bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel β‐carboline‐based indole‐4,7‐quinone derivatives as NAD(P)H: Quinone‐oxidoreductase‐1 inhibitor with potent antitumor activities by inducing reactive oxygen species, apoptosis, and DNA damage
Authors: Guo Yibing , Xu Liancheng , Ling Changchun , Yang Tao , Zheng Wenjie , Lv Jin , Guo Qingsong , Chen Bohua
Published: June 2020

Eighteen new β‐carboline‐based indole‐4,7‐quinone derivatives (12a–i and 13a–i) were designed and synthesized, and their in vitro and in vivo antiproliferative activities were studied. Most of target compounds showed strong inhibition on three human tumor cells' proliferation. In particular, the most active compound 13g not only displayed more prominent antiproliferative activities than β‐lapachone, a clinical antitumor candidate, but also exerted significant NAD(P)H: quinone‐oxidoreductase‐1 (NQO1) inhibitory activity and NQO1‐dependent cytotoxicity in HT29 cells. Furthermore, 13g dose‐dependently induced high ROS levels in HT29 cells, and selectively inhibited cancer cell but not non‐tumor colon cell proliferation in vitro. Importantly, 13g promoted HT29 cell apoptosis and DNA damage by regulating relative apoptotic proteins and H2AX expression. Finally, 13g displayed significant growth inhibition of HT29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.
Are trust and satisfaction similar in dental care settings?
Authors: Song YoungHa , Luzzi Liana , Chrisopoulos Sergio , Brennan David S.
Published: June 2020

Objectives

Trust and satisfaction in dental care settings are salient constructs to operationalize the concept of dentist‐patient relationships (DPR). This study aimed to compare the similarity of both constructs with regard to factor structure and revise the scales for better psychometric properties.

Methods

Data analysed in the study were collected in self‐complete questionnaires from a random sample of 4011 adults living in South Australia. Trust and satisfaction were assessed using the Dentist Trust Scale and the Dental Care Satisfaction scale. Items in the scales were initially examined with a split‐half sample in exploratory factor analysis and cluster analysis. Factor structures of different model designs were tested on the other half sample in confirmatory factor analysis. The final model was cross‐validated on the first half sample for structural invariance.

Results

Exploratory factor analysis revealed a three‐factor structure consisting of ‘trust’, ‘satisfaction’ and ‘distrust/dissatisfaction’ (60.2% of the variance explained; Cronbach's α = 0.94, 0.81, 0.73, respectively). Cluster analysis supported the factor solution with the same three major clusters except for a single‐item independent branch of the ‘cost’ domain from the satisfaction scale. The final model was designed with two correlated but distinct factors, ‘trust’ and ‘satisfaction’, with the modification of one inter‐item covariance and deleting the least associated item (GFI = 0.96, CFI = 0.98, RMSEA = 0.06). The stability of the final model was achieved through cross‐validation (P = .143, ∆CFI < 0.001).

Conclusions

Trust and satisfaction in dental care settings are unidimensionally different yet highly correlated factors concurrently. Demonstrating the discriminant and complementary functions of both constructs can justify the rationale to apply them together in further studies for DPR.
Occupational airborne contact urticaria, anaphylaxis and asthma in farmers and agronomists due to Bruchus pisorum
Authors: Armentia Alicia , Alvarez Rafael , Moreno‐González Víctor , Martín Blanca , Fernández Sara , Martín Sara , Moro Angela , Vega Jose M , Barrios Abel , Castillo Miriam , Pineda Fernando
Published: June 2020

Background

Occupational contact urticaria due to inhalation of legume pest allergens has rarely been described.

Objective

To determine the cause of an outbreak of airborne contact urticaria, asthma, and anaphylaxis in farmers and agronomists studying the disinsectization of dried peas. Peas were treated with aluminum phosphide (EPA).

Methods

Extracts prepared from Bruchus lentis and Bruchus pisorum bodies and from healthy legumes, EPA‐treated legumes, and infested legumes, were used for in vivo tests (skin prick testing, oral, and specific bronchial challenge for the diagnosis of asthma and anaphylaxis) in affected patients and in five control patients with severe legume hypersensitivity. Open application, patch testing with the most common legume insecticides, molecular analysis, and IgE immunoblotting were undertaken.

Results

We found positive responses (prick, provocation, immune detection) to parasitic pea extracts and B. pisorum. A 25 kDa band was detected in the western blot of all patients who worked with infested EPA‐treated peas. Bands from B. pisorum extract were detected in all patients. No responses to pea allergens were found in any patient, unlike in legume allergy controls. Oral provocation tests were negative.

