bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic profiling of long- and short-lived mutant mice implicates mitochondrial metabolism in ageing and shows signatures of normal ageing in progeroid mice
Authors: Fuentealba Matias , Fabian Daniel K. , Dönertaş Handan Melike , Thornton Janet M. , Partridge Linda
Published: October 2020

Genetically modified mouse models of ageing are the living proof that lifespan and healthspan can be lengthened or shortened, yet the molecular mechanisms behind these opposite phenotypes remain largely unknown. In this study, we analysed and compared gene expression data from 10 long-lived and 8 short-lived mouse models of ageing. Transcriptome-wide correlation analysis revealed that mutations with equivalent effects on lifespan induce more similar transcriptomic changes, especially if they target the same pathway. Using functional enrichment analysis, we identified 58 gene sets with consistent changes in long- and short-lived mice, 55 of which were up-regulated in long-lived mice and down-regulated in short-lived mice. Half of these sets represented genes involved in energy and lipid metabolism, among whichPpargc1a,Mif,Aldh5a1andIdh1were frequently observed. Based on the gene sets with consistent changes and also the whole transcriptome, we observed that the gene expression changes during normal ageing resembled the transcriptome of short-lived models, suggesting that accelerated ageing models reproduce partially the molecular changes of ageing. Finally, we identified new genetic interventions that may ameliorate ageing, by comparing the transcriptomes of 51 mouse mutants not previously associated with ageing to expression signatures of long- and short-lived mice and ageing-related changes.

Highlights

Transcriptomic changes are more similar within mutant mice that show either lengthened or shortened lifespan

The major transcriptomic differences between long- and short-lived mice are in genes controlling mitochondrial metabolism

Gene expression changes in short-lived, progeroid, mutant mice resemble those seen during normal ageing
Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins
Authors: Basu Souradip , Mukhopadhyay Suparba , Das Rajdeep , Mukhopadhyay Sarmishta , Singh Pankaj Kumar , Ganguli Sayak
Published: October 2020

The SARS-CoV-2 is a positive stranded RNA virus with a genome size of ~29.9 kilobase pairs which spans 29 open reading frames. Studies have revealed that the genome encodes about 16 non-structural proteins (nsp), four structural proteins, and six or seven accessory proteins. Based on prevalent knowledge on SARS-CoV and other coronaviruses, functions have been assigned for majority of the proteins. While, researchers across the globe are engrossed in identifying a potential pharmacological intervention to control the viral outbreak, none of the work has come up with new antiviral drugs or vaccines yet. One possible approach that has shown some positive results is by treating infected patients with the plasma collected from convalescent COVID-19 patients. Several vaccines around the world have entered their final trial phase in humans and we expect that these will in time be available for application to worldwide population to combat the disease. In this work we analyse the effect of prevalent mutations in the major pathogenesis related proteins of SARS-COV2 and attempt to pinpoint the effects of those mutations on the structural stability of the proteins. Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. Our binary scoring scheme identifies L84S mutation in ORF8 as the most disruptive of the mutations under study. We believe that, the virus is under the influence of an evolutionary phenomenon similar to Muller’s ratchet where the continuous accumulation of these mutations is making the virus less virulent which may also explain the reduction in fatality rates worldwide.
Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
Authors: Bui Linh T. , Winters Nichelle I. , Chung Mei-I , Joseph Chitra , Gutierrez Austin J. , Habermann Arun C. , Adams Taylor S. , Schupp Jonas C. , Poli Sergio , Peter Lance M. , Taylor Chase J. , Blackburn Jessica B. , Richmond Bradley W. , Nicholson Andrew G. , Rassl Doris , Wallace William A. , Rosas Ivan O. , Jenkins R. Gisli , Kaminski Naftali , Kropski Jonathan A. , Banovich Nicholas E. ,   the Human Cell Atlas Lung Biological Network
Published: October 2020

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observed a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD epithelial cells expressed higher levels of genes linked directly to the efficiency of viral replication and innate immune response. Additionally, we identified basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.
Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics
Authors: Mondino Alejandra , Hambrecht-Wiedbusch Viviane , Li Duan , York A. Kane , Pal Dinesh , González Joaquin , Torterolo Pablo , Mashour George A. , Vanini Giancarlo
Published: October 2020

Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. Activation of preoptic glutamatergic neurons also causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons may initiate -but not maintain- arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the conclusion that the preoptic area causally contributes to the regulation of both sleep and wakefulness.
Spatial Heterogeneity of Delta-like 4 Within a Multinucleated Niche Cell Maintains Muscle Stem Cell Diversity
Authors: Eliazer Susan , Sun Xuefeng , Brack Andrew S.
Published: October 2020

