosis, evaluation, and optimal patient management of cystic mediastinal masses in infants, children, or adults imaging plays an important role. A non-invasive and sensitive imaging modality is an efficient and cost-effective tool. Multidetector computed tomography (MDTC) with volumetric acquisition provides fast acquisition of high resolution images and multiplanar reconstruction. Both 2D and 3D imaging in mediastinal imaging help in surgical planning and assessing resectability of mediastinal lesions. MR imaging has many advantages over other modalities for detecting and identifying cystic, or fluid-filled mediastinal masses, because of its intrinsic high soft tissue contrast and direct multiplanar imaging capabilities. However, histological tissue analysis may be required to differentiate a cystic lesion from other cyst-like or low-attenuation lesions.

Odev|Kemal|K|
Arıbaş|Bilgin K|BK|
Nayman|Alaaddin|A|
Arıbaş|Olgun K|OK|
Altınok|Tamer|T|
Küçükapan|Ahmet|A|

mediastinum
computed tomography
Cysts
magnetic resonance imaging
radiograph


A quasi-incompressible and quasi-inextensible finite element analysis of fibrous soft biological tissues.

Abstract: The contribution presents an extension and application of a recently proposed finite element formulation for quasi-inextensible and quasi-incompressible finite hyperelasticity to fibrous soft biological tissues and touches in particular upon computational aspects thereof. In line with theoretical framework presented by Dal (Int J Numer Methods Eng 117:118-140, 2019), the mixed variational formulation is extended to two families of fibers as often encountered while dealing with fibrous tissues. Apart from that, the purely Eulerian setting features the additive decomposition of the free energy function into volumetric, isotropic and anisotropic parts. The multiplicative split of the deformation gradient and all the outcomes thereof, e.g., unimodular invariants, are simply dispensed with in the three element formulations investigated, namely Q1, Q1P0 and the proposed Q1P0F0. For the quasi-incompressible response, the Q1P0 element formulation is briefly outlined where the pressure-type Lagrange multiplier and its conjugate enter the variational formulation as an extended set of variables. Using the similar argumentation, an extended Hu-Washizu-type mixed variational potential is introduced where the volume averaged squares of fiber stretches and associated fiber stresses are additional field variables. The resulting finite element formulation called Q1P0F0 is very attractive as it is based on mean values of the additional field variables at element level through integration over the element domain in a preprocessing step, earning the model vast utilization areas. The proposed approach is examined through representative boundary value problems pertaining to fibrous biological tissues. For all the cases studied, the proposed Q1P0F0 formulation elicits the most compliant mechanical response, thereby outperforming the standard Q1 and Q1P0 element formulations through mesh-refinement analyses. Results prompt further experimental investigations as to true deformation fields under biologically relevant loading conditions which would make the assessment of Q1P0 and Q1P0F0 more based on physical grounds.

Quasi-incompressibility
Quasi-inextensibility
Hyperelasticity
Fibrous biological tissues
Anisotropy
Mixed finite element formulation


Pulmonary embolism in severe traumatic brain injury.

Abstract:
INTRODUCTION
Pulmonary emboli (PE) is a significant source of morbidity and mortality in the trauma patients. The use of chemical prophylaxis to prevent deep venous thrombosis and subsequent PE is still controversial given its risk of increased intracranial hemorrhage expansion.

OBJECTIVE
In the present study, we evaluated the incidence of PE in severe traumatic brain injury.

METHODS
Retrospective review of patients who were admitted to a Neurosurgery unit from 2011 to 2013 with severe TBI who developed PE.

RESULTS
155 patients met the study criteria. The incidence of PE was 2.58%. The cohort was mainly composed of white (71.6%), male (76.77%) with the mean age of 23.03 ± 15.79. There was no statistical difference between the patients who developed PE with prophylaxis and without (p = 0.58). Hospital length of stay was significantly increased by the development of a PE (27.82 ± 21.78 vs. 61.24 ± 25.74 days, p = 0.01).

CONCLUSION
Our data is limited by a low incidence of PE in this cohort, but does show an increased hospital length of stay. The true incidence of PE is unknown, so large-scale population studies are urgently needed and a high index of suspicion is required for diagnosis.

Seifi|Ali|A|
Dengler|Bradley|B|
Martinez|Paola|P|
Godoy|Daniel Agustin|DA|

Pulmonary embolism
Traumatic brain injury
Prophylaxis
Anticoagulation
Deep vein thrombosis
Venous thromboembolism


Plant-Based Alternatives to Yogurt: State-of-the-Art and Perspectives of New Biotechnological Challenges.

Abstract: Due to the increasing demand for milk alternatives, related to both health and ethical needs, plant-based yogurt-like products have been widely explored in recent years. With the main goal to obtain snacks similar to the conventional yogurt in terms of textural and sensory properties and ability to host viable lactic acid bacteria for a long-time storage, several plant-derived ingredients (e.g., cereals, pseudocereals, legumes, and fruits) as well as technological solutions (e.g., enzymatic and thermal treatments) have been investigated. The central role of fermentation in yogurt-like production led to specific selections of lactic acid bacteria strains to be used as starters to guarantee optimal textural (e.g., through the synthesis of exo-polysaccharydes), nutritional (high protein digestibility and low content of anti-nutritional compounds), and functional (synthesis of bioactive compounds) features of the products. This review provides an overview of the novel insights on fermented yogurt-like products. The state-of-the-art on the use of unconventional ingredients, traditional and innovative biotechnological processes, and the effects of fermentation on the textural, nutritional, functional, and sensory features, and the shelf life are described. The supplementation of prebiotics and probiotics and the related health effects are also reviewed.

milk alternatives
yogurt-like
lactic acid bacteria
plant-based foods


The Weakening of Kin Ties: Exploring the Need for Life-World Led Interventions.

Abstract: The protective features that families and wider social relationships can have are required to meet the demands of life in contemporary Western societies. Choice and detraditionalization, however; impede this source of solidarity. Family Group Conferencing (FGC) and other life-world led interventions have the potential to strengthen primary groups. This paper explores the need for such a social intervention, using insights from sociological and philosophical theories and empirical findings from a case study of the research project 'FGC in mental health'. This need is understandable considering the weakening of kin ties, the poor qualities of state agencies to mobilise self-care and informal care, its capacity to produce a shift of power from public to private spheres and its capacity to mitigate the co-isolation of individuals, families and communities. A life-world led intervention like FGC with a specific and modest ambition contributes to small-scale solidarity. This ambition is not inclined to establish a broad social cohesion within society but to restore; in terms of the German philosopher Peter Sloterdijk; immunity (protection) and solidarity in primary groups, and consequently, resolve issues with those (family, neighbours, colleagues) who share a sphere (a situation, a process, a fate).

D003419:Crisis Intervention
D005195:Family Relations
D006801:Humans
D007398:Interpersonal Relations
D011615:Psychotherapy, Group

kin ties
life-world led interventions
Family Group Conferencing
Sloterdijk’s sphere theory
social embeddedness
thick and thin solidarity


Painless squeaking following cervical disc replacement: A case report.

Abstract:
BACKGROUND
We present a case of painless squeaking following cervical disc replacement which to our knowledge has not previously been reported in the literature.

METHODS
A 45 year old gentleman presented with severe right sided C6 radiculopathy. He complained of more than 6 weeks of severe dysaesthesia in the right arm with pain radiating into the hand, thumb, index, middle and ring fingers. MRI confirmed severe impingement of C6 and C7 nerve roots. After trying a period of conservative treatment he underwent anterior cervical decompression with total cervical disc replacement of C5-6 and C6-7.

RESULTS
Being a keen athlete he started running at 6 months post operatively. At his 12 month outpatient he presented us with an audio file containing squeaking from his neck. This was recorded immediately following a 9.5 mile hard surface run. The squeak got progressively less in intensity over 12 hours and disappeared after 24 hours. All instances of squeaking occurred after exercise where impact (running) or vibration (cycling) took place. This was first noticed 6 months post operatively when he restarted exercising. All episodes were completely painless. At his 18 month outpatient review the squeaking had reduced in frequency and intensity. At his 24 month review it had abated completely.

CONCLUSION
The aetiology of this painless squeaking has been elusive and is likely to be multifactorial. However we hypothesise that the audible squeak associated with the prestige LP disc maybe related to specific design characteristics and needs further evaluation.

Squeaking
Cervical
case report
prestige LP disc
Total disc arthroplasty


A Public Health Priority: Disparities in Gynecologic Cancer Research for African-Born Women in the United States.

Abstract: African-born immigrants comprise one of the fastest growing populations in the U.S., nearly doubling its population size in recent years. However, it is also one of the most underrepresented groups in health-care research, especially research focused on gynecologic and breast malignancies. While the opportunity exists for access to an advanced health-care system, as immigrants migrate to the U.S., they encounter the same health-care inequalities that are faced by the native-born population based on ethnicity and social class, potentiated by limitations of health literacy and lack of familiarity with U.S. health systems. Given the continued influx of African-born immigrants in the U.S., we sought to understand the representation of this population in cervical and breast cancer research, recognizing the population's high risk for these diseases at baseline while residing in their native countries. We determined that there is limited research in these diseases that disproportionately affect them; yet, there are identifiable and potentially modifiable factors that contribute to this paucity of evidence. This clinical commentary seeks to underscore the clear lack of research available involving African-born immigrants with respect to gynecologic and breast malignancies in the existing literature, demonstrate the need for more robust research in this population, and provide fundamental insights into barriers and solutions critical to the continued health of this growing population.

