Computer-aided drug discovery approach finds calcium sensitizer of cardiac troponin.

Abstract: In the fight against heart failure, therapeutics that have the ability to increase the contractile power of the heart are urgently needed. One possible route of action to improve heart contractile power is increasing the calcium sensitivity of the thin filament. From a pharmaceutical standpoint, calcium sensitizers have the distinct advantage of not altering cardiomyocyte calcium levels and thus have lower potential for side-effects. Small chemical molecules have been shown to bind to the interface between cTnC and the cTnI switch peptide and exhibit calcium-sensitizing properties, possibly by stabilizing cTnC in an open conformation. Building on existing structural data of a known calcium sensitizer bound to cardiac troponin, we combined computational structure-based virtual screening drug discovery methods and solution NMR titration assays to identify a novel calcium sensitizer 4-(4-(2,5-dimethylphenyl)-1-piperazinyl)-3-pyridinamine (NSC147866) which binds to cTnC and the cTnC-cTnI147-163 complex. Its presence increases the affinity of switch peptide to cTnC by approximately a factor of two. This action is comparable to that of known levosimendan analogues.

Lindert|Steffen|S|
Li|Monica X|MX|
Sykes|Brian D|BD|
McCammon|J Andrew|JA|

drug discovery
NMR spectroscopy
molecular modeling


Chemical composition of Eastern Black Sea aerosol--preliminary results.

Abstract: Trace element composition of atmospheric particles collected at a high altitude site on the Eastern Black Sea coast of Turkey was investigated to understand atmospheric transport of pollutants to this semi-closed basin. Aerosol samples were collected at a timber-storage area, which is operated by the General Directorate of Forestry. The site is situated at a rural area and is approximately 50 km to the Black Sea coast and 200 km to the Georgia border of Turkey. Coarse (PM2.5-10) and fine (PM2.5) aerosol samples were collected between 2011 and 2013 using a "stacked filter unit". Collected samples were shipped to the Middle East Technical University in Ankara, where Na, Mg, Al, Si, S, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Ba, Pb were measured by Energy dispersive x-ray fluorescence technique (EDXRF). Comparison of measured concentrations of elements with corresponding data generated at other parts of Turkey demonstrated that concentrations of pollution derived elements are higher at Eastern Black Sea than their corresponding concentrations measured at other parts of Turkey, which is attributed to frequent transport of pollutants from north wind sector. Positive matric factorization revealed four factors including three anthropogenic and a crustal factor. Southeastern parts of Turkey, Georgia and Black Sea coast of Ukraine were identified as source regions affecting composition of particles at our site, using trajectory statistics, namely "potential source contribution function" (PSCF).

Balcılar|Ilker|I| Zararsız|Abdullah|A| Kalaycı|Yakup|Y| Doğan|Güray|G| Tuncel|Gürdal|G|

Eastern Black Sea
Trace elements
Atmospheric transport
Aerosol


Reduction of intra-fraction prostate motion - Determining optimal bladder volume and filling for prostate radiotherapy using daily 4D TPUS and CBCT.

Abstract:
Background and purpose
Inconsistent bladder and rectal volumes have been associated with motion uncertainties during prostate radiotherapy. This study investigates the impact of these volumes to determine the optimal bladder volume.

Materials and methods
60 patients from two Asian hospitals were recruited prospectively. 1887 daily cone-beam computed tomography (CBCT) images were analysed. Intra-fraction motion of the prostate was monitored real-time using a four-dimension transperineal ultrasound (4D TPUS) Clarity® system. The impact of planned bladder volume, adequacy of daily bladder filling, and rectum volume on mean intra-fraction motion of the prostate was analysed. Patients' ability to comply with the full bladder hydration protocol and level of frustration was assessed using a questionaire. Acute side effects were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and quality of life (QoL) assessed using the International Prostate Symptom Score (IPSS).

Results
The mean (SD) bladder and rectum volumes achieved during daily treatment were 139.7 cm3 (82.4 cm3) and 53.3 cm3 (18 cm3) respectively. Mean (SD) percentage change from planned CT volumes in bladder volume was reduced by 8.2% (48.7%) and rectum volume was increased by 12.4% (42.2%). Linear Mixed effect model analysis revealed a reduction in intra-fraction motion in both the Sup/Inf (p = 0.008) and Ant/Post (p = 0.0001) directions when the daily bladder was filled between 82 and 113% (3rd Quartiles) of the planned CT volumes. A reduction in intra-fraction motion of the prostate in the Ant/Post direction (z-plane) (p = 0.03) was observed when the planned bladder volume was greater than 200 ml. Patients complied well with the hydration protocol with minimal frustration (mean (SD) scores of 2.1 (1.4) and 1.8 (1.2) respectively). There was a moderate positive correlation (0.496) between mean bladder volume and IPSS reported post-treatment urinary straining (p = 0.001).

Conclusions
A planned bladder volume >200 cm3 and daily filling between 82 and 113%, reduced intra-fraction motion of the prostate. The hydration protocol was well tolerated.

Pang|Eric Pei Ping|EPP|
Knight|Kellie|K|
Hussain|Ashik|A|
Fan|Qiao|Q|
Baird|Marilyn|M|
Tan|Sheena Xue Fei|SXF|
Mui|Wing-Ho|WH|
Leung|Ronnie Wing-Kin|RW|
Seah|Irene Kai Ling|IKL|
Master|Zubin|Z|
Tuan|Jeffrey Kit Loong|JKL|

Prostate radiotherapy
Intra-fraction motion
Full bladder hydration protocol
4D TPUS clarity
Real-time tracking


Low-Temperature Preparation of Tungsten Oxide Anode Buffer Layer via Ultrasonic Spray Pyrolysis Method for Large-Area Organic Solar Cells.

Abstract: Tungsten oxide (WO₃) is prepared by a low-temperature ultrasonic spray pyrolysis method in air atmosphere, and it is used as an anode buffer layer (ABL) for organic solar cells (OSCs). The properties of the WO₃ transition metal oxide material as well as the mechanism of ultrasonic spray pyrolysis processes are investigated. The results show that the ultrasonic spray pyrolysized WO₃ ABL exhibits low roughness, matched energy level, and high conductivity, which results in high charge transport efficiency and suppressive recombination in OSCs. As a result, compared to the OSCs based on vacuum thermal evaporated WO₃, a higher power conversion efficiency of 3.63% is reached with low-temperature ultrasonic spray pyrolysized WO₃ ABL. Furthermore, the mostly spray-coated OSCs with large area was fabricated, which has a power conversion efficiency of ~1%. This work significantly enhances our understanding of the preparation and application of low temperature-processed WO₃, and highlights the potential of large area, all spray coated OSCs for sustainable commercial fabrication.

Ji|Ran|R| Zheng|Ding|D| Zhou|Chang|C| Cheng|Jiang|J| Yu|Junsheng|J| Li|Lu|L|

tungsten oxide
anode buffer layer
ultrasonic spray pyrolysis method
organic solar cells
large area


Effects of Syllable Position, Fundamental Frequency, Duration and Amplitude on Word Stress in Mandarin Chinese.

Abstract: This study examined the importance of syllable position, duration, and tone/pitch for the assignment of stress in Chinese hums. Twenty native Mandarin speakers and 20 native English speakers were asked to assign primary stress to two-syllable Chinese hums. The importance of acoustic cues for stress assignment was also evaluated. Our findings indicate that syllable position plays the most prominent role in stress assignment. Native Chinese listeners preferred to assign stress to final syllables whereas native English listeners preferred to assign stress to initial syllables. Both language groups were sensitive to different acoustic cues in assigning stress. The effects of complex interactions of syllable position, tone, duration and intensity on stress assignment in Chinese hums for both language groups support the hypothesis that linguistic experience affects speech perception at the suprasegmental level.

Word stress
Linguistic experience
Speech perception
Acoustic properties
Chinese tone
Suprasegmental processing


Evaluation of sleep quality and risk of obstructive sleep apnea in patients referred for aesthetic rhinoplasty.

Abstract:
Importance
Aesthetic rhinoplasty is the fifth surgical procedure most performed worldwide by plastic surgeons. With the growing demand for rhinoplasty, there is an unmet need for research into the profile of patients who seek aesthetic nasal surgery in an attempt to improve not only cosmetic dissatisfactions, but also the manifestations of other, possibly interrelated disorders, especially sleep disturbances.

Objective
To evaluate the sleep quality and the risk of Obstructive Sleep Apnea in patients referred for aesthetic rhinoplasty, as well as the association of these conditions with nasal symptoms. Design: Cross-sectional study performed at the period of June/2016 to August/2017. Setting: Department of Otolaryngology and Head and Neck Surgery - Universidade Federal de São Paulo. Participants: Patients of both sexes, aged 18 to 65 years, who were referred for aesthetic rhinoplasty. We evaluated 46 patients, two of whom were excluded because they were outside the inclusion age criteria. Main Outcome(s) and Measure(s): Anterior rhinoscopy and the following validated surveys were used. Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Nasal Obstruction Symptom Evaluation scale; Berlin Questionnaire. The visual analog scale for snoring was also used.

Results
Of the 44 participants, 18 (41%) were males and 26 (59%) were females. 82% had poor sleep quality. 46% presented excessive daytime sleepiness. There was a high risk for Obstructive Sleep Apnea in 27%. Regarding to nasal symptoms, the mean score in the Nasal Obstructive Symptoms Evaluation was 66.25±25.38. When comparing the groups with good and poor sleep quality, we observed a higher risk for Obstructive Sleep Apnea (p=0.05) in patients with poor sleep quality. Patients at high risk for Obstructive Sleep Apnea had higher scores on the Nasal Obstructive Symptoms Evaluation (p=0.001) and on the analogue snoring scale (p<0.001) compared to patients at low risk.

Conclusions
We observed a high occurrence of poor sleep quality in participants. All participants who were at high risk for obstructive sleep apnea were also classified as having poor sleep quality. An association was also observed between the presence of high risk for obstructive sleep apnea and presence of nasal symptoms.

Miyahara|Lucas Kenzo|LK|
Stefanini|Renato|R|
Suguri|Vinicius Magalhães|VM|
Wawginiak|Guilherme Henrique|GH|
Balsalobre|Rafael de Andrade|RA|
Haddad|Fernanda Louise Martinho|FLM|

Sleep
Rhinoplasty
Sleep Apnea, Obstructive


Sepsis: mechanisms of bacterial injury to the patient.

