bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic effects of carvedilol through β‐arrestin proteins: investigations in a streptozotocin‐induced diabetes rat model and in C2C12 myoblasts
Authors: Güven Berna , Kara Zümra , Onay‐Beşikci Arzu 
Published: September 2020

Background and PurposeCarvedilol is a third‐generation β‐adrenoceptor antagonist, which also stimulates β‐arrestins. β‐arrestins initiate intracellular signalling and are involved in insulin release and sensitivity. Carvedilol is superior in effectiveness to other drugs that are used for similar indications and does not cause insulin resistance or diabetes, which can occur with other β‐antagonists. We have shown that carvedilol increased glucose usage in C2C12 cells. We investigate the biased agonist efficacy of carvedilol on β‐arrestins.Experimental ApproachStreptozotocin (STZ)‐induced diabetes rat model was used to induce metabolic and cardiac disorders. After 8 weeks of diabetes, animals were treated with carvedilol or vehicle for another 4 weeks. In vitro heart function was evaluated at baseline as well as with increasing concentrations of isoprenaline. Effects of diabetes and carvedilol treatment on β‐arrestins, ERK, PPARα, CD36 proteins and pyruvate kinase activity were evaluated. β‐arrestins were silenced in C2C12 cells by using siRNA. Acute effects of carvedilol on ERK, CD36, mitochondrial transcription factor A, cardiolipin proteins and citrate synthase activity were investigated.Key ResultsCarvedilol reversed the deterioration of cardiac function in diabetes and diabetes‐induced decrease in β‐arrestins in rats. Carvedilol decreased the expression of CD36 in diabetes and increased mitochondrial transcription factor A and cardiolipin proteins. Silencing of β‐arrestins in cells prevented the effects of carvedilol on these proteins.Conclusion and ImplicationsThe metabolic effects of carvedilol seem to be related to biased activation of β‐arrestins. Patients with cardiovascular and metabolic disorders may benefit from new compounds that selectively act on β‐arrestins.
Oxysterols in cancer management: From therapy to biomarkers
Authors: Kloudova‐Spalenkova Alzbeta , Holy Petr , Soucek Pavel 
Published: September 2020

Oxysterols are oxidized derivatives of cholesterol, both endogenous and exogenous. They have been implicated in numerous pathologies, including cancer. In addition to their roles in carcinogenesis, proliferation, migration, apoptosis, and multiple signalling pathways, they have been shown to modulate cancer therapy. They are known to affect therapy of hormonally positive breast cancer through modulating oestrogen receptor activity. Oxysterols have also been shown in various in vitro models to influence efficacy of chemotherapeutics, such as doxorubicin, vincristine, cisplatin, 5‐fluorouracil, and others. Their effects on the immune system should also be considered in immunotherapy. Selective anti‐cancer cytotoxic properties of some oxysterols make them candidates for new therapeutic molecules. Finally, differences in oxysterol levels in blood of cancer patients in different stages or versus healthy controls, and in tumour versus non‐tumour tissues, show potential of oxysterols as biomarkers for cancer management and patient stratification for optimization of therapy.LINKED ARTICLESThis article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
Adipose tissue is a key organ for the beneficial effects of GLP‐2 metabolic function
Authors: Ejarque Miriam , Sabadell‐Basallote Joan , Beiroa Daniel , Calvo Enrique , Keiran Noelia , Nuñez‐Roa Catalina , Rodríguez Maria del Mar , Sabench Fatima , del Castillo Daniel , Jimenez Veronica , Bosch Fatima , Nogueiras Ruben , Vendrell Joan , Fernández‐Veledo Sonia 
Published: September 2020