Pinder|Leeya F|LF|
Nelson|Brett D|BD|
Eckardt|Melody|M|
Goodman|Annekathryn|A|

African-born immigrants
cancer screening
immigrant health
maternal health
refugee health
research disparities


The prion 2018 round tables (I): the structure of PrPSc.

Abstract: Understanding the structure of PrPSc is without doubt a sine qua non to understand not only PrPSc propagation, but also critical features of that process such as the strain phenomenon and transmission barriers. While elucidation of the PrPSc structure has been full of difficulties, we now have a large amount of structural information that allows us to begin to understand it. This commentary article summarizes a round table that took place within the Prion 2018 meeting held in Santiago de Compostela to discuss the state of the art in this matter. Two alternative models of PrPSc exist: the PIRIBS and the 4-rung β-solenoid models. Both of them have relevant features. The 4-rung β-solenoid model agrees with experimental constraints of brain derived PrPSc obtained from cryo-EM and X-ray fiber diffraction studies. Furthermore, it allows facile accommodation of the bulky glycans that decorate brain-derived PrPSc. On the other hand, the infectious PrP23-144 amyloid exhibits a PIRIBS architecture. Perhaps, both types of structure co-exist.

Baskakov|Ilia V|IV|
Caughey|Byron|B|
Requena|Jesús R|JR|
Sevillano|Alejandro M|AM|
Surewicz|Witold K|WK|
Wille|Holger|H|

PIRIBS
4-rung β-solenoid
PrP structure
PrP syalilation
PrP23-144 infectious amyloid
Prion2018
cryo-electron microscopy
solid state NMR


Impaired development of intrinsic connectivity networks in children with medically intractable localization-related epilepsy.

Abstract: Typical childhood development is characterized by the emergence of intrinsic connectivity networks (ICNs) by way of internetwork segregation and intranetwork integration. The impact of childhood epilepsy on the maturation of ICNs is, however, poorly understood. The developmental trajectory of ICNs in 26 children (8-17 years) with localization-related epilepsy and 28 propensity-score matched controls was evaluated using graph theoretical analysis of whole brain connectomes from resting-state functional magnetic resonance imaging (fMRI) data. Children with epilepsy demonstrated impaired development of regional hubs in nodes of the salience and default mode networks (DMN). Seed-based connectivity and hierarchical clustering analysis revealed significantly decreased intranetwork connections, and greater internetwork connectivity in children with epilepsy compared to controls. Significant interactions were identified between epilepsy duration and the expected developmental trajectory of ICNs, indicating that prolonged epilepsy may cause progressive alternations in large-scale networks throughout childhood. DMN integration was also associated with better working memory, whereas internetwork segregation was associated with higher full-scale intelligence quotient scores. Furthermore, subgroup analyses revealed the thalamus, hippocampus, and caudate were weaker hubs in children with secondarily generalized seizures, relative to other patient subgroups. Our findings underscore that epilepsy interferes with the developmental trajectory of brain networks underlying cognition, providing evidence supporting the early treatment of affected children.

Ibrahim|George M|GM|
Morgan|Benjamin R|BR|
Lee|Wayne|W|
Smith|Mary Lou|ML|
Donner|Elizabeth J|EJ|
Wang|Frank|F|
Beers|Craig A|CA|
Federico|Paolo|P|
Taylor|Margot J|MJ|
Doesburg|Sam M|SM|
Rutka|James T|JT|
Snead|O Carter|OC|

intrinsic connectivity network
graph theoretical analysis
functional connectivity
generalized tonic clonic (GTC)
resting-state fMRI


Superchilling in combination with modified atmosphere packaging resulted in long shelf-life and limited microbial growth in Atlantic cod (Gadus morhua L.) from capture-based-aquaculture in Greenland.

Abstract: Sensory, chemical and microbial changes for Atlantic cod (Gadus morhua L.) filets from capture-based-aquaculture in Greenland were studied. The objective was to determine shelf-life and indices of spoilage for iced or superchilled fillets when stored in air, or modified atmosphere packed (MAP; 40% CO2 and 60% N2). MAP iced storage extended the sensory shelf-life from 15 days to 21 days compared to storage in air. With superchilling at -1.7 °C sensory shelf-life was above 32 days, and no formation of total volatile nitrogen (TVN) was observed irrespective of storage in air or MAP. pH of ≥7.0, TVN (≥35 mg-N/100 g) and trimethylamine (≥20 mg-N TMA/100 g) were promising indices of spoilage. Aerobic viable counts were less valuable indices of spoilage as the dominating microbiota of cod in air (Pseudomonas spp., Photobacterium spp., Shewanella spp., Acinetobacter spp.) changed to Photobacterium spp. in MAP cod. Spoilage activity determined as the yield factor for TVN formation was 6-200 folds higher for Photobacterium spp. compared to Shewanella spp. and Pseudomonas spp. Photobacterium carnosum was responsible for TVN formation in iced cod irrespective of storage in air or MAP, and it was identified at the specific spoilage organism that limited iced product shelf-life.

Sørensen|Jonas Steenholdt|JS|
Bøknæs|Niels|N|
Mejlholm|Ole|O|
Dalgaard|Paw|P|

Indices of spoilage
Total volatile nitrogen (TVN)
Spoilage activity
16S rRNA gene amplicon sequencing
Specific spoilage organisms (SSO)
Storage trial


Varicose vein appearance caused by perforating vein incompetence detected after intense cycling.

Abstract: The role of incompetent perforating veins in the aetiology of varicose veins is not well understood. Anecdotally, competitive cyclists appeared to be more prone to varicose veins than the general population. We present a case of a 63-year-old amateur competitive cyclist who acutely developed a painful varicosity of her left calf while straining during a hill climb in 106-mile cycle race. Duplex ultrasonography has shown an underlying incompetent perforating vein, feeding the varicosity directly through the underlying muscle. With no other significant venous reflux in either leg, we believe this case shows a clear causative association between the stresses put across the lower leg during competitive cycling and developing a varicose vein via an incompetent perforating vein. We believe this should lead to further investigations as to any link between cycling, perforator vein incompetence and the development of varicose veins.


Extended nasolabial flaps in the management of oral submucous fibrosis.

Abstract:
PURPOSE
We evaluated the use of extended nasolabial flaps in the management of oral submucous fibrosis.

METHODS
We evaluated the use of extended nasolabial flaps in the management of 27 randomly selected patients with histologically confirmed oral submucous fibrosis. They all had interincisal opening of less than 20 mm and were treated by bilateral release of fibrous bands and extended grafting with a nasolabial flap. All patients had postoperative physiotherapy, and were followed up for one year.

RESULTS
Their interincisal opening improved significantly from a mean of 11mm (range 3-19) to a mean of 39 mm (range 23-48).

CONCLUSIONS
The procedure was effective in the management of patients with oral submucous fibrosis, the main disadvantage being the extraoral scars.

Agarwal|Mohit|M|
Gupta|D K|DK|
Tiwari|Anjali Dave|AD|

Extended Nasolabial flap
Oral submucous fibrosis


1HN, 13C, and 15N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A transporter (CaMBP2).

Abstract: Vitamin A is a necessary nutrient for all mammals, and it is required for the transcription of many genes and vital for vision. While fasting, the vitamin A alcohol form (Retinol) from storage in the liver is mobilized and transported through the bloodstream while bound to retinol binding protein (RBP). Details of how exactly vitamin A is released from RBP and taken into the cells are still unclear. As part of the effort to elucidate the specifics of this process, single-particle cryo-electron microscopy structural studies of STRA6 (the RBP receptor 75-kDa transmembrane receptor protein) were recently reported by Chen et al. (Science, https://doi.org/10.1126/science.aad8266 , 2016). Interestingly, STRA6 from zebrafish was shown to be a stable dimer and bound to calmodulin (CaM), forming a 180-kDa complex. The topology of the STRA6 complex includes 18 transmembrane helices (nine per protomer) and two long horizontal intramembrane helices interacting at the dimer core (Chen et al., in Science, https://doi.org/10.1126/science.aad8266 , 2016). CaM was shown to interact with three regions of STRA6, termed CaMBP1, CaMBP2, and CaMBP3, with the most extensive interactions involving CaMBP2. To further our understanding of Ca2+-dependence of CaM-STRA6 complex formation, studies of the structure and dynamic properties of the CaMBP2-CaM complex were initiated. For this, the 1HN, 13C, and 15N backbone resonance assignments of the 148 amino acid Ca2+-bound calmodulin protein bound to the 27-residue CaMBP2 peptide derived from STRA6 were completed here using heteronuclear multidimensional NMR spectroscopy.

D019906:Nuclear Magnetic Resonance, Biomolecular

Calmodulin
STRA6
Vitamin A
Retinoic acid


Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I.

Abstract: Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril-associated disordered 1-93 fragment of this protein, in wild-type and mutated (G26R, S36A, K40L, W50R) forms. In atomic-level Monte Carlo simulations of the free monomer, validated by circular dichroism spectroscopy, we observe changes in the position-dependent β-strand probability induced by mutations. We find that these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy experiments. Together, our results point to molecular mechanisms that may have a key role in disease-linked aggregation of apolipoprotein A-I.