Abstract: In bacteremia the majority of bacterial species are killed by oxidation on the surface of erythrocytes and digested by local phagocytes in the liver and the spleen. Sepsis-causing bacteria overcome this mechanism of human innate immunity by versatile respiration, production of antioxidant enzymes, hemolysins, exo- and endotoxins, exopolymers and other factors that suppress host defense and provide bacterial survival. Entering the bloodstream in different forms (planktonic, encapsulated, L-form, biofilm fragments), they cause different types of sepsis (fulminant, acute, subacute, chronic, etc.). Sepsis treatment includes antibacterial therapy, support of host vital functions and restore of homeostasis. A bacterium killing is only one of numerous aspects of antibacterial therapy. The latter should inhibit the production of bacterial antioxidant enzymes and hemolysins, neutralize bacterial toxins, modulate bacterial respiration, increase host tolerance to bacterial products, facilitate host bactericidal mechanism and disperse bacterial capsule and biofilm.

Sepsis
Treatment
Antibacterial therapy
Bactericidals
Antibiotics
Bacteriostatics


Computational analysis of Alzheimer-causing mutations in amyloid precursor protein and presenilin 1.

Abstract: Single-point mutations in the genes coding for amyloid precursor protein (APP) and presenilin 1 (PS1), the active subunit of γ-secretase that cleaves APP to produce Aβ, are the main causes of rare but severe familial Alzheimer's disease (fAD). Recent structures of the transmembrane parts of APP and γ-secretase with a fragment of APP bound enable us to study the origins of the pathogenicity of the single amino acid changes in the context of the actual enzyme-substrate complex, which has not previously been possible. We used the new structures as input for several state-of-the-art computational methods that predict the folding stability effect of mutations. We find that pathogenic mutations almost exclusively reduce the stability of the proteins. Since most "random" mutations of an evolutionarily optimized protein tend to destabilize, we also show that the APP mutations destabilize the complex-bound substrate more than the free substrate, indicating reduced affinity of APP to γ-secretase. We confirmed this using two other methods, BEATMUSIC and mCSM PPI, specifically developed for calculating binding affinities of mutants. Although pathogenic PS1 mutations destabilize the complex and substrate-free form to the same extent, they significantly destabilize the protein more than the control set of random mutations. We conclude that fAD mutations most likely reduce the stability of the protein-substrate complex and thus retention time of APP-C99, leading to premature release of longer toxic Aβ42 in accordance with the FIST model of Aβ production, whereas the observed general destabilization of the protein may reduce activity towards other substrates.

D053829:Amyloid Precursor Protein Secretases

Mutations
Presenilin
γ-secretase
Alzheimer's disease
Protein stability


Survey of surgical specialists' content preferences in radiology reports for extrahepatic portosystemic shunts.

Abstract: The aim of this prospective, survey study was to assess the opinions of specialist surgeons as to the preferred content, nomenclature, and classification of extrahepatic portosystemic shunts for inclusion in radiology reports. A link to an online survey was sent by email to members of the European College of Veterinary Surgeons and the Association of Veterinary Soft Tissue Surgeons, and was made available on the American College of Veterinary Surgeons web forum and Facebook page. There were 93 respondents (survey sent to over 2500 email addresses and made available in two online locations). Most respondents agreed that they both review the images themselves (87/92, 95%) and read the radiology report (82/92, 89%) prior to surgery. Most respondents believed that the radiology report should contain a detailed anatomic description of the insertion (83/92, 90%), origin (54/91, 59%), and course (70/92, 76%) of the shunt, as well as a measure of the diameter of the shunting vessel at its insertion (54/92, 59%). Most respondents (70/90, 78%) disagreed that a brief description of shunt type, such as portocaval or portophrenic, was sufficient. Respondents were undecided regarding the use of an alphanumeric classification system (36/92, 39% agree; 32/92, 35% disagree). There was agreement that details of the presence or absence of urolithiasis (91/93, 98%), renomegaly (54/93, 58%), and peritoneal fluid (72/92, 78%) should be included in the report. The results of this study will help to guide reporting radiologists in providing descriptions of extrahepatic portosystemic shunts that include information most preferred by the recipient surgeons.

portosystemic shunt
radiologist
computed tomography
structured reporting


TRP Channels and Migraine: Recent Developments and New Therapeutic Opportunities.

Abstract: Migraine is the second-most disabling disease worldwide, and the second most common neurological disorder. Attacks can last many hours or days, and consist of multiple symptoms including headache, nausea, vomiting, hypersensitivity to stimuli such as light and sound, and in some cases, an aura is present. Mechanisms contributing to migraine are still poorly understood. However, transient receptor potential (TRP) channels have been repeatedly linked to the disorder, including TRPV1, TRPV4, TRPM8, and TRPA1, based on their activation by pathological stimuli related to attacks, or their modulation by drugs/natural products known to be efficacious for migraine. This review will provide a brief overview of migraine, including current therapeutics and the link to calcitonin gene-related peptide (CGRP), a neuropeptide strongly implicated in migraine pathophysiology. Discussion will then focus on recent developments in preclinical and clinical studies that implicate TRP channels in migraine pathophysiology or in the efficacy of therapeutics. Given the use of onabotulinum toxin A (BoNTA) to treat chronic migraine, and its poorly understood mechanism, this review will also cover possible contributions of TRP channels to BoNTA efficacy. Discussion will conclude with remaining questions that require future work to more fully evaluate TRP channels as novel therapeutic targets for migraine.

TRP
CGRP
botulinum toxin A
cortical spreading depression
dura mater
ion channel
meninges
neurogenic inflammation
reactive nitrogen species
reactive oxygen species


Behavioral investigation of the influence of social categorization on empathy for pain: a minimal group paradigm study.

Abstract: Research on empathy for pain has provided evidence of an empathic bias toward racial ingroup members. In this study, we used for the first time the "minimal group paradigm" in which participants were assigned to artificial groups and required to perform pain judgments of pictures of hands and feet in painful or non-painful situations from self, ingroup, and outgroup perspectives. Findings showed that the mere categorization of people into two distinct arbitrary social groups appears to be sufficient to elicit an ingroup bias in empathy for pain.

Montalan|Benoît|B| Lelard|Thierry|T| Godefroy|Olivier|O| Mouras|Harold|H|

social categorization
empathy for pain
minimal group paradigm
ingroup bias


Leishmania Infection Induces Macrophage Vascular Endothelial Growth Factor A Production in an ARNT/HIF-Dependent Manner.

Abstract: Cutaneous leishmaniasis is characterized by vascular remodeling. Following infection with Leishmania parasites, the vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 (VEGFR-2) signaling pathway mediates lymphangiogenesis, which is critical for lesion resolution. Therefore, we investigated the cellular and molecular mediators involved in VEGF-A/VEGFR-2 signaling using a murine model of infection. We found that macrophages are the predominant cell type expressing VEGF-A during Leishmania major infection. Given that Leishmania parasites activate hypoxia-inducible factor 1α (HIF-1α) and this transcription factor can drive VEGF-A expression, we analyzed the expression of HIF-1α during infection. We showed that macrophages were also the major cell type expressing HIF-1α during infection and that infection-induced VEGF-A production is mediated by ARNT/HIF activation. Furthermore, mice deficient in myeloid ARNT/HIF signaling exhibited larger lesions without differences in parasite numbers. These data show that L. major infection induces macrophage VEGF-A production in an ARNT/HIF-dependent manner and suggest that ARNT/HIF signaling may limit inflammation by promoting VEGF-A production and, thus, lymphangiogenesis during infection.

Weinkopff|Tiffany|T| Roys|Hayden|H| Bowlin|Anne|A| Scott|Phillip|P|

D051784:Aryl Hydrocarbon Receptor Nuclear Translocator

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

D042461:Vascular Endothelial Growth Factor A

Leishmania
vascular remodeling
lymphangiogenesis
VEGF-A
HIF-1α


Endometriosis revisited: an imaging review of the usual and unusual manifestations with pathological correlation.

Abstract: The manifestations of endometriosis commonly present a diagnostic challenge to the gynecologist and radiologist. Familiarity with its varied presentations may allow for a more accurate diagnosis. The goal of this review is to the present the imaging spectrum of endometriosis, less common sites of involvement as well as the potential rare complications. Relevant surgical and histopathological correlation is also provided. In addition to clinical evaluation and sonography, MRI is a highly accurate imaging modality in the diagnosis of endometriosis. It possesses a distinctive advantage over other modalities in that it allows a complete survey of the pelvic compartments. The potentially devastating effects of endometriosis include pelvic pain and even infertility. Since standard treatment is surgical, the radiologist needs to be familiar with the various manifestations in order to aid diagnosis for appropriate management.

Tran-Harding|Karen|K|
Nair|Rashmi T|RT|
Dawkins|Adrian|A|
Ayoob|Andres|A|
Owen|Joseph|J|
Deraney|Sarah|S|
Lee|James T|JT|
Stevens|Scott|S|
Ganesh|Halemane|H|

Endometriosis
Endometrioma
Malignant transformation
Müllerian
Scar endometriosis
T2-weighted images


Sexual Identity and Motivations for Prescription Drug Misuse Among U.S. Adults.

Abstract: Although we know that sexual minority populations, particularly bisexual individuals, tend to be at increased risk for substance use, less research has focused on prescription drug misuse (PDM). The current study is the first to assess differences in motivations for PDM by sexual identity and sex. This is important as research has established a link between certain motivations and adverse outcomes.  This study used data from multiple years of the National Survey on Drug Use and Health (2015-2018). Respondents who reported past-year PDM were asked follow-up questions to identify motivations for PDM. We ran several weighted cross-tabulations to estimate the prevalence and 95% confidence intervals for motivations for PDM by sexual identity (i.e., heterosexual, lesbian or gay, and bisexual) for males and females separately. When chi-square tests were significant, post hoc comparisons using design-based multivariable regressions were conducted.  Prevalence rates for both PDM and substance use disorder associated with prescription drugs were higher among sexual minority adults than heterosexual adults. With regard to motives, bisexual females were more likely to endorse recreational motives (i.e., to get high) for prescription opioids, tranquilizers, and stimulants than heterosexual females. Gay males were more likely to endorse self-treatment motives (e.g., to relax, to lose weight) than both bisexual and heterosexual males.  High prevalence rates and endorsement of recreational motives identify bisexual females as an important at-risk population. It is important for clinicians to consider how prevention, treatment, and intervention strategies focused on PDM may be improved to best target this unique population.

Diaz|Madelyn|M|
Tenney|Caralyn|C|
Boyd|Kelsey E|KE|
Ford|Jason A|JA|

sexual identity
motivations
prescription drug misuse
opioids


Prognostic factors of T4 gastric cancer patients undergoing potentially curative resection.

Abstract:
AIM
To investigate the prognostic factors of T4 gastric cancer patients without distant metastasis who could undergo potentially curative resection.