Background and PurposeGlucagon‐like peptide‐2 (GLP‐2) is a gastrointestinal hormone released in response to nutritional intake that exerts a wide range of effects by activating GLP‐2 receptors. In addition to its intestinotrophic effects, GLP‐2 also positively influences glucose metabolism under conditions of obesity, but the mechanisms behind this remain unclear. Here, we have investigated the molecular role of the GLP‐2/GLP‐2 receptor axis in energetic metabolism, focusing on its potential modulatory effects on adipose tissue.Experimental ApproachPhysiological measurements (body weight, food intake, locomotor activity, and energy expenditure) and metabolic studies (glucose and insulin tolerance tests) were performed on lean and obese mice treated with the protease‐resistant GLP‐2 analogue teduglutide.Key ResultsAcute but not chronic centrally administered teduglutide decreased food intake and weight‐gain. By contrast, chronic activation of peripheral GLP‐2 receptors increased body weight‐independent glucose tolerance and had anti‐inflammatory effects on visceral adipose tissue. Using a gene silencing approach, we found that adipose tissue is necessary for these beneficial effects of teduglutide. Finally, teduglutide regulates the inflammatory state and acts as an anabolic signal in human adipocytes.Conclusion and ImplicationsOverall, our data identify adipose tissue as a new, clinically relevant, site of action for GLP‐2 activity in obesity.LINKED ARTICLESThis article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
Associations and risk factors for dental trauma: A systematic review of systematic reviews
Authors: Magno Marcela Baraúna , Nadelman Patricia , Leite Karla Lorene de França , Ferreira Daniele Masterson , Pithon Matheus Melo , Maia Lucianne Cople 
Published: September 2020

AbstractObjectiveWe sought to revise, qualify and summarize the body of evidence based on current information on the known associations and risk factors for traumatic dental injury (TDI) occurrence with an overview of systematic reviews.MethodsElectronic searches were performed with no language nor date restrictions.According to the PECO strategy, systematic reviews that investigated participants (P) with (E) and without (O) the presentation of factors relating to TDI and these factors’ association with TDI episodes (O) as primary or secondary outcomes were included. Quality assessment and bias control were carried out according to the AMSTAR 2 checklist. In cases of systematic review results of discordance, the Jadad decision algorithm was applied.ResultsAfter titles, abstracts and full texts were read, 19 systematic reviews were included in this overview. Four were classified with critically low, eleven with low and four with moderate methodological quality, respectively. In all studies, 249 cross‐sectional, 34 epidemiological surveys, 22 cohort, 9 case‐control, 4 longitudinal, 3 ecological and 30 unspecified studies were included. Male gender, child age, greater overjet, inadequate lip coverage, anterior open bite, caries in the permanent dentition, overweight, a previous history of TDI, tongue piercing, the use of alcoholic beverages and participation in sports were all associated with a greater chance of suffering TDI.ConclusionsSociodemographic, clinical and environmental factors are associated with a greater chance of TDI occurrence. However, most of the systematic reviews included were of a low quality and may not provide an accurate and comprehensive summary of the available research that addresses the question of interest. Well‐designed primary studies on different aspects of TDI are encouraged to provide higher quality scientific evidence.
Impaired small airway function in non‐asthmatic chronic rhinosinusitis with nasal polyps
Authors: Du Kun , Zheng Ming , Zhao Yan , Xu Wenbin , Hao Yun , Wang Yue , Zhao Jinming , Zhang Nan , Wang Xiangdong , Zhang Luo , Bachert Claus 
Published: September 2020

AbstractBackgroundThere is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non‐asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non‐asthmatic patients with CRSwNPs remains unclear.ObjectiveThis study analysed the lung function of non‐asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs.MethodsThe clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non‐asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients.ResultsNon‐asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF75) and FEF50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non‐asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF50 was associated with the recurrence of non‐asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type‐2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non‐asthmatic CRSwNP patients was related to serum IgE levels.Conclusions and clinical relevanceThis study provides evidence that non‐asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type‐2 inflammation.
Antithymocyte induction dosing and incidence of opportunistic viral infections using steroid‐free maintenance immunosuppression
Authors: Von Stein Lauren , Leino Abbie D. , Pesavento Todd , Rajab Amer , Winters Holli 
Published: September 2020