Petrlova|Jitka|J|
Bhattacherjee|Arnab|A|
Boomsma|Wouter|W|
Wallin|Stefan|S|
Lagerstedt|Jens O|JO|
Irbäck|Anders|A|

amyloidogenic mutations
disordered protein
fibril formation
molecular simulation
secondary-structure probability


Geriatric-Oriented High Dose Nutraceutical ODTs: Formulation and Physicomechanical Characterization.

Abstract:
CONTEXT
Oral disintegrating tablets (ODTs) represent a better option than conventional tablets for geriatric population, owing to their fast onset of action and their better patient compliance.

OBJECTIVE
Two principal therapeutic high-dose nutraceuticals; chondroitin sulphate and glucosamine were formulated into an oral disintegration tablet (ODT) intended for sublingual administration, and optimized to improve compliance and achieve rapid onset of action in osteoarthritis treatment.

MATERIALS AND METHODS
Different formulations were prepared either by melt granulation or direct compression techniques. Excipients at different ratios such as superdisintegrants, pharmaburst™ C1, spray-dried mannitol, and polyethylene glycols were used to enhance the disintegration time for the ODT systems.

RESULTS
Although the ODT systems weighed around 1.3 gm with 60% drug load, some systems disintegrated within 2-3 min with 100% drug release. Pharmaburst™ C1 turned out to be the key excipient responsible for the superdisintegration properties of the ODTs. Dissolution enhancement of the two nutraceuticals could be achieved compared to the marketed conventional tablets.

CONCLUSION
The improved disintegration and dissolution properties of our prepared ODTs are expected to enhance the bioavailability of the high dose glucosamine and chondroitin sulphate in comparison with conventional tablets, which delineates them as a promising dosage form for the aforementioned nutraceuticals.

Agiba|Ahmed M|AM|
Abdel-Hamid|Sameh|S|
Nasr|Maha|M|
Geneidi|Ahmed S|AS|


Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies.

Abstract:
BACKGROUND
Studies have shown that skeletal muscle and adipose tissue are linked to overall survival (OS) and progression-free survival (PFS). Because targeted therapies have improved the outcome in patients with metastatic renal cell carcinoma (mRCC), new prognostic parameters are required. The objective of the current study was to analyze whether body composition parameters play a prognostic role in patients with mRCC.

METHODS
Adipose tissue, skeletal muscle, and skeletal muscle density (SMD) were assessed with computed tomography imaging by measuring cross-sectional areas of the tissues and mean muscle Hounsfield units (HU). A high level of mean HU indicates a high SMD and high quality of muscle. OS and PFS were estimated using the Kaplan-Meier method and compared with the log-rank test. The multivariable Cox proportional hazards model was adjusted for Heng risk score and treatment.

RESULTS
In the 149 patients studied, the median OS was 21.4 months and was strongly associated with SMD; the median OS in patients with low SMD was approximately one-half that of patients with high SMD (14 months vs 29 months; P = .001). After adjustment for Heng risk score and treatment, high SMD was associated with longer OS (hazards ratio, 1.85; P = .004) and longer PFS (hazards ratio, 1.81; P = .002). Adding SMD will separate the intermediate-risk and favorable-risk groups into 3 groups, with different median OS periods ranging from 8 months (95% confidence interval [95% CI], 6 months-12 months) for an intermediate-risk Heng score/low SMD to 22 months (95% CI, 14 months-27 months) for an intermediate-risk Heng score/high SMD and a favorable-risk Heng score/low SMD to 35 months (95% CI, 24 months-43 months) for a favorable-risk Heng score/high SMD.

CONCLUSIONS
High muscle density appears to be independently associated with improved outcome and could be integrated into the prognostic scores thereby enhancing the management of patients with mRCC.

Antoun|Sami|S|
Lanoy|Emilie|E|
Iacovelli|Roberto|R|
Albiges-Sauvin|Laurence|L|
Loriot|Yohann|Y|
Merad-Taoufik|Mansouriah|M|
Fizazi|Karim|K|
di Palma|Mario|M|
Baracos|Vickie E|VE|
Escudier|Bernard|B|

muscle density
prognosis
renal cell carcinoma
targeted therapy
body composition


Bolus epidural infusion improves spread compared with continuous infusion in a cadaveric porcine spine model.

Abstract:
BACKGROUND
The administration of epidural anesthesia during labor is a common technique used to reduce the pain of childbirth. We sought to compare standard infusion strategies of continuous epidural infusions (CEI) with programmed intermittent epidural bolus (PIEB) to assess the length of spread in terms of vertebral body length. Based on previous clinical data in humans, the PIEB was associated with improved pain control and decreased total dose of local anesthetic. We hypothesized that the PIEB was associated with increased spread when compared with CEI.

METHODS
Thirty female Yorkshire-cross swine cadavers were used to compare three infusion strategies, continuous infusion (CEI) 10 mL/hour programmed continuously, multiple bolus (MB) 2 mL given every 12 min for 10 mL total and 10 mL delivered in a single bolus (SB). Radiographs were used to identify the spread of the radiopaque contrast dye, and a number of vertebral bodies covered were measured to assess spread.

RESULTS
Overall, the CEI had an average spread of 5.6 levels, MB 7.9 and SB 10.4. The differences between SB and MB (p=0.011), SB and CEI (p<0.001) and MB and CEI (p=0.028) were all found to be significant.

CONCLUSIONS
We demonstrated increased spread of epidural contrast with programmed intermittent bolus strategies. This supports previous evidence of improved patient outcomes with PIEB strategy compared with CEI, and encourages the use of PIEB in the appropriate patient population.

neuraxial blocks: continuous techniques
neuraxial blocks: epidural
obstetrics


Ion-pumping microbial rhodopsins.

Abstract: Rhodopsins are light-sensing proteins used in optogenetics. The word "rhodopsin" originates from the Greek words "rhodo" and "opsis," indicating rose and sight, respectively. Although the classical meaning of rhodopsin is the red-colored pigment in our eyes, the modern meaning of rhodopsin encompasses photoactive proteins containing a retinal chromophore in animals and microbes. Animal and microbial rhodopsins possess 11-cis and all-trans retinal, respectively, to capture light in seven transmembrane α-helices, and photoisomerizations into all-trans and 13-cis forms, respectively, initiate each function. Ion-transporting proteins can be found in microbial rhodopsins, such as light-gated channels and light-driven pumps, which are the main tools in optogenetics. Light-driven pumps, such as archaeal H(+) pump bacteriorhodopsin (BR) and Cl(-) pump halorhodopsin (HR), were discovered in the 1970s, and their mechanism has been extensively studied. On the other hand, different kinds of H(+) and Cl(-) pumps have been found in marine bacteria, such as proteorhodopsin (PR) and Fulvimarina pelagi rhodopsin (FR), respectively. In addition, a light-driven Na(+) pump was found, Krokinobacter eikastus rhodopsin 2 (KR2). These light-driven ion-pumping microbial rhodopsins are classified as DTD, TSA, DTE, NTQ, and NDQ rhodopsins for BR, HR, PR, FR, and KR2, respectively. Recent understanding of ion-pumping microbial rhodopsins is reviewed in this paper.

retinal
light-driven pump
H+ transfer
hydrogen bond
photocycle
photoisomerizatoin
structural change


Confocal Microendoscopy of Neuromuscular Synapses in Living Mice.

Abstract: Here we describe a step-by-step method for vital imaging of neuromuscular junctions (NMJ) and axons using fiber-optic confocal microendoscopy (CME). A commercially available system, the Cellvizio Lab, can be applied to transgenic mouse lines expressing yellow fluorescent protein in all or pseudorandom sub-subsets of motor neurons. Microscopic imaging in vivo is achieved by means of a flexible optical fiber probe that excites and collects the emitted light from fluorescently labeled structures. The hand-held probe is introduced through small skin incisions to visualize nerves and neuromuscular junctions from superficial muscles. Interpolation software then reconstructs the images in real time. The images are of sufficient quality to permit screening of axonal and neuromuscular synaptic integrity and other aspects of their phenotype in live animals. Curr. Protoc. Mouse Biol. 2:1-8 © 2012 by John Wiley & Sons, Inc.

imaging
neuromuscular junction
microscopy


Mid- to long-term results of total disc replacement for lumbar degenerative disc disease: a systematic review.

Abstract:
BACKGROUND
Lumbar total disc replacement (TDR) has shown satisfactory clinical outcomes with few complications and reoperations at short-term follow-up, but the mid- to long-term results are not clear.

PURPOSE
The objective of this study was to evaluate the mid- to long-term clinical outcomes of artificial TDR for lumbar degenerative disc diseases.

PATIENTS AND METHODS
A systematic search was conducted using the PubMed database to identify studies of TDR surgery that included at least 3 years of follow-up. The search keywords were as follows: lumbar, total disc replacement, and arthroplasty. The following data were extracted: patient demographics, visual analogue scale (VAS) and Oswestry disability index (ODI) scores, satisfactory rate, clinical success rate, complications, and reoperations.