METHODS
We retrospectively analyzed the clinical data of 71 consecutive patients diagnosed with T4 gastric cancer and who underwent curative gastrectomy at our institutions. The clinicopathological factors that could be associated with overall survival were evaluated. The cumulative survival was determined by the Kaplan-Meier method, and univariate comparisons between the groups were performed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model and a step-wise procedure.

RESULTS
The study patients comprised 53 men (74.6%) and 18 women (25.4%) aged 39-89 years (mean, 68.9 years). Nineteen patients (26.8%) had postoperative morbidity: pancreatic fistula developed in 6 patients (8.5%) and was the most frequent complication, followed by anastomosis stricture in 5 patients (7.0%). During the follow-up period, 28 patients (39.4%) died because of gastric cancer recurrence, and 3 (4.2%) died because of another disease or accident. For all patients, the estimated overall survival was 34.1% at 5 years. Univariate analyses identified the following statistically significant prognostic factors in T4 gastric cancer patients who underwent potentially curative resection: peritoneal washing cytology (P < 0.01), number of metastatic lymph nodes (P < 0.05), and venous invasion (P < 0.05). In multivariate analyses, only peritoneal washing cytology was identified as an independent prognostic factor (HR = 3.62, 95% CI = 1.37-9.57) for long-term survival.

CONCLUSION
Positive peritoneal washing cytology was the only independent poor prognostic factor for T4 gastric cancer patients who could be treated with potentially curative resection.

Prognostic factors
T4
Gastric cancer
Venous invasion
Peritoneal cytology


Tubuloreticular inclusions in peritubular capillaries of renal allografts.

Abstract:
BACKGROUND
Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored.

METHODS
We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec. 2015 to Dec. 2016.

RESULTS
TRIs were present in peritubular capillaries in seven cases and were concomitantly present in glomerular endothelial cells in two cases. The diagnoses included polyomavirus nephropathy (n=2), acute T cell-mediated rejection (ACR) (n=1), combined ACR and antibody-mediated rejection (AMR) (n=1), suspicious for ACR (n=1), chronic active AMR (n=1), and moderate tubular atrophy and interstitial fibrosis (n=1). Six patients had recent or current viral infections (BK polyomavirus, hepatitis B virus, herpes simplex virus, and cytomegalovirus in two, two, one, and one case, respectively). DSA was positive in one case. Five cases had moderate to severe interstitial inflammation and four cases had peritubular capillaritis.

CONCLUSION
TRIs are not rare in peritubular capillaries. They are associated with various viral infections and their appearance seems to be related to peritubular capillary injury.

Lee|Jee Youn|JY|
Song|Seung Hwan|SH|
Kim|Yu Seun|YS|
Lim|Beom Jin|BJ|
Kim|Soon Il|SI|
Kim|Myoung Soo|MS|
Jeong|Hyeon Joo|HJ|

Tubuloreticular inclusion
Peritubular capillary
Transplant


Group IID, IIE, IIF and III secreted phospholipase A2s.

Abstract: Among the 11 members of the secreted phospholipase A2 (sPLA2) family, group IID, IIE, IIF and III sPLA2s (sPLA2-IID, -IIE, -IIF and -III, respectively) are "new" isoforms in the history of sPLA2 research. Relative to the better characterized sPLA2s (sPLA2-IB, -IIA, -V and -X), the enzymatic properties, distributions, and functions of these "new" sPLA2s have remained obscure until recently. Our current studies using knockout and transgenic mice for a nearly full set of sPLA2s, in combination with comprehensive lipidomics, have revealed unique and distinct roles of these "new" sPLA2s in specific biological events. Thus, sPLA2-IID is involved in immune suppression, sPLA2-IIE in metabolic regulation and hair follicle homeostasis, sPLA2-IIF in epidermal hyperplasia, and sPLA2-III in male reproduction, anaphylaxis, colonic diseases, and possibly atherosclerosis. In this article, we overview current understanding of the properties and functions of these sPLA2s and their underlying lipid pathways in vivo.

Murakami|Makoto|M| Miki|Yoshimi|Y| Sato|Hiroyasu|H| Murase|Remi|R| Taketomi|Yoshitaka|Y| Yamamoto|Kei|K|

Transgenic mice
Lipidomics
Knockout mice
Lipid-metabolic pathways
Pathophysiological function
Secreted phospholipase A(2)


Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance.

Abstract: Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance and subjective alertness in a 32-d inpatient protocol in which participants were scheduled to wakefulness durations below 16 h while on a 20-h "day," with randomization into standard sleep:wake ratio (1:2) or chronic sleep restriction (CSR) ratio (1:3.3) conditions. This protocol allowed determination of the contribution of sleep deficiency independent of extended wakefulness, since individual episodes of wakefulness in the CSR condition were only 15.33 h in duration (less than the usual 16 h of wakefulness in a 24-h day) and sleep episodes were 4.67 h in duration each cycle. We found that chronic short sleep duration, even without extended wakefulness, doubled neurobehavioral reaction time performance and increased lapses of attention fivefold, yet did not uniformly decrease self-reported alertness. Further, these impairments in neurobehavioral performance were worsened during the circadian night and were not recovered during the circadian day, indicating that the deleterious effect from the homeostatic buildup of CSR is expressed even during the circadian promotion of daytime arousal. These findings reveal a fundamental aspect of human biology: Chronic insufficient sleep duration equivalent to 5.6 h of sleep opportunity per 24 h impairs neurobehavioral performance and self-assessment of alertness, even without extended wakefulness.

McHill|Andrew W|AW|
Hull|Joseph T|JT|
Wang|Wei|W|
Czeisler|Charles A|CA|
Klerman|Elizabeth B|EB|

alertness
circadian
insufficient sleep
forced desynchrony
sleepiness


Hepatitis C Positive Organ Donation in Heart Transplantation.

Abstract:
Purpose of Review
To summarize outcomes to date, as well as important considerations and unanswered questions related to the use of hepatitis C virus (HCV) positive donors for heart transplantation.

Recent Findings
Outcomes from single-center studies and registry data to date suggest that among patients who develop donor-transmitted HCV after heart transplantation, direct-acting antiviral therapies (DAAT) are effective and well-tolerated, and that short-term survival is similar to that of patients transplanted with HCV - donors.

Summary
In an era marked by increasing numbers of HCV positive deceased donors and a growing imbalance between the demand and supply of donor hearts, utilization of HCV + donors is a feasible strategy to expand the donor pool and reduce waitlist times. Ongoing work is needed to clarify longer-term outcomes with the use of this strategy.

Siddiqi|Hasan K|HK|
Schlendorf|Kelly H|KH|

Heart transplantation
Hepatitis C virus
Direct-acting antiviral therapies
Donor pool


A novel mutation of CLCNKB in a Korean patient of mixed phenotype of Bartter-Gitelman syndrome.

Abstract: Bartter syndrome (BS) is an inherited renal tubular disorder characterized by low or normal blood pressure, hypokalemic metabolic alkalosis, and hyperreninemic hyperaldosteronism. Type III BS is caused by loss-of-function mutations in CLCNKB encoding basolateral ClC-Kb. The clinical phenotype of patients with CLCNKB mutations has been known to be highly variable, and cases that are difficult to categorize as type III BS or other hereditary tubulopathies, such as Gitelman syndrome, have been rarely reported. We report a case of a 10-year-old Korean boy with atypical clinical findings caused by a novel CLCNKB mutation. The boy showed intermittent muscle cramps with laboratory findings of hypokalemia, severe hypomagnesemia, and nephrocalcinosis. These findings were not fully compatible with those observed in cases of BS or Gitelman syndrome. The CLCNKB mutation analysis revealed a heterozygous c.139G>A transition in exon 13 [p.Gly(GGG)465Glu(GAG)]. This change is not a known mutation; however, the clinical findings and in silico prediction results indicated that it is the underlying cause of his presentation.

Cho|Hee-Won|HW|
Lee|Sang Taek|ST|
Cho|Heeyeon|H|
Cheong|Hae Il|HI|


α-Aminoxy-Acid-Auxiliary-Enabled Intermolecular Radical γ-C(sp3 )-H Functionalization of Ketones.

Abstract: A method for site-specific intermolecular γ-C(sp3 )-H functionalization of ketones has been developed using an α-aminoxy acid auxiliary applying photoredox catalysis. Regioselective activation of an inert C-H bond is achieved by 1,5-hydrogen atom abstraction by an oxidatively generated iminyl radical. Tertiary and secondary C-radicals thus formed at the γ-position of the imine functionality undergo radical conjugate addition to various Michael acceptors to provide, after reduction and imine hydrolysis, the corresponding γ-functionalized ketones.

ketone
iminyl radical
C−H bond functionalization
photoredox chemistry
redox-neutral


CXCL8(3-72) K11R/G31P protects against sepsis-induced acute kidney injury via NF-κB and JAK2/STAT3 pathway.

Abstract:
BACKGROUND
Acute kidney injury (AKI), which is mainly caused by sepsis, has high morbidity and mortality rates. CXCL8(3-72) K11R/G31P (G31P) can exert therapeutic effect on inflammatory diseases and malignancies. We aimed to investigate the effect and mechanism of G31P on septic AKI.

METHODS
An AKI mouse model was established, and kidney injury was assessed by histological analysis. The contents of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured by commercial kits, whereas neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were detected by enzyme-linked immunosorbent assay (ELISA) kits. The expressions of CXCL8 in serum and kidney tissues were determined using ELISA and immunohistochemical analysis, respectively. Apoptosis rate of renal tissue was detected by terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL) analysis. The expressions of inflammatory cytokines were measured by quantitative real-time PCR and Western blot, respectively. The apoptosis-related proteins, JAK2, STAT3, NF-κB and IκB were determined by Western blot.

RESULTS
G31P could reduce the levels of SCr, BUN, HGAL and KIM-1 and inhibit the renal tissue injury in AKI mice. G31P was also found to suppress the serum and nephric CXCL8 expressions and attenuated the apoptosis rate. The levels of inflammatory cytokines, pro-apoptotic proteins were decreased, while the anti-apoptotic proteins were increased by G31P in AKI mice. G31P also inhibited the activation of JAK2, STAT3 and NF-κB in AKI mice.

CONCLUSION
These results suggest that G31P could protect renal function and attenuate the septic AKI. Our findings provide a potential target for the treatment of AKI.


Evolution of the Telomere-Associated Protein POT1a in Arabidopsis thaliana Is Characterized by Positive Selection to Reinforce Protein-Protein Interaction.