The quiescent muscle stem cell (QSC) pool is heterogeneous and generally characterized by the presence and levels of intrinsic myogenic transcription factors. Whether extrinsic factors maintain the diversity of states across the QSC pool remains unknown. The muscle fiber is a multinucleated syncytium that serves as a niche to QSCs, raising the possibility that the muscle fiber regulates the diversity of states across the QSC pool. Here we show that the muscle fiber maintains a continuum of quiescent states, through a gradient of Notch ligand, Dll4, produced by the fiber and captured by QSCs. The abundance of Dll4 captured by the QSC correlates with levels of the SC identity gene, Pax7. Niche-specific loss of Dll4 decreases QSC diversity and shifts the continuum, towards more proliferative and committed states. We reveal that fiber-derived Mindbomb1 (Mib1), an E3 ubiquitin ligase activates Dll4 and controls the spatial localization of Dll4. In response to injury, with a Dll4-replenished niche, the normal continuum and diversity of SC pool is restored, demonstrating bi-directionality within the SC continuum. Our data shows that a post-translational mechanism controls spatial heterogeneity of Notch ligands in a multinucleated niche cell to maintain a continuum of diverse states within the SC pool during tissue homeostasis.
The prion protein is not required for peripheral nerve repair after crush injury
Authors: Henzi Anna , Aguzzi Adriano
Published: October 2020

The cellular prion protein (PrP) is essential to the long-term maintenance of myelin sheaths in peripheral nerves. PrP activates the adhesion G-protein coupled receptor Adgrg6 on Schwann cells and initiates a pro-myelination cascade of molecular signals. Because Adgrg6 is crucial for peripheral myelin development and regeneration after nerve injury, we investigated the role of PrP in peripheral nerve repair. We performed experimental sciatic nerve crush injuries in co-isogenic wild-type and PrP-deficient mice, and examined peripheral nerve repair processes. Generation of repair Schwann cells, macrophage recruitment and remyelination were similar in PrP-deficient and wild-type mice. We conclude that PrP is dispensable for sciatic nerve regeneration after crush injury. Adgrg6 may sustain its function in peripheral nerve repair independently of its activation by PrP.
Local structure change of luminescent Ag zeolite-A and -X studied by in situ XAFS and IR spectroscopy
Authors: Miyanaga Takafumi , Suzuki Yushi , Narita Sho , Nakamura Reki
Published: October 2020

The in situ X-ray absorption fine structure (XAFS) for the structural changes of Ag clusters produced in the cavity of luminescent zeolites by thermal treatment of Ag zeolite-A and Ag zeolite-X has been studied. The following procedures are compared: (i) samples are heated and cooled to room temperature under atmosphere (under air); (ii) samples are heated and cooled to room temperature in a vacuum and then exposed to air. It was confirmed that the Ag clusters were broken when the Ag zeolite was exposed to air for Ag zeolite-X, which complements our previous results for Ag12-A. It is suggested that the deformation of the Ag clusters plays an important role in the generation of a strong photoluminescence band, and Ag clusters may not be direct species producing the strong photoluminescence. The local structure of the Ag ions was found to be slightly different from that of the unheated species. The difference may originate from the formation and breakdown of Ag clusters in the zeolite cavity.
Australian university and medical school life during the 1919 influenza pandemic
Authors: Waghorne James
Published: October 2020

Purpose

This article examines the impact of the 1919 influenza pandemic on the life and culture of Australian universities, and the curious absence of sustained discussion about the crisis in university magazines. It considers two contexts, from the perspective of the general university population, and from the particular focus of medical students.

Design/methodology/approach

The primary source for this analysis is based on detailed reading of university magazines across three universities, as well as other primary and secondary literature. The article was written during the 2020 COVID-19 pandemic, which has limited access to some other magazines held in library collections, but the corpus of material is more than sufficient.

Findings

This article shows that the pandemic further deferred the resumption of university life after a hiatus during the First World War. The failure to identify the causal agent limited technical discussion in medical school magazines.

Originality/value

This is one of the first dedicated studies of the effect of the 1919 influenza pandemic on Australian universities. It joins a growing body of work considering the effect of the influenza on different community groups.
Personal values and SME innovation in a Muslim ethnic group in Indonesia
Authors: Games Donard , Soutar Geoffrey , Sneddon Joanne
Published: October 2020

Purpose

This study aims to examine the relationship between personal values and small and medium enterprise (SME) innovation in Minangkabau, a Muslim ethnic group in Indonesia.

Design/methodology/approach

A quantitative approach was used to survey 400 small business owners. Structural models were estimated using WarpPLS.

Findings

The study established that SME owners had mixed values. This highlights the context of entrepreneurship because it provides an understanding of the links between personal values and some innovation-related constructs.

Research limitations/implications

The study made a little comparison of personal values in other Muslim societies. It is beneficial as a reference for future studies on comparisons between the Minangkabau and other ethnic Muslim groups.

Practical implications

Minangkabau small enterprise entrepreneurs need reflection on their values and business innovation because integrating these two aspects strengthens business identity.

Social implications

The entrepreneurs may need to balance personal and socio-cultural values to implement both business innovation and social harmony successfully.