Conclusion

B. pisorum is a cause of contact urticaria and may cause occupational hives, anaphylaxis, and asthma. The allergen may enter by inhalation or puncture of setae released by B. pisorum.
Incentivizing co‐management for impact: mechanisms driving the successful national expansion of Tonga's Special Management Area program
Authors: Smallhorn‐West Patrick F. , Sheehan Jason , Malimali Siola'a , Halafihi Tuikolongahau , Bridge Tom C. L. , Pressey Robert L. , Jones Geoffrey P.
Published: June 2020

The expansion of coastal marine protected areas can suffer from two key drawbacks: (a) the difficulty of incentivizing local communities to manage areas for conservation when their livelihoods also depend on resource use; and (b) that many protected areas get situated residually, or in locations with limited value for either biodiversity conservation or livelihoods. Here, we discuss and analyze key characteristics of Tonga's Special Management Area (SMA) program, including both the mechanisms that have motivated its successful national expansion and its ability to configure no‐take reserves in areas that are considered to have high value to resource users. Granting communities exclusive access zones in exchange for implementing no‐take reserves has encouraged conservation actions while fostering long‐term relationships with resources. Ensuring no‐take reserves occurred within the boundaries of exclusive access zones enabled communities to protect areas of greater extractive values than they would have otherwise. We conclude that the success of this program offers a way forward for achieving targets in the global expansion marine protected areas.
Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours
Authors: Cheng Ya Qi , Wang Shou Bi , Liu Jia Hui , Jin Lin , Liu Ying , Li Chao Yang , Su Ya Ru , Liu Yu Run , Sang Xuan , Wan Qi , Liu Chang , Yang Liu , Wang Zhi Chong
Published: June 2020

The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti‐tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti‐tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME—such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell‐based microenvironment therapies—to provide novel ideas for producing breakthroughs in tumour therapy strategies.
A cross‐sectional analysis of electronic cigarette use in US adults by asthma status
Authors: Tran Lam , Tran Phoebe , Tran Liem
Published: June 2020

Objective

Electronic cigarette (e‐cigarette) use has been shown to worsen the asthma symptoms, but there is little information on current e‐cigarette use patterns in the general US adult asthma population. We examined the unadjusted and adjusted estimates of current e‐cigarette use in a nationally representative sample of US adults by asthma status and what factors influence this use.

Methods

We determined the prevalence of current e‐cigarette use in adults with and without asthma using the 2016‐2018 Behavioural Risk Factor Surveillance System datasets. A multinomial logistic regression model was used to obtain adjusted estimates of e‐cigarette use by asthma status while also identifying which sociodemographic and clinical factors are associated with e‐cigarette use in adults with asthma.

Results

Of the 23,071 adults with asthma in the study, 22.5% were currently using e‐cigarettes. After adjusting for sociodemographic and clinical factors associated with asthma and current e‐cigarette use, adults with asthma had similar odds of every day e‐cigarette use (odds ratio (OR): 1.04, 95% confidence interval (CI): 0.93‐1.15) but higher odds of e‐cigarette use on some days (OR: 1.18, 95% CI: 1.10‐1.27) compared to adults without asthma. Younger age, male sex and former or current traditional cigarette use were significantly associated with both e‐cigarette use on some days and every day in adults with asthma.

Conclusion

Current e‐cigarette use estimates among US adults with asthma indicate a need for further e‐cigarette education and cessation interventions that are specifically tailored to sociodemographic and clinical groups who are especially prone to e‐cigarette use within this population.
Attenuated early inflammatory response in solid organ recipients with COVID‐19
Authors: Bösch Florian , Börner Nikolaus , Kemmner Stephan , Lampert Christopher , Jacob Sven , Koliogiannis Dionysios , Stangl Manfred , Michel Sebastian , Kneidinger Nikolaus , Schneider Christian , Fischereder Michael , Irlbeck Michael , Denk Gerald , Werner Jens , Angele Martin K. , Guba Markus O.
Published: June 2020

Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS‐CoV‐2) infection. The specific features of coronavirus disease 2019 (COVID‐19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Seven transplanted patients (two liver, three kidneys, one double lung, one heart) admitted to the Ludwig‐Maximilians‐University Munich because of COVID‐19 and tested positive for SARS‐CoV‐2 were included. The clinical course and the clinical findings were extracted from the medical record. The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18, and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours. One kidney and the lung transplant recipients were required to intubate after 10 and 15 days, respectively. Immunosuppression was adapted in five patients, but continued in all patients. Compared to non‐transplanted patients at the ICU (n = 19) the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL‐6 blood values. This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS‐CoV‐2, their clinical course seems to be similar to immunocompetent patients.
Use and validation of a survey tool to measure the perceived effectiveness of insulin prescribing safety interventions in UK hospitals
Authors: Bain A. , Hasan S. S. , Kavanagh S. , Babar Z.‐U.‐D.
Published: June 2020

Aims

To describe the use and validation of a survey tool to elicit the opinion of hospital pharmacists and medicines safety officers in the UK regarding the perceived effectiveness of strategies to improve insulin prescribing safety in hospitals.

Methods

One respondent from each participating organization completed the survey on behalf of the main acute hospital in their trust (n = 92). A five‐point Likert scale was used to determine opinion on how effective 22 different interventions were at promoting insulin safety at the respondent’s trust. The tool, the Perception of Effectiveness of Prescribing Safety Interventions for Insulin (PEPSII) questionnaire, underwent content validity testing. The reliability was estimated using Cronbach’s alpha (α).