Abstract: Gene duplication is a major driving force in genome evolution. Here, we explore the nature and origin of the POT1 gene duplication in Arabidopsis thaliana. Protection of Telomeres (POT1) is a conserved multifunctional protein that modulates telomerase activity and its engagement with telomeres. Arabidopsis thaliana encodes two divergent POT1 paralogs termed AtPOT1a and AtPOT1b. AtPOT1a positively regulates telomerase activity, whereas AtPOT1b is proposed to negatively regulate telomerase and promote chromosome end protection. Phylogenetic analysis uncovered two independent POT1 duplication events in the plant kingdom, including one at the base of Brassicaceae. Tests for positive selection implemented in PAML revealed that the Brassicaceae POT1a lineage experienced positive selection postduplication and identified three amino acid residues with signatures of positive selection. A sensitive and quantitative genetic complementation assay was developed to assess POT1a function in A. thaliana. The assay showed that AtPOT1a is functionally distinct from single-copy POT1 genes in other plants. Moreover, for two of the sites with a strong signature of positive selection, substitutions that swap the amino acids in AtPOT1a for residues found in AtPOT1b dramatically compromised AtPOT1a function in vivo. In vitro-binding studies demonstrated that all three sites under positive selection specifically enhance the AtPOT1a interaction with CTC1, a core component of the highly conserved CST (CTC1/STN1/TEN1) telomere protein complex. Our results reveal a molecular mechanism for the role of these positively selected sites in AtPOT1a. The data also provide an important empirical example to refine theories of duplicate gene retention, as the outcome of positive selection here appears to be reinforcement of an ancestral function, rather than neofunctionalization. We propose that this outcome may not be unusual when the duplicated protein is a component of a multisubunit complex whose function is in part specified by other members.

Beilstein|Mark A|MA|
Renfrew|Kyle B|KB|
Song|Xiangyu|X|
Shakirov|Eugene V|EV|
Zanis|Michael J|MJ|
Shippen|Dorothy E|DE|

D000595:Amino Acid Sequence
D029681:Arabidopsis Proteins
D019143:Evolution, Molecular
D009687:Nuclear Proteins
D010802:Phylogeny
D060066:Protein Interaction Maps
D012641:Selection, Genetic
D034501:Telomere-Binding Proteins

Arabidopsis
positive selection
POT1
telomere
Brassicaceae
CTC1


Application of a new HPLC-ICP-MS method for simultaneous determination of Al(3+) and aluminium fluoride complexes.

Abstract: The paper presents the new HPLC-ICP-MS method used for conducting speciation analysis of aluminum as free Al(3+) and aluminum fluoride complexes during one analysis. In the study, 5% HNO3 was used as a derivative reagent in order to minimize the possibility of clogging the torch in ICP-MS. Using the new HPLC-ICP-MS method, speciation analysis of aluminum and aluminum fluoride complexes was conducted on the basis of model solutions and real samples (soil-water extracts and groundwater samples). The analysis in the presented analytical system lasts only 4 min.

Analytical chemistry
Analytical chemistry applications
Chemistry
Earth sciences
HPLC


Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens.

Abstract: Influenza, an acute, highly contagious respiratory disease, remains a significant threat to public health. More effective vaccination strategies aimed at inducing broad cross-protection not only against seasonal influenza variants, but also zoonotic and emerging pandemic influenza strains are urgently needed. A number of conserved protein targets to elicit such cross-protective immunity have been under investigation, with long alpha-helix (LAH) from hemagglutinin stalk and ectodomain of matrix protein 2 ion channel (M2e) being the most studied ones. Recently, we have reported the three-dimensional structure and some practical applications of LAH expressed in Escherichia coli system (referred to as tri-stalk protein). In the present study, we investigated the immunogenicity and efficacy of a panel of broadly protective influenza vaccine prototypes based on both influenza tri-stalk and triple M2e (3M2e) antigens integrated into phage AP205 virus-like particles (VLPs). While VLPs containing the 3M2e alone induced protection against standard homologous and heterologous virus challenge in mice, only the combination of both conserved influenza antigens into a single VLP fully protected mice from a high-dose homologous H1N1 influenza infection. We propose that a combination of genetic fusion and chemical coupling techniques to expose two different foreign influenza antigens on a single particle is a perspective approach for generation of a broadly-effective vaccine candidate that could protect against the constantly emerging influenza virus strains.

Kirsteina|Anna|A| Akopjana|Inara|I| Bogans|Janis|J| Lieknina|Ilva|I| Jansons|Juris|J| Skrastina|Dace|D| Kazaka|Tatjana|T| Tars|Kaspars|K| Isakova-Sivak|Irina|I| Mezhenskaya|Daria|D| Kotomina|Tatiana|T| Matyushenko|Victoria|V| Rudenko|Larisa|L| Kazaks|Andris|A|

vaccines
influenza
hemagglutinin stalk
protection
virus-like particles
M2e protein
conserved antigens


A Special Risk Group for Hepatitis E Infection: The First Record of North Cyprus.

Abstract:
Hepatitis E virus (HEV) is transmitted by a fecal oral route from animals to humans following exposure to the body fluids of infected animals. We investigated the seroprevalence of anti-hepatitis E (anti-HEV) antibodies by monitoring IgG and IgM virus antibodies amongst employees in the animal industry in North Cyprus through a cross-sectional study. Samples were taken from individuals without occupational exposure to animals and from those who worked with animals (doing animal husbandry, veterinary work or butchery). Enzyme-linked immunoassays were used to detect anti-HEV IgG and IgM in the blood samples. The prevalence of anti-HEV IgG antibodies was 3.0% (12/400), while the prevalence of anti-HEV IgM antibodies was 0.25% (1/400). The prevalence of anti-HEV IgG amongst the samples received from females was approximately 2.5-fold higher than samples received from males (2.4%). Anti-HEV IgG was detected amongst 7% of animal husbandry workers and amongst 2% of veterinarians and butchers. The current findings represent the first records of HEV surveillance in Cyprus. We investigated the seroprevalence of anti-HEV by monitoring IgG and IgM virus antibodies amongst employees.

Hepatitis E virus (HEV) is transmitted by a fecal oral route from animals to humans following exposure to the body fluids of infected animals. We investigated the seroprevalence of anti-hepatitis E (anti-HEV) antibodies by monitoring IgG and IgM virus antibodies amongst employees in the animal industry in North Cyprus through a cross-sectional study. Samples were taken from individuals without occupational exposure to animals and from those who worked with animals (doing animal husbandry, veterinary work or butchery). Enzyme-linked immunoassays were used to detect anti-HEV IgG and IgM in the blood samples. The prevalence of anti-HEV IgG antibodies was 3.0% (12/400), while the prevalence of anti-HEV IgM antibodies was 0.25% (1/400). The prevalence of anti-HEV IgG amongst the samples received from females was approximately 2.5-fold higher than samples received from males (2.4%). Anti-HEV IgG was detected amongst 7% of animal husbandry workers and amongst 2% of veterinarians and butchers. The current findings represent the first records of HEV surveillance in Cyprus. We investigated the seroprevalence of anti-HEV by monitoring IgG and IgM virus antibodies amongst employees.

hepatitis E
Cyprus
animals
seroprevalence
epidemiology
zoonoses


para-Menthane as a Stable Terpene Derived from Orange By-Products as a Novel Solvent for Green Extraction and Solubilization of Natural Substances.

Abstract: This study aims at investigating p-menthane, a novel bio-based solvent resulting from the hydrogenation of d-limonene, as a green alternative to n-hexane or toluene for the extraction and solubilization of natural substances. First, conductor-like combination of quantum chemistry (COSMO) coupled with statistical thermodynamics (RS) calculations show a comparable solubilization profile of p-menthane and n-hexane for carotene, volatile monoterpenes such as carvone and limonene, and model triglycerides. Other data obtained experimentally in solid/liquid extraction conditions further indicate that p-menthane showed similar performances to n-hexane for extracting carotenes from carrots, aromas from caraway seeds, and oils from rapeseeds, as these products showed a comparable composition. p-Menthane was also tested using common analytical extraction procedures such as Soxhlet for determination of oil content via multiple extraction stages, and Dean-Stark for determination of water content via azeotropic distillation. For both systems, yields were comparable, but for Dean-Stark, the distillation curve slope was higher when using p-menthane, and the time needed to attain 100% water recovery was 55% shorter than for toluene. Taken together, these results reveal the potential of p-menthane as a green replacer for petroleum-based solvents such as n-hexane or toluene.

Madji|Sara|S| Hilali|Soukaina|S| Fabiano-Tixier|Anne-Sylvie|AS| Tenon|Mathieu|M| Bily|Antoine|A| Laguerre|Mickaël|M| Chemat|Farid|F|

extraction
p-menthane
hydrogenation
Soxhlet
Citrus by-products
Dean–Stark
green solvent


Mouse models of glioma.

Abstract: Gliomas are the most common primary tumour in the central nervous system in adults. The pathological hallmark of gliomas is their propensity for extensive infiltration into the surrounding brain parenchyma which results in tumour recurrence. Despite the use of optimal surgical removal and adjuvant therapies the most aggressive of these tumours, glioblastoma multiforme, has a poor patient prognosis, with median survival of less than 15 months. In this review, we discuss mouse glioma models that have been utilised to advance our basic knowledge of the processes involved in gliomagenesis and their use in the testing of novel therapies and treatment regimens in the preclinical setting.

Stylli|Stanley S|SS|
Luwor|Rodney B|RB|
Ware|Thomas M B|TM|
Tan|Fiona|F|
Kaye|Andrew H|AH|


Safety Profile of Anticancer and Immune-Modulating Biotech Drugs Used in a Real World Setting in Campania Region (Italy): BIO-Cam Observational Study.

Abstract: Objectives: To investigate the occurrence of adverse events (AEs) in naïve patients receiving biotech drugs. Design: A prospective observational study. Setting: Onco-hematology, Hepato-gastroenterology, Rheumatology, Dermatology, and Neurology Units in Campania Region (Italy). Participants: 775 patients (53.81% female) with mean age 56.0 (SD 15.2). The mean follow-up/patient was 3.48 (95% confidence interval 3.13-3.84). Main outcome measures: We collected all AEs associated to biotech drugs, including serious infections and malignancies. Serious AEs were defined according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, clinical safety data management: definitions and standards for expedited reporting E2A guideline. Results: The majority of the study population was enrolled in Onco-hematology and Rheumatology Units and the most common diagnosis were hematological malignancies, followed by rheumatoid arthritis, colorectal cancer, breast cancer, and psoriatic arthritis. The most commonly prescribed biotech drugs were rituximab, bevacizumab, infliximab, trastuzumab, adalimumab, and cetuximab. Out of 775 patients, 320 experienced at least one AE. Most of patients experienced AEs to cetuximab therapy, rituximab and trastuzumab. Comparing female and male population, our findings highlighted a statistically significant difference in terms of AEs for adalimumab (35.90% vs. 7.41%, p < 0.001) and etanercept (27.59% vs. 10.00%, p = 0.023). Considering all biotech drugs, we observed a peak for all AEs occurrence at follow-up 91-180 days category. Bevacizumab, brentuximab, rituximab, trastuzumab and cetuximab were more commonly associated to serious adverse events; most of these were possibly related to biotech drugs, according to causality assessment. Three cases of serious infections occurred. Conclusions: The results of our study demonstrated that the majority of AEs were not serious and expected. Few cases of serious infections occurred, while no case of malignancy did. Overall, the safety profile of biotech drugs used in our population was similar to those observed in pivotal trials. Notwithstanding the positive results of our study, some safety concerns still remain unresolved. In order to collect more effectiveness and safety data on biotech drugs, the collection and analysis of real world data should be endorsed as well as the management of post-authorization studies.