Originality/value

To the best of the authors’ knowledge, this is the first study that takes into account the innovation concept. It examines personal values related to some concepts on innovation. It can partly be explained by the high level of religiosity in the Minangkabau ethnic group.
Chemical repertoire and biosynthetic machinery of the Aspergillus flavus secondary metabolome: A review
Authors: Uka Valdet , Cary Jeffrey W. , Lebar Matthew D. , Puel Olivier , De Saeger Sarah , Diana Di Mavungu José
Published: October 2020

Filamentous fungi represent a rich source of extrolites, including secondary metabolites (SMs) comprising a great variety of astonishing structures and interesting bioactivities. State‐of‐the‐art techniques in genome mining, genetic manipulation, and secondary metabolomics have enabled the scientific community to better elucidate and more deeply appreciate the genetic and biosynthetic chemical arsenal of these microorganisms. Aspergillus flavus is best known as a contaminant of food and feed commodities and a producer of the carcinogenic family of SMs, aflatoxins. This fungus produces many SMs including polyketides, ribosomal and nonribosomal peptides, terpenoids, and other hybrid molecules. This review will discuss the chemical diversity, biosynthetic pathways, and biological/ecological role of A. flavus SMs, as well as their significance concerning food safety and security.
Credentialing of emergency medicine trainees in point‐of‐care ultrasound: An effective, efficient and enjoyable model
Authors: Toffoli Andrew , Hartnett Leanne , Mattick Anthony , Goudie Adrian
Published: October 2020

Objective

The Australasian College for Emergency Medicine Curriculum Framework contains numerous mentions of point‐of‐care ultrasound (PoCUS). However, obtaining formal PoCUS credentials is often problematic. The Fiona Stanley Hospital ED PoCUS training programme was devised to assist emergency medicine trainees to meet the credentialing requirements of the Australasian College for Emergency Medicine and the Australasian Society for Ultrasound in Medicine.

Methods

Six emergency medicine registrars are selected for each 6‐month semester. Successful applicants nominate two modules of Australasian Society for Ultrasound in Medicine's Certificate in Clinician Performed Ultrasound and receive dedicated non‐clinical time. For 3 h a week, an emergency physician holding formal PoCUS credentials supervises a pair of trainees while they perform scans on ED patients. During these sessions, trainee logbooks can be reviewed and assessments occur as required by the module.

Results

Over an 18‐month period, 18 emergency registrars were involved, averaging eight 3‐h sessions each. All selected the Extended Focused Abdominal Scan for Trauma module, 14 chose Abdominal Aortic Aneurysm and eight chose Basic Echo in Life Support. Overall, 30 (75%) of 40 modules were completed within the trainees' 6‐month semester. Just under half of logged scans were obtained during the supervised sessions. Overall, the average number of scans performed exceeded each module's logbook requirements. Trainees perceived that involvement in the programme benefited their ability to manage patients. There was overwhelming support for the structure of the programme.

Conclusions

The Fiona Stanley Hospital ED model is effective in assisting emergency medicine trainees to gain formal PoCUS credentials. As it requires relatively little organisation, time and staffing, it could be adopted in many EDs around Australia and New Zealand.
The effects of seed priming with sodium hydrosulphide on drought tolerance of sunflower (Helianthus annuus L.) in germination and early growth
Authors: Ocvirk Dijana , Špoljarević Marija , Kristić Marija , Hancock John T. , Teklić Tihana , Lisjak Miroslav
Published: October 2020

Sunflower seeds (hybrid Luka) were primed with water (hydropriming) or sodium hydrosulphide (NaHS) solutions (0.1, 0.5, 1.0 and 1.5 mM NaHS) and subsequently dried to initial moisture content. Unprimed (control) and primed seeds were germinated in a growth chamber on paper towels moistened with water or polyethylene glycol (PEG) 6000 solutions (2.5, 5.0 and 10%), mimicking different drought stress levels. To evaluate the response of the primed seeds to drought in the germination stage, the germination energy (GE), germination rate (SG), seedling fresh mass (SW), hydrogen peroxide and free proline content (PRO), as well as lipid peroxidation rate (malondialdehyde; MDA) were established. The results show strong effects of the imposed drought stress and the metabolic response to oxidative stress through lower germinability and proline accumulation in seedlings. NaHS priming showed some positive effects on seed germination depending on stress level and the concentration of NaHS. Sunflower seeds were also germinated in pots filled with soil, at optimal (70% of field water capacity [FWC 70%]) and drought conditions (FWC 30%), in natural outdoors conditions. When plantlets developed the first pair of leaves, the number of plants (emergence rate [ER]), shoot mass (SM) and leaves mass (LM) were determined, as well as the total activities of catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR) and dehydroascorbate reductase (DHAR). There was a significant influence of an interaction between drought stress and priming, whereas drought stress inhibited plant emergence and early growth (SW and LW), and strong antioxidative enzymatic response to drought stress was clearly established in the leaves. Although seed priming showed some influence on enzyme activities, it was mostly related to seed hydropriming effects, while NaHS seed priming was less effective, influencing only DHAR. Altogether, the results imply that sunflower seed priming with NaHS may not have a prolonged impact on the antioxidative defence mechanism based on CAT and ascorbate/glutathione cycle during sunflower early growth in drought conditions.
Semen quality and waiting time to pregnancy explored using association mining
Authors: Romero Herrera Jose Alejandro , Bang Anne Kirstine , Priskorn Lærke , Izarzugaza Jose M. G. , Brunak Søren , Jørgensen Niels
Published: October 2020

Background

Assessment of semen quality is a key pillar in the evaluation of men from infertile couples. Usually, semen parameters are interpreted individually because the interactions between parameters are difficult to account for.

