Late presentation increases risk and costs of non-infectious comorbidities in people with HIV: an Italian cost impact study.

Abstract:
BACKGROUND
Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells/mm. The objective of our study was to assess the prevalence of non-infectious comorbidities (NICM) and multimorbidity among HIV-positive individuals with and without a history of LP (HIV + LP and HIV + EP, respectively), and compare them to matched HIV-negative control participants from a community-based cohort. The secondary objective was to provide estimates and determinants of direct cost of medical care in HIV patients.

METHODS
We performed a matched cohort study including HIV + LP and HIV + EP among people attending the Modena HIV Metabolic Clinic (MHMC) in 2014. HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ≥2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and multimorbidity.

RESULTS
We analyzed 452 HIV + LP and 73 HIV + EP participants in comparison to 1575 HIV-negative controls. The mean age was 46 ± 9 years, 27.5% were women. Prevalence of NICM and multimorbidity were fourfold higher in the HIV + LP compared to the general population (p < 0.001), while HIV + EP present an intermediate risk. LP was associated with increased total costs in all age strata, but appear particularly relevant in patients above 50 years of age, after adjusting for age, multimorbidity, and antiretroviral costs.

CONCLUSIONS
LP with HIV infection is still very frequent in Italy, is associated with higher prevalence of NICM and multimorbidity, and contributes to higher total care costs. Encouraging early testing and access to care is still urgently needed.

Guaraldi|Giovanni|G|
Zona|Stefano|S|
Menozzi|Marianna|M|
Brothers|Thomas D|TD|
Carli|Federica|F|
Stentarelli|Chiara|C|
Dolci|Giovanni|G|
Santoro|Antonella|A|
Da Silva|Ana Rita Domingues|AR|
Rossi|Elisa|E|
Falutz|Julian|J|
Mussini|Cristina|C|

Late presentation
Costs
Comorbidities
HIV


Morbidity after laparoscopic and open rectal cancer surgery: a comparative analysis of morbidity in octogenarians and younger patients.

Abstract:
AIM
Although the oncological adequacy of laparoscopic rectal resection (LR) appears equivalent to open resection (OR), its benefit is controversial in the elderly. The aim of this study was to investigate the influence of LR on morbidity and mortality in octogenarians.

METHOD
This was a retrospective analysis of all patients who underwent rectal surgery for cancer between 2003 and 2013 in a teaching hospital. The primary aim of the study was to assess the influence of surgical approach on mortality and morbidity of rectal resection in patients ≥ 80 years old. Regression analysis was performed to control the effect of covariables on the clinical outcome.

RESULTS
Of 408 patients 203 were in the LR group and 205 in the OR group including 303 (74.3%) less than 80 years and 105 (25.7%) over 80 years. The mortality was lower in the LR group compared with the OR group for patients under 80 years (0% vs 4.6%; P = 0.049) and no different in the over 80 group (11.5% vs 9.4%; P = 0.859). In younger patients, the OR group showed longer hospital stay (9 vs 7 days; P < 0.001) and more complications (44.1% vs 29.8%; P = 0.042). Medical complications were more frequent in LR group than OR group octogenarians (40.4% vs 20.8%; P = 0.009) as well as grade C anastomotic leakage (13.8 vs 10.7; P = 0.041).

CONCLUSION
LR for rectal cancer showed clinical advantages in patients under 80 years and was as safe as OR in patients over 80 years, although the advantages of laparoscopic surgery were lost in the elderly group due to a higher rate of medical complications. OR may be an option in elderly patients with important comorbidities.

D013505:Digestive System Surgical Procedures

Rectal cancer surgery
morbidity and mortality
elderly patients
laparoscopic versus open rectal surgery


Urokinase-type plasminogen activator protects human umbilical vein endothelial cells from apoptosis in sepsis.

Abstract: The aim of this study was to investigate the effect of urokinase-type plasminogen activator (uPA) on cell viability, apoptosis, and inflammatory cytokine levels in septic human umbilical vein endothelial cells (HUVECs). Lipopolysaccharides (LPS) were added to construct septic HUVECs, then the septic HUVECs were treated by uPA, and cell viability, apoptosis, TNF-α, IL-6, GMCSF and uPAR levels were evaluated by CCK-8, AV/PI, qPCR, western blot and ELISA, respectively. Subsequently, uPA shRNA was transferred into septic HUVECs, and the cells viability, cell apoptosis and the expressions of TNF-α, IL-6, GMCSF, as well as uPAR were assessed by the same methods. uPA promoted viability while reducingapoptosis in septic HUVECs. However, uPA had no effect on the regulation of TNF-α or IL-6 expression in septic HUVECs. In addition, uPA elevated the expressions of GMCSF and uPAR in septic HUVECs. After the transfection of uPA shRNA, cell viability was decreased, apoptosis was enhanced, and GMCSF and uPAR expressions were reduced, while TNF-α or IL-6 expression did not vary in septic HUVECs. In conclusion, uPA promotes cell viability, represses apoptosis,and has no effect on regulating inflammatory cytokines in septic HUVECs.

Long|Ding|D| Yang|Junhui|J| Wu|Xiaoling|X| Gui|Yun|Y| Yu|Li|L|

Urokinase-type plasminogen activator
apoptosis
cell viability
inflammatory cytokine
septic HUVECs


Exploring the Selective Demethylation of Aryl Methyl Ethers with a Pseudomonas Rieske Monooxygenase.

Abstract: Biocatalytic dealkylation of aryl methyl ethers is an attractive reaction for valorization of lignin components, as well as for deprotection of hydroxy functionalities in synthetic chemistry. We explored the demethylation of various aryl methyl ethers by using an oxidative demethylase from Pseudomonas sp. HR199. The Rieske monooxygenase VanA and its partner electron transfer protein VanB were recombinantly coexpressed in Escherichia coli and they constituted at least 25 % of the total protein content. Enzymatic transformations showed that VanB accepts NADH and NADPH as electron donors. The VanA-VanB system demethylates a number of aromatic substrates, the presence of a carboxylic acid moiety is essential, and the catalysis occurs selectively at the meta position to this carboxylic acid in the aromatic ring. The reaction is inhibited by the by-product formaldehyde. Therefore, we tested three different cascade/tandem reactions for cofactor regeneration and formaldehyde elimination; in particular, conversion was improved by addition of formaldehyde dehydrogenase and formate dehydrogenase. Finally, the biocatalyst was applied for the preparation of protocatechuic acid from vanillic acid, giving a 77 % yield of the desired product. The described reaction may find application in the conversion of lignin components into diverse hydroxyaromatic building blocks and generally offers potential for new, mild methods for efficient unmasking of phenols.

Rieske monooxygenases
O-demethylation
biocatalysis
methoxy groups
protein expression


The mechanism of activation of monomeric B-Raf V600E.

Abstract: Oncogenic mutations in the serine/threonine kinase B-Raf, particularly the V600E mutation, are frequent in cancer, making it a major drug target. Although much is known about B-Raf's active and inactive states, questions remain about the mechanism by which the protein changes between these two states. Here, we utilize molecular dynamics to investigate both wild-type and V600E B-Raf to gain mechanistic insights into the impact of the Val to Glu mutation. The results show that the wild-type and mutant follow similar activation pathways involving an extension of the activation loop and an inward motion of the αC-helix. The V600E mutation, however, destabilizes the inactive state by disrupting hydrophobic interactions present in the wild-type structure while the active state is stabilized through the formation of a salt bridge between Glu600 and Lys507. Additionally, when the activation loop is extended, the αC-helix is able to move between an inward and outward orientation as long as the DFG motif adopts a specific orientation. In that orientation Phe595 rotates away from the αC-helix, allowing the formation of a salt bridge between Lys483 and Glu501. These mechanistic insights have implications for the development of new Raf inhibitors.

Maloney|Ryan C|RC|
Zhang|Mingzhen|M|
Jang|Hyunbum|H|
Nussinov|Ruth|R|

B-Raf
Oncogene
Kinase
Activation mechanism
Protein structure


Teachers' teleworking job satisfaction during the COVID-19 pandemic in Europe.

Abstract: This research takes insights from the job demand resource model to examine the teleworking job satisfaction of teachers for the period of COVID-19 pandemic. This study evidenced that teachers' satisfaction with teleworking has been reduced as a consequence of the job demand increase. In contrast, access to adequate resources has allowed them to confront the challenges of teleworking, thus increasing their job satisfaction. The adverse effect of job demands on teleworking job satisfaction is buffered by job resources as teachers' required extra means to confront unexpected and increased job demands. The technological gap between younger and older teachers was uncovered.

Teleworking
Job satisfaction
COVID-19
Job demands
Job resources
JD-R model


Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque.

Abstract: Evolution of plaque that is prone to rupture is characterized by inflammation and physical changes. Accumulation of low-density lipoprotein in the sub-intima provides esterified cholesterol (ESC) to macrophages and smooth muscle cells that convert it into free cholesterol (FRC) by cholesteryl ester hydrolases (CEHs). Membrane-bound cholesterol carriers transport FRC to high-density lipoprotein (HDL). Impaired HDL transport function and altered composition can lead to extracellular accumulation of FRC, whereas impaired membrane carrier activity can lead to intracellular FRC accumulation. Saturation of FRC can result in cholesterol crystallization with cell death and intimal injury. Disequilibrium between ESC and FRC can impact foam cell and cholesterol crystal (CC) formation. Cholesterol crystals initiate inflammation via NLRP3 inflammasome leading to interleukin-1β (IL-1β) production inducing C-reactive protein. Eventually, crystals growing from within the plaque and associated inflammation destabilize the plaque. Thus, inhibition of inflammation by antagonists to IL-1β or agents that dissolve or prevent CC formation may stabilize vulnerable plaques.

Janoudi|Abed|A|
Shamoun|Fadi E|FE|
Kalavakunta|Jagadeesh K|JK|
Abela|George S|GS|

Cholesterol crystals
IL-1β
Vulnerable plaque
Atherosclerosis
Vascular inflammation
Vulnerable patient


Assessment of acquired capability for suicide in clinical practice.

Abstract: The Interpersonal Psychological Theory of suicide proposes that the interaction between Thwarted Belongingness, Perceived Burdensomeness, and Acquired Capability for Suicide (ACS) predicts proximal risk of death by suicide. Instruments to assess all three constructs are available. However, research on the validity of one of them, the acquired capability for suicide scale (ACSS), has been limited, especially in terms of its clinical relevance. This study aimed to explore the utility of the different versions of the ACSS in clinical assessment. Three versions of the scale were investigated, the full 20-item version, a 7-item version and a single item version representing self-perceived capability for suicide. In a sample of patients recruited from a clinic specialising in the treatment of suicidality and in a community sample, all versions of the ACSS were found to show reasonable levels of reliability and to correlate as expected with reports of suicidal ideation, self-harm, and attempted suicide. The item assessing self-perceived acquired capacity for suicide showed highest correlations with all levels of suicidal behaviour. However, no version of the ACSS on its own showed a capacity to indicate suicide attempts in the combined sample. It is concluded that the versions of the scale have construct validity, but their clinical utility is limited. An assessment using a single item on self-perceived ACS outperforms the full and shortened versions of ACSS in clinical settings and can be recommended with caution for clinicians interested in assessing this characteristic.