AbstractBackgroundCurrently, there is limited literature evaluating rATG induction dosing and incidence of opportunistic viral infections when using steroid‐free maintenance immunosuppression.MethodsThis single‐center, retrospective, study compared high rATG (>4.5 mg/kg) versus low (<4.5 mg/kg) induction dosing and the overall incidence of early opportunistic viral infection at 180 days in the setting of maintenance immunosuppression consisting of tacrolimus, mycophenolate, rapid steroid withdrawal, and a tiered antiviral prevention strategy based on donor‐recipient Cytomegalovirus (CMV) serostatus.ResultsA total of 209 patients were included; 76 patients received low‐dose and 133 patients received high‐dose rATG. Incidence of overall opportunistic viral infection occurred more frequently in patients who received high compared to low dose (29.8% vs 25% p = .030). Incidence of CMV infection was also significantly increased in the high‐dose group (31.6% vs 18.4% p = .039). In a multivariable model, rATG dose, as a continuous variable, remained a significant independent predictor of infection along with CMV risk (OR 1.46, 95% CI 1.02‐2.09) controlling for age and CMV risk. There were no differences in graft‐related outcomes at 180 days.ConclusionHigher cumulative rATG induction dose was associated with increased incidence of opportunistic viral infections, in the setting of a steroid‐free maintenance immunosuppression in the early post‐transplant period.
Update on dermatomyositis in adults
Authors: Schlecht Nora , Sunderkötter Cord , Niehaus Sabine , Nashan Dorothée 
Published: September 2020

SummaryDermatomyositis (DM) in adults has a prevalence of 6–7 per 100,000 population per year. This dedicated compact overview was prepared due to an increasing incidence as well as an often underestimated systemic involvement and new developments in myositis‐specific antibodies (MSA). The spectrum of clinical dermatological and systemic symptoms is described. Related diagnostic procedures are depicted, and therapeutic regimens based on the German S2k guidelines and the current literature are presented.The urgency of an early diagnosis is emphasized as about 30 % of patients with DM manifest a tumor. Etiopathology is often associated with pulmonary fibrosis, and inflammation of myositis can cause irreversible muscle damage. Clinical signs and correct interpretation of serological markers can deliver valuable information on the extent of DM, and provide an indication for further diagnostic procedures, prognosis and choice of therapy.
Psychosocial stress of dermatology inpatients and their relatives – Comparison of patients with and without cancer
Authors: Buchhold Britta , Wiesmann Ulrich , Röske Kathrin , Lutze Stine , Arnold Andreas , Jülich Andreas , Ramp Marleen , Jünger Michael , Hannich Hans‐Joachim 
Published: September 2020

SummaryBackgroundIn the clinical treatment pathways of certified oncological centers, psychotherapeutic services are mandatory. Although patients with somatic, non‐oncological illnesses show an equally high prevalence of psychosocial stress, these guidelines do not exist for the general hospital sector. Are these patients really less burdened and is psychological support only needed in individual cases? The example of dermatological patients will be used to show whether the need for psychosocial care and the desire for support vary between individuals with and without malignant disease.Patients and methodsUsing the Hornheider screening instrument and distress thermometer, 216 dermatological inpatients assessed their psychosocial stress and that of a close relative. In addition, they were asked about their desire for support and preferred support provider.Resultsi) Patients without skin cancer were more frequently and more severely distressed than cancer patients. ii) Patients of both groups assessed their relatives to be approximately equally distressed. Compared with their own distress, cancer patients assessed their relatives as more frequently and on average more severely distressed. More than 50 % of all patients regarded their own disease as the cause of their relatives’ distress. iii) The desire for support in both groups was about 18 %. iv) Doctors and psychologists were usually named as potential contact persons.ConclusionsThe expansion of psychosocial support services for non‐tumor patients and their relatives seems necessary. The establishment of appropriate screening methods should be considered. Further studies in other clinical areas are required.
2020 New World Order
Authors: Wallace Beverly 
Published: September 2020