RESULTS
Thirteen studies, including eight prospective studies and five retrospective studies, met the criteria. A total of 946 patients were identified who reported at least 3 years of follow-up results. The artificial prostheses in these studies were ProDisc-L, Charité, AcroFlex, Maverick, and XL TDR. Patients with lumbar TDR demonstrated significant improvements in VAS scores of 51.1 to 70.5% and of - 15.6 to - 44.4 for Oswestry disability index (ODI) scores at the last follow-up. Patient satisfaction rates were reported in eight studies and ranged from 75.5 to 93.3%. Complication rates were reported in 11 studies, ranging from 0 to 34.4%. The overall reoperation rate was 12.1% (119/986), ranging from 0 to 39.3%, with eight of the 13 studies reporting a reoperation rate of less than 10%.

CONCLUSIONS
This review shows that lumbar TDR effectively results in pain relief and an improvement in quality of life at mid- to long-term follow-up. Complication and reoperation rates were acceptable. However, this study did not provide sufficient evidence to show that lumbar TDR is superior to fusion surgery. To answer that question, a greater number of high-quality randomized controlled trials (RCTs) are needed.

Cui|Xu-Dong|XD| Li|Hai-Tao|HT| Zhang|Wen|W| Zhang|Lin-Lin|LL| Luo|Zong-Ping|ZP| Yang|Hui-Lin|HL|

Systematic review
Lumbar total disc replacement
Mid- to long-term follow-up


Functional Improvement of Chimeric Antigen Receptor Through Intrinsic Interleukin-15Rα Signaling.

Abstract:
INTRODUCTION
Recent studies on CD19-specific chimeric antigen receptor (CAR)-modified T cells (CARTs) have demonstrated unprecedented successes in treating refractory and relapsed B cell malignancies. The key to the latest CART therapy advances can be attributed to the improved costimulatory signals in the CAR design.

METHODS
Here, we established several novel CARs by incorporating T cell signaling domains of CD28 in conjunction with intracellular signaling motif of 4-1BB, CD27, OX40, ICOS, and IL-15Rα. These novel CARs were functionally assessed based on a simple target cell killing assay.

RESULTS
The results showed that the CD28/IL-15Rα co-signaling (153z) CAR demonstrated the fastest T cell expansion potential and cytotoxic activities. IL-15 is a key cytokine that mediates immune effector activities. The 153z CARTs maintained prolonged killing activities after repetitive rounds of target cell engagement. Consistent with the enhanced target killing function, the 153z CARTs produced increased amount of effector cytokines including IFN-γ, TNFα and IL-2 upon interaction with the target cells.

CONCLUSION
In a follow-up clinical study, an acute lymphoblastic leukemia (ALL) patient, who experienced multiple relapses of central nervous system leukemia (CNSL) and failed all conventional therapies, was enrolled to receive the CD19-specific 153z CART treatment. The patient achieved complete remission after the 153z CART cell infusion. The translational outcome supports further investigation into the safety and enhanced therapeutic efficacy of the IL-15Rα-modified CART cells in cancer patients.

Nair|Sushmita|S|
Wang|Jing-Bo|JB|
Tsao|Shih-Ting|ST|
Liu|Yuchen|Y|
Zhu|Wei|W|
Slayton|William B|WB|
Moreb|Jan S|JS|
Dong|Lujia|L|
Chang|Lung-Ji|LJ|

D053720:Interleukin-15 Receptor alpha Subunit

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma


Comparing nationwide prevalences of hypertension and depression based on claims data and survey data: An example from Germany.

Abstract:
INTRODUCTION
Coded diagnoses in claims data offer a comprehensive basis for health sciences and health policy decisions. For example, morbidity-based risk adjustment schemes use coded diagnoses to allocate resources. Therefore a routinely performed validation is important. Data reconciliation with medical records would be first best, but is not possible here. This paper validates population-based prevalences of hypertension and depression based on claims data by comparing them with prevalences stem from two different epidemiological survey data.

METHOD
Data sources accessible are a nationwide sample based on outpatient claims data (GSPR), a nationwide health interview and examination survey (DEGS1) and a nationwide telephone interview survey (GEDA). The analysis includes SHI-insured aged 18-79 who live in 2010 in Germany.

RESULTS
There was high agreement for hypertension prevalences between GSPR (28.98% [28.95-29.02]) and DEGS1 (28.0% [26.5-29.5]) but not with GEDA (22.9% [22.1-23.7]). The agreement for depression prevalences was high between the two surveys (DEGS1: 7.6% [6.7-8.5] and GEDA: 6.7% [6.3-7.2]) and moderate compared to GSPR (12.23% [12.21-12.26]).

CONCLUSION
For an objectifiable disease, such as hypertension, diagnostic coding with claims data seems to be valid to be used for risk adjustment in German outpatient health care. Even though depression prevalences differ between claims data and survey data, more effort is required to understand the magnitude of a reference systems impact on prevalence estimates.

Hypertension
Depression
Surveys
Germany
Administrative claims
External validation
Healthcare


Reward and punishment-based compound cue learning and generalization in opiate dependency.

Abstract: Substance dependence is thought to be mediated by abnormalities in cognitive abilities, but how this impacts decision-making remains unclear. This study aimed to test whether people who are opiate dependent differed from never-dependent controls in learning from reward and punishment or in the generalization of learning to novel conditions. Participants with opiate dependency consisted of 21 people who were outpatients in a methadone maintenance program; the control group consisted of 21 healthy participants with no histories of substance abuse. Subjects completed a computer-based task that involved two phases: the training phase involved participants being presented with compound stimulus (a shape and color) in each trial, with the goal of learning which compounds to 'pick' for rewards or 'skip' to avoid punishment. The test phase involved a transfer test, where stimuli from the first phase were combined together to form novel compounds without feedback. The control group demonstrated fewer errors compared to opiate-dependent individuals during the training phase. In the test phase, controls used prior knowledge of both shapes and colors in responding; however, opiate-dependent individuals used shapes but did not use their knowledge of color to modulate responding. When performance during training was equated in the groups using a learning threshold, this difference between groups on the generalization test remained. A deficit in learning generalization might be indicative of group differences in learning strategies in operation during training; however, future work is necessary to uncover the specific neural substrates in action during transfer tasks, and to determine the effects of acute methadone dosage on decision-making.

Mahlberg|Justin|J|
Haber|Paul|P|
Morley|Kirsten|K|
Weidemann|Gabrielle|G|
Hogarth|Lee|L|
Beck|Kevin D|KD|
Myers|Catherine E|CE|
Moustafa|Ahmed A|AA|

Generalization
Opiate dependence
Heroin addiction
Punishment learning
Reward learning


Efficient delivery of micro RNA to bone-metastatic prostate tumors by using aptamer-conjugated atelocollagen in vitro and in vivo.

Abstract: Bone is the primary site of skeletal metastasis in prostate cancer (PCa). Atelocollagen (ATE)-mediated siRNA delivery system can be used to silence endogenous genes involved in PCa metastatic tumor cell growth. However, we hope that the delivery system can target PCa cells to reduce damage to the bone tissue and improve the therapeutic effect. RNA aptamer (APT) A10-3.2 has been used as a ligand to target PCa cells that express prostate-specific membrane antigen (PSMA). APT was investigated as a PSMA-targeting ligand in the design of an ATE-based microRNA (miRNA; miR-15a and miR-16-1) vector to PCa bone metastasis. To observe the targeted delivery and transfection efficiency of ATE-APT in PSMA-overexpressing cells, luciferase activity and biodistribution of nanoparticles in Balb/c mice was analyzed. The anticancer effect of nanoparticles in vivo was investigated using the survival times of human PCa bone metastasis mice model. Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells showed that the transfection efficiency of the synthesized DNA/ATE-APT complex was higher than that of the DNA/ATE complex. The anticancer efficacy of miRNA/ATE-APT was superior to those of other treatments in vivo. This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of PCa cells in bone metastatic foci.

Hao|Zhao|Z|
Fan|Wei|W|
Hao|Jian|J|
Wu|Xin|X|
Zeng|Guo Qing|GQ|
Zhang|Li Juan|LJ|
Nie|Sui Feng|SF|
Wang|Xu Dong|XD|

atelocollagen
Aptamer
prostate-specific membrane antigen
miRNA
targeted delivery
prostate cancer metastasis


Transposons As Tools for Functional Genomics in Vertebrate Models.

Abstract: Genetic tools and mutagenesis strategies based on transposable elements are currently under development with a vision to link primary DNA sequence information to gene functions in vertebrate models. By virtue of their inherent capacity to insert into DNA, transposons can be developed into powerful tools for chromosomal manipulations. Transposon-based forward mutagenesis screens have numerous advantages including high throughput, easy identification of mutated alleles, and providing insight into genetic networks and pathways based on phenotypes. For example, the Sleeping Beauty transposon has become highly instrumental to induce tumors in experimental animals in a tissue-specific manner with the aim of uncovering the genetic basis of diverse cancers. Here, we describe a battery of mutagenic cassettes that can be applied in conjunction with transposon vectors to mutagenize genes, and highlight versatile experimental strategies for the generation of engineered chromosomes for loss-of-function as well as gain-of-function mutagenesis for functional gene annotation in vertebrate models, including zebrafish, mice, and rats.