Rimkeviciene|Jurgita|J|
Hawgood|Jacinta|J|
O'Gorman|John|J|
De Leo|Diego|D|

D011569:Psychiatric Status Rating Scales

interpersonal psychological theory of suicide


Non-lens-based surgical techniques for presbyopia correction.

Abstract:
INTRODUCTION
Presbyopia is the most prevalent refractive error. With a progressive aging population, its surgical correction is an important challenge for the ophthalmology community, as well as the millions of patients who suffer from it, and who are increasingly demanding alternatives to its correction with glasses or contact lenses.

MATERIAL AND METHODS
A review is presented with a synthesised discussion on the pathophysiological theories of presbyopia and an updated and analytical description of the non-lens involvement surgical techniques used to treat presbyopia.

RESULTS
Corneal procedures include various types of corneal implants and photo-ablative techniques that generate a multifocal cornea, or monovision. Scleral procedures exert a traction on supralenticular sclera that supposedly would improve the amplitude of accommodation.

CONCLUSIONS
None of the techniques are able to completely eliminate the need for near -vision glasses, but many of them manage to improve the refractive status of the patients. More studies with rigorous and standardised methods and longer follow-up are needed to evaluate the changes in the near vision of the patients, in order to corroborate the real and practical usefulness of many of these techniques.

Monovision
Cirugía de la presbicia
Conductive keratoplasty
Corneal inlays
Implantes corneales
Láser multifocal
Monovisión
Multifocal laser
PresbiLASIK
PresbyLASIK
Presbyopia surgery
Queratoplastia conductiva


The Algorithms of Distributed Learning and Distributed Estimation about Intelligent Wireless Sensor Network.

Abstract: The intelligent wireless sensor network is a distributed network system with high "network awareness". Each intelligent node (agent) is connected by the topology within the neighborhood which not only can perceive the surrounding environment, but can adjusts its own behavior according to its local perception information to constructs a distributed learning algorithms. Therefore, three basic intelligent network topologies of centralized, non-cooperative, and cooperative are intensively investigated in this paper. The main contributions of the paper include two aspects. First, based on algebraic graph, three basic theoretical frameworks for distributed learning and distributed parameter estimation of cooperative strategy are surveyed: increment strategy, consensus strategy, and diffusion strategy. Second, based on classical adaptive learning algorithm and online updating law, the implementation process of distributed estimation algorithm and the latest research progress of above three distributed strategies are investigated.

distributed learning
intelligent wireless sensor network
distributed estimation strategy
distributed topological structure


A unique composite follicular lymphoma and mantle cell lymphoma with a mixed cell pattern and aggressive course.

Abstract:
OBJECTIVES
There are a limited number of reports of composite follicular lymphoma (FL) and mantle cell lymphoma (MCL) in the literature, and all previous cases report that FL and MCL components are separated, even within a single lymph node. Here we report a case of a patient with a distinctive composite FL and MCL with a mixed cell pattern.

METHODS
A 34-year-old man presented with left supraclavicular lymphadenopathy for one month. The lymph node contained closely packed nodules of lymphocytes. Immunostaining and fluorescence in situ hybridization demonstrated the FL nature of the Bcl-2- and CD10-positive tumor cells, as well as the scattered cyclin D1-positive MCL tumor cells in the nodules. Double immunohistochemical staining showed an unusual mixed pattern of both types of tumor cells.

RESULTS
The patient received a regimen of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and achieved partial remission following four cycles of chemotherapy but relapsed 1 month after the last treatment and died of meninges involvement 8 months after the first presentation.

CONCLUSIONS
To our knowledge, this is the first report of composite FL and MCL with a mixed pattern. A mixture of grade IIIb FL and MCL may explain the poor prognosis of the patient.

Liu|Yixiong|Y| Li|Peifeng|P| Guo|Ying|Y| Fan|Linni|L| Wang|Lu|L| Zhu|Jin|J| Huang|Gaosheng|G| Yan|Qingguo|Q| Wang|Zhe|Z|

D000971:Antineoplastic Combined Chemotherapy Protocols

Follicular lymphoma
Mantle cell lymphoma
Mixed cell pattern
Composite lymphoma


Robotic resection of lingual thyroglossal duct cyst in an infant.

Abstract: Thyroglossal duct cysts (TDCs) are the most common congenital midline neck masses. Lingual TDC is a rare variant that emerges as an isolated cyst at the tongue base. Unlike conventional procedures aiming removal of cyst, duct, and hyoid bone via open surgical access, a transoral cystectomy is mostly sufficient in cases with lingual TDC. We present a case describing a 3-month-old infant patient with lingual TDC who was successfully treated with transoral robotic surgery. The cyst wall was completely excised with no complications or obvious bleeding occurred. The operating time was 10 min. He had an uneventful postoperative course. Six months postoperatively, he is free of symptoms with no evidence of recurrence. Surgical treatment of lingual TDC in an infant is possible with transoral robotic approach and minimal risk of complication. Further studies are strongly needed to confirm the safety of robotic surgery in pediatric population.

D019060:Minimally Invasive Surgical Procedures

Lingual thyroglossal duct cyst
Infant
Transoral robotic surgery


Role of arbuscular mycorrhizal fungus Rhizophagus custos in the dissipation of PAHs under root-organ culture conditions.

Abstract: Polycyclic aromatic hydrocarbons (PAHs) are one of the most common contaminants in soil. Arbuscular mycorrhizal (AM) fungi make host plants resistant to pollutants. This study aims to evaluate the impact of anthracene, phenanthrene and dibenzothiophene on the AM fungus Rhizophagus custos, isolated from soil contaminated by heavy metals and PAHs, under monoxenic conditions. We found a high level of tolerance in R. custos to the presence of PAHs, especially in the case of anthracene, in which no negative effect on AM-colonized root dry weight (root yield) was observed, and also a decrease in the formation of anthraquinone was detected. Increased PAH dissipation in the mycorrhizal root culture medium was observed; however, dissipation was affected by the level of concentration and the specific PAH, which lead us to a better understanding of the possible contribution of AM fungi, and in particular R. custos, to pollutant removal.

Aranda|Elisabet|E|
Scervino|José Martín|JM|
Godoy|Patricia|P|
Reina|Rocío|R|
Ocampo|Juan Antonio|JA|
Wittich|Regina-Michaela|RM|
García-Romera|Inmaculada|I|

Rhizophagus custos
Dissipation
Arbuscular mycorrhiza fungi
Heterocycles
PAH pollution


The association between the Nutrition-Related index and morbidity following head and neck microsurgery.

Abstract:
OBJECTIVES/HYPOTHESIS
Despite consensus that preoperative nutritional assessment is of importance in the head and neck surgical oncology population, it remains unclear how exactly malnutrition is associated with perioperative morbidity especially among those undergoing microvascular surgery. We aimed to study this association to help inform preoperative risk stratification, guide the use of nutritional interventions, and ultimately help prevent malnutrition related morbidity.

STUDY DESIGN
Database analysis.

METHODS
Retrospective, linked analysis of the 2011 to 2016 National Surgical Quality Improvement Program. After identifying eligible patients and stratifying according to the Nutrition-Related Index, a univariate screen of preoperative demographic and clinical covariates was performed. Subsequently, propensity score matching was utilized to control for differences in baseline covariates. Perioperative complications and mortality were then analyzed using the propensity score-matched cohorts.

RESULTS
Among 977 identified patients, 276 (28.2%) were malnourished. Malnourished patients had higher rates of comorbidity, were more likely to actively smoke, and were more likely to have primaries in the oropharynx or hypopharynx/larynx. After propensity score matching to control for confounders, malnourished patients had higher rates of pulmonary complications (21.5% vs. 11.6%, P < .01), higher rates of bleeding or need for transfusion (56.6% vs. 43.0%, P < .01), higher rates of venous thromboembolism (3.7% vs. 0.8%, P = .03), and a higher 30-day mortality rates (3.7% vs. 0.0%, P < .01).

CONCLUSIONS
This nationwide analysis finds that 28.2% of patients undergoing surgery for head and neck cancers with free flap reconstruction are malnourished. Malnourishment was found to be independently associated with postoperative pulmonary complications, bleeding or need for transfusion, and 30-day mortality.

LEVEL OF EVIDENCE
NA Laryngoscope, 130:375-380, 2020.

Parhar|Harman S|HS|0000-0001-7975-8452
Durham|J Scott|JS|
Anderson|Donald W|DW|
Rush|Barret|B|
Prisman|Eitan|E|0000-0001-7201-6181

nutrition
quality improvement
Head and neck surgery
preoperative optimization


The Diverse Contributions of Fucose Linkages in Cancer.

Abstract: Fucosylation is a post-translational modification of glycans, proteins, and lipids that is responsible for many biological processes. Fucose conjugation via α(1,2), α(1,3), α(1,4), α(1,6), and O'- linkages to glycans, and variations in fucosylation linkages, has important implications for cancer biology. This review focuses on the roles that fucosylation plays in cancer, specifically through modulation of cell surface proteins and signaling pathways. How L-fucose and serum fucosylation patterns might be used for future clinical diagnostic, prognostic, and therapeutic approaches will be discussed.

Keeley|Tyler S|TS|
Yang|Shengyu|S|
Lau|Eric|E|

fucose
cancer
fucosylation
fucosyltransferase
signal transduction


Collaboration between GI surgery & Gastroenterology improves understanding of the optimal antireflux valve-the omega flap valve.

Abstract:
BACKGROUND
Gastroesophageal reflux disease (GERD) is a chronic and sometimes disabling disease. An important component in the surgical management of GERD is either laparoscopic or endoscopic restoration of the native gastroesophageal flap valve (GEFV). Recently, a procedure combining laparoscopic hiatal hernia repair with transoral incisionless fundoplication (cTIF) was introduced. This relatively new operation is performed in collaboration between the gastrointestinal (GI) surgeon and the gastroenterologist.

METHODS
By working together, both interventionalists gain new insight into the ideal GEFV by observing the same operation being performed from different perspectives. In the cTIF, the gastroenterologist learns from an external perspective, through the laparoscopic view, the importance of the crura in contributing to the antireflux barrier. Similarly, the GI surgeon gains understanding of the elements that define an effective and desirable GEFV through an endoscopic perspective.

RESULTS
This collaboration with cTIF and seeing the procedure from different perspectives have led to our improved understanding of 1) factors contributing to an optimal surgically constructed GEFV and 2) the limitations of the GEFV constructed by the conventional laparoscopic total and partial fundoplications.