AbstractThis paper proposes that as the nation move toward the 2020 election, civil harmony might be possible with an ideological shift. Using the words of writer Sylvia Wynter in her work, “ 1492: New World View” who suggest that although this country was structured with domination and subjugation from its inception, this nation could be reimagined to embrace diverse people co‐existing. Understanding too that reconciliation must be defined by those who are marginalized, the author using an Afro‐futuristic ideology for a 2020 New World Order suggest that the Black Lives Matter movement could carry the torch.
Globalization of the #chatsafe guidelines: Using social media for youth suicide prevention
Authors: Robinson Jo , Teh Zoe , Lamblin Michelle , Hill Nicole T. M. , La Sala Louise , Thorn Pinar 
Published: September 2020

AbstractYoung people use social media to communicate about suicide, however, they often feel ill‐equipped to share their own experiences or to respond to expressions of risk by others.AimsTo describe the adaptation of the Australian #chatsafe guidelines for an international audience, and their initial roll out via social media.MethodsAn online survey (n = 48) and two workshops (n = 47) conducted between August and December 2019. Thirty‐eight countries were represented.ResultsMinimal adaptation of the Australian guidelines was required however, an abbreviated version and a suite of social media assets were developed. In the 6 weeks following publication the international guidelines were downloaded ~4100 times and the social media content reached over one million young people.ConclusionThe fact that the guidelines and campaign content appear to have had such success speaks to the need for young people to feel better equipped to communicate safely about suicide online.
Modulation of binocular rivalry with rapid monocular visual stimulation
Authors: Abuleil Dania , McCulloch Daphne L. , Patterson Heidi , Thompson Benjamin 
Published: September 2020

AbstractRapid visual stimulation can increase synaptic efficacy by repeated synaptic activation. This long‐term potentiation‐like (LTP‐like) effect can induce increased excitability in the human visual cortex. To examine the effect of rapid visual stimulation on perception, we tested the hypothesis that rapid monocular visual stimulation would increase the dominance of the stimulated eye in a binocular rivalry task. Participants (n = 25) viewed orthogonal 0.5 cpd gratings presented in a dichoptic anaglyph to induce binocular rivalry. Rivalry dynamics (alternation rate, dominance, and piecemeal durations) were recorded before and after 2 min of rapid monocular stimulation (9 Hz flicker of one grating) or a binocular control condition (9 Hz alternation of the orthogonal gratings viewed binocularly). Rapid monocular stimulation did not affect alternation rates or piecemeal percept duration. Unexpectedly, the rivalry dominance of the stimulated eye was significantly reduced. A further experiment revealed that this effect could not be explained by monocular adaptation. Together, the results suggest that rapid monocular stimulation boosts dominance in the non‐stimulated eye, possibly by activating homeostatic interocular gain control mechanisms.
Wolff on duties of esteem in the law of peoples
Authors: Blank Andreas 
Published: September 2020

AbstractThe role that the desire for self‐worth plays in international relations has become a prominent topic in contemporary political theory. Contemporary accounts are based on the notion of national self‐worth as a function of status; therefore, the desire for national self‐worth is seen as a source of anxiety and conflict over status. By contrast, according to Christian Wolff, there exists a duty to take care that both one's own and other political communities deserve to be esteemed. In his view, this duty is grounded in the duty of self‐perfection because the qualities for which communities deserve to be esteemed are those that promote the self‐perfection of individuals. From this perspective, he argues that duties of esteem toward political communities should not be seen as an outcome of power relations but rather as an outcome of the fulfillment of functions of the law of peoples. Wolff's line of argument draws attention to the possibility that anger over a violation of the desire for honor could be mistaken for an expression of specific culture‐specific sensitivities, while what really may be expressed is a diverging interpretation of the implications of dependence in international relations.
Left Wittgensteinianism
Authors: Queloz Matthieu , Cueni Damian 
Published: September 2020