Kawakami|Koichi|K|
Largaespada|David A|DA|
Ivics|Zoltán|Z|

genomics
animal models
forward genetics
genetic screens
insertional mutagenesis
stem cells


Von Willebrand Factor Facilitates Intravascular Dissemination of Microsporidia Encephalitozoon hellem.

Abstract: Microsporidia are a group of spore-forming, fungus-related pathogens that can infect both invertebrates and vertebrates including humans. The primary infection site is usually digestive tract, but systemic infections occur as well and cause damages to organs such as lung, brain, and liver. The systemic spread of microsporidia may be intravascular, requiring attachment and colonization in the presence of shear stress. Von Willebrand Factor (VWF) is a large multimeric intravascular protein and the key attachment sites for platelets and coagulation factors. Here in this study, we investigated the interactions between VWF and microsporidia Encephalitozoon hellem (E. hellem), and the modulating effects on E. hellem after VWF binding. Microfluidic assays showed that E. hellem binds to ultra-large VWF strings under shear stress. In vitro germination assay and infection assay proved that E. hellem significantly increased the rates of germination and infection, and these effects would be reversed by VWF blocking antibody. Mass spectrometry analysis further revealed that VWF-incubation altered various aspects of E. hellem including metabolic activity, levels of structural molecules, and protein maturation. Our findings demonstrated that VWF can bind microsporidia in circulation, and modulate its pathogenicity, including promoting germination and infection rate. VWF facilitates microsporidia intravascular spreading and systemic infection.

Bao|Jialing|J| Mo|Biying|B| An|Guozhen|G| Luo|Jian|J| Poncz|Mortimer|M| Pan|Guoqing|G| Li|Tian|T| Zhou|Zeyang|Z|

von Willebrand factor
intravascular dissemination
microsporidia
Encephalitozoon hellem
infection


Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadal elderly men: real-life experience from an observational registry study.

Abstract: Subnormal levels of testosterone are associated with significant negative health consequences, with higher risks of all-cause and cardiovascular mortality. The numbers of studies reporting on the benefits of normalisation of testosterone is increasing but longer-term data on (elderly) men receiving testosterone treatment are almost nonexistent. In this single-centre, cumulative, prospective, registry study, 115 hypogonadal men (mean age 59.05 years) received injections with testosterone undecanoate in 12-week intervals for up to 10 years. Waist circumference, body weight and mean BMI dropped progressively with statistical significance versus previous year for 7 years and, respectively, 8 years for weight and body mass index. Similarly, fasting glucose displayed a significant decrease after the first year continuing to decrease thereafter. A decline in HbA1c , from 6.4% to 5.6% (mean <6%), was observed from year 2 on, together with a decrease in the ratio of triglycerides:high-density lipoprotein (HDL), a surrogate marker of insulin resistance, with an increase in HDL levels. The total cholesterol:HDL ratio and non-HDL cholesterol declined significantly. A decrease was also observed in systolic and diastolic blood pressure, with a decrease in levels of the inflammation marker C-reactive protein. No major adverse cardiovascular events were observed throughout the study.

Yassin|A A|AA|
Nettleship|J|J|
Almehmadi|Y|Y|
Salman|M|M|
Saad|F|F|

testosterone
glucose
Ageing men
cardiovascular risks
lipids
long-term treatment


TREC Screening for WHIM Syndrome.

Abstract:
PURPOSE
T cell receptor excision circle (TREC) quantification is a recent addition to newborn screening (NBS) programs and is intended to identify infants with severe combined immunodeficiencies (SCID). However, other primary immunodeficiency diseases (PID) have also been identified as the result of TREC screening. We recently reported a newborn with a low TREC level on day 1 of life who was diagnosed with WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome, a non-SCID primary immunodeficiency caused by mutations in the chemokine receptor CXCR4.

METHODS
We have now retrospectively reviewed the birth and clinical histories of all known WHIM infants born after the implementation of NBS for SCID.

RESULTS
We identified six infants with confirmed WHIM syndrome who also had TREC quantification on NBS. Three of the six WHIM infants had low TREC levels on NBS. All six patients were lymphopenic but only one infant had a T cell count below 1,500 cells/μL. The most common clinical manifestation was viral bronchiolitis requiring hospitalization. One infant died of complications related to Tetralogy of Fallot, a known WHIM phenotype.

CONCLUSION
The results suggest that WHIM syndrome should be considered in the differential diagnosis of newborns with low NBS TREC levels.

TRIAL REGISTRATION
Not applicable.

newborn screen
CXCR4
Tetralogy of Fallot
neutropenia


Newborn measles antibody profile in a teaching hospital: Can sex of babies determine measles IgG acquisition from their respective mothers?

Abstract: Known sex specific differences in fetal, neonatal morbidity and mortality have been documented. Sex differences also exist in birth-weight centile with males being larger than females at birth. However, these sex differences are not fully explored when studying passive measles immunity acquired by babies from their mothers. Moreover, the mechanisms that confer these sex differences are to a large extent unknown. Therefore, this study assessed sex of babies as a determinant of measles immunoglobulin G acquisition from their respective mothers. One hundred and seventy four newborn babies were enrolled in this study. Enzyme linked immunosorbent assay was used to measure maternal measles antibodies (MMA) from sera collected from these babies at birth. Gestational age of the newborn babies was determined using the Nagele rule, ultrasound scan reports and the Dubowitz criteria. Sex and mean MMA of these babies was compared using the Student's t test. Significant comparison existed between mean MMA and sex of post term babies (P = 0.000), such that post term males had higher levels of MMA than females. However, overall sex and mean MMA comparison of these babies was not significant (P = 0.977). There were more MMA in male post term babies relative to their female peers; however, overall sex comparison of MMA was not significant. Therefore, there is the need for further study.

Ahmadu|Baba Usman|BU|
Yakubu|Mava|M|
Abdullahi|Ibrahim Bello|IB|
Pwavimbo|Ambe Jose|AJ|
Mahmud|Talba Aliyu|TA|
Clapton|Difirwiti Harry|DH|

teaching hospital
sex
newborn babies
Maternal measles antibodies
Nigeria


Draft genome sequence of a CTX-M-8, CTX-M-55 and FosA3 co-producing Escherichia coli ST117/B2 isolated from an asymptomatic carrier.

Abstract:
OBJECTIVES
Asymptomatic carriers can act as reservoirs of multidrug-resistant (MDR) bacteria. The aim of this study was to describe the draft genome sequence of a MDR Escherichia coli lineage recovered from a faecal sample of a healthy carrier.

METHODS
Genomic DNA was sequenced on an Illumina NextSeq platform. Sequence reads were de novo assembled using CLC Genomics Workbench and the whole genome sequence was evaluated through bioinformatics tools available from the Center of Genomic Epidemiology as well as additional in silico analysis.

RESULTS
The genome size was calculated as 5178340 bp, with 5442 protein-coding sequences and 5492 total genes. Presence of the blaCTX-M-8, blaCTX-M-55 and fosA3 genes was detected in addition to other antimicrobial resistance genes. Interestingly, the strain was assigned to serotype O8:H4-fimH97 and was classified within the highly virulent phylogroup B2.

CONCLUSION
This draft genome can provide helpful information to elucidate genetic features that contribute to colonisation and adaptation of MDR and virulent pathogens in asymptomatic carriers.

Fernandes|Miriam R|MR|
Sellera|Fábio P|FP|
Moura|Quézia|Q|
Souza|Tiago A|TA|
Lincopan|Nilton|N|

D024901:Drug Resistance, Multiple, Bacterial

Escherichia coli
Virulent
ESBL
Extended-spectrum β-lactamase
Human
Whole-genome sequencing


Visible-Light Induced Sustainable Water Treatment Using Plasmo-Semiconductor Nanogap Bridge Array, PNA.

Abstract: The development of sustainable methods for energy-intensive water treatment processes continues to be a challenging issue. Plasmonic-semiconductor nanoparticles, which absorb large amounts of sunlight in the visible range for conversion into chemical energy efficiently, can form the basis of a sustainable water treatment method. However, the potential uses of plasmonic semiconductor particles for water treatment have not been fully explored yet because of the limitations associated with the imbalance between light capture, charge transfer, and the required recycling steps for the particles themselves. Herein, a significantly improved visible-light-induced water treatment method that uses a plasmo-semiconductor nanogap bridge array (PNA) is reported. As an arrangement of antenna-reactors, the PNA enables the balancing of the largely enhanced electromagnetic field in the plasmonic nanogap coupling region and optimal separation of charge carriers in the semiconductor. The simultaneous effects of visible-light absorption and charge transfer lead to the generation of a highly enhanced visible-light-induced OH radical (•OH). Consequently, visible-light-induced 5-log N/N0 water disinfection and 100% chemical decomposition for sustainable water treatment were demonstrated. Owing to the large light absorption, charge carrier utilization, and array-oriented scalability, the PNA will be valuable in various sustainable energy and environmental applications.

Murphy|Emma|E|
Liu|Yunbo|Y|
Krueger|Daniel|D|
Prasad|Meghna|M|
Lee|Somin Eunice|SE|
Park|Younggeun|Y|0000-0002-8346-6142

localized surface plasmon resonance (LSPR)


Identification and characterization of Arabidopsis AtNUDX9 as a GDP-d-mannose pyrophosphohydrolase: its involvement in root growth inhibition in response to ammonium.