CONCLUSION
The collaboration between GI surgery and gastroenterology with cTIF has led to an improved understanding in characteristics of an optimal antireflux barrier and allowed for a proposed technical modification of the current fundoplication technique to optimize the construct of the surgical GEFV.

Omega flap valve
Transoral incisionless fundoplication
Partial fundoplication
Nissen fundoplication
Omega fundoplication


Sensitization predicts asthma development among wheezing toddlers in secondary healthcare.

Abstract:
INTRODUCTION
Some wheezing toddlers develop asthma later in childhood. Sensitization is known to predict asthma in birth cohorts. However, its predictive value in secondary healthcare is uncertain.

AIM
This study examines the predictive value of sensitization to inhalant allergens among wheezing toddlers in secondary healthcare for the development of asthma at school age (≥6 years).

METHODS
Preschool children (1-3 years) who presented with wheezing in secondary healthcare were screened on asthma at school age with the International Study of Asthma and Allergies in Childhood questionnaire. The positive and negative predictive value (PPV and NPV) of specific IgE to inhalant allergens (cut-off concentration 0.35 kU/L) and several non-invasive variables from a child's history (such as hospitalization, eczema, and parental atopy) were calculated. The additional predictive value of sensitization when combined with non-invasive predictors was examined in multivariate analysis and by ROC curves.

RESULTS
Of 116 included children, 63% developed asthma at school age. Sensitization to inhalant allergens was a strong asthma predictor. The odds ratio (OR), PPV and NPV were 7.4%, 86%, and 55%, respectively. Eczema (OR 3.4) and hospital admission (OR 2.6) were significant non-invasive determinants. Adding sensitization to these non-invasive predictors in multivariate analysis resulted in a significantly better asthma prediction. The area under the ROC curve increased from 0.70 with only non-invasive predictors to 0.79 after adding sensitization.

CONCLUSION
Sensitization to inhalant allergens is a strong predictor of school age asthma in secondary healthcare and has added predictive value when combined with non-invasive determinants. Pediatr Pulmonol. 2017;52:729-736. © 2017 Wiley Periodicals, Inc.

Boersma|Nienke A|NA|
Meijneke|Ruud W H|RWH|
Kelder|Johannes C|JC|
van der Ent|Cornelis K|CK|
Balemans|Walter A F|WAF|

sensitization
asthma
wheezing
child
secondary care


Received Wisdom Regarding the Roles of Craving and Dopamine in Addiction: A Response to Lewis's Critique of Addiction: A Disorder of Choice.

Abstract: Lewis's review of my book (2011, this issue) repeats widely shared understandings of the nature of addiction and the role that dopamine plays in the persistence of self-destructive drug use. These accounts depict addiction as a chronic relapsing disease and claim that drug-induced changes in dopamine function explain the transition from drug experimentation to compulsive drug use. In my book, I test the idea that addiction is a chronic, persistent state. Lewis fails to mention the results of the various tests, although they provide a handy test for his account of addiction and are surprising in light of the common verbal formula "addiction is a chronic, relapsing disease." Consequently, I review a few of the key findings in this response. Lewis faults me for not giving enough attention to dopamine. In my book, I conclude that there is more to the biology of addiction than dopamine, and in this response, I describe research that tests the idea that drug-induced increases in dopamine markedly reduce an individual's capacity to choose nondrug reinforcers. In one experiment, rats readily gave up cocaine for saccharin, even when they had been consuming massive amounts of the drug for weeks. Put more generally, well-established research results call for a revision of currently accepted understandings of addiction and the role that dopamine plays in drug use.

craving
dopamine
addiction
drug dependence
recovery
remission rates
treatment seeking


Different processes in attractiveness assessments for unattractive and highly attractive faces-The role of presentation duration and rotation.

Abstract: Assessing facial attractiveness is a central aspect of the human ability to process the visual properties of faces. Recent studies have demonstrated that disrupting the upright orientation of faces by rotation can lead to enhanced attractiveness ratings, especially for unattractive faces, which might indicate that attractiveness assessments are mainly based on the absence of unattractive facial characteristics. Other studies have shown that shorter exposure times can result in greater facial attractiveness ratings. In the present experiment, we tested the influence of both rotation (0°, ±90°, 180°) and presentation duration (40ms, 100ms, 250ms, 2000ms) on attractiveness ratings for faces, while also controlling for their pre-rated attractiveness (which was assessed in upright orientation during a pre-test). We found that unattractive faces were rated as most attractive when observed for 40ms, but presentation duration had no effect on ratings for highly attractive faces. Unattractive faces rotated by ±90° or inverted (rotated by 180°) were rated as more attractive than in the upright orientation and these effects were found under various presentation durations (40ms, 250ms, 2000ms). Importantly, a contrary relationship was found for highly attractive faces, which were rated as less attractive when inverted, but only under intermediate presentation durations (100ms or 250ms). Our results support the notion that facial attractiveness can be assessed on the basis of both the absence of unattractive characteristics and the presence of attractive features, depending on the initial attractiveness of the face and its exposure time.

Presentation duration
Rotation
Facial attractiveness
Face inversion


Improved determination of dynamic balance using the centre of mass and centre of pressure inclination variables in a complete golf swing cycle.

Abstract: Golf requires proper dynamic balance to accurately control the club head through a harmonious coordination of each human segment and joint. In this study, we evaluated the ability for dynamic balance during a golf swing by using the centre of mass (COM)-centre of pressure (COP) inclination variables. Twelve professional, 13 amateur and 10 novice golfers participated in this study. Six infrared cameras, two force platforms and SB-Clinic software were used to measure the net COM and COP trajectories. In order to evaluate dynamic balance ability, the COM-COP inclination angle, COM-COP inclination angular velocity and normalised COM-COP inclination angular jerk were used. Professional golfer group revealed a smaller COM-COP inclination angle and angular velocity than novice golfer group in the lead/trail direction (P < 0.01). In the normalised COM-COP inclination angular jerk, the professional golfer group showed a lower value than the other two groups in all directions. Professional golfers tend to exhibit improved dynamic balance, and this can be attributed to the neuromusculoskeletal system that maintains balance with proper postural control. This study has the potential to allow for an evaluation of the dynamic balance mechanism and will provide useful basic information for swing training and prevention of golf injuries.

Choi|Ahnryul|A|
Sim|Taeyong|T|
Mun|Joung Hwan|JH|

balance
centre of mass
centre of pressure
Golf
smoothness


Attending Heart School and long-term outcome after myocardial infarction: A decennial SWEDEHEART registry study.

Abstract:
BACKGROUND
The Heart School is a standard component of cardiac rehabilitation after myocardial infarction in Sweden. The group-based educational intervention aims to improve modifiable risks, in turn reducing subsequent morbidity and mortality. However, an evaluation with respect to mortality is lacking.

AIMS
Using linked population registries, we estimated the association of attending Heart School with both all-cause and cardiovascular mortality, two and five years after admission for first-time myocardial infarction.

METHODS
Patients with first-time myocardial infarction (<75 years) were identified as consecutively registered in the nationwide heart registry, SWEDEHEART (2006-2015), with >99% complete follow-up in the Causes of Death registry for outcome events. Of 192,059 myocardial infarction admissions, 47,907 unique patients with first-time myocardial infarction surviving to the first cardiac rehabilitation visit constituted the study population. The exposure was attending Heart School at the first cardiac rehabilitation visit 6-10 weeks post-myocardial infarction. Data on socioeconomic status was acquired from Statistics Sweden. After multiple imputation, propensity score matching was performed. The association of exposure with mortality was estimated with Cox regression and survival curves.

RESULTS
After matching, attending Heart School was associated (hazard ratio (95% confidence interval)) with a markedly lower risk of both all-cause (two-year hazard ratio = 0.53 (0.44-0.64); five-year hazard ratio = 0.62 (0.55-0.69)) and cardiovascular (0.50 (0.38-0.65); 0.57 (0.47-0.69)) mortality. The results were robust in several sensitivity analyses.

CONCLUSIONS
Attending Heart School during cardiac rehabilitation is associated with almost halved all-cause and cardiovascular mortality after first-time myocardial infarction. The result warrants further investigation through adequately powered randomised trials.

Wallert|John|J|
Olsson|Erik Mg|EM|
Pingel|Ronnie|R|
Norlund|Fredrika|F|
Leosdottir|Margret|M|
Burell|Gunilla|G|
Held|Claes|C|

D007722:Health Knowledge, Attitudes, Practice

cardiac rehabilitation
Patient education
cardiovascular disease
prognosis
secondary prevention


Mycobacterium tuberculosis: Rewiring host cell signaling to promote infection.

Abstract: The ability of Mycobacterium tuberculosis to cause disease hinges upon successfully thwarting the innate defenses of the macrophage host cell. The pathogen's trump card is its armory of virulence factors that throw normal host cell signaling into disarray. This process of subverting the macrophage begins upon entry into the cell, when M. tuberculosis actively inhibits the fusion of the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array of host signal transduction pathways, which dampens the macrophage's host-protective cytokine response, while simultaneously adapting host cell metabolism to stimulate lipid body accumulation. Mycobacterium tuberculosis also renovates the surface of its innate host cells by altering the expression of key molecules required for full activation of the adaptive immune response. Finally, the pathogen coordinates its exit from the host cell by shifting the balance from the host-protective apoptotic cell death program toward a lytic form of host cell death. Thus, M. tuberculosis exploits its extensive repertoire of virulence factors in order to orchestrate the infection process to facilitate its growth, dissemination, and entry into latency. This review offers critical insights into the most recent advances in our knowledge of how M. tuberculosis manipulates host cell signaling. An appreciation of such interactions between the pathogen and host is critical for guiding novel therapies and understanding the factors that lead to the development of active disease in only a subset of exposed individuals.

Stutz|Michael D|MD|
Clark|Michelle P|MP|
Doerflinger|Marcel|M|
Pellegrini|Marc|M|

macrophages
virulence factors
host-pathogen interactions


Paclitaxel-associated reticulate hyperpigmentation: Report and review of chemotherapy-induced reticulate hyperpigmentation.

Abstract: Drug-induced reticulate hyperpigmentation is uncommon. Including the patient described in this report, chemotherapy-associated reticulate hyperpigmentation has only been described in ten individuals. This paper describes the features of a woman with recurrent and metastatic breast cancer who developed paclitaxel-induced reticulate hyperpigmentation and reviews the characteristics of other oncology patients who developed reticulate hyperpigmentation from their antineoplastic treatment. A 55-year-old Taiwanese woman who developed reticulate hyperpigmentation on her abdomen, back and extremities after receiving her initial treatment for metastatic breast cancer with paclitaxel is described. The hyperpigmentation became darker with each subsequent administration of paclitaxel. The drug was discontinued after five courses and the pigment faded within two months. PubMed was searched with the key words: Breast, cancer, chemotherapy, hyperpigmentation, neoplasm, reticulate, tumor, paclitaxel, taxol. The papers generated by the search, and their references, were reviewed. Chemotherapy-induced reticulate hyperpigmentation has been described in four men and six women. Bleomycin, cytoxan, 5-fluorouracil, idarubacin, and paclitaxel caused the hyperpigmentation. The hyperpigmentation faded in 83% of the patients between two to six months after the associated antineoplastic agent was discontinued. In conclusion, chemotherapy-induced reticulate hyperpigmentation is a rare reaction that may occur during treatment with various antineoplastic agents. The hyperpigmentation fades in most individuals once the treatment is discontinued. Therefore, cancer treatment with the associated drug can be continued in patients who experience this cutaneous adverse event.