Objectives

To determine how combinations of classical semen parameters and female partner age were associated with waiting time to pregnancy (TTP).

Materials and methods

Semen results of 500 fertile men, information of TTP, and partner age were used for regressions and to detect breaking points. For a modified Association Rule Mining algorithm, semen parameters were categorized as High, Medium, and Low.

Results

Men ≤32.1 years and women ≤32.9 years had shorter TTP than older. Decreasing TTP was associated with increasing level of individual semen parameters up to threshold values: sperm concentration 46 mill/mL, total sperm count 179 mill, progressive motility 63%, and normal morphology 11.5%. Using association mining, approximately 100 combinations of semen parameters and partner age were associated with TTP. TTP ≤ 1 month often co‐occurred with high percentages of progressive motility (≥62%) and morphologically normal spermatozoa (≥10.5%). Furthermore, TTP ≤ 1 did not tend to appear with lower percentages of these two semen parameters or high partner age (≥32 years). However, high percentages of motile or normal spermatozoa could not compensate for sperm concentration ≤42 mill/mL or total sperm count ≤158 mill. The prolonging effect of high partner age could not be compensated for by the man's semen quality.

Discussion and Conclusion

Using association mining, we observed that TTP was best predicted when combinations of semen parameters were accounted for. Sperm counts, motility, and morphology were all important, and no single semen parameter was inferior. Additionally, female age above 32 years had a negative impact on TTP that could not be compensated for by high semen parameters of the man.
Hemodynamic findings in normotensive women with small‐for‐gestational‐age and growth‐restricted fetuses
Authors: Di Pasquo Elvira , Ghi Tullio , Dall’Asta Andrea , Angeli Laura , Ciavarella Sara , Armano Giulia , Sesenna Veronica , Di Peri Antonio , Frusca Tiziana
Published: October 2020

Introduction

Fetal growth restriction (FGR) in most instances is a consequence of primary placental dysfunction due to inadequate trophoblastic invasion. Maternal cardiac maladaptation to pregnancy has been proposed as a possible determinant of placental insufficiency and impaired fetal growth. This study aimed to compare the maternal hemodynamic parameters between normotensive women with small‐for‐gestational‐age (SGA) and FGR fetuses and to evaluate their correlation with neonatal outcome.

Material and methods

An observational cohort study including singleton pregnancies referred to our tertiary care center due to fetal smallness. At the time of diagnosis, fetuses were classified as SGA or FGR according to the Delphi consensus criteria, and pregnant women underwent hemodynamic assessment using a cardiac output monitor. A group of women with singleton uncomplicated pregnancies ar ≥35 weeks of gestation were recruited as controls. Cardiac output, systemic vascular resistance, stroke volume, and heart rate were measured and compared among the three groups (controls vs FGR vs SGA). The correlation between antenatal findings and neonatal outcome was also evaluated by multivariate logistic regression analysis.

Results

A total of 51 women with fetal smallness were assessed at 34.8 ± 2.6 weeks. SGA and FGR were diagnosed in 22 and 29 cases, respectively. The control group included 61 women assessed at 36.5 ± 0.8 weeks of gestation. Women with FGR had a lower cardiac output Z‐score (respectively, −1.3 ± 1.2 vs −0.4 ± 0.8 vs −0.2 ± 1.0; P < .001) and a higher systemic vascular resistance Z‐score (respectively, 1.2 ± 1.2 vs 0.2 ± 1.1 vs −0.02 ± 1.2; P < .001) compared with both SGA and controls, whereas no difference in the hemodynamic parameters was found between women with SGA and controls. The incidence of neonatal intensive care unit admission did not differ between SGA and FGR fetuses (18.2% vs 41.4%; P = .13), but FGR fetuses had a longer hospitalization compared with SGA fetuses (14.2 ± 17.7 vs 4.5 ± 1.6 days; P = .02). Multivariate analysis showed that the cardiac output Z‐score at diagnosis (P = .012) and the birthweight Z‐score (P = .007) were independent predictors of the length of neonatal hospitalization.