Abstract: GDP-d-mannose (GDP-d-Man) is an important intermediate in ascorbic acid (AsA) synthesis, cell wall synthesis, protein N-glycosylation, and glycosylphosphatidylinositol-anchoring in plants. Thus, the modulation of intracellular levels of GDP-d-Man could be important for maintaining various cellular processes. Here an Arabidopsis GDP-d-Man pyrophosphohydrolase, AtNUDX9 (AtNUDT9; At3g46200), which hydrolysed GDP-d-Man to GMP and mannose 1-phosphate, was identified. The K m and V max values for GDP-d-Man of AtNUDX9 were 376±24 μM and 1.61±0.15 μmol min(-1) mg(-1) protein, respectively. Among various tissues, the expression levels of AtNUDX9 and the total activity of GDP-d-Man pyrophosphohydrolase were the highest in the roots. The GDP-d-Man pyrophosphohydrolase activity was increased in the root of plants grown in the presence of ammonium. No difference was observed in the levels of AsA in the leaf and root tissues of the wild-type and knockout-nudx9 (KO-nudx9) plants, whereas a marked increase in N-glycoprotein levels and enhanced growth were detected in the roots of KO-nudx9 plants in the presence of ammonium. These results suggest that AtNUDX9 is involved in the regulation of GDP-d-Man levels affecting ammonium sensitivity via modulation of protein N-glycosylation in the roots.

Tanaka|Hiroyuki|H| Maruta|Takanori|T| Ogawa|Takahisa|T| Tanabe|Noriaki|N| Tamoi|Masahiro|M| Yoshimura|Kazuya|K| Shigeoka|Shigeru|S|

Arabidopsis
GDP-d-mannose pyrophosphohydrolase
protein N-glycosylation
Ammonium response
Nudix hydrolase.
l-ascorbic acid


"Worried about relapse": Family members' experiences and perspectives of relapse in first-episode psychosis.

Abstract:
BACKGROUND
The purpose of this study was to gain an in-depth understanding on the subject of relapse from the perspectives of family members of young people receiving services for a first-episode psychosis (FEP).

METHODS
A qualitative descriptive approach, using focus group methods, was used to elicit experiences, understandings, and knowledge of relapse in FEP. Family members were recruited from 4 specialized early intervention programmes for psychosis in Canada. A total of 24 (6 male, 18 female) family members participated in the study. Thematic analysis was used to examine the data.

RESULTS
The core underlying theme in all focus groups was worrying about relapse, which was often accompanied by significant levels of fear and anxiety, and was influenced by: (1) impact of an episode of psychosis; (2) limited confidence in recognizing and coping with relapse; (3) unmet needs for coping skills and emotional support and (4) unmet needs regarding frequency and continuity of communication with clinicians.

CONCLUSIONS
Family members' unmet needs for relapse-focused education, support and communication with service providers and peers, can have a negative impact on relapse prevention. Addressing family members' education and support needs in a tailored manner (including preferences for types of peer support) can contribute positively to their confidence and ability to recognize and respond to relapse. This can help reduce fear and anxieties about relapse, and positively influence the ability to function as caregivers. Future research should focus on best approaches for providing education, sustained contact with the clinical team and family peer support.

Lal|Shalini|S| Malla|Ashok|A| Marandola|Gina|G| Thériault|Joanie|J| Tibbo|Phil|P| Manchanda|Rahul|R| Williams|Richard|R| Joober|Ridha|R| Banks|Nicola|N|

qualitative
peer support
caregivers
psychoeducation
recovery


Anesthesia for a Rare Case of Uncorrected Pentalogy of Fallot Undergoing Craniotomy and Drainage of Brain Abscess.

Abstract: Children with uncorrected cyanotic congenital heart diseases can present for non cardiac surgeries. They pose several challenges to the Anaesthesiologist, especially when they are posted for emergency surgery, due to the complex haemodynamic changes secondary to the heart disease. Pentalogy of Fallot (POF) is a rare form of congenital heart disease characterized by the association of Tetralogy of Fallot (TOF) with an atrial septal defect (ASD). TOF is the leading cause of intracardiac right to left shunt and is the commonest type of cyanotic congenital heart disease to cause a brain abscess. Children with POF presenting with brain abscess pose several challenges to the anaesthesiologist due to the altered haemodynamics and warrant a meticulous anaesthetic plan. There are very few case reports of Anaesthesia management of a child with Pentalogy of Fallot (POF) presenting for non cardiac surgery. We report the anaesthetic management of a rare case of a 5-year-old child with uncorrected POF, who presented to our Superspeciality hospital with a brain abscess and underwent an emergency craniotomy with drainage of the brain abscess successfully.

Cyanotic congenital heart disease
Intracardiac shunt
Intracerebral abscess
Neurosurgery


Comparing about three types of endoscopic therapy methods for upper gastrointestinal submucosal tumors originating from the muscularis propria layer.

Abstract: Background: Endoscopic submucosal excavation (ESE), endoscopic full-thickness resection (EFTR) and submucosal tunneling endoscopic resection (STER) have been widely applied to upper gastrointestinal submucosal tumors (SMTs) originating from the muscularis propria (MP) layer in recent years. But until now, there are few studies that comparing the efficacy and safety of three endoscopic therapy methods.Method: From January 2013 to August 2018, a total of 218 patients with SMTs who underwent ESE, EFTR or STER were enrolled in this retrospective study. Clinicopathological characteristics, endoscopic features, complication and follow-up data were analyzed.Result: There were 114 patients underwent ESE, 61 underwent EFTR and 43 underwent STER, respectively. The en bloc and complete resection rates in STER group (83.7% and 90.0%) were significantly lower and postoperative complication rate (62.8%) was significantly higher than those of the other 2 methods. Furthermore, for lesions <40 mm, no significant differences were found in the en bloc rate, complete rate and postoperative complication rate among 3 methods. The perforation rate decreased in the order of EFTR (100%), ESE (23.7%), STER (7.0%). The median number of clips, fasting time and hospital stay were lowest in ESE group (5, 2 days, and 7 days). And the cost was highest in EFTR group ($4993.1). There were no differences in the bleeding and recurrence rates among three groups.Conclusion: For SMTs <40 mm, the efficacy among 3 ER methods are comparative. The choice of ER methods mainly based on the comprehensive consideration of lesion size, location, growth pattern and clinical experience of endoscopists. For benign SMTs ≥40 mm in stomach, ESE and EFTR becomes alternative choices.

Xiu|Hui|H| Zhao|Cheng-Ye|CY| Liu|Fu-Guo|FG| Sun|Xue-Guo|XG| Sun|Hui|H| Liu|Xi-Shuang|XS|

D010043:Outcome and Process Assessment, Health Care


Acute exacerbation of chronic disseminated intravascular coagulation associated with thoracoabdominal aortic aneurysm after tooth extraction.

Abstract:
OBJECTIVE
To present a rare case of persistent bleeding from the tooth extraction socket in a patient with chronic disseminated intravascular coagulation (DIC).

BACKGROUND
Acute exacerbation of chronic DIC occurs by various trigger factors.

CLINICAL REPORT
The patient's chronic DIC in association with thoracoabdominal aortic aneurysm was activated by tooth extraction, resulting in persistent bleeding from the socket.

CONCLUSION
Patients with chronic DIC may have persistent bleeding following tooth extraction.


Lower Extremity Biomechanics Are Altered Across Maturation in Sport-Specialized Female Adolescent Athletes.

Abstract: Sport specialization is a growing trend in youth athletes and may contribute to increased injury risk. The neuromuscular deficits that often manifest during maturation in young, female athletes may be exacerbated in athletes who specialize in a single sport. The purpose of this study was to investigate if sport specialization is associated with increased lower extremity biomechanical deficits pre- to post-puberty in adolescent female athletes. Seventy-nine sport-specialized female adolescent (Mean ± SD age = 13.4 ± 1.8 years) basketball, soccer, and volleyball athletes were identified and matched with seventy-nine multi-sport (soccer, basketball, and volleyball) female athletes from a database of 1,116 female adolescent basketball, soccer, and volleyball athletes who were enrolled in one of two large prospective, longitudinal studies. The athletes were assessed over two visits (Mean ± SD time = 724.5 ± 388.7 days) in which they were classified as pre-pubertal and post-pubertal, respectively. Separate 2 × 2 analyses of covariance were used to compare sport-specialized and multi-sport groups and dominant/non-dominant limbs with respect to pubertal changes in peak knee sagittal, frontal, and transverse plane joint angular measures and moments of force recorded while performing a drop vertical jump task. The sport-specialized group were found to exhibit significantly larger post-pubertal increases in peak knee abduction angle (p = 0.005) and knee abduction moment (p = 0.006), as well as a smaller increase in peak knee extensor moment (p = 0.032) during landing when compared to the multi-sport group. These biomechanical changes are indicative of potentially compromised neuromuscular control that may increase injury risk pre- to post-puberty in sport-specialized female athletes. Consideration of maturation status may be an important factor in assessing the injury risk profiles of adolescent athletes who specialize in sport.

