Theoretical investigation of phenothiazine-triphenylamine-based organic dyes with different π spacers for dye-sensitized solar cells.

Abstract: Three phenothiazine-triphenylamine-based organic dyes (CD-1, CD-2 and CD-3) are designed based on the dye WD-8. The geometries, electronic structures, and electronic absorption spectra of these dyes before and after binding to TiO2 are studied by density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The calculated geometries indicate that these dyes show good steric hindrance effect which is advantage to inhibit the close intermolecular π-π aggregation effectively. The lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels of these dyes could ensure positive effect on the process of electron injection and dye regeneration. The simulated spectra of CD-1∼3 show better absorption than that of WD-8 in the low energy zone. All the calculated results demonstrate that these dyes could be used as potential sensitizers for DSSCs and show better performances than WD-8.

Chen|Ximing|X| Jia|Chunyang|C| Wan|Zhongquan|Z| Zhang|Jiaqiang|J| Yao|Xiaojun|X|

D000814:Aniline Compounds
D004396:Coloring Agents
D011211:Electric Power Supplies
D004583:Electrons
D008958:Models, Molecular
D010640:Phenothiazines
D012993:Solar Energy
D013056:Spectrophotometry, Ultraviolet

Time-dependent density functional theory (TD-DFT)


TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding.

Abstract: The various effects of native protein folding on the stability and folding rate of intrinsically disordered proteins (IDPs) in crowded intracellular environments are important in biomedicine. Although most studies on protein folding have been conducted in vitro, providing valuable insights, studies on protein folding in crowded intracellular environments are scarce. This study aimed to explore the effects of intracellular molecular crowding on the folding of mutant transactivator HIV-1 Tat based on intracellular interactions, including TAR RNA, as proof of the previously reported chaperna-RNA concept. Considering that the Tat-TAR RNA motif binds RNA, we assessed the po tential function of TAR RNA as a chaperna for the refolding of R52Tat, a mutant in which the argi nine (R) residues at R52 have been replaced with alanine (A) by site-directed mutagenesis. We mon itored Tat-EGFP and Tat folding in HeLa cells via time-lapse fluorescence microscopy and biolayer interferometry using EGFP fusion as an indicator for folding status. These results show that the refolding of R52A Tat was stimulated well at a 0.3 μM TAR RNA concentration; wild-type Tat refolding was essentially abolished because of a reduction in the affinity for TAR RNA at that con centration. The folding and refolding of R52Tat were mainly promoted upon stimulation with TAR RNA. Our findings provide novel insights into the therapeutic potential of chaperna-mediated fold ing through the examination of as-yet-unexplored RNA-mediated protein folding as well as viral genetic variants that modulate viral evolutionary linkages for viral diseases inside a crowded intra cellular environment.

D054322:tat Gene Products, Human Immunodeficiency Virus

TAR RNA
Tat
chaperna
arginine-rich domains
crowding effects
folding kinetics


Glucocorticoids for therapeutic immunosuppression: Clinical pearls for the practicing neurologist.

Abstract: Given widespread use of glucocorticoid therapy in neurologic disease, understanding glucocorticoid pharmacology and risk is paramount for the practicing neurologist. While dosing and tapering regimens vary depending on the neurological disease and indication being treated, there are important general principles of glucocorticoid prescribing and monitoring that can guide clinical decision-making. Glucocorticoid-related toxicities can occur across multiple organ systems, including hypertension; dyslipidemia; weight gain; hyperglycemia; osteoporosis and avascular necrosis; myopathy; gastrointestinal bleeding; infection; and neuropsychiatric effects with sleep, mood disturbance and cognition. This narrative review provides a practical framework for safe and responsible prescribing of this therapeutic class of medications, including appreciation of immunosuppressive consequences, risk mitigation strategies, dosing and tapering, and recognition of adrenal insufficiency and glucocorticoid withdrawal.

Galati|Alexandra|A|
Brown|E Sherwood|ES|
Bove|Riley|R|
Vaidya|Anand|A|
Gelfand|Jeffrey|J|

Glucocorticoid
Neurology
Risk mitigation
Side effect


Improvement of a patient's circadian rhythm sleep disorders by aripiprazole was associated with stabilization of his bipolar illness.

Abstract: Splitting of the behavioural activity phase has been found in nocturnal rodents with suprachiasmatic nucleus (SCN) coupling disorder. A similar phenomenon was observed in the sleep phase in the diurnal human discussed here, suggesting that there are so-called evening and morning oscillators in the SCN of humans. The present case suffered from bipolar disorder refractory to various treatments, and various circadian rhythm sleep disorders, such as delayed sleep phase, polyphasic sleep, separation of the sleep bout resembling splitting and circabidian rhythm (48 h), were found during prolonged depressive episodes with hypersomnia. Separation of sleep into evening and morning components and delayed sleep-offset (24.69-h cycle) developed when lowering and stopping the dose of aripiprazole (APZ). However, resumption of APZ improved these symptoms in 2 weeks, accompanied by improvement in the patient's depressive state. Administration of APZ may improve various circadian rhythm sleep disorders, as well as improve and prevent manic-depressive episodes, via augmentation of coupling in the SCN network.

D006970:Disorders of Excessive Somnolence

D020178:Sleep Disorders, Circadian Rhythm

circadian rhythm sleep disorders
aripiprazole
suprachiasmatic nucleus
bipolar disorder
biological oscillator


Central pain.

Abstract: Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

central pain
neuropathic pain
sensory process


Reasons for first line ART modification over the years during the ART scale up in Uganda.

Abstract:
BACKGROUND
During the initial scale up of ART in sub-Saharan Africa, prescribed regimens included drugs with high potential for toxicity (particularly stavudine). More recently a growing number of patients requires second line treatment due to treatment failure, especially following the expansion of viral load testing. We aim to determine the reasons and risk factors for modification of first line ART across the years.

METHODS
We included patients started on standard first line ART (2NRTI + 1 NNRTI) between 2005 and 2016 at the Infectious Diseases Institute, Kampala, Uganda. We described the reasons for treatment modification categorized in (1) toxicity (2) treatment failure (3) other reason (new TB treatment, new pregnancy). We used Cox proportional hazard to identify factors associated with treatment modification due to toxicity.

RESULTS
We included 14,261 patients; 9114 (63.9%), were female, the median age was 34 years (IQR: 29-40), 60.8% were in WHO stage 3 and 4. The median BMI and CD4 count were 21.9 (IQR: 19.6-24.8) and 188 cell/µL (IQR: 65-353) respectively; 27.5% were started on stavudine, 46% on zidovudine, and 26.5% on a tenofovir containing regimens. We observed 6248 ART modifications in 4868/14,261 patients (34.1%); 1615 were due to toxicity, 1077 to treatment failure, 1330 to contraindications, and 1860 patients following WHO recommendation of phasing out stavudine and substituting with another NRTI. Modification for drug toxicity declined rapidly after the phase out of stavudine (2008), while switches to second line regimes increased after the implementation of viral load monitoring (2015). Patients with normal BMI compared to underweight, (HR: 0.79, CI 0.69-0.91), with CD4 counts 200-350 cells/µL compared to < 200 cells/µL (HR: 0.81- CI 0.71-0.93), and started on zidovudine (HR: 0.51 CI 0.44-0.59) and tenofovir (HR: 0.16, CI 0.14-0.22) compared to stavudine were less likely to have ART modification due to toxicity. Older patients (HR: 1.14 per 5-year increase CI 1.11-1.18), those in WHO stage 3 and 4 (HR: 1.19, CI 1.06-1.34) were more likely to have ART modification due to toxicity.

CONCLUSIONS
Toxicity as reason for drugs substitution decreased over time mirroring the phase out of stavudine, while viral load expansion identified more patients in need of second line treatment.

Castelnuovo|B|B| Mubiru|F|F| Kalule|I|I| Kiragga|A|A|

Sub-Saharan Africa
Toxicity
Antiretroviral treatment modifications


Heart Rate of Nursing Home Residents with Advanced Dementia and Persistent Vocalizations.

Abstract: Persistent vocalizations (PVs) are a common behavioral symptom of dementia. There are currently no known studies examining physiological measurement in nursing home (NH) residents with dementia exhibiting PVs. Measures of heart rate (HR) could provide objective evidence of a person's response to a disruption in their internal or external environment. This was a two-case observational study involving NH residents with advanced dementia. HRs were collected via a sensor belt. We found a 39-45 bpm increase in HRs in both participants when comparing a day without PVs to a day exhibiting PVs. This is the first study to demonstrate a change in HR associated with PVs and potential evidence of stress in the person in response to either an internal or external stimuli.

Sefcik|Justine S|JS|
Ersek|Mary|M|
Libonati|Joseph R|JR|
Hartnett|Sasha C|SC|
Hodgson|Nancy A|NA|
Cacchione|Pamela Z|PZ|

heart rate
behavioral symptom of dementia
stress
(3–6) Persistent vocalizations
case study


A small, computationally flexible network produces the phenotypic diversity of song recognition in crickets.

Abstract: How neural networks evolved to generate the diversity of species-specific communication signals is unknown. For receivers of the signals, one hypothesis is that novel recognition phenotypes arise from parameter variation in computationally flexible feature detection networks. We test this hypothesis in crickets, where males generate and females recognize the mating songs with a species-specific pulse pattern, by investigating whether the song recognition network in the cricket brain has the computational flexibility to recognize different temporal features. Using electrophysiological recordings from the network that recognizes crucial properties of the pulse pattern on the short timescale in the cricket Gryllus bimaculatus, we built a computational model that reproduces the neuronal and behavioral tuning of that species. An analysis of the model's parameter space reveals that the network can provide all recognition phenotypes for pulse duration and pause known in crickets and even other insects. Phenotypic diversity in the model is consistent with known preference types in crickets and other insects, and arises from computations that likely evolved to increase energy efficiency and robustness of pattern recognition. The model's parameter to phenotype mapping is degenerate - different network parameters can create similar changes in the phenotype - which likely supports evolutionary plasticity. Our study suggests that computationally flexible networks underlie the diverse pattern recognition phenotypes, and we reveal network properties that constrain and support behavioral diversity.

cricket
neural networks
Gryllus bimaculatus
acoustic communication
evolution
evolutionary biology
mating signals
neuroscience


Assessing acceptability and feasibility of provider-initiated HIV testing and counseling in Ghana.

Abstract: t In Ghana, HIV voluntary counseling and testing remains poorly utilized. The World Health Organization (WHO) has recommended opt-out, provider-initiated testing and counseling (PITC) in order to increase utilization and earlier intervention. Yet implementation challenges remain in resource-scarce settings. This study sought to better understand the dynamics of providing PITC at Apam Catholic Hospital, a district referral hospital in Ghana. Semi-structured interviews were conducted with healthcare providers and patients exploring attitudes regarding PITC, community stigma, and HIV knowledge. Results showed healthcare providers believed PITC would lead to earlier diagnosis and intervention, but concerns persisted over increased costs. Patients welcomed PITC, but expressed discomfort in opting-out. Patients demonstrated incomplete HIV knowledge and widely believed spiritual healers and prayer can cure the infection. Acceptance of PITC by both healthcare providers and patients remains high, but concerns over resource costs and HIV knowledge persist as challenges. [Full article available at http://rimed.org/rimedicaljournal-2017-08.asp].