Conclusions

Different maternal hemodynamic profiles characterize women with SGA or FGR fetuses. Furthermore, a negative correlation was found between the maternal cardiac output and the length of neonatal hospitalization.
Hemoadsorption cartridge and coronavirus disease 2019 infections: A case report and brief literature review
Authors: Melegari Gabriele , Bertellini Elisabetta , Melegari Alessandra , Trenti Tommaso , Malaguti Silvio , Barbieri Alberto
Published: October 2020

The cytokine storm has been frequently reported to occur in patients with severe coronavirus disease 2019 (COVID‐19). Data from the literature suggest that elevated levels of inflammatory mediators, such as interleukin (IL)‐6, IL‐8, and tumor necrosis factor, indicate a severe course or the fatality of the disease. Several therapeutic options have been employed to treat critically ill patients, including hemoadsorption of inflammatory mediators. We here present a case of severe acute respiratory syndrome caused by COVID‐19 and acute renal failure. The patient was admitted to our intensive care unit and treated with mechanical ventilation, renal replacement therapy, and hemoadsorption to reduce the cytokine release syndrome, which plays a fundamental role in the clinical presentation of COVID‐19 patients. We also discuss the potential advantages of reducing cytokine plasma levels using a hemoadsorption cartridge.
Does adherence to lipid‐lowering medications improve cancer survival? A nationwide study of breast and colorectal cancer, and melanoma
Authors: Feng Jia‐Li , Qin Xiwen
Published: October 2020

Aims

Inconclusive findings of lipid‐lowering medications (LLMs) on cancer survival benefit require more evidence. We tested the hypothesis that adherence to this drug is associated with reduced cancer‐specific mortality in a homogeneous population who had used this drug before cancer diagnosis.

Methods

The Australian Cancer Database was linked to the Pharmaceutical Benefits Scheme database, and to the National Death Index (up to 2015). Medication adherence was calculated by proportion of days covered. Cox regression models with time‐varying covariates were used to derive multivariable‐adjusted cause‐specific hazard ratio (HR) and 95% confidence interval (CI) for the associations between adherence to LLMs, statins, lipophilic, and hydrophilic statins and cancer‐specific mortality.

Results

From 2003 to 2013, 3 separate cohorts of 20 046, 11 719 and 6430 female patients with newly diagnosed breast, colorectal cancer, and melanoma respectively were identified. The 1‐year adherence was similar at 1‐year prediagnosis in the 3 cohorts, on average 82%. Each 10% increase in 1‐year adherence to LLMs was inversely associated with cancer‐specific mortality among women with breast cancer (fully adjusted HR = 0.92, 95% CI 0.91–0.93), colorectal cancer (fully adjusted HR = 0.92, 95% CI 0.91–0.93), or melanoma (fully adjusted HR = 0.97, 95% CI 0.94–1.00). The reductions in cancer‐specific mortality were more pronounced for women who adhered to lipophilic than hydrophilic statins in all 3 cancers albeit not statistically significant for melanoma.

Conclusion

Among LLM users, adherence to this drug is associated with a decrease in cancer‐specific mortality. If confirmed, LLMs could be considered as an adjuvant cancer therapy to improve prognosis in cancer survivors.
Autonomy and social influence in predictive genetic testing decision‐making: A qualitative interview study
Authors: Zimmermann Bettina M. , Koné Insa , Shaw David , Elger Bernice
Published: October 2020

Beauchamp and Childress’ definition of autonomous decision‐making includes the conditions of intentionality, understanding, and non‐control. In genetics, however, a relational conception of autonomy has been increasingly recognized. This article aims to empirically assess aspects of social influence in genetic testing decision‐making and to connect these with principlist and relational theories of autonomy. We interviewed 18 adult genetic counsellees without capacity issues considering predictive genetic testing for cancer predisposition for themselves and two counselling physicians in Switzerland. We conducted a qualitative analysis, building on a grounded theory study about predictive genetic testing decision‐making. We found that some participants agreed to predictive genetic testing predominantly because relatives wanted them to do it, with some even acting contrary to their own convictions. Others, in contrast, based their decision on purely individualistic reasons but expressed difficulties in explaining their decision to their social environment. Healthcare professionals had a critical influence on decision‐making in many cases without being manipulative, as perceived by counsellees. Still, cases of coercion and social pressure occurred within social relationships. In conclusion, predictive genetic testing decision‐making includes relational and individualistic aspects, and both are compatible with autonomous decision‐making. While the principlist and relational notions of autonomy compete on a theoretical level, they are two sides of the same coin when used as analytical lenses for genetic testing decision‐making. Social acceptance of refusal of testing should be improved to mitigate social pressure. Individuals should be encouraged to decide for themselves how much their social environment influences their decision regarding predictive genetic testing.
Three‐dimensional analysis of dimensional changes after alveolar ridge preservation with bone substitutes or plasma rich in growth factors: Randomized and controlled clinical trial
Authors: Stumbras Arturas , Galindo‐Moreno Pablo , Januzis Gintaras , Juodzbalys Gintaras
Published: October 2020

Objectives

To evaluate alveolar ridge dimensional changes of different alveolar ridge preservation techniques after 3 months of tooth extraction and to compare the efficacy of autologous plasma rich in growth factor (PRGF) to the bone substitutes in alveolar ridge preservation and sites left to heal spontaneously.