DiCesare|Christopher A|CA|
Montalvo|Alicia|A|
Barber Foss|Kim D|KD|
Thomas|Staci M|SM|
Ford|Kevin R|KR|
Hewett|Timothy E|TE|
Jayanthi|Neeru A|NA|
Stracciolini|Andrea|A|
Bell|David R|DR|
Myer|Gregory D|GD|

biomechanics
maturation
female
sport specialization
injury risk


Unruptured Giant Intracranial Aneurysm of the Internal Carotid Artery: Late Ocular Symptoms.

Abstract: An unruptured giant intracranial aneurysm of the internal carotid artery may tend to present with late ocular symptoms. This is the case of a 58-year-old female patient with a giant unruptured aneurysm of the right internal carotid artery. The patient presented with exclusively progressive reduction of visual acuity and visual field defects due to the mass effect of the growing aneurysm. The rupture of the aneurysm occurred before planned treatment. Clinical suspicion and timely recognition as well as prompt treatment play an important role in the final outcome of the management of giant unruptured intracerebral aneurysms.

Zorić Geber|Mia|M|
Krolo|Iva|I|
Zrinscak|Ognjen|O|
Tedeschi Reiner|Eugenia|E|
Zivkovic|Dario Josip|DJ|

D017542:Aneurysm, Ruptured
D002340:Carotid Artery Diseases
D002343:Carotid Artery, Internal
D002543:Cerebral Hemorrhage
D005260:Female
D005451:Fluorescein Angiography
D006801:Humans
D002532:Intracranial Aneurysm
D018810:Magnetic Resonance Angiography
D008875:Middle Aged
D041623:Tomography, Optical Coherence
D014786:Vision Disorders
D014792:Visual Acuity
D014794:Visual Fields

visual field defect
mass effect
Aneurysm size
anterior intracranial circulation
subarachnoid hemorrhage
vascular abnormalities


The Ageing Brain: Age-dependent changes in the electroencephalogram during propofol and sevoflurane general anaesthesia.

Abstract:
BACKGROUND
Anaesthetic drugs act at sites within the brain that undergo profound changes during typical ageing. We postulated that anaesthesia-induced brain dynamics observed in the EEG change with age.

METHODS
We analysed the EEG in 155 patients aged 18-90 yr who received propofol (n=60) or sevoflurane (n=95) as the primary anaesthetic. The EEG spectrum and coherence were estimated throughout a 2 min period of stable anaesthetic maintenance. Age-related effects were characterized by analysing power and coherence as a function of age using linear regression and by comparing the power spectrum and coherence in young (18- to 38-yr-old) and elderly (70- to 90-yr-old) patients.

RESULTS
Power across all frequency bands decreased significantly with age for both propofol and sevoflurane; elderly patients showed EEG oscillations ∼2- to 3-fold smaller in amplitude than younger adults. The qualitative form of the EEG appeared similar regardless of age, showing prominent alpha (8-12 Hz) and slow (0.1-1 Hz) oscillations. However, alpha band dynamics showed specific age-related changes. In elderly compared with young patients, alpha power decreased more than slow power, and alpha coherence and peak frequency were significantly lower. Older patients were more likely to experience burst suppression.

CONCLUSIONS
These profound age-related changes in the EEG are consistent with known neurobiological and neuroanatomical changes that occur during typical ageing. Commercial EEG-based depth-of-anaesthesia indices do not account for age and are therefore likely to be inaccurate in elderly patients. In contrast, monitoring the unprocessed EEG and its spectrogram can account for age and individual patient characteristics.

Purdon|P L|PL|
Pavone|K J|KJ|
Akeju|O|O|
Smith|A C|AC|
Sampson|A L|AL|
Lee|J|J|
Zhou|D W|DW|
Solt|K|K|
Brown|E N|EN|

ageing
propofol
sevoflurane
EEG
elderly
brain monitoring
electroencephalography


A System for Supporting Development and Update of the International Classification of Health Interventions (ICHI).

Abstract: The International Classification of Health Interventions (ICHI) is a member of the WHO Family of International Classifications, being developed to provide a common tool for reporting and analysing health interventions for statistical purposes. A web-based platform for classification development and update has been specifically developed to support the initial development step and then, after final approval, the continuous revision and update of the classification. The platform provides features for classification editing, versioning, comment management and URI identifiers. During the last 12 months it has been used for developing the ICHI Beta version, replacing the previous process based on the exchange of Excel files. At November 2017, 90 users have provided input to the development of the classification, which has resulted in 2913 comments and 2971 changes in the classification, since June 2017. Further work includes the development of an URI API for machine to machine communication, following the model established for ICD-11.

Donada|Marc|M|
Della Mea|Vincenzo|V|
Cumerlato|Megan|M|
Rankin|Nicole|N|
Madden|Richard|R|

Health Interventions
Biomedical classifications


The compensatory effect of regular exercise on long-term memory impairment in sleep deprived female rats.

Abstract: Previous studies have been shown that exercise can improve short-term spatial learning, memory and synaptic plasticity impairments in sleep deprived female rats. The aim of the present study was to investigate the effects of treadmill exercise on sleep deprivation (SD) induced impairment in hippocampal dependent long-term memory in female rats. Intact and ovariectomized female rats were used in the current study. Exercise protocol was 4 weeks treadmill running. Twenty four hour SD was induced by using multiple platform apparatus after learning phase. Spatial learning and long-term memory was examined by using the Morris Water Maze (MWM) test. Our results indicated that sleep deprivation impaired long term memory in the intact and ovariectomized female rats, regardless of reproductive status (p<0.05) and treadmill exercise compensated this impairment (p<0.05). In conclusion the results of the current study confirmed the negative effect of SD on cognitive functions and regular exercise seems to protect rats from these factors, however more investigations need to be done.

Salari|Maryam|M| Sheibani|Vahid|V| Saadati|Hakimeh|H| Pourrahimi|Alimohammad|A| khaksarihadad|Mohammad|M| Esmaeelpour|Khadijeh|K| Khodamoradi|Mehdi|M|

Regular exercise
Long-term memory
Sleep deprivation
Female rats
Morris water maze


Psychiatric considerations in deep brain stimulation for Parkinson's disease.

Abstract: Deep brain stimulation targeting the subthalamic nucleus or globus pallidus internus are highly effective for the symptomatic treatment of Parkinson's disease. The assessment and management of psychiatric issues is relevant to preoperative patient selection and to optimal postoperative outcomes. This chapter reviews the evidence on psychiatric symptoms in the perioperative state including suicidal behaviors, depression, anxiety, mania, apathy, and impulse control disorders.

Voon|Valerie|V|
Howell|Nicholas Araki|NA|
Krack|Paul|P|

D046690:Deep Brain Stimulation
D006801:Humans
D001523:Mental Disorders
D010300:Parkinson Disease

deep brain stimulation
subthalamic nucleus
suicide
depression
Parkinson’s disease


Metabonomics based NMR in Crohn's disease applying PLS-DA.

Abstract:
AIM
The aim of this study was to search for metabolic biomarkers of Crohn's disease (CD).

BACKGROUND
Crohn's disease (CD) is a type of inflammatory bowel disease that causing a wide variety of symptoms. CD can influence any part of the gastrointestinal tract from mouth to anus. CD is not easily diagnosed because monitoring tools are currently insufficient. Thus, the discovery of proper methods is needed for early diagnosis of CD.

PATIENTS AND METHODS
We utilized metabolic profiling using proton nuclear magnetic resonance spectroscopy ((1)HNMR) to find the metabolites in serum. Classification of CD and healthy subject was done using partial least squares discriminant analysis (PLS-DA).

RESULTS
According to PLS-DA model, we concluded that just using one descriptor CD and control groups could be classified separately. The level of lipid in blood serum of CD compared to healthy cohorts was decreased. For the external test set, the classification model showed a 94% correct classification of CD and healthy subject.

CONCLUSION
The result of classification model presents that NMR based metabonomics is key tool as well as insight into potential targets for disease therapy and prevention.

Fathi|Fariba|F|
Oskouie|Afsaneh Arefi|AA|
Tafazzoli|Mohsen|M|
Naderi|Nosratollah|N|
Sohrabzedeh|Kaveh|K|
Fathi|Soraya|S|
Norouzinia|Mohsen|M|
Rostami Nejad|Mohammad|M|

Metabonomics
PLS-DA
1HNMR
Crohn's diseasel


Rhabdorrhynchus echii (Brahm, 1790), a "forgotten" name (Coleoptera, Curculionidae, Lixinae).

Abstract: The application of the name Curculio echii Brahm, 1790 is discussed. Based on the description it is evident that it should be applied to a German species of the genus Rhabdorrhynchus, and that it has priority over the name currently applied to the species, Rhabdorrhynchus seriegranosus Chevrolat, 1873. The new combination Rhab-dorrhynchus echii (Brahm, 1790) is proposed. As there is a lack of any type material of Curculio echii a neotype is designated. Based on the study of the type specimen, Rhabdorrhynchus seriegranosus is restored as a valid species.

new combination
Neotype
European fauna
Palaearctic weevils
nomenclature


Comparison of clinical, serological, and prognostic differences among juvenile-, adult-, and late-onset lupus nephritis in Korean patients.