Results

The PEPSII questionnaire demonstrated good reliability (α = 0.867). Outreach team review and mandatory insulin education were the highest‐scoring interventions; the insulin passport was amongst the lowest scoring interventions. Most interventions were considered more effective by trusts using them compared to those who didn't, except for self‐administration policies, electronic prescribing and the insulin passport.

Conclusions

The perceived effectiveness of a variety of insulin prescribing safety strategies in UK hospitals was described by leveraging a purposely developed survey tool. The results describe current levels of support for recommended interventions, and may facilitate the direction of both local and national insulin prescribing safety improvement efforts.
Bleeding risk in patients with acute coronary syndrome in a Turkish population: Results from the Turkish Acute Coronary Syndrome Registry (TACSER) study
Authors: Avci Eyüp , Kiriş Tuncay , Akgün Didar Elif , Celik Aykan , Akçay Filiz Akyildiz , Acar Burak , Kurmuş Özge , Altındag Rojuva , Safak Özgen , Demirtas Abdullah Orhan , Güzel Tuncay , Öztürk Önder , Yildirim Tarik , Yüksek Umit , Ergene Asim Oktay
Published: June 2020

Objective

Bleeding is one of the most important causes of mortality in patients with acute coronary syndrome (ACS). This study therefore aimed to investigate bleeding risk in patients with ACS who were scheduled to receive dual antiplatelet therapy (DAPT) in Turkey.

Methods

This was a multicentre, observational, cross‐sectional cohort study. The study population included 963 patients with ACS from 12 centres in Turkey. We used the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE‐DAPT) score to predict the bleeding risk for all the patients. The patients were divided into high (≥25) or low (˂25) bleeding risk groups based on their PRECISE‐DAPT scores.

Results

The mean PRECISE‐DAPT score was 21.9. Overall, 32.2% of the patients had high PRECISE‐DAPT scores (≥25). Compared with the male patients, the female patients had higher PRECISE‐DAPT scores (28.2 ± 15.7 vs 18.4 ± 13.6, P ˂ .001). Among the females, the rate of patients with a PRECISE‐DAPT score ≥25 was 53%, while among the male patients, the score occurred at a rate of 22%. The female patients had lower haemoglobin (Hb) levels than the male patients (12.1 ± 1.7 vs 13.8 ± 1.9, P ˂ .001) and lower creatinine clearance (70.7 ± 27.5 vs 88.7 ± 26.3, P ˂ .001). The in‐hospital bleeding rates were higher among the patients with high PRECISE‐DAPT scores than among those who did not have high scores. Furthermore, the patients with high PRECISE‐DAPT scores had a higher in‐hospital mortality rate compared with those with low PRECISE‐DAPT scores (1% vs 0%, P = .11).

Conclusions

The mean PRECISE‐DAPT score was high among the patients with ACS in this study, indicating that the bleeding tendency was high. This study showed that the PRECISE‐DAPT score may help physicians determine the type and duration of DAPT, especially in patients with ACS in Turkey.
COVID‐19 and non‐alcoholic fatty liver disease: Two intersecting pandemics
Authors: Portincasa Piero , Krawczyk Marcin , Smyk Wiktor , Lammert Frank , Di Ciaula Agostino
Published: June 2020

Background

Initial evidence from China suggests that most vulnerable subjects to COVID‐19 infection suffer from pre‐existing illness, including metabolic abnormalities. The pandemic characteristics and high‐lethality rate of COVID‐19 infection have raised concerns about interactions between virus pathobiology and components of the metabolic syndrome.

Methods

We harmonized the information from the recent existing literature on COVID‐19 acute pandemic and mechanisms of damage in non‐alcoholic fatty liver disease (NAFLD), as an example of chronic (non‐communicable) metabolic pandemic.

Results

COVID‐19‐infected patients are more fragile with underlying metabolic illness, including hypertension, cardiovascular disease, type 2 diabetes, chronic lung diseases (e.g. asthma, chronic obstructive pulmonary disease and emphysema) and metabolic syndrome. During metabolic abnormalities, expansion of metabolically active fat ('overfat condition') parallels chronic inflammatory changes, development of insulin resistance and accumulation of fat in configuring NAFLD. The deleterious interplay of inflammatory pathways chronically active in NAFLD and acutely in COVID‐19‐infected patients, can explain liver damage in a subgroup of patients and might condition a worse outcome in metabolically compromised NAFLD patients. In a subgroup of patients with NAFLD, the underlying liver fibrosis might represent an additional and independent risk factor for severe COVID‐19 illness, irrespective of metabolic comorbidities.