Materials and Methods

Forty patients requiring tooth extraction in the anterior maxilla were randomly allocated to the four following treatment modalities: spontaneous healing (control), natural bovine bone mineral covered with resorbable native collagen membrane (BBM/CM), freeze‐dried bone allograft covered with resorbable native collagen membrane (FDBA/CM) and PRGF alone. Cone beam computed tomography (CBCT) scans were taken after surgery and 3 months later. The measurements of height and width (at 1, 3, and 5 mm below the crest) were performed after superimposing the 2 consecutive CBCT scans.

Results

The greatest horizontal alveolar bone resorption at 1 mm below bone crest was observed in the control group (−1.61 ± 1.76 mm, P = .037), whereas the least reduction in width was found in the BBM/CM group (−0.68 ± 0.67 mm, P = .037). The most pronounced alveolar height reduction was observed in the control group (−0.86 ± 0.43 mm), whereas alveolar ridge preservation with BBMC/CM (−0.26 ± 0.91 mm) and PRGF (−0.54 ± 0.86 mm) successfully reduced the alveolar height reduction as compared to the control group.

Conclusions

Alveolar ridge preservation technique in the esthetic zone using BBM/CM or using PRGF is beneficial to reduce horizontal and vertical bone changes.
Increased occurrence of hand eczema in young children following the Danish hand hygiene recommendations during the COVID‐19 pandemic
Authors: Simonsen Anne B. , Ruge Iben F. , Quaade Anna S. , Johansen Jeanne D. , Thyssen Jacob P. , Zachariae Claus
Published: October 2020

Background

During the first wave of the COVID‐19 pandemic of Spring 2020, Denmark was one of the first countries to introduce lockdown measures, including closing of all daycare centers. Following the reopening of daycare centers, Danish Health Authorities implemented a mandatory intensive hand hygiene regimen.

Objectives

To examine the occurrence and point prevalence of hand eczema as a consequence of more intensive hand hygiene among Danish children attending daycare.

Methods

The heads of 1667 daycare centers in Denmark were contacted and asked to forward a link to a questionnaire to parents of the children attending the daycare center.

Results

Among 6858 children, 12.1% had hand eczema before reopening of daycare centers, whereas 38.3% reported hand eczema after the children returned to daycare. Of the children who never had hand eczema, 28.6% developed hand eczema after returning to daycare. The risk of hand eczema was significantly associated with atopic dermatitis, female gender, higher age, and frequency of handwashing.

Conclusion

Following the implemented hygiene regimen, a high proportion of young children rapidly developed hand eczema. Well‐established prophylactic skin care might have spared a proportion of the children from developing hand eczema.
BLACK LIVES MATTER PROTESTS, FATAL POLICE INTERACTIONS, AND CRIME
Authors: Skoy Evelyn
Published: October 2020

The Black Lives Matter (BLM) movement was a prominent social movement largely focused on raising awareness of and reducing police use‐of‐force and fatal interactions with police. However, opponents of the movement have feared it could lead to decreased proactive policing and increased crime. Using a state‐by‐month fixed effects model, I find evidence that an additional protest in the preceding month leads to a decrease of .225 fatal interactions between Blacks and police per 10 million Black population. In addition, I find no evidence supporting increased crime or arrests as a result of the BLM movement. (JEL J15, D91, Z13)
Foot ulcer recurrence, plantar pressure and footwear adherence in people with diabetes and Charcot midfoot deformity: A cohort analysis
Authors: Keukenkamp R. , Busch‐Westbroek T. E. , Barn R. , Woodburn J. , Bus S. A.
Published: October 2020

Aims

To investigate people with Charcot midfoot deformity with regard to plantar pressure, footwear adherence and plantar foot ulcer recurrence.

Methods

Twenty people with diabetes, Charcot midfoot deformity, plantar foot ulcer history and custom‐made footwear were assessed with regard to barefoot and in‐shoe plantar pressures during walking, footwear adherence (% of daily steps over 7‐day period) and plantar foot ulcer recurrence over 18 months. In a cohort design, they were compared to 118 people without Charcot foot (non‐Charcot foot group) with custom‐made footwear and similar ulcer risk factors.

Results

Median (interquartile range) barefoot midfoot peak pressures were significantly higher in the Charcot foot group than in the non‐Charcot foot group [756 (260–1267) vs 146 (100–208) kPa;P<0.001]. In‐shoe midfoot peak pressures were not significantly higher in the Charcot foot group [median (interquartile range) 152 (104–201) vs 119 (94–160) kPa] and significantly lower for all other foot regions. Participants in the Charcot foot group were significantly more adherent, especially at home, than participants in the non‐Charcot foot group [median (interquartile range) 94.4 (85.4–95.0)% vs. 64.3 (25.4–85.7)%;P=0.001]. Ulcers recurred in 40% of the Charcot foot group and in 47% of the non‐Charcot foot group (P=0.63); midfoot ulcers recurred significantly more in the Charcot foot group (4/8) than in the non‐Charcot foot group (1/55;P=0.001).