Abstract: We investigated whether lupus nephritis (LN) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features and long-term prognosis in ethnically homogeneous Korean patients. We enrolled 117 systemic lupus erythematosus patients with available clinical data at the time of renal biopsy of LN. Sociodemographic, clinical, and laboratory data and concomitant diseases were evaluated at the time of renal biopsy. We divided LN patients, according to age at LN diagnosis, into three groups: juvenile-onset LN (JLN, diagnosed at ≤18 years), adult-onset LN (ALN, diagnosed at 18-50 years), and late-onset LN (LLN, diagnosed at >50 years) and compared demographic, clinical, histological, and laboratory findings. We also compared treatment and long-term prognosis of LN. Of the 117 LN patients, 20 (17.8%), 84 (71.3%), and 13 (10.9%) were JLN, ALN, and LLN patients, respectively. LLN patients showed higher white blood cell counts and lower estimated glomerular filtration rate than ALN or LLN patients. LLN patients had higher chronicity indices and scores. Anti-Ro antibodies were found more frequently in ALN patients, and lower complement levels were more common in JLN patients. During a mean follow-up of 76.5 months, development of chronic kidney disease and death were higher in LLN patients than in JLN and ALN patients. LLN patients showed higher chronicity indices and deterioration of kidney function and death in long-term follow-up compared with JLN and ALN patients. Therefore, LLN patients should be carefully monitored to avoid poor outcomes.

Kang|Ji-Hyoun|JH|
Park|Dong-Jin|DJ|
Lee|Kyung-Eun|KE|
Lee|Ji Shin|JS|
Choi|Yoo-Duk|YD|
Lee|Shin-Seok|SS|

Lupus nephritis
Onset
Systemic lupus erythematosus
Age


Monetized health benefits attributable to mobile source emission reductions across the United States in 2025.

Abstract: By-products of mobile source combustion processes, such as those associated with gasoline- and diesel-powered engines, include direct emissions of particulate matter as well as precursors to particulate matter and ground-level ozone. Human exposure to fine particulate matter with an aerodynamic diameter smaller than 2.5 μm (PM2.5) is associated with increased incidence of premature mortality and morbidity outcomes. This study builds upon recent, detailed source-apportionment air quality modeling to project the health-related benefits of reducing PM2.5 from mobile sources across the contiguous U.S. in 2025. Updating a previously published benefits analysis approach, we develop national-level benefit per ton estimates for directly emitted PM2.5, SO2/pSO4, and NOX for 16 mobile source sectors spanning onroad vehicles, nonroad engines and equipment, trains, marine vessels, and aircraft. These benefit per ton estimates provide a reduced-form tool for estimating and comparing benefits across multiple mobile source emission scenarios and can be applied to assess the benefits of mobile source policies designed to improve air quality. We found the benefit per ton of directly emitted PM2.5 in 2025 ranges from $110,000 for nonroad agriculture sources to $700,000 for onroad light duty gas cars and motorcycles (in 2015 dollars and based on an estimate of PM-related mortality derived from the American Cancer Society cohort study). Benefit per ton values for SO2/pSO4 range from $52,000 for aircraft sources (including emissions from ground support vehicles) to $300,000 for onroad light duty diesel emissions. Benefit per ton values for NOX range from $2100 for C1 and C2 marine vessels to $7500 for "nonroad all other" mobile sources, including industrial, logging, and oil field sources. Benefit per ton estimates increase approximately 2.26-fold when using an alternative concentration response function to derive PM2.5-related mortality. We also report benefit per ton values for the eastern and western U.S. to account for broad spatial heterogeneity patterns in emissions reductions, population exposure and air quality benefits.

Wolfe|Philip|P|
Davidson|Kenneth|K|
Fulcher|Charles|C|
Fann|Neal|N|
Zawacki|Margaret|M|
Baker|Kirk R|KR|

Health benefits
Mobile source
Particulate matter
Benefits per ton
Air pollution


Effect of extrusion conditions on the anthocyanin content, functionality, and pasting properties of obtained nixtamalized blue corn flour (Zea mays L.) and process optimization.

Abstract: The aim of this study was to evaluate the effect of extrusion factors on the properties of extruded nixtamalized corn flours (ENCFs), determine the optimal conditions, and produce a tortilla with texture and nutraceutical characteristics acceptable for consumers. The processing factors used were feed moisture (FM, 15 to 30%), extruder temperature (T, 70 to 110 °C), and screw speed (SS, 50 to 145 rpm). The properties evaluated in the flours were total anthocyanins (TA), subjective water absorption capacity, and peak viscosity (PV). Response surface methodology and analysis of variance were used in the evaluation. The linear and quadratic terms of FM had a greater effect on all evaluated parameters. The optimization was performed using the numerical method of global desirability. The response variables that were optimized in the ENCF were TAs (maximize) and PV (maximize). The optimal region was the following: FM (18.17%), T (92.03 °C), and SS (76.61 rpm). The experimental value for the TA in the optimized ENCF was 226.07 mg/kg, and the PV was 1063.9 cP. The results of this study could help develop nixtamalized corn flours with desirable characteristics to make tortillas using the extrusion process. PRACTICAL APPLICATION: The results obtained would be useful for the tortilla industry, developing nixtamalized corn flours with desirable characteristics to make healthy tortillas using the extrusion process, with minimum losses in biologically active compounds such as anthocyanins (health promoters) without affect negatively the eating quality of the product (good texture).

viscosity
Tortilla texture
bioactive compounds
pigmented corn
starch


Effectiveness of urethral catheterization under ultrasound guidance for semen collection from Asiatic black bears (Ursus thibetanus).

Abstract: The Asiatic black bear (ABB; Ursus thibetanus ussuricus) is a globally endangered species, and measures to help increase their population are necessary. For the successful restoration of this species, artificial breeding as well as conservation translocation are considered important. The aims of the present study were to evaluate the feasibility and effectiveness of urethral catheterization (UC), which is effectively used in feline species, for semen collection from ABBs and establish the optimal protocol for semen collection via this technique. Seven clinically healthy, adult male ABBs (age, 6-13 years; weight, 130-180 kg) housed at the Species Restoration Technology Institute, Korea were included in this study. All study procedures were performed during the breeding season (June to August) over 3 consecutive years. Semen samples were collected once or three times from all bears by ultrasound-guided UC or electroejaculation (EE) under general anesthesia, and their characteristics, including sperm motility, were evaluated. The day of semen collection was defined as Day 0. The semen collected by the UC method was stored at 4 °C, and sperm motility was evaluated at the same time every day for 16 days. The successful collection rates for the UC and EE methods were 92.3% and 53.8%, respectively. The sperm concentration (4718.9 ± 1526.1 vs. 185.0 ± 34.2 × 106/ml), total sperm count (1196.6 ± 955.5 vs. 100.9 ± 70.0 × 106), sperm motility score (4.39 ± 0.78 vs. 3.00 ± 1.73), viability (98.2 ± 2.3 vs. 82.7 ± 19.6), and the proportion of spermatozoa with intact acrosomes (92.2% ± 9.3% vs. 75.6% ± 10.6%) were higher with the UC method than with the EE method, whereas the proportion of spermatozoa with an abnormal morphology (23.1% ± 4.6% vs. 45.6% ± 19.5%) was lower with the former than with the latter. Over the course of cool storage, there was an overall decrease in the total motility, progressive motility, and viability, although viability was >50% until Day 10. These findings suggest that ultrasound-guided UC is a useful and feasible tool for the collection of high-quality semen from ABBs. The collected semen remains viable for up to 10 days, with high sperm motility maintained for up to 7 days, when stored at 4 °C.

Jeong|Dong-Hyuk|DH| Yang|Jeong-Jin|JJ| Seo|Myeong-Kyo|MK| Lee|An-Na|AN| Lim|Yoon-Kyu|YK|

Urethral catheterization
Ultrasound
Semen
Bear
Sperm motility
Cool storage


KSHV cell attachment sites revealed by ultra sensitive tyramide signal amplification (TSA) localize to membrane microdomains that are up-regulated on mitotic cells.

Abstract: Cell surface structures initiating attachment of Kaposi's sarcoma-associated herpesvirus (KSHV) were characterized using purified hapten-labeled virions visualized by confocal microscopy with a sensitive fluorescent enhancement using tyramide signal amplification (TSA). KSHV attachment sites were present in specific cellular domains, including actin-based filopodia, lamellipodia, ruffled membranes, microvilli and intercellular junctions. Isolated microdomains were identified on the dorsal surface, which were heterogeneous in size with a variable distribution that depended on cellular confluence and cell cycle stage. KSHV binding domains ranged from scarce on interphase cells to dense and continuous on mitotic cells, and quantitation of bound virus revealed a significant increase on mitotic compared to interphase cells. KSHV also bound to a supranuclear domain that was distinct from microdomains in confluent and interphase cells. These results suggest that rearrangement of the cellular membrane during mitosis induces changes in cell surface receptors implicated in the initial attachment stage of KSHV entry.

Garrigues|H Jacques|HJ|
Rubinchikova|Yelena E|YE|
Rose|Timothy M|TM|

D005456:Fluorescent Dyes
D006566:Herpesviridae Infections
D019288:Herpesvirus 8, Human
D006801:Humans
D021962:Membrane Microdomains
D018613:Microscopy, Confocal
D008938:Mitosis
D015854:Up-Regulation
D053585:Virus Attachment


Advances in Membranous Nephropathy.

Abstract: Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leap combining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four "new antigens" were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.