Reticulate Hyperpigmentation Breast Cancer Paclitaxel Chemotherapy Neoplasm Tumor Taxol


Sensorless Force Sensing for Minimally Invasive Surgery.

Abstract: Robotic minimally invasive surgery (R-MIS) has achieved success in various procedures; however, the lack of haptic feedback is considered by some to be a limiting factor. The typical method to acquire tool-tissue reaction forces is attaching force sensors on surgical tools, but this complicates sterilization and makes the tool bulky. This paper explores the feasibility of using motor current to estimate tool-tissue forces and demonstrates acceptable results in terms of time delay and accuracy. This sensorless force estimation method sheds new light on the possibility of equipping existing robotic surgical systems with haptic interfaces that require no sensors and are compatible with existing sterilization methods.

robotic minimally invasive surgery
sensorless force estimation
force feedback


Sit-to-walk performance in Parkinson's disease: A comparison between faller and non-faller patients.

Abstract:
BACKGROUND
Falls are one of the main concerns in people with Parkinson's disease, leading to poor quality of life and increased mortality. The sit-to-walk movement is the most frequent postural transition task during daily life and is highly demanding in terms of balance maintenance and muscular strength.

METHODS
With the aim of identifying biomechanical variables of high risk of falling, we investigated the sit-to-walk task performed by 9 Parkinson's disease patients with at least one fall episode in the six months preceding this study, 15 Parkinson's disease patients without previous falls, and 20 healthy controls. Motor performance was evaluated with an optoelectronic system and two dynamometric force plates after overnight suspension of all dopaminergic drugs and one hour after consumption of a standard dose of levodopa/benserazide.

FINDINGS
Poor trunk movements critically influenced the execution of the sit-to-walk movement in patients with a history of falling. The peak velocity of the trunk in the anterior-posterior direction discriminated faller from non-faller patients, with high specificity and sensitivity in both the medication-off and -on state.

INTERPRETATION
Our results confirm the difficulties in merging consecutive motor tasks in patients with Parkinson's disease. Trunk movements during the sit-to-walk can provide valuable measurements to monitor and possibly predict the risk of falling.

Palmisano|Chiara|C|
Brandt|Gregor|G|
Pozzi|Nicoló Gabriele|NG|
Leporini|Alice|A|
Maltese|Virginia|V|
Canessa|Andrea|A|
Volkmann|Jens|J|
Pezzoli|Gianni|G|
Frigo|Carlo Albino|CA|
Isaias|Ioannis Ugo|IU|

Sit-to-walk
Parkinson's disease
Falls
Trunk movement
Timed up and go


Attenuated BK channel function promotes overactive bladder in a rat model of obesity.

Abstract: Overactive bladder (OAB) is mostly observed in obese individuals, and is associated with enhanced excitability and contractility of the detrusor smooth muscle (DSM). Large-conductance voltage- and Ca2+-activated K+ (BK) channels reduce the excitability and contractility of the DSM. We tested whether obesity-induced OAB is associated with altered BK channel expression and activity in the DSM. Seven-week-old female Sprague-Dawley rats (N=80) were fed a normal or high-fat diet (HFD) for 12 weeks. HFD-fed rats exhibited a higher average bodyweight and urodynamically established detrusor overactivity. mRNA levels of the Kcnma1 (BKα subunit) and Kcnmb1 (BKβ1 subunit) in whole tissues and cells from the DSM were reduced in HFD-fed rats. A selective BK channel opener, NS1619, was then applied to DSM cells from the two groups of rats. Patch-clamp techniques revealed that spontaneous transient outward currents, NS1619-induced activation of spontaneous transient outward currents, and whole-cell BK currents, as well as NS1619-induced membrane hyperpolarization, were attenuated in DSM cells from HFD-fed rats. The relaxation effect of NS1619 on contractility was reduced in DSM strips from HFD-fed rats. Thus, impaired expression of Kcnma1 and Kcnmb1 in the DSM contributes to obesity-induced OAB, suggesting that BK channels could be a useful treatment targets in OAB.

Li|Ning|N| Ding|Honglin|H| Zhang|Peng|P| Li|Zizheng|Z| Liu|Yili|Y| Wang|Ping|P|

D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits

D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits

BK channel
overactive bladder
obesity
detrusor smooth muscle
electrophysiology


Reimagining pilocytic astrocytomas in the context of pediatric low-grade gliomas.

Abstract: Pediatric low-grade gliomas (pLGGs) are the most common brain tumor in children and are associated with lifelong clinical morbidity. Relative to their high-grade adult counterparts or other malignant childhood brain tumors, there is a paucity of authenticated preclinical models for these pLGGs and an incomplete understanding of their molecular and cellular pathogenesis. While large-scale genomic profiling efforts have identified the majority of pathogenic driver mutations, which converge on the MAPK/ERK signaling pathway, it is now appreciated that these events may not be sufficient by themselves for gliomagenesis and clinical progression. In light of the recent World Health Organization reclassification of pLGGs, and pilocytic astrocytoma (PA), in particular, we review our current understanding of these pediatric brain tumors, provide a conceptual framework for future mechanistic studies, and outline the challenges and pressing needs for the pLGG clinical and research communities.

pilocytic astrocytoma
low-grade glioma
pediatric brain tumor
BRAF
MEK
cellular senescence
neurofibromatosis type 1
tumor microenvironment


A novel inflatable left ventricular partitioning device.

Abstract: Percutaneous ventricular restoration (PVR) is an established treatment for patients with combined ischemic coronary artery disease and hear failure (HF). The left ventricle (LV) partitioning device is an interventional medical device that can be implanted into the ventricles of patients to reduce LV volumes, resulting in improved LV remodeling. However, the isolation surface area of the device is invariant, while the LV size of each patient is different. Thus, we designed a novel inflatable LV partitioning device. The functional volume of our ventricular isolation device can be adjusted by inflating and exhausting the device via the stomata based on a patient's ventricle size. The novel design could potentially reduce ventricular functional volume and improve the LV hemodynamic environment, thus resulting in favorable outcomes with reassuring safety and efficacy.

D006333:Heart Failure
D006352:Heart Ventricles
D006801:Humans
D019736:Prostheses and Implants
D016896:Treatment Outcome
D020257:Ventricular Remodeling

Percutaneous ventricular restoration
LV partitioning device
Heart failure
Parachute device


Low frequency pulse stimulation of Schaffer collaterals in Trpm4-/- knockout rats differently affects baseline BOLD signals in target regions of the right hippocampus but not BOLD responses at the site of stimulation.

Abstract: Electrical stimulation of right Schaffer collateral in Trpm4-/- knockout and wild type rats were used to study the role of Trpm4 channels for signal processing in the hippocampal formation. Stimulation induced neuronal activity was simultaneously monitored in the CA1 region by in vivo extracellular field recordings and in the entire brain by BOLD fMRI measurements. In wild type and Trpm4-/- knockout rats, consecutive 5 Hz pulse trains elicited similar neuronal responses in the CA1 region and similar BOLD responses in the stimulated right hippocampus. Stimulus-related positive BOLD responses were also found in the left dorsal hippocampus. In contrast to the right dorsal hippocampus, baseline BOLD signals in the left hippocampus significantly decreased during consecutive stimulation trains. Similarly, slowly developing significant declines in baseline BOLD signals, in absence of any positive BOLD responses, were also observed in the right entorhinal, right piriform cortex, right basolateral amygdala and right dorsal striatum whereas baseline BOLD signals remained almost stable in the corresponding left regions. Furthermore, significant declines in baseline BOLD signals were found in the prefrontal cortex and prelimbic/infralimbic cortex. Because significant baseline BOLD declines were only observed in target regions of the right dorsal hippocampus, it might reflect functional connectivity between these regions. In all observed regions the decline in baseline BOLD signals was significantly delayed and less pronounced in Trpm4-/- knockout rats when compared to wild type rats. Thus, either Trpm4 channels are involved in mediating these baseline BOLD shifts or functional connectivity of the hippocampus is impaired in Trpm4-/- knockout rats.

Bovet-Carmona|Marta|M| Krautwald|Karla|K| Menigoz|Aurélie|A| Vennekens|Rudi|R| Balschun|Detlef|D| Angenstein|Frank|F|


Adenovirus disease in six small bowel, kidney and heart transplant recipients; pathology and clinical outcome.

Abstract: Adenoviruses are emerging as important viral pathogens in hematopoietic stem cell and solid organ transplant recipients, impacting morbidity, graft survival, and even mortality. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung, and small bowel transplant recipients. Most of the adenovirus diseases develop in the first 6 months after transplantation, particularly in pediatric patients. Among abdominal organ recipients, small bowel grafts are most frequently affected, presumably due to the presence of a virus reservoir in the mucosa-associated lymphoid tissue. Management of these infections may be difficult and includes the reduction of immunosuppression, whenever possible, combined with antiviral therapy, if necessary. Therefore, an awareness of the pathology associated with such infections is important in order to allow early detection and specific treatment. We reviewed six transplant recipients (small bowel, kidney, and heart) with adenovirus graft involvement from two institutions. We sought to compare the diagnostic morphology and the clinical and laboratory findings. The histopathologic features of an adenovirus infection of the renal graft and one native kidney in a heart transplant recipient included a vaguely granulomatous mixed inflammatory infiltrate associated with rare cells showing a cytopathic effect (smudgy nuclei). A lymphocytic infiltrate, simulating T cell rejection, with admixture of eosinophils was also seen. In the small bowel grafts, there was a focal mixed inflammatory infiltrate with associated necrosis in addition to cytopathic effects. In the heart, allograft adenovirus infection was silent with no evidence of inflammatory changes. Immunohistochemical stain for adenovirus was positive in all grafts and in one native kidney. All patients were subsequently cleared of adenovirus infection, as evidenced by follow-up biopsies, with no loss of the grafts. Adenovirus infection can involve allografts as well as native organs in solid organ transplant recipients. Infection is associated with variable necrosis and acute inflammation, in addition to a rejection-like infiltrate. Hematuria in non-renal solid organ transplant recipients may be associated with adenovirus nephritis and clinically silent graft involvement. Prompt diagnosis (aided by immunohistochemistry (IHC) and serology), with specific treatment, can prevent graft loss.