Tabb|Zachary|Z|
Moriarty|Kathleen|K|
Schrier|Madeleine W|MW|
Amekah|Ebenezer|E|
Flanigan|Timothy P|TP|
Lartey|Margaret|M|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care


Functional analysis and evaluation of respiratory cilia in healthy Chinese children.

Abstract:
BACKGROUND
To aid in the diagnosis of Primary Ciliary Dyskinesia (PCD) and to evaluate the respiratory epithelium in respiratory disease, normal age-related reference ranges are needed for ciliary beat frequency (CBF), beat pattern and ultrastructure. Our aim was to establish reference ranges for healthy Chinese children.

METHODS
Ciliated epithelial samples were obtained from 135 healthy Chinese children aged below 18 years by brushing the inferior nasal turbinate. CBF and beat pattern were analysed from high speed video recordings. Epithelial integrity and ciliary ultrastructure were assessed using transmission electronic microscopy.

RESULTS
The mean CBF from 135 children studied was 10.1 Hz (95% CI 9.8 to 10.4). Approximately 20% (ranged 18.0-24.2%) of ciliated epithelial edges were found to have areas of dyskinetically beating cilia. Normal beat pattern was observed in ciliated epithelium from all subjects. We did not find any effect of exposure to second hand smoke on CBF in our subjects. Microtubular defects were found in 9.3% of all of the cilia counted in these children, while other ciliary ultrastructural defects were found in less than 3%.

CONCLUSIONS
We established the reference range for CBF, beat pattern and ultrastructure in healthy Chinese children. Using similar methodology, we found a lower overall mean CBF than previously obtained European values. This study highlights the need to establish normative data for ciliary function in different populations.

Chinese children
Beat frequency
Beat pattern
Ultrastructure
Nasal cilia
Reference data


Do artists see their retinas?

Abstract: Our perception starts with the image that falls on our retina and on this retinal image, distant objects are small and shadowed surfaces are dark. But this is not what we see. Visual constancies correct for distance so that, for example, a person approaching us does not appear to become a larger person. Interestingly, an artist, when rendering a scene realistically, must undo all these corrections, making distant objects again small. To determine whether years of art training and practice have conferred any specialized visual expertise, we compared the perceptual abilities of artists to those of non-artists in three tasks. We first asked them to adjust either the size or the brightness of a target to match it to a standard that was presented on a perspective grid or within a cast shadow. We instructed them to ignore the context, judging size, for example, by imagining the separation between their fingers if they were to pick up the test object from the display screen. In the third task, we tested the speed with which artists access visual representations. Subjects searched for an L-shape in contact with a circle; the target was an L-shape, but because of visual completion, it appeared to be a square occluded behind a circle, camouflaging the L-shape that is explicit on the retinal image. Surprisingly, artists were as affected by context as non-artists in all three tests. Moreover, artists took, on average, significantly more time to make their judgments, implying that they were doing their best to demonstrate the special skills that we, and they, believed they had acquired. Our data therefore support the proposal from Gombrich that artists do not have special perceptual expertise to undo the effects of constancies. Instead, once the context is present in their drawing, they need only compare the drawing to the scene to match the effect of constancies in both.

visual constancy
art
scene perception
vision
visual search


Effect of quercetin on impaired immune function in mice exposed to irradiation.

Abstract: Radiation used in cancer treatment may cause side effects such as inflammation. Quercetin is a polyphenol that reduces inflammation. This study evaluated the recovery efficacy of quercetin on impaired immune function in irradiation-induced inflammatory mice. Quercetin administered at two concentrations of 10 and 40 mg/kg body weight was initiated 2 weeks before irradiation and was continued 30 days after irradiation. The animals exposed/not exposed to radiation were sacrificed on radiation days 10 and 30. Splenocyte proliferation, which was diminished after irradiation, was enhanced significantly by quercetin supplementation after 30 days of irradiation. Cytokine secretion increased in the radiation group compared to that in the non-radiation control group. After 30 days of radiation, interleukin (IL)-1β and IL-6 secretion decreased significantly in the radiation-quercetin groups. When quercetin was administered for 44 days, it showed a possible protective effect against irradiation-induced inflammation in mice. Quercetin could be beneficial in the recovery of irradiation-induced increases in cytokine secretion.

Quercetin mice irradiation cytokines anti-inflammatory


Levels of anti-cytokine antibodies may be elevated in patients with pulmonary disease associated with non-tuberculous mycobacteria.

Abstract: Pulmonary disease due to non-tuberculous mycobacteria (NTM) is caused by several species (particularly Mycobacterium avium, Mycobacterium intracellulare) that are abundant in the environment. Th1 cytokines such as interferon (IFN)-γ are important in the control of mycobacteria, but in vitro production of IFN-γ is not deficient in adult patients with pulmonary NTM disease. Antibodies reactive with IFN-γ have been described in patients with disseminated NTM disease, but it is not clear whether they are common in pulmonary disease. Here we show that patients with pulmonary NTM have a higher level of anti-IFN-γ and anti-GM-CSF antibodies than healthy controls, although some controls also have high levels. Levels of anti-IFN-γ antibodies did not correlate with levels of total immunoglobulin. Longitudinal studies are required to determine whether anti-cytokine autoantibodies are consequence rather than a cause of pulmonary NTM disease.

Kim|Kyungchul|K|
Waterer|Grant|G|
Thomson|Rachel|R|
Yang|Ian A|IA|
Nashi|Najla|N|
Tan|Dino B A|DB|
Price|Patricia|P|

Pulmonary disease
Non-tuberculous mycobacteria
Cytokine
Autoantibody
Interferon-γ


Associations between land cover categories, gaseous PAH levels in ambient air and endocrine signaling predicted from gut bacterial metagenome of the elderly.

Abstract: There is evidence that polycyclic aromatic hydrocarbons (PAHs) and human gut microbiota are associated with the modulation of endocrine signaling pathways. Independently, studies have found associations between air pollution, land cover and commensal microbiota. We are the first to estimate the interaction between land cover categories associated with air pollution or purification, PAH levels and endocrine signaling predicted from gut metagenome among urban and rural populations. The study participants were elderly people (65-79 years); 30 lived in rural and 32 in urban areas. Semi-Permeable Membrane devices were utilized to measure air PAH concentrations as they simulate the process of bioconcentration in the fatty tissues. Land cover categories were estimated using CORINE database and geographic information system. Functional orthologues for peroxisome proliferator-activated receptor (PPAR) pathway in endocrine system were analyzed from gut bacterial metagenome with Kyoto Encyclopaedia of Genes and Genomes. High coverage of broad-leaved and mixed forests around the homes were associated with decreased PAH levels in ambient air, while gut functional orthologues for PPAR pathway increased along with these forest types. The difference between urban and rural PAH concentrations was not notable. However, some rural measurements were higher than the urban average, which was due to the use of heavy equipment on active farms. The provision of air purification by forests might be an important determining factor in the context of endocrine disruption potential of PAHs. Particularly broad-leaved forests around homes may reduce PAH levels in ambient air and balance pollution-induced disturbances within commensal gut microbiota.

Vari|Heli K|HK|
Roslund|Marja I|MI|
Oikarinen|Sami|S|
Nurminen|Noora|N|
Puhakka|Riikka|R|
Parajuli|Anirudra|A|
Grönroos|Mira|M|
Siter|Nathan|N|
Laitinen|Olli H|OH|
Hyöty|Heikki|H|
Rajaniemi|Juho|J|
Rantalainen|Anna-Lea|AL|
Sinkkonen|Aki|A|
|||

Land cover categories
PAH
Pollution
Endocrine disruption
Gut bacteria
Urban/rural gradient


Palmitoylated transmembrane adaptor proteins in leukocyte signaling.

Abstract: Transmembrane adaptor proteins (TRAPs) are structurally related proteins that have no enzymatic function, but enable inducible recruitment of effector molecules to the plasma membrane, usually in a phosphorylation dependent manner. Numerous surface receptors employ TRAPs for either propagation or negative regulation of the signal transduction. Several TRAPs (LAT, NTAL, PAG, LIME, PRR7, SCIMP, LST1/A, and putatively GAPT) are known to be palmitoylated that could facilitate their localization in lipid rafts or tetraspanin enriched microdomains. This review summarizes expression patterns, binding partners, signaling pathways, and biological functions of particular palmitoylated TRAPs with an emphasis on the three most recently discovered members, PRR7, SCIMP, and LST1/A. Moreover, we discuss in silico methodology used for discovery of new family members, nature of their binding partners, and microdomain localization.

D048868:Adaptor Proteins, Signal Transducing

Palmitoylation Adaptor LAT PRR7 SCIMP LST1


The Challenges of Monoaxial Bone Transport in Orthopedics and Traumatology.

Abstract:
BACKGROUND
Bone defects represent the main challenging problem for the orthopedic surgeon and, consequently, they increase the duration of hospitalization, risk of complications and health expenditures. The aim of our observational, descriptive and retrospective study is to evaluate the outcomes of patients treated with a mo-nolateral external fixator for bone defects greater than 3 cm.

MATERIAL AND METHODS
Between January 2003 and January 2013, 21 patients were treated at our center by bone transfer with a monolateral external fixator. The main etiologies were trauma in 17 cases (80.9%) and tumors in 4 cases (19.1%). Mean follow-up was 5 years for non-union and 3 years for tumors. Our clinical evaluation was based on ASAMI (Association for the Study ad Application of the Methods of Ilizarov) scores during this follow-up period.

RESULTS
The functional outcomes, based on ASAMI scores, were excellent in 12 cases, good in 7 and poor in 2.

CONCLUSION
1. A review of the literature related to our experience shows that bone transport is an effective tech-nique to repair loss of bone in the lower limbs. The use of a system of external fixation enables corrective actions throughout the treatment that can be in-dividualized on a case-by-case basis. In our experience, the LRS fixator (Orthofix) is a sta-ble, easy-to-use and very handy device. 2. In situations where soft tissue reconstruction procedures are needed, the size and shape of the splint should be such as not to constitute an obstacle. Fur-thermore, the use of pins rather than transfixation wires eliminates the risk of neuro / vascu-lar injury such as may occur during the application of a circular fixator. 3. The analysis of the cases presented here indicates that where possible the technique of bone transport produces good results and can often salvage the limb. Amputation should be reserved only for cases where the general and / or local preoperative status indicate that the surgeon can expect a poor result or when the compliance of the patient is determined to be inadequate.