AbstractSocial and political concepts are indispensable yet historically and culturally variable in a way that poses a challenge: how can we reconcile confident commitment to them with awareness of their contingency? In this article, we argue that available responses to this problem—Foundationalism,Ironism, andRight Wittgensteinianism—are unsatisfactory. Instead, we draw on the work of Bernard Williams to tease out and develop aLeft Wittgensteinianresponse. In present‐day pluralistic and historically self‐conscious societies,mereconfidence in our concepts is not enough. For modern individuals who are ineluctably aware of conceptual change, engaged concept‐use requiresreasonableconfidence, and in the absence of rational foundations, the possibility of reasonable confidence is tied to the possibility of critically discriminating between conceptual practices worth endorsing and those worth rejecting. We show that Left Wittgensteinianism offers such a basis for critical discrimination throughpoint‐based explanationsof conceptual practices which relate them to the needs of concept‐users. We end by considering how Left Wittgensteinianism guides our understanding of how conceptual practices can be revised in the face of new needs.
Head down tilt 15° in experimental intracerebral hemorrhage: a randomized noninferiority safety trial
Authors: Beretta S. , Versace A. , Martini B. , Viganò M. , Diamanti S. , Pini C. , Paternò G. , Carone D. , Mariani J. , Monza L. , Riva M. , Padovano G. , Rossi E. , Citerio G. , Castoldi G. , Padelli F. , Giachetti I. , Aquino D. , Giussani C. , Sganzerla E. P. , Ferrarese C. 
Published: September 2020

Background and purposeHead down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage.MethodsIntracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized noninferiority trial design was used to assign rats to HDT15° or flat position (n = 64). HDT15° was applied for 1 h during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 h. Secondary outcomes were mass effect, mortality, and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth, and cardiorespiratory parameters in separate sets of randomized animals (n = 32).ResultsHDT15° achieved the specified criteria of noninferiority for hematoma volume at 24 h. Mass effect, mortality, and functional deficit at 24 h showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pretreatment values (+2.91 ± 1.76 mmHg). HDT15° had a neutral effect on MRI‐based analysis of hematoma growth and cardiorespiratory parameters.ConclusionsApplication of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.
Clinical pathology and ultrasonographic findings from a Warmblood gelding with primary, severe, acute pancreatitis
Authors: Lack A. C. , Crabtree N. E. , Won W. W. , Fontenot R. L. 
Published: September 2020

SummaryA 24‐year‐old Warmblood gelding presented with a 6‐hour history of recurrent colic signs of increasing severity. Upon presentation, he was mildly painful, tachycardic and tachypnoeic and had decreased borborygmi. Nasogastric intubation resulted in no net reflux and rectal palpation revealed an ascending colon impaction. Percutaneous abdominal ultrasonography revealed dilated, thickened and hypomotile loops of small intestine. Complete blood count revealed leucopenia with neutropenia and an increased packed cell volume. Serum biochemistry revealed hyperproteinaemia, hyperglycaemia, hypocalcaemia, hyperbilirubinaemia, hypercholesterolaemia and elevated liver enzymes. Despite sedation and fluid resuscitation, the gelding became severely colicky. A repeat ultrasound was performed, revealing a moderate amount of free fluid and a mass effect between the liver and right dorsal colon. Abdominocentesis yielded a yellow, turbid fluid containing free‐floating white debris with an increased total protein and lactate concentration. Cytology of the fluid revealed necrotic mesothelial cells. The gelding was humanely euthanised due to poor prognosis. Necropsy revealed acute, severe pancreatitis and duodenitis. The mass effect on ultrasonography was retrospectively identified as the pancreas exhibiting a similar architecture to that seen in cases of acute pancreatitis in small animals.