Conclusions

NAFLD can play a role in the outcome of COVID‐19 illness due to frequent association with comorbidities. Initial evidences suggest that increased liver fibrosis in NAFLD might affect COVID‐19 outcome. In addition, long‐term monitoring of post‐COVID‐19 NAFLD patients is advisable, to document further deterioration of liver damage. Further studies are required in this field.
Effect of thickness and occlusal accommodation on the degree of satisfaction with mouthguard use among water polo players: A randomized crossover trial
Authors: Flores‐Figueiras Carla , Zamora‐Olave Carla , Willaert Eva , Martinez‐Gomis Jordi
Published: June 2020

Background/Aim

The optimal mouthguard type and design for each player and sport are currently unknown. The aim of this study was to assess the effect of using a thicker custom‐made mouthguard with occlusal accommodation on the degree of satisfaction among water polo players.

Material and Methods

Twenty‐five elite water polo players participated in this randomized four‐period crossover trial conducted from February to May 2019. For each participant, two customized mouthguards were fabricated using 4‐mm ethyl vinyl acetate foil: Type A included no occlusal accommodation, and Type B included a 2‐mm occlusal accommodation. Players wore each mouthguard during training sessions and competitions for 2 weeks in one of two randomized sequences. After each match or training session, players were asked to evaluate the mouthguards on 10‐point scales across three domains: discomfort or interference with function, protection, and general satisfaction. Mouthguard preference was also recorded.

Results

The mouthguard with occlusal accommodation was reported to interfere more with speech and swallowing (P < .001) and with esthetics, breathing, and athletic performance (P < .05) compared with the conventional mouthguard. Although occlusal accommodation was associated with a higher perceived degree of protection (mean difference 0.5; 95% CI: 0.2‐0.8), players were still more satisfied with the conventional mouthguard (mean difference 1.5; 95% CI: 0.8‐2.3). Two players preferred the occlusal mouthguard, whereas 22 preferred the conventional mouthguard (P = .007).

Conclusions

Among water polo players, occlusal accommodation increasing the thickness of the custom‐made mouthguards may offer a greater perceived sense of protection, but this comes at the cost of greater discomfort and reduced overall satisfaction. Dentists can recommend conventional mouthguards for most water polo players.
Sickle cell trait and the potential risk of severe coronavirus disease 2019—A mini‐review
Authors: Kehinde Tawakalitu Abosede , Osundiji Mayowa Azeez
Published: June 2020

Coronavirus Disease 2019 (COVID‐19) pandemic is a rapidly evolving public health problem. The severity of COVID‐19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID‐19 among African Americans, although detailed epidemiological study data is pending. Sickle cell disease (SCD) disproportionately affects Black/African Americans in the United States as well as forebearers from sub‐Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America), and some Mediterranean countries. The carrier frequency for SCD is high among African Americans. This article underscores the putative risks that may be associated with COVID‐19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine.
Time trends and patient selection in the use of continuous electrocardiography for detecting atrial fibrillation after stroke: a nationwide cohort study
Authors: Lyckhage L. F. , Hansen M. L. , Butt J. H. , Hilmar Gislason G. , Gundlund A. , Wienecke T.
Published: June 2020

Background and purpose

Clinical use of continuous electrocardiography (cECG) for detecting atrial fibrillation (AF) after stroke is unclear. In a Danish nationwide cohort, we described post‐stroke time trends in outpatient cECG usage and AF incidence and characterized factors associated with cECG use.

Methods

Patients without AF discharged after their first ischaemic stroke between 2010 and 2016 were identified from Danish nationwide registries. cECG included Holter or event recording within 120 days from discharge. Cumulative incidence analysis and multivariable adjusted logistic regression were used to assess time trends and factors associated with cECG usage and AF.

Results

The study population comprised 39 641 patients. Cumulative use of cECG increased threefold from 3.3% [95% confidence intervals (CI), 2.8–3.8] in 2010 to 10.5% (95% CI, 9.7–11.3) in 2016. Correspondingly, cumulative incidence of post‐stroke AF increased from 1.9% (95% CI, 1.5–2.3) to 2.8% (95% CI, 2.4–3.2). Of all cECG‐evaluated patients, 6.3% received an AF diagnosis versus 2.2% of the unevaluated. Receiving cECG was associated with increased odds of AF (odds ratio, 3.4; 95% CI, 2.8–4.0). Lower age, milder strokes and less comorbidity were associated with increased odds of receiving cECG. In contrast, risk factors for AF were increasing age and more comorbidity.