Scavone|Cristina|C|
Sportiello|Liberata|L|
Sullo|Maria G|MG|
Ferrajolo|Carmen|C|
Ruggiero|Rosanna|R|
Sessa|Maurizio|M|
Berrino|Pasquale M|PM|
di Mauro|Gabriella|G|
Berrino|Liberato|L|
Rossi|Francesco|F|
Rafaniello|Concetta|C|
Capuano|Annalisa|A|
|||

safety
biotech drugs
observational study
real world data
pharmacovigilance


Burnout is Associated With Emotional Intelligence but not Traditional Job Performance Measurements in Surgical Residents.

Abstract:
OBJECTIVE
To evaluate whether burnout was associated with emotional intelligence and job performance in surgical residents.

DESIGN
General surgery residents at a single institution were surveyed using the Maslach Burnout Inventory (MBI) and trait EI questionnaire (TEIQ-SF). Burnout was defined as scoring in 2 of the 3 following domains; Emotional Exhaustion (high), Depersonalization (high), and Personal Accomplishment (low). Job performance was evaluated using faculty evaluations of clinical competency-based surgical milestones and standardized test scores including the American Board of Surgery In-Training Exam (ABSITE) and the United States Medical Licensing Examination (USMLE) Step 3. USMLE Step 1 and USMLE Step 2, which were taken prior to residency training, were included to examine possible associations of burnout with USMLE examinations. Statistical comparison was made using Pearson correlation and simple linear regression adjusting for PGY level.

SETTING
This study was conducted at the University of Alabama at Birmingham (UAB) general surgery residency program.

PARTICIPANTS
All current and incoming general surgery residents at UAB were invited to participate in this study.

RESULTS
Forty residents participated in the survey (response rate 77%). Ten residents, evenly distributed from incoming residents to PGY-4, had burnout (25%). Mean global EI was lower in residents with burnout versus those without burnout (3.71 vs 3.9, p = 0.02). Of the 4 facets of EI, mean self-control values were lower in residents with burnout versus those without burnout (3.3 vs 4.06, p < 0.01). Each component of burnout was associated with global EI, with the strongest correlation being with personal accomplishment (r = 0.64; p < 0.01). Residents with burnout did not have significantly different mean scores for USMLE Step 1 (229 vs 237, p = 0.12), Step 2 (248 vs 251, p = 0.56), Step 3 (223 vs 222, p = 0.97), or ABSITE percentile (44.6 vs 58, p = 0.33) compared to residents without burnout. Personal accomplishment was associated with ABSITE percentile scores (r = 0.35; p = 0.049). None of the 16 surgical milestone scores were significantly associated with burnout.

CONCLUSIONS
Burnout is present in surgery residents and associated with emotional intelligence. There was no association of burnout with USMLE scores, ABSITE percentile, or surgical milestones. Traditional methods of assessing resident performance may not be capturing burnout and strategies to reduce burnout should consider targeting emotional intelligence.

Cofer|Kevin D|KD|
Hollis|Robert H|RH|
Goss|Lauren|L|
Morris|Melanie S|MS|
Porterfield|John R|JR|
Chu|Daniel I|DI|

D000046:Academic Medical Centers
D000328:Adult
D000407:Alabama
D002055:Burnout, Professional
D002983:Clinical Competence
D004503:Education, Medical, Graduate
D056348:Emotional Intelligence
D005260:Female
D013502:General Surgery
D006801:Humans
D007396:Internship and Residency
D016014:Linear Models
D008297:Male
D018570:Risk Assessment
D011795:Surveys and Questionnaires
D000066477:Work Performance

burnout
emotional intelligence
surgical residency
ABSITE
Interpersonal and Communication Skills
Medical Knowledge
Practice-Based Learning and Improvement
clinical competency


Effects of changes in occupational stress on the depressive symptoms of Korean workers in a large company: a longitudinal survey.

Abstract:
Background
Prospective studies on occupational stress and depression among Korean workers are scarce. This study aimed to investigate the causal relationship between changes in occupational stress and the presence of depression.

Methods
This study analyzed data from a survey conducted with workers in a large Korean company (2015-2016). Occupational stress was measured using the Korean Occupational Stress Scale, and depression was screened using the WHO-5 Well-being Index. The levels of occupational stress were grouped in quartiles based on subjects' occupational stress scores in 2015, and changes in occupational stress were measured using the score changes between the 2015 and 2016 surveys. Subjects were divided into four groups according to the presence or absence of depression in 2015 and 2016: a non-depressed group whose mental health did not change, a non-depressed group whose mental health deteriorated, a depressed group that continued to be depressed, and a depressed group whose symptoms of depression were alleviated. Logistic regression analysis was used to calculate the odds ratios (ORs) and confidence intervals (CIs) of the subjects' deterioration in mood or alleviation of depression by occupational stress levels and changes.

Results
The OR for developing depressive symptoms was 2.51 (95% CI 1.46-4.33) and 2.73 (95% CI 1.39-5.36) in the third and the fourth quartiles of occupational stress, respectively, compared to the first quartile. When the occupational stress score increased by 1 point, the OR for increasing depressive symptoms was 1.07 (95% CI 1.04-1.10). There was no significant difference in the alleviation of depressive symptoms between the groups by level of occupational stress. However, when the occupational stress score decreased by 1 point, the OR for alleviating depressive symptoms was 1.08 (95% CI 1.05-1.11).

Conclusion
The results showed that increased occupational stress increased the presence of depressive symptoms, and that reduced occupational stress suppressed the development of depressive symptoms. More attention should be paid to stress management among workers.

Jung|Jaehyuk|J|
Jeong|Inchul|I|
Lee|Kyung-Jong|KJ|
Won|Guyeon|G|
Park|Jae Bum|JB|0000-0002-5959-0477

Occupational stress
Depression
Korean workers
Korean occupational stress scale


Cis-acting elements in its 3' UTR mediate post-transcriptional regulation of KRAS.

Abstract: Multiple RNA-binding proteins and non-coding RNAs, such as microRNAs (miRNAs), are involved in post-transcriptional gene regulation through recognition motifs in the 3' untranslated region (UTR) of their target genes. The KRAS gene encodes a key signaling protein, and its messenger RNA (mRNA) contains an exceptionally long 3' UTR; this suggests that it may be subject to a highly complex set of regulatory processes. However, 3' UTR-dependent regulation of KRAS expression has not been explored in detail. Using extensive deletion and mutational analyses combined with luciferase reporter assays, we have identified inhibitory and stabilizing cis-acting regions within the KRAS 3' UTR that may interact with miRNAs and RNA-binding proteins, such as HuR. Particularly, we have identified an AU-rich 49-nt fragment in the KRAS 3' UTR that is required for KRAS 3' UTR reporter repression. This element contains a miR-185 complementary element, and we show that overexpression of miR-185 represses endogenous KRAS mRNA and protein in vitro. In addition, we have identified another 49-nt fragment that is required to promote KRAS 3' UTR reporter expression. These findings indicate that multiple cis-regulatory motifs in the 3' UTR of KRAS finely modulate its expression, and sequence alterations within a binding motif may disrupt the precise functions of trans-regulatory factors, potentially leading to aberrant KRAS expression.

Kim|Minlee|M|
Kogan|Nicole|N|
Slack|Frank J|FJ|

D015972:Gene Expression Regulation, Neoplastic

D012045:Regulatory Sequences, Nucleic Acid

post-transcriptional regulation
KRAS
microRNAs (miRNAs)
miR-185
3′ UTR


OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

Abstract: Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.

Kloppenburg|M|M|
Maheu|E|E|
Kraus|V B|VB|
Cicuttini|F|F|
Doherty|M|M|
Dreiser|R-L|RL|
Henrotin|Y|Y|
Jiang|G-L|GL|
Mandl|L|L|
Martel-Pelletier|J|J|
Nelson|A E|AE|
Neogi|T|T|
Pelletier|J-P|JP|
Punzi|L|L|
Ramonda|R|R|
Simon|L S|LS|
Wang|S|S|
|||

D002986:Clinical Trials as Topic
D019468:Disease Management
D050823:Hand Joints
D006801:Humans
D010003:Osteoarthritis
D017410:Practice Guidelines as Topic

Hand osteoarthritis
Clinical tools
Clinical trials guidelines
Methodology
Radiological assessment
Recommendations osteoarthritis


Detection of a negative correlation between prescription of Chinese herbal products containing coumestrol, genistein or daidzein and risk of subsequent endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan between 1998 and 2008: A population-based study.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Tamoxifen users sometimes seek complementary and alternative medicine advice for treatment of a variety of illness and co-administer with phytoestrogen-containing herbs, resulting in an increasing concern of its influence in subsequent endometrial cancer risk. Our study aims to determine the prevalence of Chinese herbal products containing coumestrol, genistein, or daidzein and their association with subsequent endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan.

METHODS
We selected all patients who were newly diagnosed with invasive breast cancer and received tamoxifen treatment between January 1, 1998, and December 31, 2008, from the National Health Insurance Research Database. Among the 26,656 tamoxifen-treated breast cancer survivors, we evaluated the usage, frequency of service, and prescription of Chinese herbal products containing coumestrol, genistein, or daidzein. The logistic regression method was employed to calculate the odds ratios for utilization of those herbal products. Cox proportional hazard regression was set to calculate the hazard ratios of endometrial cancer associated with such usage.

RESULTS
Of the patients surveyed, 36.2% (n=9652) of the tamoxifen-treated breast cancer survivors examined in the study had consumed Chinese herbal products containing coumestrol, genistein, or daidzein during the study period. Exposure to Ge Gen(Puerariae Radix) specifically was the most extensive. For it, the population consumed an average cumulative dose of above 180g. Compared to those who had never used Chinese herbal products, breast cancer survivors who had taken Chinese herbal products containing coumestrol, genistein, or daidzein concurrently with tamoxifen treatment did not have a higher hazard ratio for subsequent development of endometrial cancer.