Mehta|Vikas|V|
Chou|Pauline C|PC|
Picken|Maria M|MM|

Adenovirus
Solid organ transplant
Nephritis
Enteritis
Heart involvement


Iatrogenic left main coronary artery stenosis following aortic and mitral valve replacement.

Abstract: Iatrogenic coronary artery disease following prosthetic valve implantation is a rare complication. This may result from mechanical injury in the intraoperative period. The use of balloon tip perfusion catheter presumably provides the initial insult with local vessel wall hypoxia. Once the diagnosis of coronary ostial stenosis is established, the procedure of choice is coronary artery bypass surgery. We report a case of a young lady who underwent aortic and mitral valves replacement for infective endocarditis. She was then diagnosed with ostial left main stem coronary stenosis after presenting with atypical symptoms. The patient eventually underwent coronary artery bypass surgery.

Iatrogenic
valve replacement
left main stenosis


The Effect of Helicobacter pylori Eradication on Gastric Wall Thickness in Patients Undergoing Laparoscopic Sleeve Gastrectomy.

Abstract:
PURPOSE
The most important cause affecting the thickness of the gastric wall other than the tumor is chronic gastritis caused by Helicobacter pylori (Hp), which is most frequently detected in the antrum. This study aims to investigate the effect of bismuth-based treatment (BBT) combined with proton pump inhibitor (PPI) on wall thicknesses measured in the postoperative gastric specimen and early postoperative complications in patients with Hp-positive pre-LSG endoscopic gastric biopsies.

MATERIALS AND METHODS
The patients who underwent LSG procedure for morbid obesity were divided into three groups as follows: Hp-negative, Hp-positive without eradication treatment, and Hp-positive, and LSG was performed after eradication treatment. Macroscopic and microscopic gastric wall thickness measurements were made at a distance of 1 cm from the proximal surgical margin, from the middle part of the specimen, and 1 cm from the distal surgical margin in the gastric specimen and the results were compared.

RESULTS
A total of 132 patients were included in the study, 44 patients in each group. Microscopically measured antrum mucosal thickness was found to be statistically significantly higher in group 2 compared to other groups (groups 1.15, 1.35, 1.16 mm, respectively, p = 0.000). There was no difference between the groups in terms of early complications such as bleeding, wound site infection, or leakage from the staple line within the first 28 days after surgery.

CONCLUSION
This study found that LSG had no effect on early complications due to Hp positivity or eradication of Hp.

KEY POINTS
• The presence of HP increases the wall thickness of the gastric antrum mucosa. • After HP eradication, stomach antrum wall thickness returns to normal. • HP eradication before LSG reduces the wall thickness of the gastric antrum mucosa. • It was determined that HP scanning and eradication before LSG had no effect on postoperative complications.

Ergin|Anıl|A|0000-0001-6450-7124
Çiyiltepe|Hüseyin|H|
Karip|Aziz Bora|AB|
Fersahoğlu|Mehmet Mahir|MM|
Bulut|Nuriye Esen|NE|
Çakmak|Ahmet|A|
Topaloğlu|Berk|B|
Bilgili|Ali Cihan|AC|
Somay|Adnan|A|
Taşdelen|İksan|İ|
Akyüz|Ümit|Ü|
Memişoğlu|Kemal|K|

Helicobacter pylori
Gastric wall thickness
Laparoscopic sleeve gastrectomy


Effect of residence time during hydrothermal carbonization of biogas digestate on the combustion characteristics of hydrochar and the biogas production of process water.

Abstract: The biogas digestate from anaerobic digestion of cow manure and energy crops was treated by hydrothermal carbonization (HTC) at 210 °C for 0.5 to 5 h to understand the effect of HTC residence time on the combustion characteristics of hydrochar and the biogas production of process water. The increase in HTC residence time slightly reduced the higher heating values (16.3-16.0 MJ/kg) but improved most slagging and fouling indices of the hydrochar. However, the slagging and fouling during hydrochar combustion were almost impossible to avoid. The specific methane yield of the process water was not significantly influenced by the HTC residence time. Energy assessment demonstrated that HTC for 0.5 h achieved the highest process efficiency and net energy gain when the combustion energy was obtained from hydrochar and CH4 (from process water). Therefore, the HTC condition of 210 °C, 0.5 h is suggested to valorize biogas digestate for energy production.

Cao|Zebin|Z| Hülsemann|Benedikt|B| Wüst|Dominik|D| Oechsner|Hans|H| Lautenbach|Armin|A| Kruse|Andrea|A|

Hydrothermal carbonization
Biogas digestate
Combustion characteristics
Anaerobic digestion
Bioeconomy


Using a deep convolutional neural network to predict 2017 ozone concentrations, 24 hours in advance.

Abstract: In this study, we use a deep convolutional neural network (CNN) to develop a model that predicts ozone concentrations 24 h in advance. We have evaluated the model for 21 continuous ambient monitoring stations (CAMS) across Texas. The inputs for the CNN model consist of meteorology (e.g., wind field, temperature) and air pollution concentrations (NO x and ozone) from the previous day. The model is trained for predicting next-day, 24-hour ozone concentrations. We acquired meteorological and air pollution data from 2014 to 2017 from the Texas Commission on Environmental Quality (TCEQ). For 19 of the 21 stations in the study, results show that the yearly index of agreement (IOA) is above 0.85, confirming the acceptable accuracy of the CNN model. The results also show the model performed well, even for stations with varying monthly trends of ozone concentrations (specifically CAMS-012, located in El-Paso, and CAMS-013, located in Fort Worth, both with IOA=0.89). In addition, to ensure that the model was robust, we tested it on stations where fewer meteorological variables are monitored. Although these stations have fewer input features, their performance is similar to that of other stations. However, despite its success at capturing daily trends, the model mostly underpredicts the daily maximum ozone, which provides a direction for future study and improvement. As this model predicts ozone concentrations 24 h in advance with greater accuracy and computationally fewer resources, it can serve as an early warning system for individuals susceptible to ozone and those engaging in outdoor activities.

Sayeed|Alqamah|A| Choi|Yunsoo|Y| Eslami|Ebrahim|E| Lops|Yannic|Y| Roy|Anirban|A| Jung|Jia|J|

Convolutional
Neural network
Deep learning
Ozone prediction
Real-time forecasting


CPEB1, a novel risk gene in recent-onset schizophrenia, contributes to mitochondrial complex I defect caused by a defective provirus ERVWE1.

Abstract:
BACKGROUND
Schizophrenia afflicts 1% of the world population. Clinical studies suggest that schizophrenia patients may have an imbalance of mitochondrial energy metabolism via inhibition of mitochondrial complex I activity. Moreover, recent studies have shown that ERVWE1 is also a risk factor for schizophrenia. Nevertheless, there is no available literature concerning the relationship between complex I deficits and ERVWE1 in schizophrenia. Identifying risk factors and blood-based biomarkers for schizophrenia may provide new guidelines for early interventions and prevention programs.

AIM
To address novel potential risk factors and the underlying mechanisms of mitochondrial complex I deficiency caused by ERVWE1 in schizophrenia.

METHODS
Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay were used to detect differentially expressed risk factors in blood samples. Clinical statistical analyses were performed by median analyses and Mann-Whitney U analyses. Spearman's rank correlation was applied to examine the correlation between different risk factors in blood samples. qPCR, western blot analysis, and luciferase assay were performed to confirm the relationship among ERVWE1, cytoplasmic polyadenylation element-binding protein 1 (CPEB1), NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), and NDUFV2 pseudogene (NDUFV2P1). The complex I enzyme activity microplate assay was carried out to evaluate the complex I activity induced by ERVWE1.

RESULTS
Herein, we reported decreasing levels of CPEB1 and NDUFV2 in schizophrenia patients. Further studies showed that ERVWE1 was negatively correlated with CPEB1 and NDUFV2 in schizophrenia. Moreover, NDUFV2P1 was increased and demonstrated a significant positive correlation with ERVWE1 and a negative correlation with NDUFV2 in schizophrenia. In vitro experiments disclosed that ERVWE1 suppressed NDUFV2 expression and promoter activity by increasing NDUFV2P1 level. The luciferase assay revealed that ERVWE1 could enhance the promoter activity of NDUFV2P1. Additionally, ERVWE1 downregulated the expression of CPEB1 by suppressing the promoter activity, and the 400 base pair sequence at the 3' terminus of the promoter was the minimum sequence required. Advanced studies showed that CPEB1 participated in regulating the NDUFV2P1/NDUFV2 axis mediated by ERVWE1. Finally, we found that ERVWE1 inhibited complex I activity in SH-SY5Y cells via the CPEB1/NDUFV2P1/NDUFV2 signaling pathway.

CONCLUSION
In conclusion, CPEB1 and NDUFV2 might be novel potential blood-based biomarkers and pathogenic factors in schizophrenia. Our findings also reveal a novel mechanism of ERVWE1 in the etiology of schizophrenia.

Xia|Ya-Ru|YR| Wei|Xiao-Cui|XC| Li|Wen-Shi|WS| Yan|Qiu-Jin|QJ| Wu|Xiu-Lin|XL| Yao|Wei|W| Li|Xu-Hang|XH| Zhu|Fan|F|


Congenital Acinar Cystic Transformation of the Pancreas with Proximal Jejunal Atresia and Hepatic Iron Overload: An Autopsy Case.

Abstract: Acinar cystic transformation (ACT) of the pancreas is characterized by multiple cysts lined by dual ductal and acinar-type of epithelium. ACT is typically a disease of adulthood and has not been described in a neonate. Case report: Autopsy of this term 3-day old male demonstrated cystic transformation of the entire pancreas measuring 42 mm in its largest dimension. The main pancreatic duct was patent. The numerous variable-sized cysts were lined by both ductal (CK7-positive) and acinar (trypsin-positive) epithelium. Congenital hemochromatosis of the liver, complete proximal jejunal atresia, gangrene of the post-atretic jejunum, and subglottic stenosis were associated features. Discussion/Conclusion: ACT may occur in the neonate in association with other abnormalities.

Mitra|Suvradeep|S|
Kalra|Manisha|M|
Purkait|Suvendu|S|
Mishra|Purbasha|P|
Mohanty|Pankaj Kumar|PK|
Som|Tapas Kumar|TK|
Adhya|Amit Kumar|AK|
Das|Prasenjit|P|

Acinar cystic transformation
pancreas
jejunal atresia
hemochromatosis
liver
subglottic stenosis


In Vitro Evaluation of Lavandula angustifolia Essential Oil on Anti-Toxoplasma Activity.