Conclusions

Post‐stroke outpatient cECG use and AF incidence have increased over time, but screening rates were low. cECG use was associated with tripled odds of detecting AF. There was a disparity between factors associated with cECG use and risk factors of AF. This raise questions as to the appropriateness of the current clinical approach to post‐stoke AF detection.
Light‐microscopic examinations of sperm in several lineages of Carabidae (Insecta: Coleoptera): Implications for the evolution of sperm conjugation
Authors: Sasakawa Kôji
Published: June 2020

Sperm show marked morphological diversity, but the processes and mechanisms driving this diversity have not been fully elucidated. The beetle family Carabidae represents a potential model system for studying sperm trait evolution. In this study, sperm traits (mainly conjugation and sperm conjugate gross morphology) of 42 species from nine subfamilies of Carabidae were examined using light microscopy. Except in Harpalinae, the type of conjugation was shared by all members of a particular subfamily: in Carabinae, Elaphrinae, Patrobinae and Brachinae, sperm conjugates were observed in which variable numbers of sperm clumped together; in Nebriinae, Cicindelinae and Trechinae, sperm were not organized as conjugates but were present individually; and in Broscinae, both individual sperm and sperm conjugates were observed. In the remaining subfamily, Harpalinae, sperm conjugates were formed in most species, but a loss of conjugation was observed in some species. Mapping the observed sperm traits onto within‐family molecular phylogenetic trees suggested that sperm conjugation was ancestral, with loss of conjugation evolving in several lineages. In sperm conjugates, a short spermatostyle (the axis of sperm conjugates) was the ancestral state, while a long spermatostyle evolved in subsequent lineages. In the long spermatostyle trait, the flexible type without a conspicuous 3D structure was ancestral, while the type with a conspicuous 3D structure, such as the spiral structure, evolved in derived lineages.
Biological effects of a new ultraviolet A1 prototype based on light‐emitting diodes on the treatment of localized scleroderma
Authors: Arndt Stephanie , Lissner Clara , Unger Petra , Bäumler Wolfgang , Berneburg Mark , Karrer Sigrid
Published: June 2020

Ultraviolet A1 (UVA1) phototherapy (spectral range 340‐400 nm) is a well‐established treatment option for various skin diseases such as localized scleroderma. Recent improvements of conventional UVA1 light sources (metal‐halide or fluorescent lamps) have brought attention to a new light‐emitting diode (LED) technology with remarkable advantages in handling and clinical routine. This study provides a preclinical histological and molecular evaluation of an LED‐based UVA1 prototype with a narrower spectral range (360‐400 nm) for treating localized scleroderma. Scleroderma mouse models and fibroblasts in vitro were exposed to LED‐based UVA1 phototherapy or to irradiation with a commercially available metal‐halide lamp emitting low‐dose (20, 40 J/cm2), medium‐dose (60 J/cm2) and high‐dose (80, 100 J/cm2) UVA1 light. Both UVA1 light sources affected inflammatory genes (IL‐1α and IL‐6) and growth factors (TGFß‐1 and TGFß‐2). Increased collagen type 1 was reduced after UVA1 phototherapy. Matrix metalloproteinase‐1 was more enhanced after a medium dose of LED‐based UVA1 phototherapy than after conventional treatment. In vivo, dermal thickness and the amount of collagen were reduced after both treatment methods. Remarkably, myofibroblasts were more effectively reduced by a medium dose of LED‐based UVA1 phototherapy. The study indicates that LED‐based UVA1 phototherapy yields similar or even better results than conventional treatment. In terms of biosafety and patient comfort, LED‐based UVA1 phototherapy offers clear advantages over conventional treatment because of the use of a narrower and less harmful UVA1 spectrum, less heat generation and shorter treatment times at the same irradiation intensity. Clinical studies are required to confirm these results in patients with localized scleroderma.
Wnt antagonist DKK‐1 levels in systemic sclerosis are lower in skin but not in blood and are regulated by microRNA33a‐3p
Authors: Henderson John , Pryzborski Stefan , Stratton Richard , O’Reilly Steven
Published: June 2020

Background

Systemic sclerosis is an autoimmune skin disease which is associated with inflammation and resulting skin fibrosis. Myofibroblasts are the key cell type associated with the fibrosis but how they are differentiated is not clear. DKK‐1 is a Wnt antagonist that blocks Wnt‐mediated fibrosis and is reduced in fibrotic conditions. Thus, DKK‐1 is a clear negative regulator of fibrosis in systemic sclerosis and its regulation is unknown. The aim of this work is to determine the levels of DKK‐1 in serum and tissues of SSc and its regulation.

Methods

Skin biopsies were taken from early diffuse systemic sclerosis patients and healthy controls and DKK‐1 measured by ELISA; serum was also isolated and DKK‐1 quantified. DKK‐1 was also measured by qRT‐PCR. MicroRNA33a‐3p was measured by TaqMan PCR. miR mimics and controls were transfected into dermal fibroblasts. Bleomycin mouse model was employed and compared to vehicle control treated mice, and gene expression was employed for DKK‐1 and various extracellular matrix genes.

Results

DKK‐1 is reduced in SSc skin and fibroblasts but is not reduced in the circulation in patients. MicroRNA33a‐3p regulates DKK‐1 levels epigenetically and is significantly reduced in SSc cells and whole tissue. DKK‐1 is also reduced in the bleomycin mouse model and pro‐fibrotic genes elevated.