CONCLUSION
Among those tamoxifen-treated female breast cancer survivors in Taiwan, consumption of Chinese herbal products containing coumestrol, genistein, or daidzein is negatively correlated with subsequent endometrial cancer risk.

Hu|Yi-Cheng|YC| Wu|Chien-Tung|CT| Lai|Jung-Nien|JN| Tsai|Yueh-Ting|YT|

National health insurance research database


The Intention-Outcome Asymmetry Effect.

Abstract: Knowledge of intention and outcome is integral to making judgments of responsibility, blame, and causality. Yet, little is known about the effect of conflicting intentions and outcomes on these judgments. In a series of four experiments, we combine good and bad intentions with positive and negative outcomes, presenting these through everyday moral scenarios. Our results demonstrate an asymmetry in responsibility, causality, and blame judgments for the two incongruent conditions: well-intentioned agents are regarded more morally and causally responsible for negative outcomes than ill-intentioned agents are held for positive outcomes. This novel effect of an intention-outcome asymmetry identifies an unexplored aspect of moral judgment and is partially explained by extra inferences that participants make about the actions of the moral agent.

Sarin|Arunima|A|
Lagnado|David A|DA|
Burgess|Paul W|PW|

intention
outcome
responsibility
causality
moral judgments
blame-praise


Competitive adsorption of Cd(II), Zn(II) and Ni(II) from their binary and ternary acidic systems using tourmaline.

Abstract: The adsorption of Cd(II), Zn(II) and Ni(II) from aqueous solutions in binary and ternary component systems by tourmaline was investigated. Kinetic data were accurately fitted to pseudo-second order and internal diffusion models, which indicated that the adsorption of heavy metals occurred on the interior surface of the sorbent and internal diffusion was the controlling mechanism during heavy metal ion adsorption but was not the only rate-controlling step. Additionally, tourmaline had a very good adsorption capacity for Cd(II), Zn(II) and Ni(II) in multi-component aqueous solutions at strongly acidic pH values (in contrast to industrial wastewater pH values). This good adsorption capacity is attributed to the fact that tourmaline can automatically adjust the pH values of acidic (except pH 2.0 and 3.0), neutral or alkaline aqueous solutions to 6.0. Adsorption isotherms and separation factors showed that tourmaline displays a high selectivity toward one metal in a two-component or a three-component system with an affinity order of Cd(II) > Zn(II) > Ni(II). Thermodynamic parameters indicated that heavy metal adsorption was feasible, spontaneous, and endothermic. Therefore, tourmaline should be explored as a material for removing pollutants from the strongly acidic wastewater.

Liu|Haibin|H| Wang|Cuiping|C| Liu|Jingting|J| Wang|Baolin|B| Sun|Hongwen|H|

Competitive adsorption
Tourmaline
Kinetic
Heavy metals
Adsorption model
Equilibrium


Clinical predictors of patient related delay in the VIENNA ST-elevation myocardial infarction network and impact on long-term mortality.

Abstract:
BACKGROUND
While contributors to system delay in ST-elevation myocardial infarction (STEMI) are well described, predictors of patient-related delays are less clear. The aim of this study was to identify predictors that cause delayed diagnosis of STEMI in a metropolitan system of care (VIENNA STEMI network) and to investigate a possible association with long-term mortality.

METHODS
The study population investigated consisted of 2366 patients treated for acute STEMI in the Vienna STEMI registry from 2003-2009. Multivariable regression modelling was performed for (a) onset of pain to first medical contact (FMC) as a categorical variable (pain-to-FMC⩽60 min versus >60 min: 'early presenters' versus 'late presenters'); and for (b) onset of pain-to-FMC (min) as a continuous variable.

RESULTS
After multivariable adjustment, female sex (odds ratio (OR) 1.348; 95% confidence interval (CI) 1.013-1.792; p=0.04) and diabetes mellitus (OR 1.355; 95% CI 1.001-1.835; p=0.05) were independently associated with late presentation in STEMI patients, whereas cardiogenic shock (OR 0.582; 95% CI 0.368-0.921; p=0.021) was a predictor of early diagnosis. When onset of pain-to-FMC was treated as a continuous variable, female sex ( p=0.003), anterior infarction ( p=0.004) and diabetes mellitus ( p=0.035) were independently associated with longer delay, while hyperlipidaemia ( p=0.002) and cardiogenic shock ( p=0.017) were strong predictors of short pain-to-FMC times. Three-year-all cause mortality was 9.6% and 11.3% ( p=0.289) for early and late presenters, respectively. After adjustment for clinical factors (sex, age, diabetes, current smoking, hypertension, hyperlipidaemia, cardiogenic shock and location of myocardial infarction) only a trend for increased risk of all-cause death was observed for longer pain-to-FMC times in a cox regression model (hazard ratio (HR) 1.012; 95% CI 0.999-1.025 for every 10 min of delay; p=0.061). Interestingly, early presentation within one hour of symptom onset was not associated with three-year mortality survival (HR 1.031; 95% CI 0.676-1.573; p=0.886).

CONCLUSION
In this all-comers study of STEMI patients in the VIENNA STEMI network, cardiogenic shock was the strongest predictor of short patient-related delays, whereas a history of diabetes and female sex were independent associated with late diagnosis in STEMI. After adjustment for clinical confounders, patient related delay did not significantly impact on long-term all-cause mortality.

Jäger|Bernhard|B|
Farhan|Serdar|S|
Rohla|Miklos|M|
Christ|Günter|G|
Podczeck-Schweighofer|Andrea|A|
Schreiber|Wolfgang|W|
Laggner|Anton N|AN|
Weidinger|Franz|F|
Stefenelli|Thomas|T|
Delle-Karth|Georg|G|
Kaff|Alfred|A|
Maurer|Gerald|G|
Huber|Kurt|K|
|||

D000072657:ST Elevation Myocardial Infarction

primary percutaneous coronary intervention


Ammonia inhibition of waste degradation in landfills - A possible consequence of leachate recirculation in arid climates.

Abstract: Ammonia inhibition of anaerobic waste degradation has been extensively investigated on a laboratory scale. It is hence well known that at ammonium levels above 2500 mg/l, methanogenic bacteria are inhibited, which leads to both reduced methane (CH4) production and increased organic pollution of the leachate. In the present paper, and for the first time, data on a full-scale landfill indicating ammonia inhibition of waste degradation is presented. The leachate of the landfill is characterized by extremely high concentrations of chloride (up to 70,000 mg/l) and ammonium-nitrogen (up to 20,000 mg/l). These high pollution levels are explained by the following facts: first, the landfill is located in an arid climate (annual precipitation of 200 mm), resulting in low fresh water infiltration; and second, leachate or concentrate resulting from reverse osmosis treatment at the site has been recirculated. The high ammonium levels obviously caused inhibitory effects on the anaerobic degradation, which resulted in chemical oxygen demand concentrations in the leachate of far above 300,000 mg/l. Furthermore, a comparatively low level of landfill gas (LFG) generation and a shift towards higher carbon dioxide and lower CH4 contents in the collected LFG was observed. Based on the gas compositional data, the overall reduction in CH4 generation was assessed to be 50%. In order to reduce organic leachate pollution and to enhance LFG production at the site investigated, fresh (rain) water infiltration should be enhanced and the recirculation of leachate or treatment residues derived thereof should be terminated.

inhibition
leachate recirculation
Ammonium
biodegradation
municipal solid waste landfill


Neural networks in bottom up 'experiential emotion regulation'.

Abstract: Emotion regulation influences how and when we experience emotion, impacting our sense of self and well being. While previous brain research on emotion regulation has focused on gray matter correlates of emotion regulation, this study represents a first exploratory study on white matter integrity of brain networks of 'emotional approach' as a bottom up experiential emotion regulation-strategy. Responding to the gap between cognitive and affective approaches of emotion regulation, pertaining to some of the daily emotional stressors, the present study investigates brain pathways of individual differences in 'emotional approach', or the tendency to affectively acknowledge, understand and express emotional experience (cf. [1]). Diffusion tensor magnetic resonance imaging (DTI-MRI) measures of fractional anisotropy (FA) and mean diffusion (MD) evaluated dispositional emotion regulation in a group of 21 women with a 'high emotional approach' (HEA) (N = 11) and a 'low emotional approach' (LEA) (N = 10). HEA exhibited more FA of the cingulum, supporting emotion processing and emotion regulation, whereas LEA correlated to a higher FA in the right corticospinal tracts, supporting automatic action tendencies and a higher FA in the superior longitudinal fasciculus (SLF), supporting cognitive control and monitoring of emotion. LEA also correlated with an increase in MD in the body (p. = 0.05) and in the splenium of the corpus callosum (CC). A higher FA in the inferior longitudinal fasciculus (IFL) may indicate higher visual- affective integration within emotion processing, whereas more MD in the body and splenium of the CC decreases interhemispheric integration of emotional information within emotion processing and emotion regulation.

Emotion
pathways
dispositional emotion regulation
DTI
white matter.


A pan-genomic approach to genome databases using maize as a model system.

Abstract: Research in the past decade has demonstrated that a single reference genome is not representative of a species' diversity. MaizeGDB introduces a pan-genomic approach to hosting genomic data, leveraging the large number of diverse maize genomes and their associated datasets to quickly and efficiently connect genomes, gene models, expression, epigenome, sequence variation, structural variation, transposable elements, and diversity data across genomes so that researchers can easily track the structural and functional differences of a locus and its orthologs across maize. We believe our framework is unique and provides a template for any genomic database poised to host large-scale pan-genomic data.

Woodhouse|Margaret R|MR|
Cannon|Ethalinda K|EK|
Portwood|John L|JL|
Harper|Lisa C|LC|
Gardiner|Jack M|JM|
Schaeffer|Mary L|ML|
Andorf|Carson M|CM|

D000068598:Data Accuracy
D003625:Data Collection
D019992:Databases as Topic
D014644:Genetic Variation
D018745:Genome, Plant
D023281:Genomics
D003313:Zea mays

Pan-genome
Genomes
Databases
Maize
Browsers
NAM founders
Nomenclature


Integration of the Nurse Practitioner Into Your Child Abuse Team.

Abstract: Child maltreatment is a leading cause of childhood morbidity in the United States, often leading to lifelong adverse health consequences. Currently, there is a nationwide shortage of child abuse pediatricians (CAPs), resulting in many unfilled child abuse positions throughout the United States. In addition, the number of future CAPs currently in fellowship training will meet neither the current need for CAPs nor provide replacements for the senior CAPs who will be retiring in the next 5 to 10 years. Although it is recognized that pediatric nurse practitioners (PNPs) play an important role in the care of maltreated children, there are few available data on the impact of the PNP as an integral member of the child abuse team. Using the outcomes logic model, we present a systematic process through which the PNP can be effectively integrated into a medical child abuse team. The outcomes from this process show that the addition of PNPs to the child abuse team not only provides immediate relief to the nationwide CAP shortage but also significantly augments the diverse clinical skills and expertise available to the child abuse team.