Conclusions

Effective offloading and very high footwear adherence were found in people with diabetes and Charcot midfoot deformity. While this may help protect against plantar foot ulcer recurrence, a large proportion of such people still experience ulcer recurrence. Further improvements in adherence and custom‐made footwear design may be required to improve clinical outcome.
Empagliflozin treatment effects across categories of baseline HbA1c, body weight and blood pressure as an add‐on to metformin in patients with type 2 diabetes
Authors: Inzucchi Silvio E. , Davies Melanie J. , Khunti Kamlesh , Trivedi Prabhav , George Jyothis T. , Zwiener Isabella , Johansen Odd Erik , Sattar Naveed
Published: October 2020

Aim

To investigate the association of different categories of baseline cardio‐metabolic risk factors on the treatment effects of empagliflozin 10 and 25 mg when added as second‐line therapy to metformin in patients with type 2 diabetes (T2D).

Materials and Methods

Patients aged 18 years or older with HbA1c 7.0%‐10.0% were included. Analysis of covariance compared change from baseline to weeks 24 and 76 in HbA1c, body weight (BW) and systolic blood pressure (SBP) by respective baseline categories (HbA1c <8.5/≥8.5%; BW <80/80‐90/>90 kg, SBP <130/130‐140/>140 mmHg). Analyses were also conducted with a model using continuous covariates of cardio‐metabolic factors.

Results

In total, 637 patients (56.7% males; mean [SD] age 55.7 [9.9] years, HbA1c 7.9% [0.9%], BW 81.2 [18.8] kg, SBP 129.4 [14.6] mmHg) received one or more dose of either empagliflozin 10 mg (n = 217) or 25 mg (n = 213), or placebo (n = 207). At both time points, empagliflozin 10/25 mg versus placebo significantly (P < .0001) reduced HbA1c and BW, with greater reductions in HbA1c at higher baseline HbA1c (P interaction week 24/76 categorical and continuous models: .0290/.1431 and .0004/.0042, respectively) and in BW (P interaction .1340/.0012 and .0202/<.0001, respectively). Both empagliflozin doses also significantly lowered SBP versus placebo at both time points, with similar efficacy by subgroups of baseline SBP. Adverse events were consistent with the established empagliflozin safety profile across treatment groups.

Conclusions

Empagliflozin, as add‐on to metformin, decreases HbA1c and BW, particularly in patients with higher HbA1c and BW baseline values, and effectively lowers SBP.
Evaluation of global and regional left ventricular myocardial work by echocardiography in patients with chronic kidney disease
Authors: Ke Qian‐qian , Xu Hai‐bo , Bai Jiao , Xiong Li , Li Meng‐mei
Published: October 2020

Objective

This study aimed to quantitatively evaluate the left ventricular myocardial work of patients with chronic kidney disease (CKD) by echocardiographic pressure–strain loop (PSL) analysis.

Methods

Ninety‐three patients with CKD and forty‐two age‐ and sex‐matched controls were included in the study. CKD patients were divided into group 1 (stages 2–4) and group 2 (stage 5). Left ventricular blood pressure was estimated noninvasively according to echocardiographic valvular events and brachial artery systolic pressure. Left ventricular myocardial work parameters were acquired by echocardiographic PSL analysis.

Results

The CKD groups had a significantly lower global work index (WI), global work efficiency (GWE), global constructive strain (GCW) and global longitudinal strain (GLS) and higher global waste work (GWW) than the control group. Segmental analysis showed that the myocardial WI, work efficiency (WE), and constructive work (CW) were lower in group 2 than the control group (P < .05), while the regional myocardial waste work (WW) was higher (P < .05). A Pearson correlation analysis revealed that GWE and GWW have good correlations with the LVEF and GLS. A multiple regression analysis showed that the systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), end‐diastolic volume (EDV), and GLS were associated with global work index (GWI) (b′ = 0.476, 0.252, −0.407, and −0.355, P < .05).