Bisaccia|Michele|M|
Rinonapoli|Giuseppe|G|
Meccariello|Luigi|L|
Caraffa|Auro|A|
Cukierman|Bartosz|B|
Iborra|Julio Ribes|JR|

bone transport
bone defects
monolateral external fixation
bone infection
skeletal tumor


Zirconium tetrachloride revisited.

Abstract: Zirconium tetrachloride, ZrCl4, is a strategic material with wide-ranging applications. Until now, only one crystallographic study on ZrCl4 has been reported [Krebs (1970). Z. Anorg. Allg. Chem. 378, 263-272] and that was more than 40 years ago. The compound used for the previous determination was prepared from ZrO2 and Cl2-CCl4, and single-crystal X-ray diffraction (SCXRD) studies on ZrCl4 obtained from Zr metal have not yet been reported. In this context, we prepared ZrCl4 from the reaction of Zr metal and Cl2 gas in a sealed tube and investigated its structure at 100, 150, 200, 250, and 300 K. At 300 K, the SCXRD analysis indicates that ZrCl4 crystallizes in the orthorhombic space group Pca21 [a = 6.262 (9), b = 7.402 (11), c = 12.039 (17) Å, and V = 558.0 (14) Å3] and consists of infinite zigzag chains of edge-sharing ZrCl6 octahedra. This chain motif is similar to that observed previously in ZrCl4, but the structural parameters and space group differ. In the temperature range 100-300 K, no phase transformation was identified, while elongation of intra-chain Zr...Zr [3.950 (1) Å at 100 K and 3.968 (5) Å at 300 K] and inter-chain Cl...Cl [3.630 (3) Å at 100 K and 3.687 (9) Å at 300 K] distances occurred.

Borjas Nevarez|Rosendo|R|
Balasekaran|Samundeeswari Mariappan|SM|
Kim|Eunja|E|0000-0002-3079-9680
Weck|Philippe|P|
Poineau|Frederic|F|

zirconium tetrachloride
chain motif
crystal structure
temperature study


Access to hematopoietic stem cell transplant for patients with sickle cell anemia.

Abstract: Hematopoietic stem cell transplantation (HSCT) is a curative therapy for patients with phenotypically severe sickle cell anemia, and survival rates following matched-sibling HSCT are very high. However, despite cure rates much higher than HSCT for malignant diseases, the field has been slow to adopt this treatment modality for sickle cell anemia. This article explores some of the social forces that may contribute to this dichotomy.

Meier|Emily Riehm|ER|
Johnson|Theodore|T|
Pinkney|Kerice|K|
Velez|Maria C|MC|
Kamani|Naynesh|N|
Odame|Isaac|I|

D018380:Hematopoietic Stem Cell Transplantation

hematopoietic stem cell transplant
sickle cell anemia
diversity
healthcare disparities
hydroxyurea


Lignocellulose fractionation into furfural and glucose by AlCl3-catalyzed DES/MIBK biphasic pretreatment.

Abstract: Herein, an efficient DES/MIBK biphasic pretreatment system for preparation of furfural and fermentable glucose from lignocellulose was developed with AlCl3 as catalysis. The low-cost and renewable DES (Choline chloride-Oxalic acid) served not only as a Brønsted acid catalyst, but also as a pretreatment solvent in present work, and MIBK as an extracting reagent which can increase the yield of furfural in DES phase. The effects of this biphasic pretreatment on the furfural yield and saccharification of the lignocellulose before and after pretreatment were explored using HPLC, HAPEC, FT-IR, XRD and SEM. Under the best pretreatment condition (at 140 °C for 90 min), furfural could be obtained in 70.3% yield and 80.8% of the pretreated lignocellulose was saccharified, which was 8.4 times higher than that of the raw lignocellulose without pretreatment. In a word, this pretreatment system can be considered as a potential technique for efficient valorization of lignocellulose for production of furfural and fermentable glucose.

Wang|Zhi-Kun|ZK| Shen|Xiao-Jun|XJ| Chen|Jun-Jie|JJ| Jiang|Ying-Qiu|YQ| Hu|Zhi-Yan|ZY| Wang|Xing|X| Liu|Li|L|

Furfural
Glucose
Deep eutectic solvent
Enzymatic hydrolysis


Myositis ossificans traumatica of the masticatory muscles: etiology, diagnosis and treatment.

Abstract:
BACKGROUND
Myositis ossificans describes a heterotopic bone formation within a muscle. Thereby myositis ossificans is classified in two different groups: myositis ossificans progressiva (MOP) which describes a genetic autosomal dominant rare disease and myositis ossificans traumatica (MOT). The exact pathogenesis of MOT is unclear. The aim of this article was to analyse and interpret the existing literature reporting MOT of masticatory muscles and compare the results with our own clinical experience with MOT. Risk-factors, etiology, clinical features, diagnostic imaging, as well as different treatment options were evaluated and recommendations for the prevention, diagnosis, and therapy of MOT of the masticatory muscles were given.

METHODS
Following the PRISMA-Guidelines, a systematic search within the PubMed/Medline database with a view to record literature of MOT of the masticatory muscles was performed. Furthermore, the database of our own clinic was screened for cases of MOT.

RESULTS
In total, 63 cases of MOT of the masticatory muscles which were reported in English-based literature were included in this study. Overall, 25 female and 37 male patients could be analysed whereas one patient's gender was unknown. Complication of wisdom-tooth infection (n = 3) as well as the results of dental procedures like dental extraction (n = 7), mandibular nerve block (n = 4), periodontitis therapy (n = 1) were reported as MOT cases. From the 15 reported cases that appeared after dental treatment like extraction or local anesthesia the medial pterygoid (n = 10) was the most affected muscle. Hereof, females were more affected (n = 9) than males (n = 6). The most reported clinical symptom of MOT was trismus (n = 54), followed by swelling (n = 17) and pain (n = 13). One clinical case provided by the authors was detected.

CONCLUSIONS
Dental procedures, such as local anesthesia or extractions, may cause MOT of the masticatory musculature. Demographical analyses demonstrate that females have a higher risk of developing MOT with respect to dental treatment. The most important treatment option is surgical excision. Subsequent physical therapy can have beneficial effects. Nevertheless, a benefit of interpositional materials and drugs as therapy of MOT of the masticatory muscles has not yet been proven. Myositis ossificans progressiva has to be excluded.

Myositis ossificans
Myositis ossificans traumatica
Masticatory muscles
Heterotropic ossification
Myositis ossificans circumscripta


MicroRNA-9 functions as a tumor suppressor and enhances radio-sensitivity in radio-resistant A549 cells by targeting neuropilin 1.

Abstract: Radiotherapy is commonly used to treat lung cancer but may not kill all cancer cells, which may be attributed to the radiotherapy resistance that often occurs in non-small cell lung cancer (NSCLC). At present, the molecular mechanism of radio-resistance remains unclear. Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF), was demonstrated to be associated with radio-resistance of NSCLC cells via the VEGF-phosphoinositide 3-kinase-nuclear factor-κB pathway in our previous study. It was hypothesized that certain microRNAs (miRs) may serve crucial functions in radio-sensitivity by regulating NRP1. Bioinformatics predicted that NRP1 was a potential target of miR-9, and this was validated by luciferase reporter assays. Functionally, miR-9-transfected A549 cells exhibited a decreased proliferation rate, increased apoptosis rate and attenuated migratory and invasive abilities. Additionally, a high expression of miR-9 also significantly enhanced the radio-sensitivity of A549 cells in vitro and in vivo. These data improve understanding of the mechanisms of cell radio-resistance, and suggest that miR-9 may be a molecular target for the prediction of radio-sensitivity in NSCLC.

Xiong|Kai|K|
Shao|Li Hong|LH|
Zhang|Hai Qin|HQ|
Jin|Linlin|L|
Wei|Wei|W|
Dong|Zhuo|Z|
Zhu|Yue Quan|YQ|
Wu|Ning|N|
Jin|Shun Zi|SZ|
Xue|Li Xiang|LX|

microRNA-9
radio-sensitivity
non-small cell lung cancer
ionizing radiation


Injection of Porcine Adipose Tissue-Derived Stromal Cells by a Novel Waterjet Technology.

Abstract: Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment capabilities, and biomechanical features. Porcine adipose tissue-derived stromal cells (pADSCs) were isolated, expanded, and injected by WJ technology. Cell attachment assays were employed to investigate cell-matrix interactions. Cell surface molecules were analyzed by flow cytometry. Cells injected by Williams Needle (WN), normal cannula, or not injected cells served as controls. Biomechanical properties were assessed by atomic force microscopy (AFM). pADSCs injected by the WJ were viable (85.9%), proliferated well, and maintained their in vitro adipogenic and osteogenic differentiation capacities. The attachment of pADSCs was not affected by WJ injection and no major changes were noted for cell surface markers. AFM measurements yielded a significant reduction of cellular stiffness after WJ injections (p < 0.001). WJ cell delivery satisfies several key considerations required in a clinical context, including the fast, simple, and reproducible delivery of viable cells. However, the optimization of the WJ device may be necessary to further reduce the effects on the biomechanical properties of cells.

Danalache|Marina|M|0000-0002-7217-2499
Knoll|Jasmin|J|
Linzenbold|Walter|W|
Enderle|Markus|M|
Abruzzese|Tanja|T|
Stenzl|Arnulf|A|0000-0003-4207-9928
Aicher|Wilhelm K|WK|0000-0003-2210-6773

D045164:Mesenchymal Stem Cell Transplantation

stromal cells
waterjet
viability
atomic force microscopy
elasticity
regeneration
urinary incontinence


Engineering of carbon nano-onion bioconjugates for biomedical applications.

Abstract: Engineered stimuli-responsive drug delivery strategies grasp enormous potential in biomedical applications for disease treatment due to their exploited therapeutic efficiency. In the current study, we developed poly 4-hydroxyphenyl methacrylate-carbon nano-onions (PHPMA-CNOs = f-CNOs) embedded bovine serum albumin (BSA) nanocomposite fibers by Forcespinning® (FS) technology for stimuli-responsive release of cargo, using doxorubicin (DOX) as a model drug. Nanocomposite fiber system showed thermosensitive drug release and exhibited around 72 and 95% of drug release at 37 and 43 °C, respectively. A slow and prolonged DOX release was observed over a 15-day study. The amount of drug released was determined by the concentration of the DOX payload, incubation temperature, and pH of the released medium. Owing to the f-CNOs incorporation, the mechanical strength (18.23 MPa) of hybrid BSA nanocomposite fibers was enhanced significantly. Besides, in vitro degradation, water contact angles, and thermal properties of nanocomposite fibers have augmented. During the in vitro cytotoxicity assessment, nanocomposite fibers exhibited improved cell viability against human fibroblast cells. Nonetheless, the external-stimuli-dependent and sustained DOX release perhaps reduces its circumventing side effects and show potential applications in biomedical research.