Conclusion

DKK‐1 is reduced in SSc cells and is regulated by miR33a‐3p, and restoring DKK‐1 levels through epigenetic means could be a therapeutic target in systemic sclerosis.
Measuring Perceptions of the Therapeutic Alliance in Individual, Family, and Group Therapy from a Systemic Perspective: Structural Validity of the SOFTA‐s
Authors: Alvarez Irati , Herrero Marta , Martínez‐Pampliega Ana , Escudero Valentín
Published: June 2020

This study examined the multidimensional structure of the client and therapist versions of the self‐report measure, System for Observing Family Therapy Alliances (SOFTA‐s; Friedlander, Escudero, & Heatherington, Therapeutic alliances in couple and family therapy: An empirically informed guide to practice. Washington, DC: American Psychological Association, 2006) across three distinct therapeutic modalities (individual, family, group). Specifically, we investigated whether the originally theorized model of four first‐order factors (Engagement in the Therapeutic Process, Emotional Connection with the Therapist, Safety within the Therapeutic System, and Shared Sense of Purpose within the Family) would be reflected in a second‐order factor (Therapeutic Alliance). The sample included 105 therapists who worked with 858 clients (165 individuals, 233 families, and 43 groups) in several Spanish community agencies. To control for dependent data, we used multilevel modeling. Results of the multilevel confirmatory factor analyses showed adequate reliabilities, fit indices, and factor loadings across the three therapy contexts for both versions of the measure (client and therapist). Adequate measurement invariance was also found across respondents and therapy modalities. Taken together, these results support the structural validity of the SOFTA‐s, a brief and flexible self‐report alliance measure that can be used reliably in clinical practice as well as in studies of individual, family, and group therapy.
Reaching Up, Down, In, and Around: Couple and Family Coping During the Coronavirus Pandemic
Authors: Fraenkel Peter , Cho Wonyoung L.
Published: June 2020

The worldwide coronavirus (COVID‐19) has had profound effects on all aspects of life: physical health, the ability to travel locally or to more distant destinations, material and financial resources, and psychosocial wellbeing. Couples, families, and communities and individual persons in those relationships have struggled to cope with emerging depression, anxiety, and trauma, and the rise of relational conflict. In this article, we suggest that the existential nature of the pandemic’s challenges requires more than just the usual psychosocial interventions. We propose a taxonomy of responses to foster coping and resilience—“Reaching Up, Down, In, and Around.” “Reaching Up” includes accessing spiritual, religious, and ethical values. “Reaching Down” includes ideas and practices that foster a revised relationship with the Earth and its resources, and that engage families to participate in activities that aid the Earth’s recovery from decades of human‐caused damage. “Reaching In” represents a turn towards experiences available in the mind and in shared minds in relationships that provide pleasure, excitement, joy, and peace, given that external sources of these emotions are of limited availability due to quarantine. “Reaching Around” involves reframing the mandate for “social distancing” as fostering social connection and support while maintaining physical distancing. The challenges for family therapists, whose practices are confined largely to online therapy, and who are struggling with the same fears and constraints as those persons they are attempting to help, are also discussed.
COVID‐19 Interconnectedness: Health Inequity, the Climate Crisis, and Collective Trauma
Authors: Watson Marlene F. , Bacigalupe Gonzalo , Daneshpour Manijeh , Han Wen‐Jui , Parra‐Cardona Rubén
Published: June 2020

The COVID‐19 pandemic brings to the forefront the complex interconnected dilemmas of globalization, health equity, economic security, environmental justice, and collective trauma, severely impacting the marginalized and people of color in the United States. This lack of access to and the quality of healthcare, affordable housing, and lack of financial resources also continue to have a more significant impact on documented and undocumented immigrants. This paper aims at examining these critical issues and developing a framework for family therapists to address these challenges by focusing on four interrelated dimensions: cultural values, social determinants of health, collective trauma, and the ethical and moral responsibility of family therapists. Given the fact that family therapists may unwittingly function as the best ally of an economic and political system that perpetuates institutionalized racism and class discrimination, we need to utilize a set of principles, values, and practices that are not just palliative or after the fact but bring forth into the psychotherapeutic and policy work a politics of care. Therefore, a strong call to promote and advocate for the broader continuum of health and critical thinking preparing professionals to meet the challenges of health equity, as well as economic and environmental justice, is needed. The issues discussed in this paper are specific to the United States despite their relevance to family therapy as a field. We are mindful not to generalize the United States' reality to the rest of the world, recognizing that issues discussed in this paper could potentially contribute to international discourse.
Helping Couples in the Shadow of COVID‐19
Authors: Stanley Scott M. , Markman Howard J.
Published: June 2020