Abstract: The current methods of treating toxoplasmosis have a number of side effects, and these therapies are only effective against the acute stage of the disease. Thus, development of new low toxicity and efficient anti-Toxoplasma drugs is extremely important. Natural products are important sources for screening new drugs; among them, essential oils (EOs) have efficacy in anti-bacterial, anti-inflammatory, anti-insect, and other aspects. In this study, 16 EOs were screened for their anti-T. gondii activity. Lavandula angustifolia essential oil (La EO)was found to have an anti-parasitic effect on T. gondii. The cytotoxicity of La EO was firstly evaluated using the MTT assay on human foreskin fibroblast (HFF) cells, and then the anti-T. gondii activity was evaluated by plaque assay. Finally, the invasion experiment and electron microscope observation were used to study the mechanism of La EO in anti-toxoplasma activity. The results indicated that the CC50 of La EO was 4.48 mg/ml and that La EO had activity against T. gondii and the inhibition was in a dose-dependent manner under safe concentrations. La EO was able to reduce T. gondii invasion, which may be due to its detrimental effect on changes of the morphology of tachyzoites. These findings indicated that La EO could be a potential drug for treating toxoplasmosis.

Yao|Na|N| He|Jia-Kang|JK| Pan|Ming|M| Hou|Zhao-Feng|ZF| Xu|Jin-Jun|JJ| Yang|Yi|Y| Tao|Jian-Ping|JP| Huang|Si-Yang|SY|

in vitro
Lavandula angustifolia essential oil
Toxoplasma gondii
natural medicine
treatment


Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway.

Abstract: Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.

Li|Qing-Rong|QR| Wang|Zhuo|Z| Zhou|Wei|W| Fan|Shou-Rui|SR| Ma|Run|R| Xue|Li|L| Yang|Lu|L| Li|Ya-Shan|YS| Tan|Hong-Li|HL| Shao|Qing-Hua|QH| Yang|Hong-Ying|HY|0000-0001-6740-880X

oxidative stress
polyol pathway
aldose reductase
aldose reductase inhibitor
diabetic neuropathy
peripheral nerve injury
rats
streptozotocin
antioxidant enzymes
superoxide dismutase
catalase
glutathione peroxidase
NSFC grant
nerve regeneration
neural regeneration
reactive oxygen species


Polysubstance use among youth experiencing homelessness: The role of trauma, mental health, and social network composition.

Abstract:
BACKGROUND
Substance use is common among youth experiencing homelessness (YEH). However, less is known about the use of multiple substances (polysubstance use), or factors associated with polysubstance use among YEH. The present study sought to identify subgroups of YEH based on their recent polysubstance use behavior, and investigate traumatic experiences, mental health and social network composition as predictors.

METHODS
YEH (N = 1,032; Mage = 21.3) from three drop-in centers in Los Angeles completed an in-person survey and social network interview between October 2011 and June 2013. Latent class analysis (LCA) was used to identify subgroups of youth based on nine types of substance use in the past 30 days; latent class logistic regression was used to identify variables associated with class membership.

RESULTS
Five polysubstance use classes were identified: heavy alcohol and marijuana (33.6 %), illicit drug use (4.9 %), high all polysubstance use (14.9 %), primarily marijuana (18.1 %), and low use (28.5 %). Relative to the low use class, traumatic experiences were associated with membership in every polysubstance use class. Suicide attempts were associated with membership in the high all class (OR = 9.41). Number of substance-using, homeless network members was associated with membership in the heavy alcohol and marijuana use class (OR = 1.35). Number of non-substance-using network members (homeless [OR = 0.29] and housed [OR = 0.73]) was associated with lower odds of membership in the high all class.

CONCLUSIONS
Distinct groups of YEH can be identified by their recent polysubstance use patterns. Traumatic experiences, suicidality, and social network composition are important correlates of polysubstance use among YEH.

DiGuiseppi|Graham T|GT|
Davis|Jordan P|JP|
Christie|Nina C|NC|
Rice|Eric|E|

Polysubstance use
Trauma
Social networks
Youth homelessness


The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line.

Abstract:
BACKGROUND
The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or α-L-Guluronic Acid is a new NSAID with immunomodulatory features.

OBJECTIVES
Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules.

METHODS
HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis.

RESULTS
We found that concentrations of ≤125 µg/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 µg/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively).

CONCLUSION
The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.

Farhang|Hamid|H|
Sharifi|Laleh|L|
Dallal|Mohammad Mehdi Soltan|MMS|
Moshiri|Mona|M|
Norouzbabaie|Zahra|Z|
Bokaie|Saied|S|
Aletaha|Somaye|S|
Zargar|Seyed Jalal|SJ|
Mirshafiey|Abbas|A|

D002470:Cell Survival
D005786:Gene Expression Regulation
D057809:HEK293 Cells
D019073:HT29 Cells
D006603:Hexuronic Acids
D006801:Humans
D007155:Immunologic Factors
D012333:RNA, Messenger
D051195:Toll-Like Receptor 2
D051197:Toll-Like Receptor 4


The influence of land use in a highly modified catchment: Investigating the importance of scale in riverine health assessment.

Abstract: Riverine landscapes are studied at varying scales, investigating the complex cause-effect pathways between rivers and their physical, chemical and biological attributes. Policy development, management and planning are often formulated and applied at the regional or catchment scale, however the ecological evidence required to inform at this scale is typically collected from the much smaller scale. This research was aimed at determining if patterns in diatom and macroinvertebrate community composition can be attributed to a specific/single land use in a catchment with multiple land uses. The impacts of forest, macadamia, grazing, sugar cane and urban land uses in the Richmond River Catchment of Northern NSW, Australia were investigated at 20 micro-catchment scale sites. A total of 124 diatom species from 43 genera, along with 92 families and three sub-families of macroinvertebrates, were collected and used to calculate the Richmond River Diatom Index (RRDI), AUSRIVAS and SIGNAL2 scores. Statistical analyses showed distinct groupings of land use categories providing evidence of cause-effect pathways attributed to individual land uses. The RRDI, AUSRIVAS and SIGNAL2 scores all showed distinctions between land use categories, though they were clearer in the RRDI. The RRDI indicated that the grazing sites had the poorest health of the land use categories, followed by sugar cane and urban while the macadamia and forest sites were relatively healthy. Signal 2 scores showed similar trends to the RRDI, while the AURIVAS scores did not present clear trends, particularly in the edge habitat of macadamia land use sites. The results indicated that riparian vegetation and instream habitat play an important role in attenuating inputs and that rehabilitation efforts could potentially improve water quality at a micro-catchment scale and subsequently, result in river health improvement at the catchment scale. The research collected at this micro-catchment scale presents new evidence that further informs and affects decisions made at the catchment scale, where policy and planning is developed and implemented.

Oeding|Sue|S|
Taffs|Kathryn H|KH|
Cox|Brendan|B|
Reichelt-Brushett|Amanda|A|
Sullivan|Caroline|C|

Land use
Management
Diatoms
Macroinvertebrates
Spatial scale
Stream health


Peroxynitrite induces apoptosis of mouse cochlear hair cells via a Caspase-independent pathway in vitro.

Abstract: Peroxynitrite (ONOO-) is a potent and versatile oxidant implicated in a number of pathophysiological processes. The present study was designed to investigate the effect of ONOO- on the cultured cochlear hair cells (HCs) of C57BL/6 mice in vitro as well as the possible mechanism underlying the action of such an oxidative stress. The in vitro primary cultured cochlear HCs were subjected to different concentrations of ONOO-, then, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy (TEM), the apoptosis was determined by Terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) assay, the mRNA expressions of Caspase-3, Caspase-8, Caspase-9, Apaf1, Bcl-2, and Bax were analyzed by RT-PCR, and the protein expressions of Caspase-3 and AIF were assessed by immunofluorescence. This work demonstrated that direct exposure of primary cultured cochlear HCs to ONOO- could result in a base-to-apex gradient injury of HCs in a concentration-dependent manner. Furthermore, ONOO- led to much more losses of outer hair cells than inner hair cells mainly through the induction of apoptosis of HCs as evidenced by TEM and TUNEL assays. The mRNA expressions of Caspase-8, Caspase-9, Apaf1, and Bax were increased and, meanwhile, the mRNA expression of Bcl-2 was decreased in response to ONOO- treatment. Of interesting, the expression of Caspase-3 had no significant change, whereas, the expression alteration of AIF was observed. These results suggested that ONOO- can effectively damage the survival of cochlear HCs via triggering the apoptotic pathway. The findings from this work suggest that ONOO--induced apoptosis is mediated, at least in part, via a Caspase-independent pathway in cochlear HCs.

Cao|Zhixin|Z| Yang|Qianqian|Q| Yin|Haiyan|H| Qi|Qi|Q| Li|Hongrui|H| Sun|Gaoying|G| Wang|Hongliang|H| Liu|Wenwen|W| Li|Jianfeng|J|

D053477:Apoptotic Protease-Activating Factor 1

Peroxynitrite
Apoptosis
Hair cells
Immunofluorescence
Hearing loss


Intranuclear accumulation of galectin-3 is an independent prognostic factor for patients with distal cholangiocarcinoma.

Abstract: Galectin-3 has been reported to be associated with the prognosis of patients with various malignancies; however, it has not yet been investigated in patients with extrahepatic cholangiocarcinoma (EHCC). Expression of galectin-3 was retrospectively examined in 58 patients with EHCC: 21 with perihilar cholangiocarcinoma and 37 with distal cholangiocarcinoma (DCC). The Cox proportional hazard model was used to identify independent prognostic factors. Intranuclear accumulation of galectin-3 (gal-3-INA) was associated with poorer overall survival (OS) in all patients (P=0.003), as well as in patients with DCC (P=0.004). Patients with gal-3-INA also exhibited a poorer disease-free survival (DFS) than those without gal-3-INA in all patients with EHCC (P<0.001), and in patients with DCC (P<0.001). Gal-3-INA was an independent prognostic factor of OS and DFS in all patients [OS: Hazard ratio (HR), 4.470; 95% confidence interval (CI), 1.759-11.357; P=0.002; and DFS: HR, 5.116; 95% CI, 2.025-12.925; P=0.001]. Gal-3-INA was also an independent prognostic factor in patients with DCC (OS: HR, 2.979; 95% CI, 1.035-8.570; P=0.043; and DFS: HR, 6.773; 95% CI, 1.558-29.439; P=0.011). In the analysis of patients with DCC, the number of patients with high galectin-3 expression (P=0.038), recurrence (P<0.001), distant metastases (P<0.001), R0 status (P=0.029) or microscopic vascular invasion (P=0.019) was significantly higher in the gal-3-INA-positive group than in the gal-3-INA-negative group. In conclusion, gal-3-INA was identified as a strong prognostic factor for OS and DFS in patients with DCC.

Shimura|Tatsuo|T| Kofunato|Yasuhide|Y| Okada|Ryo|R| Yashima|Rei|R| Koyama|Yoshihisa|Y| Araki|Kenichiro|K| Kuwano|Hiroyuki|H| Takenoshita|Seiichi|S|

galectin-3
prognostic factor
distal cholangiocarcinoma


Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year, Prospective, Real-World Study in France.

Abstract:
BACKGROUND AND AIMS
Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice.