Mamidi|Narsimha|N|
Delgadillo|Ramiro Manuel Velasco|RMV|
González-Ortiz|Aldo|A|

Carbon nano-onions
Forcespinning®
Mechanical strength
Cell viability
BSA-based nanocomposite fibers
Thermoresponsive drug release


Would Francisco Soca have been the first to relate toe phenomenon as pyramidal disorders?

Abstract:
INTRODUCTION
The Uruguayan physician Francisco Soca, who specialized in neurology in Jean-Martin Charcot's clinic, defended a thesis at the Paris Faculty of Medicine in 1888 on Friedreich's ataxia in eleven patients. In this work he described the presence of toe phenomenon.

OBJECTIVE
This historical note presents a toe sign described by the Soca eight years before Babiński's classic description.

DISCUSSION
In the late 1800s Soca completed a specialization in neurology at the service run by Charcot in Paris. He defended an important thesis in 1888 assessing data from 11 Friedreich's ataxia. In his thesis, Soca also described the toe phenomenon and the presence of structural changes in the feet of these patients that were not described in the Friedreich study published in 1863.

CONCLUSION
The Soca's thesis contained the description of toe extension associated with pyramidal tract lesions, eight years later described and further immortalized as Babiński's sign. Therefore, Soca had already publicized this sign as being representative of a pyramidal dysfunction before Babiński or any other neurologist.

Teive|Hélio A G|HAG|
Camargo|Carlos Henrique F|CHF|
Sommaruga|Nicolás|N|
Amorin-Costábile|Héctor Ignacio|HI|
Walusinski|Olivier|O|

Toe phenomenon
Babiński’s sign
Plantar extension sign


Iris-fixated phakic intraocular lens explantation.

Abstract:
BACKGROUND/AIMS
To evaluate the visual outcomes and indication for surgery in a series of patients who underwent explantation of a phakic intraocular lens (PIOL).

METHODS
A retrospective case series of patients who underwent PIOL explantation in our institution was performed. The indication for explantation and visual and refractive outcomes were examined. The method of explantation is described.

RESULTS
Twenty-two eyes of 16 patients underwent PIOL explantation with a mean time to explantation of 7 ± 3 years (range 3-11.4). The mean age at explantation was 50.3 ± 9.3 years. Sixteen Artisan PIOLs and six Artiflex PIOLs were explanted. The indications for explanation were cataract development (17/22), endothelial cell loss (4/22) and synechiae formation (1/22). All patients with cataract underwent a combined procedure with explantation and phacoemulsification and the placement of a posterior chamber IOL. Mean corrected vision after explantation was 0.22 ± 0.10 logMAR (range 0.1-0.3 logMAR). One patient with endothelial cell loss required a Descemet's Stripping Endothelial Keratoplasty (DSEK).

CONCLUSION
Removal of PIOLs was necessitated most frequently by cataract followed by endothelial cell loss. Both explantation alone and explantation with concurrent phacoemulsification are safe procedures with good visual outcomes and will become more frequent in the future as more patients with PIOLs reach cataractous age.

D006801:Humans
D007498:Iris
D019654:Lens Implantation, Intraocular
D054120:Phakic Intraocular Lenses
D011183:Postoperative Complications
D012189:Retrospective Studies
D014792:Visual Acuity

IOL calculations after refractive surgery


Consultancy research as a barrier to strengthening social science research capacity in Uganda.

Abstract: There is a shortage of senior African social scientists available to lead or manage research in Africa, undermining the continent's ability to interpret and solve its socio-economic and public health problems. This is despite decades of investment to strengthen research capacity. This study investigated the role of individually commissioned consultancy research in this lack of capacity. In 2006 structured interviews (N = 95) and two group discussions (N = 16 total) were conducted with a fairly representative sample of Ugandan academic social scientists from four universities. Twenty-four senior members of 22 Ugandan and international commissioning organizations were interviewed. Eight key actors were interviewed in greater depth. Much of Ugandan social science research appears to take the form of small, individually contracted consultancy projects. Researchers perceived this to constrain their professional development and, more broadly, social science research capacity across Uganda. Conversely, most research commissioners seemed broadly satisfied with the research expertise available and felt no responsibility to contribute to strengthening research capacity. Most consultancy research does not involve institutional overheads and there seems little awareness of, or interest in, such overheads. Although inequalities in the global knowledge economy are probably perpetuated primarily by macro-level factors, in line with Dependency Theory, meso-level factors are also important. The current research market and institutional structures in Uganda appear to create career paths that seriously impede the development of high quality social science research capacity, undermining donor investments and professional effort to strengthen this capacity. These problems are probably generic to much of sub-Saharan Africa. However, both commissioning and research organizations seem ready, in principle, to establish national guidelines for institutional research consultancies. These could develop both institutional and individual research capacity, improve output and accountability, and facilitate academic research funding and indigenous research agendas.

Wight|Daniel|D|
Ahikire|Josephine|J|
Kwesiga|Joy C|JC|

Social sciences
Research capacity
Uganda
Research commissioners
Global knowledge economy
Sub-Saharan Africa
Research consultancies
Institutional capacity


MAML1/2 promote YAP/TAZ nuclear localization and tumorigenesis.

Abstract: The Hippo pathway plays a pivotal role in tissue homeostasis and tumor suppression. YAP and TAZ are downstream effectors of the Hippo pathway, and their activities are tightly suppressed by phosphorylation-dependent cytoplasmic retention. However, the molecular mechanisms governing YAP/TAZ nuclear localization have not been fully elucidated. Here, we report that Mastermind-like 1 and 2 (MAML1/2) are indispensable for YAP/TAZ nuclear localization and transcriptional activities. Ectopic expression or depletion of MAML1/2 induces nuclear translocation or cytoplasmic retention of YAP/TAZ, respectively. Additionally, mutation of the MAML nuclear localization signal, as well as its YAP/TAZ interacting region, both abolish nuclear localization and transcriptional activity of YAP/TAZ. Importantly, we demonstrate that the level of MAML1 messenger RNA (mRNA) is regulated by microRNA-30c (miR-30c) in a cell-density-dependent manner. In vivo and clinical results suggest that MAML potentiates YAP/TAZ oncogenic function and positively correlates with YAP/TAZ activation in human cancer patients, suggesting pathological relevance in the context of cancer development. Overall, our study not only provides mechanistic insight into the regulation of YAP/TAZ subcellular localization, but it also strongly suggests that the miR30c-MAML-YAP/TAZ axis is a potential therapeutic target for developing novel cancer treatments.

Kim|Jiyoung|J|
Kwon|Hyeryun|H|
Shin|You Keun|YK|
Song|Gahyeon|G|
Lee|Taebok|T|0000-0002-8390-6670
Kim|Youngeun|Y|
Jeong|Wonyoung|W|
Lee|Ukjin|U|
Zhang|Xianglan|X|
Nam|Gilyeong|G|
Jeung|Hei-Cheul|HC|
Kim|Wantae|W|
Jho|Eek-Hoon|EH|0000-0003-2414-6234

D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins

MAML1/2
YAP/TAZ
nuclear localization
Hippo signaling
TEAD


Neural responses to food stimuli among individuals with eating and weight disorders: a systematic review of event-related potentials.

Abstract: A systematic review was conducted to investigate event-related potentials (ERPs) in response to food and non-food stimuli among individuals with eating and weight disorders. Limiting the search to studies that have analysed ERPs relating to motivated attention and inhibitory control, 19 research papers were extracted from a systematic search in PubMed, Ovid, and Web of Science (2000-2018). An enhanced attentional bias towards food over non-food images (as indexed by P3(00) and LPP amplitudes) was evident for all populations. Individuals with binge eating disorder showed an enhanced attentional response to food cues compared to healthy controls. Inhibitory control-related ERP components (N2(00) and P3a) increased during food-specific no-go trials, but did not differentiate overweight from 'healthy' weight groups. The N2 amplitude to food pictures were positively correlated with caloric intake and food craving among individuals with obesity and binge eating disorder, respectively, while P3(00) was sensitive to hunger levels among overweight and obese females. The heterogeneity of stimuli/paradigms adopted, component timescales extracted, ERPs analysed, and data presented has challenged this review's ability to produce a robust synthesis of results. Some recommendations for future research are discussed.

weight disorders
event-related potential
inhibitory control
Eating disorders
attentional allocation
eating behaviour


The Italian consensus conference on the role of rehabilitation for children and adolescents with leukemia, central nervous system, and bone tumors, part 1: Review of the conference and presentation of consensus statements on rehabilitative evaluation of motor aspects.

Abstract: Because of increasing survival rates in pediatric oncology, attention is focusing on cancer and its treatment-related side effects. Rehabilitation may reduce their impact. However, the literature does not provide strong evidence regarding rehabilitation pathways. Therefore, the Italian Association of Pediatric Hematology and Oncology organized a consensus conference on the role of rehabilitation of motor impairments in children/adolescents affected by leukemia, central nervous system, and bone tumors to define recommendations for daily practice. The grading of recommendation assessment, developing and evaluation (GRADE) method was used in order to formulate questions, select outcomes, evaluate evidence, and create recommendations. This paper includes the results on the rehabilitation assessment.

Rossi|Francesca|F|0000-0002-1335-5121 Ricci|Federica|F| Botti|Stefano|S| Bertin|Daniele|D| Breggiè|Simona|S| Casalaz|Roberto|R| Cervo|Marta|M| Ciullini|Paola|P| Coppo|Monica|M| Cornelli|Annalisa|A| Esposito|Maria|M| Ferrarese|Miriana|M| Ghetti|Marina|M| Longo|Lucia|L| Morri|Mattia|M| Naretto|Gabriella|G| Orsini|Nicoletta|N| Fagioli|Franca|F| |||

D016543:Central Nervous System Neoplasms

rehabilitation
rehabilitative evaluation
pediatric oncology
functional assessment


Biochar alleviates combined stress of ammonium and acids by firstly enriching Methanosaeta and then Methanosarcina.

Abstract: This investigation evaluated the effectiveness of biochar of different particle sizes in alleviating ammonium (NH4(+)) inhibition (up to 7 g-N/L) during anaerobic digestion of 6 g/L glucose. Compared to the control treatment without biochar addition, treatments that included biochar particles 2-5 mm, 0.5-1 mm and 75-150 μm in size reduced the methanization lag phase by 23.9%, 23.8% and 5.9%, respectively, and increased the maximum methane production rate by 47.1%, 23.5% and 44.1%, respectively. These results confirmed that biochar accelerated the initiation of methanization during anaerobic digestion under double inhibition risk from both ammonium and acids. Furthermore, fine biochar significantly promoted the production of volatile fatty acids (VFAs). Comparative analysis on the archaeal and bacterial diversity at the early and later stages of digestion, and in the suspended, biochar loosely bound, and biochar tightly bound fractions suggested that, in suspended fractions, hydrogenotrophic Methanobacterium was actively resistant to ammonium. However, acetoclastic Methanosaeta can survive at VFAs concentrations up to 60-80 mmol-C/L by improved affinity to conductive biochar, resulting in the accelerated initiation of acetate degradation. Improved methanogenesis was followed by the colonization of the biochar tightly bound fractions by Methanosarcina. The selection of appropriate biochar particles sizes was important in facilitating the initial colonization of microbial cells.