The pandemic caused by the SARS‐CoV‐2 virus (coronavirus) and the associated illness, COVID‐19, has caused a level of worldwide upheaval unlike any most people now living have seen in their lifetimes. This crisis affects people in their most important, committed, and intimate relationships. Although this crisis has damaged the health and well‐being of individuals, crushed economies, and led to an extensive period of uncertainty about the future, there may also be positive outcomes in the motivation people have to protect their relationships. In this paper, we focus on strategies that therapists and relationship educators can use to help couples preserve and protect their relationships during such a time. We describe four foundations of safety that allow relationships to thrive: physical, emotional, commitment, and community. We then highlight three keys from our body of work that can help guide individuals and couples in protecting their relationships on a day‐to‐day and moment‐to‐moment basis: (1) decide, don’t slide; (2) make it safe to connect; (3) do your part.
A study on the structure, mechanism, and biochemistry of kanamycin B dioxygenase (KanJ)—an enzyme with a broad range of substrates
Authors: Mrugała Beata , Miłaczewska Anna , Porebski Przemyslaw Jerzy , Niedzialkowska Ewa , Guzik Maciej , Minor Wladek , Borowski Tomasz
Published: June 2020

Kanamycin A is an aminoglycoside antibiotic isolated from Streptomyces kanamyceticus and used against a wide spectrum of bacteria, including Mycobacterium tuberculosis. Biosynthesis of kanamycin involves an oxidative deamination step catalyzed by kanamycin B dioxygenase (KanJ), thereby the C2’ position of kanamycin B is transformed into a keto group upon release of ammonia. Here, we present for the first time, structural models of KanJ with several ligands, which along with the results of ITC binding assays and HPLC activity tests explain substrate specificity of the enzyme. The large size of the binding pocket suggests that KanJ can accept a broad range of substrates, which was confirmed by activity tests. Specificity of the enzyme with respect to its substrate is determined by the hydrogen bond interactions between the methylamino group of the antibiotic and highly conserved Asp134 and Cys150 as well as between hydroxyl groups of the substrate and Asn120 and Gln80. Upon antibiotic binding, the C terminus loop is significantly rearranged and Gln80 and Asn120, which are directly involved in substrate recognition, change their conformations. Based on reaction energy profiles obtained by density functional theory (DFT) simulations, we propose a mechanism of ketone formation involving the reactive FeIV = O and proceeding either via OH rebound, which yields a hemiaminal intermediate or by abstraction of two hydrogen atoms, which leads to an imine species. At acidic pH, the latter involves a lower barrier than the OH rebound, whereas at basic pH, the barrier leading to an imine vanishes completely.

Databases

Structural data are available in PDB database under the accession numbers: 6S0R, 6S0T, 6S0U, 6S0W, 6S0V, 6S0S. Diffraction images are available at the Integrated Resource for Reproducibility in Macromolecular Crystallography at http://proteindiffraction.org under DOIs: 10.18430/m36s0t, 10.18430/m36s0u, 10.18430/m36s0r, 10.18430/m36s0s, 10.18430/m36s0v, 10.18430/m36s0w. A data set collection of computational results is available in the Mendeley Data database under DOI: 10.17632/sbyzssjmp3.1 and in the ioChem‐BD database under DOI: 10.19061/iochem‐bd‐4‐18.
An improved critical plane and cycle counting method to assess damage under variable amplitude multiaxial fatigue loading
Authors: Luo Peng , Yao Weixing , Susmel Luca
Published: June 2020

The plane with the maximum variance of the resolved shear stress is taken as the critical plane. Two algorithms are used along with the maximum variance method (MVM) to determine the orientation of the critical plane. The maximum variance of the normal stress on the potential critical planes is calculated to determine the one experiencing the maximum extent of fatigue damage. A new multiaxial cycle counting method is proposed to count cycles on the critical plane. The modified Wöhler curve method is used to assess fatigue damage. About 200 experimental results were collected from the technical literature to validate the approaches being proposed. The results show that the improved design technique being proposed is successful in assessing fatigue damage under variable amplitude multiaxial cyclic loading.
Effects of microstructural through‐thickness non‐uniformity and crack size on fatigue crack propagation and fracture of rolled Al‐7075 alloy
Authors: Ayhan Ali O. , Yaren Mehmet F.
Published: June 2020

Some of the fatigue tests performed using the standard compact tension (CT) and a non‐standard specimen made of rolled 7075 aluminium alloy exhibit fatigue crack growth (FCG) lagging in a small region along the crack front. Through‐thickness microstructural evaluation shows that material grains in this region did not flatten as much as other regions. In the non‐standard specimen, surface cracks are either grown under fatigue loading or broken under monotonically increasing quasi‐static loads at different crack sizes. The aforementioned lagging also exists in a narrow region of 3‐D FCG for specimens with microstructural through‐thickness non‐uniformity. A more important feature for this type of specimen with surface crack is the deflection of fast fracture direction into the grain interfaces, namely from L‐T orientation to S‐L and S‐T directions. It is proved that this is due to significant levels of second principal stresses near the free surface for small cracks and lower fracture toughness of the material in S‐L and S‐T directions.
Cranial Autonomic Symptoms of Migraine in Japan: Prospective Study of 373 Migraine Patients at a Tertiary Headache Center
Authors: Danno Daisuke , Wolf Johanna , Ishizaki Kumiko , Kikui Shoji , Yoshikawa Hiroo , Takeshima Takao
Published: June 2020

Objective

To clarify the detailed clinical characteristics of cranial autonomic symptoms (CAS) of Japanese patients with migraine and to get insight into the pathophysiological implications.