Conclusions

Left ventricular PSL analysis can be applied to assess global and regional myocardial work in CKD patients. This approach may serve as a noninvasive method for the detection of left ventricular systolic dysfunction at an early stage.
Diagnosis of anomalous origin of the right subclavian artery from the right pulmonary artery in a patient with D‐transposition of the great arteries utilizing transthoracic echocardiography
Authors: Makadia Luv D. , Nielsen James C. , Kumar Thittamaranahalli Kumar Susheel , Bhatla Puneet
Published: October 2020

Diagnosis of anomalous origin of the right subclavian artery (AORSA) from the right pulmonary artery (RPA) is usually made using CT, MRI, or invasive angiography. We report a patient diagnosed using transthoracic echocardiography (TTE). A newborn girl prenatally known to have d‐TGA presented with cyanosis sparing the right hemithorax and arm. Oxygen saturations on the right hand were persistently higher than on the right ear and other extremities. Repeat TTE using a modified echocardiographic imaging plane allowed for full visualization of the entire subclavian artery course, revealing AORSA from RPA. We discuss further the approach to echocardiographic diagnosis and surgical implications.
Cyclicality of commodity markets with respect to the U.S. economic policy uncertainty based on granger causality in quantiles
Authors: Apergis Nicholas , Hayat Tasawar , Saeed Tareq
Published: October 2020

Given the importance of the U.S. in global commodity markets, the goal is to explore whether U.S. economic policy uncertainty impacts the price performance of certain commodities. The analysis uses the Granger causality in quantiles method that allows us to test whether there are different effects under different market conditions. The results document that economic uncertainty impacts the returns on the commodities considered, with the effects clustering around the tail of their conditional distribution. Robust evidence was obtained under alternative definitions of uncertainty.
Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia
Authors: Navis Allison , Dallah Ifunanya , Mabeta Charles , Musukuma Kalo , Siddiqi Omar K. , Bositis Christopher M. , Koralnik Igor J. , Gelbard Harris A. , Theodore William H. , Okulicz Jason F. , Johnson Brent A. , Sikazwe Izukanji , Bearden David R. , Birbeck Gretchen L
Published: October 2020

Objective

Interactions between enzyme‐inducing anti‐seizure medications (EI‐ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co‐usage of ARVs and EI‐ASMs is associated with ARV‐resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia.

Methods

Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6‐month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI‐ASM was associated with pVL >1000/mL copies.

Results

Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm3 (interquartile range [IQR] 88‐389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464 cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200 cells/mm3. Four (8%) had a pVL >1000 copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200 cells/mm3. None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P = .58).

Significance

EI‐ASMs are commonly used in sub‐Saharan Africa. Despite concurrent use of EI‐ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV‐resistant HIV.
Significance of the electrophysiological border between hypothalamic hamartomas and the hypothalamus for the target of ablation surgery identified by intraoperative semimicrorecording
Authors: Shirozu Hiroshi , Masuda Hiroshi , Kameyama Shigeki
Published: October 2020

Objective

Ablation surgery has become the first line of treatment for hypothalamic hamartomas (HHs). For effective treatment, optimum targeting of ablation is mandatory. The present study aimed to evaluate the correspondence between the electrophysiological features of HHs and morphological targeting by semimicrorecording during stereotactic radiofrequency thermocoagulation (SRT).

Methods

Eighty HH patients who underwent SRT were involved. Semimicrorecording was performed on the first trajectory. The distance from the center of the target at the morphological border (TMB) determined by magnetic resonance imaging, differences in discharge patterns, and area potentials (APs) were measured.

Results

The electrophysiological border (EB) between the HH and hypothalamus was detected by semimicrorecording in 73 (91.3%), AP increase (API) in the HH was detected in 31 (38.8%), and spike discharges (SDs) of the HH were detected in 56 patients (70.0%). Semimicrorecording showed significantly different APs among structures passing through the trajectory, except between API and SDs. The median distances from the center of the TMB to the EB, API, SDs, and AP decline were −3.50, −2.49, −1.38, and +2.00 mm, respectively.

Significance

The electrophysiological features of HHs were shown by semimicrorecording during SRT. The EB corresponded to the morphological border. The electrophysiologically active area of HHs was located near the border. Ablation surgery should focus on disconnection at the border between the HH and the hypothalamus to maximize its effectiveness, as well as to reduce complications.
Geriatric management of older patients with multimorbidity
Authors: Kojima Taro , Mizokami Fumihiro , Akishita Masahiro
Published: October 2020

Older patients tend to have multimorbidity represented by multiple chronic diseases or geriatric conditions due to aging changes of organs, which require a variety of medical management. Currently, there are no sufficient disease treatment guidelines for older people with multimorbidity, therefore physicians have difficulty managing multimorbidity, such as which diseases should be treated intensively or to what extent the conditions should be improved. Furthermore, there are other points to be considered when initiating the treatment of diseases. For example, physicians must assess physical function. Some people have no difficulty with ambulation, but some are bedridden and have difficulty getting up on their own. As there are differences in disease severity, comorbid conditions and life expectancy, there should be differences in deciding treatment and prescribing drugs. It may be necessary to change the option for treatment depending on cognitive function, the living environment and the care environment, using comprehensive geriatric assessments. In addition, when treating multimorbidity, patients tend to have polypharmacy, which is a risk for adverse drug events. Because of this, it is necessary to consider dose reduction and drug discontinuation in patients with polypharmacy. Because of the global increase in older patients with multimorbidity, developing an essential method for managing multimorbidity is an urgent issue. More research and practices are necessary to achieve high‐quality care in patients with multimorbidity. Geriatr Gerontol Int 2020; 20: 1105–1111.