Herold|Beth|B|
St Claire|Karen|K|
Snider|Scott|S|
Narayan|Aditee|A|

D002648:Child
D002649:Child Abuse
D006801:Humans
D009722:Nurse Practitioners
D010348:Patient Care Team
D014481:United States

nurse practitioner
child maltreatment
Child abuse pediatrician
outcomes logic model


Estimating the quantile medical cost under time-dependent covariates and right censored time-to-event variable based on a state process.

Abstract: Estimating the medical costs from disease diagnosis to a terminal event is of immense interest to researchers. However, most of existing literature on such research focused on the estimation of cumulative mean function (CMF) for history process. In this paper, the combined scheme of both inverse probability of censoring weighting (IPCW) technique and longitudinal quantile regression model is used to develop a novel procedure to the estimation of cumulative quantile function (CQF) based on history process with time-dependent covariates and right censored time-to-event variable. The consistency of proposed estimator is derived. The extensive simulation study is conducted to investigate the performance of the estimator given in this paper. A medical cost data from a multicenter automatic defibrillator implantation trial (MADIT) is analyzed to illustrate the application of developed method.

D003198:Computer Simulation
D015233:Models, Statistical
D011336:Probability
D012107:Research Design


The effect of age on in-vivo spine stiffness, postures and discomfort responses during prolonged sitting exposures.

Abstract: Many industrialised working populations are ageing and prolonged sitting exposures are prevalent across occupational sectors. The purpose of this work was to determine the effect of age and sex on passive spine stiffness, postures and discomfort in response to seated work. A total of 34 participants were recruited, with 17 older adults with an average age of (standard deviation) 63.7 (±3.9) years and 17 younger adults aged 23.8 (±5.0) years. Participants were asked to sit continuously for 90 min while typing. Baseline passive spine stiffness was higher in older adults at 40% flexion compared to younger adults (p = .0233). Older adults sat in less normalised flexion, at 33.4% (±16.4) compared to 60.9% (±20.2) in the younger group (p = .0003). Discomfort was higher among older adults in the neck, right shoulder and middle back regions (p < .0086). An understanding of age-specific responses to workplace exposures is essential to determine whether age-specific interventions are warranted.   Practitioner summary: Older adults had higher passive spine stiffness and sat with less flexion during prolonged sitting. Discomfort was higher among older adults and occurred earlier in the simulation compared to younger participants, indicating that interventions, such as walking breaks may need to be implemented earlier during sitting for aged workers.

Aging
spine stiffness
prolonged sitting
ergonomics
low back pain


Molecular profiles of oxyphilic and chief cell parathyroid adenoma.

Abstract:
CONTEXT
Parathyroid adenomas may be composed of chief cells (conventional or water-clear), oxyphilic cells or a mixture of both cells. The molecular background is rarely studied.

OBJECTIVE
To molecularly characterize parathyroid adenomas of different cell type composition.

DESIGN
Chief and oxyphilic cell adenomas were compared in a cohort of 664 sporadic cases. Extensive analyses of parathyroid tissues were performed in subgroup. Gene expressions of known parathyroid-related genes were quantified by qRT-PCR. Protein expression profiles determined by liquid chromatography - tandem mass spectrometry (LC-MS/MS) were compared between each type of parathyroid adenomas. Selected proteins were analysed by Western blot and immunohistochemistry.

RESULTS
Patients with oxyphilic cell adenoma were found to be older at the time of operation than chief cell adenoma cases but did not differ in gender, serum calcium or tumor weight. The gene expression of CASR, VDR, FGFR1, CYP27B1, CYP24A1, PTHLH, GCM2, NDUFA13, CDKN1B, MEN1 and CNND1 did not differ between the groups. VDR protein levels were weaker in oxyphilic adenomas. The proteomic studies identified a set of novel dysregulated proteins of interest such as nuclear receptor subfamily 2 group C member 2 (TR4), LIM domain only protein 3 (LMO3) and calcium-binding protein B (S100B). LMO3 and S100B showed higher expression in oxyphilic adenoma and may be involve in parathyroid tumorgenesis through the p53 pathway. TR4 showed different subcellular localisation between adenoma and normal rim.

CONCLUSION
Chief and oxyphilic cell parathyroid adenomas have partly overlapping but also distinct molecular profiles. The calmodulin-eEF2K, TR4 and p53 pathways may be involved in the tumor development.

Lu|Ming|M| Kjellin|Hanna|H| Fotouhi|Omid|O| Lee|Linkiat|L| Nilsson|Inga-Lena|IL| Haglund|Felix|F| Höög|Anders|A| Lehtiö|Janne|J| Larsson|Catharina|C|

parathyroid adenoma
LC-MS/MS
Hyperparathyroidism
Proteomic analysis


Validity and reliability of SISCO inventory of academic stress among health students in Chile.

Abstract:
OBJECTIVE
To evaluate the factorial structure and internal consistency of SISCO inventory of academic stress in medical students..

METHODS
The cross-sectional study was conducted at the School of Medicine, University of Concepcion, Chile, in 2014, and comprised second and third year students.Exploratory factor analysis was carried out to determine the reliability of each of the dimensions of SISCO inventory. Descriptive and correlational analyses were also conducted.

RESULTS
Of the 155 students, 121(78.1%)were female. The overall mean age was 20.5+/- 1.55 years (range: 18.9-32.2 years). Of the total, 61(39.4%) students were in the nursing programme, 10(6.5%) in speech therapy, 16(10.3%) in kinesiology, 10(6.5%) in medicine, 20(12.9%) in midwifery and 38(24.4%) in medical technology.For stressor, somatisation and coping dimensions, a factor was identified, with Cronbach's alpha values of 0.76, 0.86 and 0.52, respectively. Correlation could only be established between the first two dimensions.

CONCLUSIONS
Stressors and somatisation dimensions of the SISCO inventory of academic stress were found to be validity and reliabile.

Castillo|Alejandra Guzman|AG|
Saez|Katia|K|
Perez|Cristhian|C|
Castillo Navarrete|Juan Luis|JL|

Academic stress, SISCO inventory, Psychometrics, Somatisation, Coping.


Nitroglycerin-Citrate-Ethanol Catheter Lock Solution Is Highly Effective for In Vitro Eradication of Candida auris Biofilm.

Abstract: Candida auris poses emerging risks for causing severe central line-associated bloodstream infections. We tested in vitro the ability of antifungal lock solutions to rapidly eradicate C. auris biofilms. Liposomal amphotericin B, amphotericin B deoxycholate, fluconazole, voriconazole, micafungin, caspofungin, and anidulafungin failed to completely eradicate all 10 tested C. auris biofilms. Conversely, nitroglycerin-citrate-ethanol (NiCE) catheter lock solution completely eradicated all replicates for all of C. auris biofilms tested.

nitroglycerin-citrate-ethanol
catheter lock solution
Candida auris
biofilm


Muscle Stem Cells and Aging.

Abstract: Satellite cells (SCs) are a population of muscle-resident stem cells that are essential for efficient tissue repair. SCs reside in a relatively quiescent state during normal tissue turnover, but are activated in response to injury through the microenvironment and cell-intrinsic signals. During aging, SC dysfunction is a major contributor to the decline in regenerative potential of muscle tissue. Recent studies have demonstrated that both cell-intrinsic and cell-extrinsic factors are deregulated during aging. Interventions that reverse age-associated changes in SCs or the niche have shown to partially rejuvenate the regenerative capacity of aged muscle SCs. In this review, we discuss recent advances in SC biology as it pertains to the deleterious effects of aging. A better understanding of how age-dependent changes in the SC and its environment niche impact muscle regeneration could lead to interventions to ameliorate the effects of aging in humans.

D032496:Satellite Cells, Skeletal Muscle

Muscle
Aging
Satellite cell
Niche
Regeneration


Vagus Nerve Stimulation: A Potential Adjunct Therapy for COVID-19.

Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through excessive end organ inflammation. Despite improved understanding of the pathophysiology, management, and the great efforts worldwide to produce effective drugs, death rates of COVID-19 patients remain unacceptably high, and effective treatment is unfortunately lacking. Pharmacological strategies aimed at modulating inflammation in COVID-19 are being evaluated worldwide. Several drug therapies targeting this excessive inflammation, such as tocilizumab, an interleukin (IL)-6 inhibitor, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, and intravenous immunoglobulin have been identified as potentially useful and reliable approaches to counteract the cytokine storm. However, little attention is currently paid for non-drug therapeutic strategies targeting inflammatory and immunological processes that may be useful for reducing COVID-19-induced complications and improving patient outcome. Vagus nerve stimulation attenuates inflammation both in experimental models and preliminary data in human. Modulating the activity of cholinergic anti-inflammatory pathways (CAPs) described by the group of KJ Tracey has indeed become an important target of therapeutic research strategies for inflammatory diseases and sepsis. Non-invasive transcutaneous vagal nerve stimulation (t-VNS), as a non-pharmacological adjuvant, may help reduce the burden of COVID-19 and deserve to be investigated. VNS as an adjunct therapy in COVID-19 patients should be investigated in clinical trials. Two clinical trials on this topic are currently underway (NCT04382391 and NCT04368156). The results of these trials will be informative, but additional larger studies are needed.

Azabou|Eric|E| Bao|Guillaume|G| Bounab|Rania|R| Heming|Nicholas|N| Annane|Djillali|D|

vagus nerve stimulation
COVID-19
inflammation
cytokine storm
outcome
neuromodulation
non-drug therapy


Dermatoglyphics and Their Relationship With Blood Group: An Exploration.

Abstract:
Introduction
Dermatoglyphics means the study of skin markings or patterns on fingers, hands, and feet. Dermatoglyphics is a heritable trait that is considered as a usual phenotype in criminology. Dermatoglyphics acts as a scientific method for identification of an individual and it is constant till demise.

Objectives
This study was conducted to correlate the dermatoglyphics and blood grouping of 150 dental students.

Materials and Methods
A pro forma was prepared on a durable white paper, rubber stamp ink pads were used for smearing each finger, imprints were taken, and each pattern of fingerprint was observed by powerful hand lens and recorded. Note was made of the sex, age, and ABO and Rh blood group for studying the relationship between types of fingerprints and relation to ABO and Rh blood type. Fingerprint was taken using the INK method as illustrated by Cummins and Mildo. Fingerprint patterns (loops, whorls, and arches) and blood data were collected.

Results
In this study, 38% of subjects belonged to O blood group followed by A, B, and AB, and 96.77% of subjects were Rh-positive and 3.23% were Rh-negative.