METHODS
This non-interventional, prospective, 36-month study included treatment-naïve and treatment-experienced patients with CHB initiating their first TDF regimen (monotherapy or combination therapy) in routine clinical practice in France. Clinical, virologic, biochemical, compliance, and safety data were collected.

RESULTS
Data from 440 consecutive patients from 58 centers were analyzed. The majority of the cohort was male (71 %), hepatitis B "e" antigen-negative (HBeAg-) (74 %), and treatment-experienced (56 %); 11 % were aged ≥65 years; and comorbidities were reported in 39 %. After 12 months, 92 % of the overall cohort achieved virologic response (HBV DNA <69 IU/mL) which was maintained to 36 months (96 %); virologic response was achieved by >90 % of patients irrespective of HBeAg status, age, or prior treatment history. At 36 months, 77 % of patients had normal alanine aminotransferase levels. Fourteen patients lost hepatis B surface (HBs) antigen, and seven seroconverted to anti-HBs. TDF was well tolerated over the 36-month study, including in 14 women who became pregnant during the study. Median estimated glomerular filtration rate did not change markedly from baseline irrespective of prior treatment history.

CONCLUSIONS
TDF demonstrated potent virologic and biochemical responses across a broad range of patients reflective of routine clinical practice. The safety profile was consistent with results from pivotal trials.

Marcellin|Patrick|P|
Zoulim|Fabien|F|
Hézode|Christophe|C|
Causse|Xavier|X|
Roche|Bruno|B|
Truchi|Régine|R|
Pauwels|Arnaud|A|
Ouzan|Denis|D|
Dumortier|Jérôme|J|
Pageaux|Georges-Philippe|GP|
Bourlière|Marc|M|
Riachi|Ghassan|G|
Zarski|Jean-Pierre|JP|
Cadranel|Jean-François|JF|
Tilliet|Valérie|V|
Stern|Christiane|C|
Pétour|Pascal|P|
Libert|Olivier|O|
Consoli|Silla M|SM|
Larrey|Dominique|D|

Tenofovir
Real-world
HBV
Routine practice


Autistic Symptoms in Children and Adolescents with Gender Dysphoria.

Abstract: Studies have shown an increase of symptoms of autism spectrum disorder (ASD) in gender dysphoria (GD). Various hypotheses try to explain this possible co-occurrence (e.g., a role of resistance to change, stereotyped behaviors or prenatal testosterone exposure). This study examined ASD symptoms with the Children's Social Behavior Questionnaire (CSBQ) in 490 children with GD compared to 2507 typically developing (TD) and 196 children with ASD. CSBQ total scores of the GD sample were in between scores from the TD and ASD sample. The GD sample showed elevated levels of autistic symptomatology on all subdomains, not only on stereotyped and resistance to change. Further, no gender differences and interaction effects were found on the total CSBQ, making a sole role for prenatal testosterone unlikely.

van der Miesen|Anna I R|AIR|
de Vries|Annelou L C|ALC|
Steensma|Thomas D|TD|
Hartman|Catharina A|CA|

D011297:Prenatal Exposure Delayed Effects

Gender dysphoria
Autism spectrum disorder
Co-occurrence
Comorbidity
Gender identity disorder


The effects of epoxiconazole and α-cypermethrin on Daphnia magna growth, reproduction, and offspring size.

Abstract: Two of the main classes of pesticides commonly used in agriculture are azole fungicides and pyrethroid insecticides. Because azoles have been shown to synergize the effect of pyrethroids, the effect of their mixture is of concern. The aim of the present study was to investigate the effect of sublethal concentrations of epoxiconazole and α-cypermethrin and their mixture on growth, reproduction, and in vivo cytochrome P450 activity of the aquatic crustacean Daphnia magna over 42 d. Continuous exposure to nonlethal concentrations of α-cypermethrin at 20 ng/L negatively affected adult growth and number and size of neonates within the first 14 d of exposure. Exposure to epoxiconazole at 25 μg/L increased protein content of adults within 1 to 3 d after initiating exposure and increased cumulative number of offspring at exposure times >31 d. Epoxiconazole enhanced the negative effect of α-cypermethrin up to 3-fold leading to decreased growth, cytochrome P450 activity, and reproduction of D. magna within the first 14 d of exposure. After 14 d, the synergistic interactions disappeared. The reported effects, although lacking direct negative consequence in the long term, might have cumulative toxicity with other stressors such as food scarcity, predation, and pathogens, posing an additional hazard for the organisms at the beginning of their life cycle. Environ Toxicol Chem 2017;36:2155-2166. © 2017 SETAC.

Gottardi|Michele|M|
Birch|Michala Rosa|MR|
Dalhoff|Kristoffer|K|
Cedergreen|Nina|N|

Pesticides
Life history
Mixture toxicity
Synergy
Trade-off or hormesis?


Optimizing fiber and protein levels in diet of lactating Murrah buffaloes to ameliorate heat stress: Effect on physiological status and production performance.

Abstract: The objective of study was to assess the outcome of feeding six total mixed rations (TMR), differing in NDF and protein content, for their synergistic effect on ameliorating heat load of lactating Murrah buffaloes evident through improved physiological and production performance. Thirty six lactating Murrah buffaloes (587 ± 12.3, MY 9 ± 2.2, Parity 2.5 ± 1.5) were arranged in a 3 × 2 factorial design with three levels of dietary NDF (30, 34.5 and 37% dietary NDF) and two levels of metabolizable protein (MP; 7.0% and 8.4%). Buffaloes were fed either of six dietary treatments: 30%NDF; 7.0% MP (CF1, as recommended), 34.5%NDF; 7.0% MP (MF1), 37%NDF; 7.0% MP (HF1), 30%NDF; 8.4% MP (CF2), 34.5%NDF; 8.4% MP (MF2) and 37%NDF; 8.4% MP (HF2). TMR offered with maize silage and respective concentrate for 90 days feeding trial. Fortnightly feed samples and weekly milk samples collection was done for analyses. Metabolic trial conducted in mid of experiment for estimating nutrient digestibility. Throughout the trial, THI level (79.7-83.8) denoted that buffaloes were exposed to stressful environment. Higher MP in diet reduced pulse rate in buffaloes as compared with lower MP diet. Rectal temperature was lower in Murrah buffaloes fed MF2 diet whereas; minimum breathing rate was recorded for high protein fed group. The MF2 diet increased dry matter intake (kg/d) by 2.7%, milk yield (kg/d) by 8.3% and feed efficiency (milk/DMI) by 7.2% as compared with CF1 group indicating reduced heat load. Increase in protein intake along with improved protein digestibility in MF2 group was recorded. Measured 6%FCM and ECM (kg/d), milk fat (%) and total solid (%) were higher in MF2 treatment group. Results revealed that 34.5% NDF and 8.4% MP have a positive influence on amelioration of heat stress in present experimental conditions.

Lakhani|Neeti|N| Tyagi|Nitin|N| Agarwal|Anjali|A| Kumar|Sachin|S| Tyagi|Amrish|A|

Murrah buffaloes
Heat stress
Dietary
Metabolizable protein
Temperature humidity index


Premedication with oral clonidine decreases intraoperative bleeding and provides hemodynamic stability in cesarean section.

Abstract:
BACKGROUND
Intentional lowering of blood pressure helps to produce a desirably clean surgical field. Many drugs can be used to induce a hypotensive state, but due to their high potency and rapid effect, drugs that more easily and safely control the induction of hypotension are desirable.

OBJECTIVES
To investigate the effects of premedication with oral clonidine on intraoperative bleeding and hemodynamic variables in patients undergoing cesarean sections.

PATIENTS AND METHODS
A total of 110 patients classified as American Society of Anesthesiologists (ASA) physical status I and II and who were scheduled for elective cesarean section under general anesthesia were enrolled. The patients were randomized to receive either oral clonidine (0.2 mg) or identical-looking placebo tablets 90 minutes before arriving at the operating room. Induction of anesthesia was performed by the same standard protocol in all patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were recorded before and after induction; immediately after intubation; 5, 10, and 15 minutes thereafter; at the time of extubation; and one hour after the operation. The surgeons were asked to rate the quality of the operative field on a four-point scale that ranged from mild (1) to abundant bleeding (2).

RESULTS
Intraoperative SBP was lower in the clonidine group. After both intubation and extubation, the increases in SBP, DBP, and HR in clonidine-treated subjects were significantly less than the changes in the control patients. The amount of fentanyl given to control blood pressure and HR was significantly less in the clonidine group (18 ± 38 vs. 39 ± 53 μg, P = 0.02). The responses to the four-point scale indicated that intraoperative bleeding in the clonidine group was less than in the placebo group (1.2 ± 0.4 vs. 1.7 ± 0.6, P < 0.05).

CONCLUSIONS
Premedication with oral clonidine can improve the hemodynamic management of cesarean cases.

Clonidine
Hemodynamic
Cesarean Section
Blood Pressure


Treating aplasia cutis congenita in a newborn with the combination of ionic silver dressing and moist exposed burn ointment: A case report.

Abstract:
BACKGROUND
Aplasia cutis congenita (ACC) in newborns is a condition in which congenital defects or hypoplasia is present in part of the epidermis, dermis and even subcutaneous tissue (including muscle and bones). First reported by Cordon in 1767, ACC is a rare disease with a low incidence of 1/100000 to 3/10000. Currently, there are 500 cases reported worldwide. ACC can be accompanied by other malformations. The onset mechanism of the disease remains unknown but is thought to be correlated to factors such as genetics, narrow uterus, foetal skin and amniotic membrane adhesion, use of teratogenic drugs in early pregnancy and viral infection.

CASE SUMMARY
In August 2018, we treated a newborn with ACC on the left lower limbs using a combination of ionic silver dressing and moist exposed burn ointment (MEBO) and achieved a satisfactory treatment outcome. The skin defects were observed on the external genitals and on areas from the left foot to 3/4 of the upper left side. Subcutaneous tissue and blood vessels were observed in the regions with skin defects. The following treatments were provided. First, the wound was rinsed with 0.9% sodium chloride solution followed by disinfection with povidone-iodine twice. And then MEBO was applied to the wound at a thickness of approximately 1 mm. After applying ionic silver dressing, the wound was covered with sterile gauze. The wound dressing was replaced every 2-3 d. At the 4-mo follow-up, the treatment outcome was satisfactory. There was minimal scar tissue formation, and limb function was not impaired.

CONCLUSION
The combination of ionic silver dressing and MEBO to ACC is helpful.

Lei|Guo-Feng|GF| Zhang|Jun-Ping|JP| Wang|Xiao-Bing|XB| You|Xiao-Li|XL| Gao|Jin-Ya|JY| Li|Xiao-Mei|XM| Chen|Mei-Ling|ML| Ning|Xiu-Qin|XQ| Sun|Jiang-Li|JL|

Aplasia cutis congenita
Newborns
Ionic silver dressing
Moist exposed burn ointment


Decreased serum levels of polyunsaturated fatty acids and folate, but not brain-derived neurotrophic factor, in childhood and adolescent females with depression.