Lü|Fan|F| Luo|Chenghao|C| Shao|Liming|L| He|Pinjing|P|

Anaerobic digestion
Ammonium toxicity
Interspecies electron transfer
Methanosarcinales
Syntrophic acetate oxidation
Waste treatment


Sleep slow-wave homeostasis and cognitive functioning in children with electrical status epilepticus in sleep.

Abstract:
STUDY OBJECTIVES
Encephalopathy with electrical status epilepticus in sleep (ESES) is characterized by non-rapid eye movement (non-REM)-sleep-induced epileptiform activity and acquired cognitive deficits. The synaptic homeostasis hypothesis describes the process of daytime synaptic potentiation balanced by synaptic downscaling in non-REM-sleep and is considered crucial to retain an efficient cortical network. We aimed to study the overnight decline of slow waves, an indirect marker of synaptic downscaling, in patients with ESES and explore whether altered downscaling relates to neurodevelopmental and behavioral problems.

METHODS
Retrospective study of patients with ESES with at least one whole-night electroencephalogram (EEG) and neuropsychological assessment (NPA) within 4 months. Slow waves in the first and last hour of non-REM-sleep were analyzed. Differences in slow-wave slope (SWS) and overnight slope course between the epileptic focus and non-focus electrodes and relations to neurodevelopment and behavior were analyzed.

RESULTS
A total of 29 patients with 44 EEG ~ NPA combinations were included. Mean SWS decreased from 357 to 327 µV/s (-8%, p < 0.001) across the night and the overnight decrease was less pronounced in epileptic focus than in non-focus electrodes (-5.6% vs. -8.7%, p = 0.003). We found no relation between SWS and neurodevelopmental test results in cross-sectional and longitudinal analyses. Patients with behavioral problems showed less SWS decline than patients without and the difference was most striking in the epileptic focus (-0.9% vs. -8.8%, p = 0.006).

CONCLUSIONS
Slow-wave homeostasis-a marker of synaptic homeostasis-is disturbed by epileptiform activity in ESES. Behavioral problems, but not neurodevelopmental test results, were related to severity of this disturbance.

van den Munckhof|Bart|B|
Gefferie|Silvano R|SR|
van Noort|Suus A M|SAM|
van Teeseling|Heleen C|HC|
Schijvens|Mischa P|MP|
Smit|William|W|
Teunissen|Nico W|NW|
Plate|Joost D J|JDJ|
Huiskamp|Geert Jan M|GJM|
Leijten|Frans S S|FSS|
Braun|Kees P J|KPJ|
Jansen|Floor E|FE|
Bölsterli|Bigna K|BK|

sleep
cognition
ESES
synaptic downscaling
slow waves
CSWS


Implementation of a Hypothesis-Driven Physical Exam Session in a Transition to Clerkship Program.

Abstract:
Introduction
The head-to-toe approach to teaching the physical examination (PE) focuses on technique and performing a comprehensive PE whereas core + clusters and hypothesis-driven PE (HDPE) approaches integrate clinical reasoning into performing a focused PE. These approaches can be implemented in a developmental sequence. We report the implementation and evaluation of an HDPE educational session.

Methods
We designed a 3-hour HDPE session as part of a transition to clerkship program. For each of five clinical vignettes, rising third-year students worked in pairs and then in small groups to generate a differential diagnosis and determine relevant PE maneuvers. Students next performed these maneuvers on peers with facilitator observation and feedback. Students completed postsession surveys on their retrospective pre- and postsession knowledge and confidence, as well as their satisfaction with the session. We completed quantitative and qualitative analyses on survey data.

Results
One hundred ninety-two students participated, and 140 (73%) completed the survey. Students were significantly more likely to report feeling confident generating a differential diagnosis and using it to select PE maneuvers for common complaints postsession. Over 80% of respondents felt the session improved critical thinking about patient presentations and would help them in clerkships.

Discussion
Our session increased student confidence in the progression to performing an HDPE just prior to the start of clerkships. The session is feasible and straightforward to implement. It requires a large number of faculty to facilitate, but the breadth of cases used allows inclusion of faculty from all fields.

Kelly|Julia|J|
Oza|Sandra K|SK|
Feinn|Richard|R|
Cassese|Todd|T|

Physical Examination
Clinical Reasoning
Clinical Reasoning/Diagnostic Reasoning
Clinical Skills
Clinical/Procedural Skills Training
Hypothesis-Driven Physical Examination


Substance Use in Undergraduate Students With Histories of Attention-Deficit/Hyperactivity Disorder (ADHD): The Role of Impulsivity.

Abstract:
BACKGROUND
Emerging adulthood (18-25 years old) is regarded as a time of identity exploration that includes a peak in risky behaviors, such as substance use and misuse. Attention-deficit/hyperactivity disorder (ADHD) is also associated with greater levels of risky behaviors, including substance use and misuse; however, there is a lack of research on substance use by emerging adults with ADHD, in particular the potential mechanisms that may facilitate this risk.

OBJECTIVES
The present study builds on the existing research regarding the association between ADHD and substance use by examining roles of multiple facets of impulsivity in facilitating this association during emerging adulthood.

METHODS
In a sample of 197 undergraduate students (24 students with an ADHD diagnostic history), we assessed for components of impulsivity (e.g., urgency, sensation-seeking) and rates of alcohol abuse, tobacco use, cannabis use, illicit drug use, and stimulant medication misuse within the past year.

RESULTS
Findings indicate that facets of impulsivity, as a whole, explained the association between an ADHD diagnostic history and both illicit drug use and alcohol abuse such that students with ADHD histories tended to report higher levels of impulsivity, which increased risk of alcohol abuse and illicit drug use. Higher levels of specific facets of impulsivity, particularly negative urgency, also facilitated associations between having ADHD and engaging in most forms of substance use tested herein. Conclusions/Importance: Specific facets of impulsivity appear to be important mediators of the association between ADHD and substance use, and should be considered as potential targets of substance use interventions for this population.

Egan|Theresa E|TE|
Dawson|Anne E|AE|
Wymbs|Brian T|BT|

D001289:Attention Deficit Disorder with Hyperactivity

substance use
ADHD
impulsivity
emerging adulthood
college students


Views of the importance of psychiatric genetic research by potential volunteers from stakeholder groups.

Abstract: Few studies have explored potential volunteers' attitudes toward genetic research. To address this gap in the literature, we developed an empirical project to document views held by individuals who may wish to enroll in genetic studies involving mental disorders. People living with mental illness, family members of people with mental illness, and community comparison volunteers were queried regarding their views on the importance of genetic research generally, in comparison with medical research, and in relation to 12 health conditions categorized in four types. T-tests and univariate and multivariate analysis of variance were used as appropriate. Participants expressed support for the importance of genetic research (mean = 9.43, scale = 1-10) and endorsed genetic research more highly compared with non-genetic medical research (mean = 9.43 vs. 8.69, P value = <0.001). The most highly endorsed genetic research was for cognitive disorders, followed by mental illness disorders, physical illness disorders, and addiction disorders (means = 8.88, 8.26, 8.16 and 7.55, respectively, P value = <0.001). Overall, this study provides evidence of strong endorsement of genetic research over non-genetic research by potential volunteers.

Roberts|Laura Weiss|LW|
Tsungmey|Tenzin|T|
Kim|Jane Paik|JP|
Hantke|Melinda|M|

Genetic research
Non-genetic research
Community groups
Disorder types
Gender
Race/ethnicity


Insulin induces phosphorylation of the AMPA receptor subunit GluR1, reversed by ZIP, and over-expression of Protein Kinase M zeta, reversed by amyloid beta.

Abstract: Insulin receptor (IR) in the brain plays a role in synaptic plasticity and cognitive functions. Phosphorylation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors GluR1 subunit at Serine 831 is regulated by calcium-calmodulin-dependent protein kinase II and protein kinase C that underlie long-term potentiation and learning/memory. Recent studies have shown that the novel Protein Kinase M zeta (PKMζ) underlies synaptic plasticity and may regulate AMPAr. In this study, we show that insulin induces phosphorylation of Serine 831 GluR1 subunit of AMPAr and induces over-expression of PKMζ; pre-treatment with either the IR inhibitor 3-Bromo-5-t-butyl-4-hydroxy-benzylidenemalonitrile (AG1024) or PKMζ inhibitor protein kinase C zeta pseudo-substrate inhibitor returned the phosphorylation value of GluR1 to control level. Amyloid beta (Aβ) peptide in the form of oligomers interferes with IR signaling. Pre-treating neuronal cultures with Aβ following incubation with insulin, we found a reduction of insulin-dependent PKMζ over-expression and MAPK/Erk (1/2) phosphorylation, i.e., signaling pathways involved in synaptic plasticity and learning/memory. These results indicate a new intracellular insulin signaling pathway, and, additionally, that insulin resistance in Alzheimer's disease is a response to the production and accumulation of Aβ.


Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death: Cohort Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five States.

Abstract:
CONTEXT
Antipsychotic drugs have been linked to QT-interval prolongation, a presumed marker of cardiac risk, and torsade de pointes.

OBJECTIVE
To examine the associations between antipsychotics and 1) outpatient-originated sudden cardiac death and ventricular arrhythmia (SD/VA) and 2) all-cause death.

DESIGN
Two retrospective cohort studies.

SETTING
Medicaid programs of California, Florida, New York, Ohio and Pennsylvania.

PATIENTS
Incident antipsychotic users aged 30-75 years.

MAIN OUTCOME MEASURES
1) Incident, first-listed emergency department or principal inpatient SD/VA diagnoses; and 2) death reported in the Social Security Administration Death Master File.

RESULTS
Among 459,614 incident antipsychotic users, the incidences of SD/VA and death were 3.4 and 35.1 per 1,000 person-years, respectively. Compared to olanzapine as the referent, adjusted hazard ratios (HRs) for SD/VA were 2.06 (95% CI, 1.20-3.53) for chlorpromazine, 1.72 (1.28-2.31) for haloperidol, and 0.73 (0.57-0.93) for quetiapine. Adjusted HRs for perphenazine and risperidone were consistent with unity. In a subanalysis limited to first prescription exposures, HRs for chlorpromazine and haloperidol were further elevated (2.54 [1.07-5.99] and 2.68 [1.59-4.53], respectively), with the latter exhibiting a dose-response relationship. Results for death were similar.