Conclusions
This study shows the association between distribution of dermatoglyphics, ABO, Rh blood group, and gender.

Manikandan|Saranya|S|
Devishamani|Leka|L|
Vijayakumar|Saranya|S|
Palanisamy|Gowri Shankar|GS|
Ponnusamy|Priyadharsana|P|
Lalpettai Jayakar|Sai Lakshmi|SL|

dermatoglyphics
Rh blood group
loops
arches
ABO blood group


Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators.

Abstract: To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum-MT, MT fusion, autophagosome-lysosome fusion, and autophagosome/endosome-lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome-lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)-MT contact, ER- plasma membrane (PM) junction, autophagosome/endosome-lysosome fusion, sarcoplasmic reticulum-MT, autophagosome-endosome/lysosome fusion, and ER-Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4+CD25- T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers.

Liu|Ming|M|
Wu|Na|N|
Xu|Keman|K|
Saaoud|Fatma|F|
Vasilopoulos|Eleni|E|
Shao|Ying|Y|
Zhang|Ruijing|R|
Wang|Jirong|J|
Shen|Haitao|H|
Yang|William Y|WY|
Lu|Yifan|Y|
Sun|Yu|Y|
Drummer|Charles|C|
Liu|Lu|L|
Li|Li|L|
Hu|Wenhui|W|
Yu|Jun|J|
Praticò|Domenico|D|
Sun|Jianxin|J|
Jiang|Xiaohua|X|
Wang|Hong|H|
Yang|Xiaofeng|X|

organelle crosstalk
inflammation
Treg
cancers and tumors
endothelial cell activation
viral infections


Simultaneous determination of leucine, isoleucine and valine in Beagle dog plasma by HPLC-MS/MS and its application to a pharmacokinetic study.

Abstract: Leucine (Leu), isoleucine (Ile) and valine (Val) are three branched-chain amino acids (BCAAs), which have been widely used as dietary supplements for professional athletes and patients with liver failure or catabolic diseases. To date, no pharmacokinetic studies of BCAAs in vivo useful for the assessment of clinical effect following daily intake has been reported. Thus in this study, an HPLC-MS/MS method for simultaneous determination of Leu, Ile and Val in Beagle dog plasma using homoarginine as the internal standard was developed and validated in terms of specificity, linearity, precision, accuracy, and stability. This assay method was then applied to a pharmacokinetic study of BCAAs in dogs following oral administration of 0.25 g/kg and 0.50 g/kg BCAAs. The HPLC-MS/MS method was found to be sensitive and reproducible for quantification of BCAAs in dog plasma and successfully applied to the pharmacokinetic study. All these BCAAs were well absorbed with a substantial increase in the plasma concentration after a baseline modification. No statistical significance was identified in different gender group and no drug accumulation was observed following multiple doses.

Wang|Ting|T| Xie|Huiru|H| Chen|Xu|X| Jiang|Xuehua|X| Wang|Ling|L|

D002851:Chromatography, High Pressure Liquid

Beagle dog plasma
Pharmacokinetics
BCAAs
Gender
HPLC–MS/MS


Absent pedicles in campomelic dysplasia.

Abstract:
OBJECTIVES
The objective of the present study is to report a case of campomelic dysplasia illustrating the absence of cervical and thoracic pedicles. This report reiterates the importance of this clinical peculiarity in the setting of spine instrumentation.

MATERIALS AND METHODS
A 10-year-old female patient with campomelic dysplasia presented with progressive kyphoscoliosis and signs of neural compromise. Imaging studies confirmed thoracic level stenosis and demonstrated absence of multiple pedicles in cervical and thoracic spine. The patient underwent decompression and instrumentation/fusion for her spinal deformity.

RESULTS
The patient was instrumented between C2 and L4 with pedicle screws and sublaminar cables. However, pedicle fixation was not possible for the lower cervical and upper-mid thoracic spine. Also, floating posterior elements precluded the use of laminar fixation in the lower cervical spine. Cervicothoracic lumbosacral orthosis (CTLSO) was used for external immobilization to supplement the tenuous fixation in the cervicothoracic area. The patient improved neurologically with no signs of implant failure at the 2-year follow-up.

CONCLUSIONS
Absence of pedicles and floating posterior elements present a challenge during spine surgery in campomelic dysplasia. Surgeons should prepare for alternative fixation methods and external immobilization when planning on spinal instrumentation in affected patients.

LEVEL OF EVIDENCE
Level IV Case Report.

McDowell|Michael M|MM|
Dede|Ozgur|O|
Bosch|Patrick|P|
Tyler-Kabara|Elizabeth C|EC|

Campomelic
Kyphoscoliosis
Camptomelic
Dysplastic
Pediatric
Skeletal dyplasia


Exergy Analysis of a Direct Contact Membrane Distillation (DCMD) System Based on Computational Fluid Dynamics (CFD).

Abstract: Understanding the energy efficiency of direct contact membrane distillation (DCMD) is important for the widespread application and practical implementation of the process. This study analyzed the available energy, known as exergy, in a DCMD system using computational fluid dynamics (CFD). A CFD model was developed to investigate the hydrodynamic and thermal conditions in a DCMD module. After the CFD model was verified, it was used to calculate the temperature polarization coefficient (TPC) and exergy destruction magnitudes under various operating conditions. The results revealed that slight decreases and increases in the TPC occurred with distance from the inlet in the module. The TPC was found to increase as the feed temperature was reduced and the feed and permeate flow rates were increased. The exergy destruction phenomenon was more significant under higher feed temperatures and higher flux conditions. Although the most significant exergy destruction in the permeate occurred near the feed inlet, the effect became less influential closer to the feed outlet. An analysis of exergy flows revealed that the efficiency loss in the permeate side corresponded to 32.9-45.3% of total exergy destruction.

Choi|Jihyeok|J|0000-0002-0798-6891 Choi|Yongjun|Y| Lee|Juyoung|J| Kim|Yusik|Y| Lee|Sangho|S|


The effects of binge alcohol exposure on tooth movement and associated root resorption in rats.

Abstract:
BACKGROUND
Considering the increasing prevalence of alcohol use and the growing number of orthodontic patients, some orthodontic patients might engage in binge drinking during treatment. Nevertheless, little is known about the effect of alcohol use on orthodontic treatment.

METHODS
Male Wistar rats were divided into ethanol and control groups (n = 32). The rats received a single daily intraperitoneal injection of 20% (vol/vol) ethanol/saline solution at a dose of 3 g/kg of ethanol or saline for three consecutive days, and no injection was given during the remaining four days each week. All rats received orthodontic appliances to draw the maxillary first molar mesially. The rats were sacrificed at days 14 and 28, respectively. The amount of tooth movement was measured. Root resorption area was evaluated by scanning electron microscope. Hematoxylin and eosin (H&E) staining and tartrate-resistant acid phosphatase (TRAP) staining were conducted. Immunohistochemistry staining was performed to evaluate the expressions of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and inducible nitric oxide synthase (iNOS).

RESULTS
There were no significant differences in tooth movement and root resorption between ethanol and control groups. The number of TRAP-positive cells was significantly higher in the ethanol group. The expression of RANKL was statistically increased in the ethanol group. In contrast, the expression of OPG was remarkably decreased in rats injected with ethanol. Moreover, the iNOS level was significantly up-regulated in the ethanol group.

CONCLUSION
The tooth movement and root resorption in rats were not affected by binge alcohol exposure.

Yang|Fan|F|
Wang|Xu Xia|XX|
Li|Jing|J|
Nie|Fu Jiao|FJ|
Cui|Qun|Q|
Fu|Ya Jing|YJ|
Zhang|Jun|J|

tooth movement
root resorption
binge drinking
scanning electron microscope


Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors.

Abstract: Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, less is publicly released regarding allergies to beta-lactamase inhibitors. This review presents and evaluates the data regarding allergic reactions with beta-lactamase inhibitors. Clavulanate, sulbactam, and tazobactam are beta-lactam-based beta-lactamase inhibitors that are combined with several penicillins or cephalosporins in order to preserve antimicrobial activity in the presence of beta-lactamases. Avibactam, relebactam, and vaborbactam are non-beta-lactam beta-lactamase inhibitors that are combined with cephalosporins or carbapenems in order to expand the antimicrobial activity against broader-spectrum beta-lactamases. Case reports document hypersensitivity reactions to clavulanate, sulbactam, and tazobactam, but not to avibactam, relebactam, or vaborbactam. Based on these reports and considering the chemical structures, cross-allergenicity with beta-lactams is likely with sulbactam and tazobactam. Considering the slightly altered beta-lactam structure, cross-allergenicity is less likely with clavulanate, but still possible. It appears that cross-allergenicity between beta-lactam antimicrobials and the newer, non-beta-lactam beta-lactamase inhibitors is unlikely. It is important for clinicians to perform allergy testing to both the beta-lactam and the beta-lactamase inhibitor in order to confirm the specific allergy and reaction type.

beta-lactam allergy
clavulanate
sulbactam
tazobactam
avibactam
relebactam
vaborbactam
hypersensitivity
cross reactivity


Formation of pure nanoparticles with solvent-fractionated lignin polymers and evaluation of their biocompatibility.

Abstract: This study aimed to determine the effects of lignin characteristics (mainly molecular weight, functional groups, and internal linkages) on nanoparticle formation. First, five different lignin fractions (Mw 1460-12,900) were obtained from commercial kraft lignin (KL) by sequential solvent extraction. Functional groups and internal linkages were determined in lignin fractions, each fraction consisting of different levels and ratios. Second, spherical lignin nanoparticles (i.d. 193-1039 nm) were synthesized by nanoprecipitation at different pre-dialysis concentrations (1, 2, 4, and 6 mg mL-1 THF) with the different fractions (F1, F2, F3, F4, and F5). The study revealed that larger particles consisted of lignin fractions of lower molecular weight and higher phenolic group content (KL-F1 and F2), while smaller but non-uniform particles were produced from fractions of higher molecular weight and lower phenolic group content (KLF4 and F5). Every zeta potential value of the particle exceeded -35 mV. The nanoparticles from raw kraft lignin exhibited no significant cytotoxicity, hemotoxicity, and hypersensitivity. This study revealed that molecular weight and hydroxyl group content in the lignin highly correlated with nanoparticle properties. The present kraft lignin nanoparticles have potential for use in various polymer-based nanotechnology.

Lee|Jae Hoon|JH|
Kim|Keoho|K|
Jin|Xuanjun|X|
Kim|Tae Min|TM|
Choi|In-Gyu|IG|
Choi|Joon Weon|JW|

Nanoparticle Lignin Biocompatibility Fractionation Nanoprecipitation