Abstract: Evidence from observational studies suggests that there is an association among depression and brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs), and folate; however, this association has yet to be examined in childhood and adolescent depression. The objective was to determine whether the BDNF, PUFAs, and folate in serum differ between first-episode childhood and adolescent depressed patients and healthy controls. We measured the serum levels of BDNF, PUFAs, and folate of cases admitted to the hospital for depression (n=24) and compared it to that of controls (n=26). Subjects and their parents were informed about the nature and the purpose of this study, and a consent form was signed by parents. The ethics committee of Hirosaki University Graduate School of Medicine approved the study protocol. There were significant differences in the docosahexanoic acid (DHA), arachidonic acid (AA), and folate levels between cases and controls. Serum levels of DHA, AA, and folate levels in the patients group were statistically lower than those in the control group, while serum levels of BDNF were not different between cases and controls. These results are in line with findings of previous studies involving adult and elderly subjects, demonstrating lower levels of PUFAs and folate in patients with depression than healthy controls. However, further studies using larger sample size are warranted.

Tsuchimine|Shoko|S| Saito|Manabu|M| Kaneko|Sunao|S| Yasui-Furukori|Norio|N|


Food portion sizes and dietary quality in Irish children and adolescents.

Abstract:
OBJECTIVE
To describe relationships between the portion sizes of a range of foods commonly consumed by Irish children and adolescents and key indicators of dietary quality on the days they were consumed.

DESIGN
Cross-sectional data from the Irish National Children's Food Survey (2003-2004; 7 d weighed record) and National Teens' Food Survey (2005-2006; 7 d semi-weighed record) were used to compare mean values for a number of dietary quality indicators (e.g. energy-adjusted intakes of saturated fat, dietary fibre and Na) across portion size tertiles for a range of foods, on the days the foods were consumed.

SETTING
The Republic of Ireland.

SUBJECTS
Nationally representative samples of children aged 5-12 years (n 594) and adolescents aged 13-17 years (n 441).

RESULTS
Relationships between food portion sizes and indicators of dietary quality on the days the foods were consumed were similar in both children and adolescents. Lower dietary energy density and saturated fat intakes, and higher dietary fibre intakes, were observed on the days larger portions of fruit and boiled potatoes were consumed. Higher dietary energy density and lower micronutrient intakes were observed on the days larger portions of sugar-sweetened beverages were consumed. Higher Na intakes were observed on the days larger portions of frying meats were consumed.

CONCLUSIONS
The current work identifies foods for which larger portion sizes may be associated with positive dietary attributes, as well as the opposite. Findings will form an evidence base from which more specific dietary guidance relating to portion size may be developed for Irish children and adolescents.


Phonemic discrimination and reproduction in 4-5-year-old children: Relations to hearing.

Abstract:
OBJECTIVE
The long-term objective of this research is to highlight the importance of speech perception assessment in children with developmental language disorder (DLD), and to investigate how hearing contributes to speech and language skills. As a first step in fulfilling this aim, the present study explored relations between phonemic discrimination and reproduction, and sensitive measures of hearing in young healthy children.

METHODS
The American Listen-Say test was developed and served as speech perception tool. This test reports speech discrimination of phonemic contrasts quantitatively for both quiet and in noise conditions, along with reproduction scores, all measured within one session. Speech tokens were perceptually homogenized in noise. Forty-one 4-5-year-old American children participated. Phonemic discrimination (quiet and speech shaped noise) and phonemic reproduction, audiometric thresholds in the conventional (1-8 kHz) and extended high frequency (EHF; 10-16 kHz) range, and distortion product otoacoustic emissions (DPOAEs) were examined.

RESULTS
All children had normal hearing thresholds within the conventional range (mean PTA bilaterally 8.6 dB HL). Ten (24.3%) of the children had elevated EHF thresholds (> 20 dB HL) for one or more frequencies or ears, and six (14.6%) had DPOAE signal to noise ratios (SNR) < 6 dB. EHF thresholds and DPOAE SNRs were significantly associated. Children's phonemic discrimination was impaired in noise, relative to quiet. There was a moderate, significant correlation between overall phonemic discrimination in noise and EHF audiometric thresholds.

CONCLUSIONS
Overall, the present study showed that sensitive hearing measures enabled the detection of subtle hearing difficulties in young healthy children. In particular, phonemic discrimination in noise showed associations with hearing. Implications of including sensitive hearing measures in children with DLD are discussed.

Young healthy children
phonemic reproduction
DPOAEs
phonemic discrimination in noise
extended high frequency hearing


Genome-wide identification of human- and primate-specific core promoter short tandem repeats.

Abstract: Recent reports of a link between human- and primate-specific genetic factors and human/primate-specific characteristics and diseases necessitate genome-wide identification of those factors. We have previously reported core promoter short tandem repeats (STRs) of extreme length (≥6-repeats) that have expanded exceptionally in primates vs. non-primates, and may have a function in adaptive evolution. In the study reported here, we extended our study to the human STRs of ≥3-repeats in the category of penta and hexaucleotide STRs, across the entire human protein coding gene core promoters, and analyzed their status in several superorders and orders of vertebrates, using the Ensembl database. The ConSite software was used to identify the transcription factor (TF) sets binding to those STRs. STR specificity was observed at different levels of human and non-human primate (NHP) evolution. 73% of the pentanucleotide STRs and 68% of the hexanucleotide STRs were found to be specific to human and NHPs. AP-2alpha, Sp1, and MZF were the predominantly selected TFs (90%) binding to the human-specific STRs. Furthermore, the number of TF sets binding to a given STR was found to be a selection factor for that STR. Our findings indicate that selected STRs, the cognate binding TFs, and the number of TF set binding to those STRs function as switch codes at different levels of human and NHP evolution and speciation.

Bushehri|A|A|
Barez|M R Mashhoudi|MR|
Mansouri|S K|SK|
Biglarian|A|A|
Ohadi|M|M|

Genome-wide
Primate-specific
Core promoter
Short tandem repeat
AP-2alpha
Sp1
MZF
Human-specific


Prosecretory effect of loperamide in ileal and colonic mucosae of mice displaying high or low swim stress-induced analgesia associated with high and low endogenous opioid system activity.

Abstract:
BACKGROUND
Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and changes in bowel habit. The aim of this study was to characterize the effect of loperamide hydrochloride (LOP) and naloxone hydrochloride (NLX), an opioid agonist and antagonist, respectively, on electrolyte equilibrium in ileal and colonic mucosae and to estimate the possible influence of divergent activity of the endogenous opioid system (EOS) on IBS therapy.

METHODS
Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low EOS activity were used in this study. To assess the effect of LOP and NLX on HA/LA lines in vivo, we used the castor oil-induced diarrhea model. Changes in electrolyte equilibrium were determined on the basis of short-circuit current (ΔIsc ) in isolated mouse ileum and colon exposed to LOP and NLX and stimulated by forskolin (FSK), veratridine (VER), and bethanechol (BET).

KEY RESULTS
In vivo, we found that LOP significantly prolonged time to appearance of diarrhea in HA and LA lines. In vitro, LOP and NLX increased ΔIsc in FSK- and VER-stimulated colonic tissue, respectively, in HA line. In the ileum, LOP increased ΔIsc in FSK- and VER-stimulated tissue and decreased ΔIsc in BET-stimulated tissues in HA line.

CONCLUSIONS & INFERENCES
Individual differences in EOS activity may play a crucial role in the response to the IBS-D therapy, thus some patients may be at an increased risk of side effects such as constipation or diarrhea.

Wasilewski|A|A| Misicka|A|A| Sacharczuk|M|M| Fichna|J|J|0000-0002-8443-4417

endogenous opioid system
irritable bowel syndrome
ion transport
secretory diarrhea


IL-6 and CD8+ T cell counts combined are an early predictor of in-hospital mortality of patients with COVID-19.

Abstract: BACKGROUNDFatal cases of COVID-19 are increasing globally. We retrospectively investigated the potential of immunologic parameters as early predictors of COVID-19.METHODSA total of 1018 patients with confirmed COVID-19 were enrolled in our 2-center retrospective study. Clinical feature, laboratory test, immunological test, radiological findings, and outcomes data were collected. Univariate and multivariable logistic regression analyses were performed to evaluate factors associated with in-hospital mortality. Receiver operator characteristic (ROC) curves and survival curves were plotted to evaluate their clinical utility.RESULTSThe counts of all T lymphocyte subsets were markedly lower in nonsurvivors than in survivors, especially CD8+ T cells. Among all tested cytokines, IL-6 was elevated most significantly, with an upward trend of more than 10-fold. Using multivariate logistic regression analysis, IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/μL were found to be associated with in-hospital mortality after adjusting for confounding factors. Groups with IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/μL had a higher percentage of older and male patients as well as a higher proportion of patients with comorbidities, ventilation, intensive care unit admission, shock, and death. Furthermore, the receiver operating curve of the model combining IL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/μL) displayed a more favorable discrimination than that of the CURB-65 score. The Hosmer-Lemeshow test showed a good fit of the model, with no statistical significance.CONCLUSIONIL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/μL) are 2 reliable prognostic indicators that accurately stratify patients into risk categories and predict COVID-19 mortality.FundingThis work was supported by funding from the National Natural Science Foundation of China (no. 81772477 and 81201848).

Luo|Miao|M| Liu|Jing|J| Jiang|Weiling|W| Yue|Shuang|S| Liu|Huiguo|H| Wei|Shuang|S|

T cells
Cytokines
Infectious disease
Pulmonology


Validation of the Zulfiqar Frailty Scale (ZFS): A New Tool for General Practitioners.

Abstract:
INTRODUCTION
The early detection of frailty, a frequent transient state that can be reversible in the elderly and is responsible for significant morbidity and mortality, helps prevent complications from it.

OBJECTIVE
To evaluate the performance of the "ZFS" tool to screen for frailty as defined SEGA scale criteria in an ambulatory population of patients at least 65 years of age.

METHODS
A prospective non-interventional study conducted in Alsace for a duration of six months that included patients aged 65 and over, judged to be autonomous with an ADL > 4/6.

RESULTS
In this ambulatory population of 102 patients with an average age of 76 years, frailty, according to modified SEGA criteria grid A, had a prevalence of 19.6%. Frailty, according to the "ZFS" tool, had a prevalence of 35.0%, and all of its elements except weight loss were significantly associated with frailty. Its threshold for identifying frailty is three criteria out of six. It was rapid (average completion time: 87 s), had a sensitivity of 100%, and a negative predictive value of 100%.

CONCLUSIONS
The "ZFS" tool makes it possible to screen for frailty with a high level of sensitivity and a negative predictive value.

prevention
ZULFIQAR Frailty Scale (ZFS)
elderly subjects
modified SEGA scale grid A
primary care