CONCLUSIONS
Haloperidol and chlorpromazine had less favorable cardiac safety profiles than olanzapine. Among atypical agents, risperidone had a similar cardiac safety profile to olanzapine, whereas quetiapine was associated with 30% and 20% lower risks of SD/VA and death, respectively, compared to olanzapine. These measured risks do not correlate well with average QT prolongation, further supporting the notion that average QT prolongation may be a poor surrogate of antipsychotic arrhythmogenicity.

Leonard|Charles E|CE|
Freeman|Cristin P|CP|
Newcomb|Craig W|CW|
Bilker|Warren B|WB|
Kimmel|Stephen E|SE|
Strom|Brian L|BL|
Hennessy|Sean|S|

International classification of diseases


Proteomics alterations in chicken jejunum caused by 24 h fasting.

Abstract: The small intestine is the longest part of the chicken (Gallus gallus) gastrointestinal system that is specialized for nutrient absorption. It is known that decrease in intestinal villi area or height in early age can cause a reduction in essential nutrient intake, which may lead to delayed growth and consequently poorer performance of broiler chickens. The small intestinal absorptive surface is known to be affected by various factors, among others things the nutritional state. In our experiment, we aimed to investigate the possible protein expression alterations that lie behind the villus area and height decrease caused by feed deprivation. A total of 24 chickens were divided into three groups, namely ad libitum fed, fasted for 24 h, fasted for 24 h then refed for 2 h. The morphometric parameters were also measured in the duodenum, jejunum and ileum tissue sections using image analysis. Differential proteome analyses from jejunum samples were performed using two-dimensional difference gel electrophoresis followed by tryptic digestion and protein identification by matrix-assisted laser desorption/ionization mass spectrometry. Overall 541 protein spots were detected after 2D. Among them, eleven showed 1.5-fold or higher significant difference in expression and were successfully identified. In response to 24 h fasting, the expression of nine proteins was higher and that of two proteins was lower compared to the ad libitum fed group. The functions of the differentially expressed proteins indicate that the 24 h fasting mainly affects the expression of structural proteins, and proteins involved in lipid transport, general stress response, and intestinal defense.

Simon|Ádám|Á|0000-0002-9504-8773 Gulyás|Gabriella|G| Mészár|Zoltán|Z| Bhide|Mangesh|M| Oláh|János|J| Bai|Péter|P| Csősz|Éva|É| Jávor|András|A| Komlósi|István|I| Remenyik|Judit|J| Czeglédi|Levente|L|

Chicken
Fasting
Small intestine
Protein
Expression
Villus
2D-DIGE
Morphometry
mRNA
qPCR


Lower urinary tract symptoms in patients with prostate cancer under and after intensity-modulated radiation therapy.

Abstract:
OBJECTIVE
The aim of the present study was to collect data on the characteristics, degree, and natural course of urinary complications, as well as self-care for such complications, in patients during and after prostate intensity-modulated radiation therapy (IMRT).

METHODS
Quality of life data were collected retrospectively for all eligible patients who underwent IMRT. In all eligible patients, urinary symptoms were evaluated using questionnaires and face-to-face interview. Participants were asked to respond to a self-administered questionnaire concerning the core lower urinary tract symptom score during the course of IMRT and up to 12 months after the completion of IMRT.

RESULTS
In all, 29 eligible patients were included in the study. The frequency of urinary symptoms increased over of the course of IMRT, decreased at ≥3 months after completion of IMRT, and disappeared 6 months after IMRT. Responses to the questionnaire revealed a variety of approaches to self-care and adaptations by patients to manage urinary symptoms.

CONCLUSIONS
During and after IMRT for localized prostate cancer, patients often developed more frequent urination and urgency than at the start of IMRT, and recovered 3-6 months after the completion of IMRT. Based on the present study, clinicians and nurses could help convey this information to patients and thus offer better support.

prostate cancer
intensity-modulated radiation therapy
genitourinary toxicity
urination disorder


Selective memory retrieval of auditory what and auditory where involves the ventrolateral prefrontal cortex.

Abstract: There is evidence from the visual, verbal, and tactile memory domains that the midventrolateral prefrontal cortex plays a critical role in the top-down modulation of activity within posterior cortical areas for the selective retrieval of specific aspects of a memorized experience, a functional process often referred to as active controlled retrieval. In the present functional neuroimaging study, we explore the neural bases of active retrieval for auditory nonverbal information, about which almost nothing is known. Human participants were scanned with functional magnetic resonance imaging (fMRI) in a task in which they were presented with short melodies from different locations in a simulated virtual acoustic environment within the scanner and were then instructed to retrieve selectively either the particular melody presented or its location. There were significant activity increases specifically within the midventrolateral prefrontal region during the selective retrieval of nonverbal auditory information. During the selective retrieval of information from auditory memory, the right midventrolateral prefrontal region increased its interaction with the auditory temporal region and the inferior parietal lobule in the right hemisphere. These findings provide evidence that the midventrolateral prefrontal cortical region interacts with specific posterior cortical areas in the human cerebral cortex for the selective retrieval of object and location features of an auditory memory experience.

memory retrieval
auditory
prefrontal cortex
fMRI
control processes


Screening and evaluating of long non-coding RNAs in prenatal and postnatal pituitary gland of sheep.

Abstract: Long non-coding RNAs are transcribed into RNA molecules that are >200 nucleotides in length. However, the expression and function analysis of lncRNAs in the sheep pituitary gland are still lacking. In this study, we identified 1755 lncRNAs (545 annotated lncRNAs and 1210 novel lncRNAs) from RNA-seq data in the pituitary gland of embryonic and adult sheep. A total of 235 lncRNAs were differentially expressed between embryonic and adult group. We verified the presence of some lncRNAs using RT-PCR and DNA sequencing, and identified some differentially expressed lncRNAs using qPCR. We also investigated the role of cis-acting lncRNAs on target genes. GO and KEGG enrichment analysis revealed that the target genes of lncRNAs were involved in the regulation of hormones secretion and some signaling pathways in the sheep pituitary gland. Our study provides comprehensive expression profiles of lncRNAs and valuable resource for understanding their function in the pituitary gland.

Li|Xiaoyue|X| Li|Cunyuan|C| Wureli|Hazi|H| Ni|Wei|W| Zhang|Mengdan|M| Li|Huixiang|H| Xu|Yueren|Y| Rizabek|Kadyken|K| Bolatkhan|Makhatov|M| Askar|Dzhunysov|D| Gulzhan|Kulmanova|K| Hou|Xiaoxu|X| Hu|Shengwei|S|

Pituitary gland
Sheep
LncRNAs
Expression profiles


Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in Melatonin Induction in Plants.

Abstract: Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl₂ or AlCl₃ and monitored the structures of subcellular organelles-such as chloroplasts, mitochondria, and the endoplasmic reticulum (ER)-using confocal microscopic analysis. Unlike AlCl₃ treatment, CdCl₂ (0.5 mM) treatment significantly disrupted chloroplasts, mitochondria, and ER. In theory, the disruption of chloroplasts enabled chloroplast-expressed serotonin N-acetyltransferase (SNAT) to encounter serotonin in the cytoplasm, leading to the synthesis of N-acetylserotonin followed by melatonin synthesis. In fact, the disruption of chloroplasts by cadmium, not by aluminum, gave rise to a huge induction of melatonin in rice leaves, which suggests that cadmium-treated chloroplast disruption plays an important role in inducing melatonin in plants by removing physical barriers, such as chloroplast double membranes, allowing SNAT to gain access to the serotonin substrate enriched in the cytoplasm.

cadmium chloroplasts rice tobacco aluminum


Getting oriented with antibodies.

Abstract: Neisseria meningitidis is a Gram-negative bacterium capable of causing deadly invasive disease. Two recently developed vaccines against N. meningitidis serogroup B include recombinant factor H binding protein (fHbp), a surface protein that meningococci use to evade the host immune system. Many anti-fHbp monoclonal antibodies (mAbs) produced against fHbp fail to trigger complement-mediated bacteriolysis when used alone in vitro, but are highly synergistic and bactericidal when used in combination. This opened the door to defining the structural basis by which mAbs activate complement synergistically when binding to different epitopes on the same antigen, a story that is told by Malito et al. in a recent issue of the Biochemical Journal. Using two separate crystal structures of fHbp bound to Fabs from synergistic mAbs, they were able to model the structure of both full length antibodies bound simultaneously to fHbp. This revealed that the bound antibodies orient their Fc domains 115-130 Å apart, a distance that is compatible with multivalent C1q binding. The need for a precise orientation of Fc domains in order to efficiently activate effector functions is an emerging theme across multiple fields, and its implications could have broad impacts on vaccinology and immunotherapy.

D000907:Antibodies, Bacterial
D000911:Antibodies, Monoclonal
D000942:Antigens, Bacterial
D001426:Bacterial Proteins
D001666:Binding Sites, Antibody
D015922:Complement C1q
D018360:Crystallography, X-Ray
D004357:Drug Synergism
D004359:Drug Therapy, Combination
D000939:Epitopes
D007140:Immunoglobulin Fab Fragments
D007141:Immunoglobulin Fc Fragments
D009345:Neisseria meningitidis
D011485:Protein Binding

antibodies
Neisseria meningitidis
vaccine
factor H binding protein
effector functions
crystallography


Genome-wide analysis of the MATE gene family in potato.

Abstract: The multidrug and toxic compound extrusion (MATE) protein family is a newly discovered family of secondary transporters that extrude metabolic waste and a variety of antibiotics out of the cell using an electrochemical gradient of H+ or Na+ across the membrane. The main function of MATE gene family is to participate in the process of plant detoxification and morphogenesis. The genome-wide analysis of the MATE genes in potato genome was conducted. At least 48 genes were initially identified and classified into six subfamilies. The chromosomal localization of MATE gene family showed that they could be distributed on 11 chromosomes except chromosome 9. The number of amino acids is 145-616, the molecular weight of proteins is 15.96-66.13 KD, the isoelectric point is 4.97-9.17, and they were located on the endoplasmic reticulum with having 4-13 transmembrane segments. They contain only two parts of the exons and UTR without introns. Some members of the first subfamily of potato MATE gene family are clustered with At2g04070 and they may be related to the transport of toxic compounds such as alkaloids and heavy metal. The function of the members of the second subfamily may be similar to that of At3g23560, which is related to tetramethylammonium transport. Some members of the third subfamily are clustered with At3g59030 and they may be involved in the transport of flavonoids. The fifth subfamily may be related to the transport of iron ions. The function of the sixth subfamily may be similar to that of At4g39030, which is related to salicylic acid transport. There are three kinds of conserved motifs in potato MATE genes, including the motif 1, motif 2, and motif 3. Each motif has 50 amino acids. The number of each motif is different in the gene sequence, of which 45 MATE genes contain at least a motif, but there is no motif in ST0015301, ST0045283, and ST0082336. These results provide a reference for further research on the function of potato MATE genes.

D018506:Gene Expression Regulation, Plant

D027701:Organic Cation Transport Proteins

MATE gene family
Potato
Function
Domain
Phylogenetic evolution
Protein characteristics


Cutaneous angiosarcoma metastatic to small bowel with nodal involvement.