Background

Recent studies reported that CAS in migraine is causing diagnostic confusion with cluster headache or sinus headache; however, most reports have concerned Caucasians, and Asian data are scarce. The regional differences in the clinical characteristics of primary headaches between Caucasians and Asians have also been revealed recently.

Method

This was a cross‐sectional study. We investigated 373 patients with migraine in a tertiary headache center with face‐to‐face interviews.

Results

According to our findings, 158/373 (42.4%) patients with migraine had CAS and were characterized by more frequent cutaneous allodynia than those without CAS, suggesting the contribution of central sensitization; however, there were no statistically significant differences in pulsating pain or motion sensitivity as signs of peripheral sensitization. In contrast to the previous study, osmophobia was found to be significantly related to CAS.

Conclusion

CAS in patients with migraine is common not only in Caucasians but also in Asians. Central sensitization seems to contribute more than peripheral sensitization to CAS manifestation, and osmophobia might be noteworthy among Asian patients with migraine. To avoid a misdiagnosis, we emphasize the need for comments on CAS in the international classification of headache disorders migraine criteria.
Autoimmune atrophic gastritis: The role of Helicobacter pylori infection in children
Authors: Demir Arzu Meltem , Berberoğlu Ateş Burcu , Hızal Gülin , Yaman Aytaç , Tuna Kırsaçlıoğlu Ceyda , Oğuz Ayşe Selcen , Karakuş Esra , Yaralı Neşe , Özbek Namık Yaşar
Published: June 2020

Background

Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children.

Materials and Methods

We evaluated the presence of AIG and H pylori infection in fifty‐three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded.

Results

The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min‐max: 5.2‐18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non‐AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin‐like cell hyperplasia.

Conclusions

Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.
Social media in academics and research: 21st‐century tools to turbocharge education, collaboration, and dissemination of research findings
Authors: Deeken Amy H , Mukhopadhyay Sanjay , Jiang Xiaoyin ‘Sara’
Published: June 2020

The near‐ubiquitous use of smartphones and the rapid emergence of free, widely used, social media platforms have combined to turbocharge the dissemination of information at a scale and speed that would have been unimaginable just a few years ago. Increasingly, internet‐savvy pathologists of all ages from every corner of the world are flipping the paradigm of traditional academia by posting educational content online free of charge, unencumbered by the limitations of traditional print media and educational conferences. These platforms are being used in innovative ways, not just to disseminate research findings, but also to create new knowledge through using them to empower research collaborations. In this review, we outline ways in which social media platforms, such as Twitter, Facebook, and YouTube, are being used by pathologists to enhance academic work and facilitate the dissemination of research. We outline key differences between the various platforms with respect to pathology academics and research, and describe key areas in which these platforms have already made an impact. These include rapid dissemination of research findings to a worldwide audience, live transnational discussion of journal articles and conference proceedings, intercontinental networking between pathologists for academic purposes, free education on a global scale at minimal or no cost, and research collaborations initiated on and facilitated by social media platforms. Finally, we provide practical tips for pathologists who wish to adopt these novel 21st‐century technologies to enhance their academic endeavours.
Comorbidity burden on receipt of adjuvant immunotherapy and survival in patients with stage III melanoma: an analysis of the National Cancer Database
Authors: Freeman S. Caleb , Satish Mohan , Walters Ryan W.
Published: June 2020

Background

Comorbidity burden is associated with development of cancer, stage at diagnosis, and treatment outcomes. We evaluated the association between comorbidity burden, receipt of adjuvant immunotherapy, and survival in patients with stage III melanoma.

Methods

Using the National Cancer Database, we identified 16,906 patients with stage III melanoma who underwent surgery of the primary site. Outcomes included receipt of adjuvant immunotherapy and overall survival; independent variables included Charlson/Deyo comorbidity index (CDI) and receipt of adjuvant immunotherapy.

Results

Patients with CDI scores of two or more averaged 30.0% and 30.9% lower adjusted odds of receiving adjuvant immunotherapy relative to patients with a CDI score of zero or one, respectively (P = 0.001 and 0.002, respectively). Longer survival was associated with lower CDI scores (all P < 0.001) and receipt of adjuvant immunotherapy (P < 0.001). Patients who received adjuvant immunotherapy averaged 16.0% lower adjusted risk of death compared to patients who did not (P < 0.001), which was constant within all CDI cohorts. Patients with a CDI score of two or more averaged 53.4% and 39.1% higher adjusted risk of death relative to patients with a CDI score of zero or one (both P < 0.001).

Conclusion

Greater comorbidity burden was associated with lower receipt of adjuvant immunotherapy; however, adjuvant immunotherapy provided similar survival benefit for patients’ irrespective comorbidity burden. Our findings suggest that patients with stage III melanoma who have a greater comorbidity burden may benefit from adjuvant immunotherapy but should not replace careful patient selection by the clinician.