Abstract: A 77-year-old male with a history of metastatic scalp angiosarcoma presented with intractable gastrointestinal bleeding from a jejunal mass detected on capsule endoscopy. He underwent laparoscopic-assisted resection of the mass. Intraoperatively, an isolated small bowel mass with bulky lymphadenopathy was seen and resected en bloc. Pathology showed a 6.8cm high-grade metastatic angiosarcoma with nodal involvement and negative margins. Angiosarcoma is a sarcoma with a grim prognosis. The incidence is 2% of all soft tissue sarcomas; cutaneous lesions comprise 27% of manifestations and usually appear on head and neck. Risk factors include lymphedema, neurofibromatosis, vinyl chloride, arsenic, and anabolic steroids. Overall 5-year survival is 30-35% and is higher in patients younger than 60, those without metastasis, tumors less than 5 cm, and favorable histology. Angiosarcoma metastasis to small bowel is rare but nodal involvement is even more unusual, reported only three times in the literature. This case is the first with nodal involvement to present at a resectable stage. To diagnose disease when still at a resectable stage, a high index of suspicion must be maintained with any gastrointestinal symptoms in a patient with a history of angiosarcoma. Laparoscopic-assisted resection is safe for the resection of small bowel angiosarcoma.

Fleetwood|Vidya A|VA|
Harris|Jamie C|JC|
Luu|Minh B|MB|

Angiosarcoma
Cancer metastasis
Small bowel cancer


The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis.

Abstract: ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome. Development and implementation of publicly available software, SAILOR, identified 7361 A-to-I editing events across the neural transcriptome. Intersecting the neural editome with adr-2 associated gene expression changes, revealed an edited mRNA, clec-41, whose neural expression is dependent on deamination. Restoring clec-41 expression in adr-2 deficient neural cells rescued the chemotaxis defect, providing the first evidence that neuronal phenotypes of ADAR mutants can be caused by altered gene expression.

C. elegans
ADAR
gene expression
genes
inosine
RNA editing
RNA biology
chromosomes
evolutionary biology
genomics
post-transcriptional gene regulation


Estrogen deprivation aggravates cardiac hypertrophy in nonobese Type 2 diabetic Goto-Kakizaki (GK) rats.

Abstract: Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats.

Apaijai|Nattayaporn|N|
Charoenphandhu|Narattaphol|N|
Ittichaichareon|Jitjiroj|J|
Suntornsaratoon|Panan|P|
Krishnamra|Nateetip|N|
Aeimlapa|Ratchaneevan|R|
Chattipakorn|Siriporn C|SC|
Chattipakorn|Nipon|N|

cardiac hypertrophy
Diabetes
oxidative stress
mitochondrial dysfunction


A comparison of nutritional intake and daily physical activity of girls aged 8-11 years old in Makkah, Saudi Arabia according to weight status.

Abstract:
BACKGROUND
Obesity rates in Saudi Arabia are amongst the highest in the world. It is known that teenage girls are less active than teenage boys, but less is known about the diet and activity patterns in younger girls. Therefore this study sought to investigate dietary intake and daily physical activity in girls aged 8-11 years old in Saudi Arabia.

METHODS
This was a cross- sectional observational study conducted in seven schools across the city of Makkah. A total of 266 girls had anthropometric measurements taken including height, weight, waist circumference and body fat estimations. Dietary assessment using a 4 day unweighed diet diary was undertaken in 136 of these participants, and 134 agreed to monitor their physical activity for the 4 days using an accelerometer. After exclusion for under-reporting, 109 remained in the dietary analysis and 78 in the physical activity analyses. Differences in means between BMI groups were determined using one-way ANOVA with post hoc Tukey test. Multivariable linear regression analysis was performed to look at the effect of multiple variables on body weight.

RESULTS
A total of 30% of participants were classified obese or overweight. There was a significant difference in the mean daily energy intake between the BMI groups with the obese group having the highest energy, fat, carbohydrate and protein intake (obese group: 2677 ± 804 kcal/d; healthy weight group: 1806 ± 403 kcal/d, p < 0.001), but the percentage contribution of the macronutrients to energy intake remained the same across the BMI groups. There were no differences in number of steps taken per day or time spent in moderate to vigorous intensity exercise according to BMI category. Most of the girls did not meet daily physical activity guidelines (5969 to 6773 steps per day and 18.5 - 22.5 mins per day of moderate to vigorous activity). Multiple linear regression showed that energy intake positively predicted body weight (Beta = 0.279, p =0 .001), whereas, total energy expenditure per kg of body weight and family income had a significant negative influence on body weight (Beta = -0.661, p < 0.001; -0.131, p = 0.028 respectively).

CONCLUSIONS
The results of this cross sectional analysis suggest that obesity in girls aged 8-11 years is linked to excessive energy intake from all macronutrients and the majority of girls in all weight categories are inactive. Research should be conducted to further investigate causal relationships in longitudinal studies and develop interventions to promote dietary change and activity that is culturally acceptable for girls in Saudi Arabia.

Al-Kutbe|Rabab|R|
Payne|Anne|A|
de Looy|Anne|A|
Rees|Gail A|GA|

Physical activity
Girls
Saudi Arabia
Energy intake
Dietary habits
Nutrient intake


Time and space resolved modelling of the heating induced by synchrotron X-ray nanobeams.

Abstract: X-ray synchrotron sources, possessing high power density, nanometric spot size and short pulse duration, are extending their application frontiers up to the exploration of direct matter modification. In this field, the use of atomistic and continuum models is now becoming fundamental in the simulation of the photoinduced excitation states and eventually in the phase transition triggered by intense X-rays. In this work, the X-ray heating phenomenon is studied by coupling the Monte Carlo method (MC) with the Fourier heat equation, to first calculate the distribution of the energy absorbed by the systems and finally to predict the heating distribution and evolution. The results of the proposed model are also compared with those obtained removing the explicit definition of the energy distribution, as calculated by the MC. A good approximation of experimental thermal measurements produced irradiating a millimetric glass bead is found for both of the proposed models. A further step towards more complex systems is carried out, including in the models the different time patterns of the source, as determined by the filling modes of the synchrotron storage ring. The two models are applied in three prediction cases, in which the heating produced in Bi2Sr2CaCu2O8+δ microcrystals by means of nanopatterning experiments with intense hard X-ray nanobeams is calculated. It is demonstrated that the temperature evolution is strictly connected to the filling mode of the storage ring. By coupling the MC with the heat equation, X-ray pulses that are 48 ps long, possessing an instantaneous photon flux of ∼44 × 1013 photons s-1, were found to be able to induce a maximum temperature increase of 42 K, after a time of 350 ps. Inversely, by ignoring the energy redistribution calculated with the MC, peaks temperatures up to hundreds of degrees higher were found. These results highlight the importance of the energy redistribution operated by primary and secondary electrons in the theoretical simulation of the X-ray heating effects.

Monte Carlo method
X-ray nanopatterning
finite element method
oxides
radiation damage


The Complementary Medicine Insurance Wars: The Unresolved but Politicised Australian Theatre of Combat.

Abstract: Debates have taken place for many years internationally, including in Australia, about the therapeutic effectiveness and safety of complementary/alternative medicine (CAM). The issues raised in such disputation go beyond the capacity for patients to make choices informed by contemporary knowledge about the status of such disciplines and the accuracy of claims made by the various stakeholders. As government subsidises rebates under private health insurance for a number of modalities of health care, the entitlements of CAM disciplines to such rebates have become controversial. This editorial traces Australian reports since 2010 about the eligibility for insurance rebates of a number of CAM disciplines and calls for the current 2019-2020 review by the Chief Medical Officer to engage in a fair, rigorous and conclusive evaluative process, utilising as its yardstick contemporary evidence about treatment efficacy. Such a process has the potential to bring to an end disputation that has only served to confuse patient decision-making, cater to vested interests and incur for government costs that cannot properly be justified.

complementary medicine
alternative medicine
treatment efficacy
health insurance rebates
homeopathy
natural therapies
naturopathy


Effects of lifestyle changes and high-dose β-blocker therapy on exercise capacity in children, adolescents, and young adults with hypertrophic cardiomyopathy.

Abstract:
AIM
The use of β-blocker therapy in asymptomatic patients with hypertrophic cardiomyopathy is controversial. This study evaluates the effect of lifestyle changes and high-dose β-blocker therapy on their exercise capacity.

METHODS AND RESULTS
A total of 29 consecutive newly diagnosed asymptomatic patients with familial hypertrophic cardiomyopathy, median age 15 years (range 7-25), were recruited. In all, 16 patients with risk factors for sudden death were treated with propranolol if no contraindications, or equivalent doses of metoprolol; 13 with no risk factors were randomised to metoprolol or no active treatment. Thus, there were three treatment groups, non-selective β-blockade (n=10, propranolol 4.0-11.6 mg/kg/day), selective β-blockade (n=9, metoprolol 2.7-5.9 mg/kg/day), and randomised controls (n=10). All were given recommendations for lifestyle modifications, and reduced energetic exercise significantly (p=0.002). Before study entry, and after 1 year, all underwent bicycle exercise tests with a ramp protocol. There were no differences in exercise capacity between the groups at entry, or follow-up, when median exercise capacity in the groups were virtually identical (2.4, 2.3, and 2.3 watt/kg and 55, 55, and 55 watt/(height in metre) 2 in control, selective, and non-selective groups, respectively. Maximum heart rate decreased in the selective (-29%, p=0.04) and non-selective (-24%, p=0.002) groups. No patient developed a pathological blood-pressure response to exercise because of β-blocker therapy. Boys were more frequently risk-factor positive than girls (75% versus 33%, p=0.048) and had higher physical activity scores than girls at study-entry (p=0.011).

CONCLUSIONS
Neither selective nor non-selective β-blockade causes significant reductions in exercise capacity in patients with hypertrophic cardiomyopathy above that induced by lifestyle changes.


Hiding in plain sight: structure and sequence analysis reveals the importance of the antibody DE loop for antibody-antigen binding.

Abstract: Antibody variable domains contain "complementarity-determining regions" (CDRs), the loops that form the antigen binding site. CDRs1-3 are recognized as the canonical CDRs. However, a fourth loop sits adjacent to CDR1 and CDR2 and joins the D and E strands on the antibody v-type fold. This "DE loop" is usually treated as a framework region, even though mutations in the loop affect the conformation of the CDRs and residues in the DE loop occasionally contact antigen. We analyzed the length, structure, and sequence features of all DE loops in the Protein Data Bank (PDB), as well as millions of sequences from HIV-1 infected and naïve patients. We refer to the DE loop as H4 and L4 in the heavy and light chains, respectively. Clustering the backbone conformations of the most common length of L4 (6 residues) reveals four conformations: two κ-only clusters, one λ-only cluster, and one mixed κ/λ cluster. Most H4 loops are length-8 and exist primarily in one conformation; a secondary conformation represents a small fraction of H4-8 structures. H4 sequence variability exceeds that of the antibody framework in naïve human high-throughput sequences, and both L4 and H4 sequence variability from λ and heavy germline sequences exceed that of germline framework regions. Finally, we identified dozens of structures in the PDB with insertions in the DE loop, all related to broadly neutralizing HIV-1 antibodies (bNabs), as well as antibody sequences from high-throughput sequencing studies of HIV-infected individuals, illuminating a possible role in humoral immunity to HIV-1.

Kelow|Simon P|SP|
Adolf-Bryfogle|Jared|J|
Dunbrack|Roland L|RL|

antibody complementarity determining regions


Traumatic pharyngeal perforation secondary to a syndesmophyte.

Abstract: We report the case of a 57-year-old man who presented at the emergency department with injuries to his face and head after falling down the stairs. A head computed tomography examination done because he complained of an intense headache revealed air bubbles in the retropharyngeal space. Given this finding, a computed tomography of the neck was done to evaluate the possibility of pharyngeal perforation. Traumatic pharyngeal perforations are uncommon, but those caused by the calcification of the anterior longitudinal ligament, as in our case, are even more uncommon.

Fernández Del Castillo Ascanio|M|M|
Eiroa Gutiérrez|D|D|

Perforation Syndesmophyte Faringe Perforación Pharynx Sindesmofito Trauma


Co-occurring attention-deficit/hyperactivity disorder and anxiety disorders differentially affect males and females with autism.

Abstract:
OBJECTIVE
To examine overlap and divergence of symptomatology in Autism Spectrum Disorder (ASD) with and without co-occurring Attention/Deficit Hyperactivity Disorder (ADHD) and/or Anxiety Disorder by age and sex.

METHOD
Participants included 25,078 individuals registered in the SPARK cohort, age 6-18 years. SPARK participation includes online consent and registration, as well as parent-reported ASD, ADHD, and Anxiety Disorder diagnoses, developmental, medical, and intervention history, and standardized rating scales. Individuals with ASD, ASD + ADHD, ASD + Anxiety, or ASD + ADHD + Anxiety were compared on measures assessing social communication, restricted and repetitive behaviors (RRBs), and motor functioning, and differences between male and female profiles were examined.

RESULTS
Significant differences in symptom presentation between females/males, school-age/adolescent individuals, and by co-occurring conditions (ASD/ADHD/Anxiety) are apparent, and the impact of co-occurring conditions differed by age and sex. Most notably, school-age femaleswith ASD without co-occurring conditions present with significantly fewer concerns about social communication skills and have better motor skills, but have more prominent RRBs as compared to same-aged males with ASD alone; co-occurring conditions were associated with increased social communication problems and motor concerns, most consistently for school-age females.

CONCLUSIONS
School-age females with ASD are at highest risk for underestimation of autism-related symptoms, including underestimation of symptoms beyond core ASD features (motor skills). Further, across ages, particular consideration should be given when probing for social communication symptoms, RRBs, and motor skills in females with ASD alone, as well as with co-occurring ADHD and/or Anxiety. For females with co-occurring symptoms and conditions, use of symptom-specific measures in lieu of omnibus measures should be considered.

Wodka|Ericka L|EL|
Parish-Morris|Julia|J|
Annett|Robert D|RD|
Carpenter|Laura|L|
Dillon|Emily|E|
Michaelson|Jacob|J|
Kim|So Hyun|SH|
Landa|Rebecca|R|
|||
Kanne|Stephen|S|

anxiety female Autism ADHD age repetitive motor sex/gender


JCL roundtable: Lipids and inflammation in atherosclerosis.

Abstract: Clinical effort in lipidology focuses largely on mitigating effects of atherosclerosis, a pathologic process localized to the intimal layer of larger arteries. This JCL Roundtable brings together 3 leading researchers to discuss the current understanding of pathogenesis in atherosclerosis. We begin by recognizing that low density lipoprotein concentrations in arterial intima far exceed concentrations in other connective tissues, consistent with the response-to-retention hypothesis of atherogenesis. High density lipoproteins facilitate reverse cholesterol transport and also have antioxidant and anti-inflammatory roles. New evidence points to remnants of triglyceride-rich lipoproteins as promoters of atherogenesis, highlighted by deleterious effects of apolipoprotein C-III. The multifaceted role of inflammation is becoming clearer through discoveries related to leukocyte recruitment, efferocytosis, resolution of inflammation, and crystal formation. MicroRNAs represent a new, complex mode of gene regulation bearing on lipoprotein and inflammation biology. Progress in understanding atherosclerosis portends a future in which residual risk related to obesity, diabetes, and other factors will yield to new targeted therapies.

Bornfeldt|Karin E|KE|
Linton|MacRae F|MF|
Fisher|Edward A|EA|
Guyton|John R|JR|

inflammation
atherosclerosis
lipoproteins
response-to-retention hypothesis
efferocytosis
resolution of inflammation
microRNAs


Predictive microRNAs for lymph node metastasis in endoscopically resectable submucosal colorectal cancer.

Abstract: Accurate prediction of regional lymph node metastasis (LNM) in endoscopically resected T1-stage colorectal cancers (CRCs) can reduce unnecessary surgeries. To identify miRNA markers that can predict LNM in T1-stage CRCs, the study was conducted in two phases; (I) miRNA classifier construction by miRNA-array and quantitative reverse transcription PCR (qRT-PCR) using 36 T1-stage CRC samples; (II) miRNA classifier validation in an independent set of 20 T1-stage CRC samples. The expression of potential downstream target genes of miRNAs was assessed by immunohistochemistry. In the discovery analysis by miRNA microarray, expression of 66 miRNAs were significantly different between LNM-positive and negative CRCs. After qRT-PCR validation, 11 miRNAs were consistently significant in the combined classifier construction set. Among them, miR-342-3p was the most significant one (P=4.3×10-4). Through logistic regression analysis, we developed a three-miRNA classifier (miR-342-3p, miR-361-3p, and miR-3621) for predicting LNM in T1-stage CRCs, yielding the area under the curve of 0.947 (94% sensitivity, 85% specificity and 89% accuracy). The discriminative ability of this system was consistently reliable in the independent validation set (83% sensitivity, 64% specificity and 70% of accuracy). Of the potential downstream targets of the three-miRNAs, expressions of E2F1, RAP2B, and AKT1 were significantly associated with LNM. In conclusion, this classifier can predict LNM more accurately than conventional pathologic criteria and our study results may be helpful to avoid unnecessary bowel surgery after endoscopic resection in early CRC.

Jung|Chan Kwon|CK|
Jung|Seung-Hyun|SH|
Yim|Seon-Hee|SH|
Jung|Ji-Han|JH|
Choi|Hyun Joo|HJ|
Kang|Won-Kyung|WK|
Park|Sung-Won|SW|
Oh|Seong-Taek|ST|
Kim|Jun-Gi|JG|
Lee|Sug Hyung|SH|
Chung|Yeun-Jun|YJ|

D015972:Gene Expression Regulation, Neoplastic

D020411:Oligonucleotide Array Sequence Analysis

endoscopically resectable colorectal cancer


BioFuelDB: a database and prediction server of enzymes involved in biofuels production.

Abstract:
BACKGROUND
In light of the rapid decrease in fossils fuel reserves and an increasing demand for energy, novel methods are required to explore alternative biofuel production processes to alleviate these pressures. A wide variety of molecules which can either be used as biofuels or as biofuel precursors are produced using microbial enzymes. However, the common challenges in the industrial implementation of enzyme catalysis for biofuel production are the unavailability of a comprehensive biofuel enzyme resource, low efficiency of known enzymes, and limited availability of enzymes which can function under extreme conditions in the industrial processes.

METHODS
We have developed a comprehensive database of known enzymes with proven or potential applications in biofuel production through text mining of PubMed abstracts and other publicly available information. A total of 131 enzymes with a role in biofuel production were identified and classified into six enzyme classes and four broad application categories namely 'Alcohol production', 'Biodiesel production', 'Fuel Cell' and 'Alternate biofuels'. A prediction tool 'Benz' was developed to identify and classify novel homologues of the known biofuel enzyme sequences from sequenced genomes and metagenomes. 'Benz' employs a hybrid approach incorporating HMMER 3.0 and RAPSearch2 programs to provide high accuracy and high speed for prediction.

RESULTS
Using the Benz tool, 153,754 novel homologues of biofuel enzymes were identified from 23 diverse metagenomic sources. The comprehensive data of curated biofuel enzymes, their novel homologs identified from diverse metagenomes, and the hybrid prediction tool Benz are presented as a web server which can be used for the prediction of biofuel enzymes from genomic and metagenomic datasets. The database and the Benz tool is publicly available at http://metabiosys.iiserb.ac.in/biofueldb& http://metagenomics.iiserb.ac.in/biofueldb.

Chaudhary|Nikhil|N|
Gupta|Ankit|A|
Gupta|Sudheer|S|
Sharma|Vineet K|VK|

Database
Biofuel
Biofuel precursors
Alcohol production
Biodiesel production
Fuel cell
Prediction tool


A putative WAVE regulatory complex (WRC) interacting receptor sequence (WIRS) in the cytoplasmic tail of HSV-1 gE does not function in WRC recruitment or neuronal transport.

Abstract: HSV-1 envelope glycoprotein E (gE) is important for viral egress and cell-to-cell spread but the host protein(s) involved in these functions have yet to be determined. We aimed to investigate a role for the Arp2/3 complex and actin regulation in viral egress based on the identification of a WAVE Regulatory Complex (WRC) Interacting Receptor Sequence (WIRS) in the cytoplasmic tail (CT) of gE. A WIRS-dependent interaction between the gE(CT) and subunits of the WRC was demonstrated by GST-pulldown assay and a role for the Arp2/3 complex in cell-to-cell spread was also observed by plaque assay. Subsequent study of a recombinant HSV-1 gE WIRS-mutant found no significant changes to viral production and release based on growth kinetics studies, or changes to plaque and comet size in various cell types, suggesting no function for the motif in cell-to-cell spread. GFP-Trap pulldown and proximity ligation assays were unable to confirm a WIRS-dependent interaction between gE and the WRC in human cell lines though the WIRS-independent interaction observed in situ warrants further study. Confocal microscopy of infected cells of neuronal origin identified no impairment of gE WIRS-mutant HSV-1 anterograde transport along axons. We propose that the identified gE WIRS motif does not function directly in recruitment of the WRC in human cells, in cell-to-cell spread of virus or in anterograde transport along axons. Further studies are needed to understand how HSV-1 manipulates and traverses the actin cytoskeleton and how gE may contribute to these processes in a WIRS-independent manner.

WAVE Regulatory Complex
gE
egress
Arp2/3 complex
WRC Interacting Receptor Sequence
herpes simplex virus