bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental animal models of aquaporin‐4‐IgG‐seropositive neuromyelitis optica spectrum disorders: progress and shortcomings
Authors: Duan Tianjiao , Verkman Alan S.
Published: October 2019

Neuromyelitis optica spectrum disorders (NMOSD) is a heterogeneous group of neuroinflammatory conditions associated with demyelination primarily in spinal cord and optic nerve, and to a lesser extent in brain. Most NMOSD patients are seropositive for IgG autoantibodies against aquaporin‐4 (AQP4‐IgG), the principal water channel in astrocytes. There has been interest in establishing experimental animal models of seropositive NMOSD (herein referred to as NMO) in order to elucidate NMO pathogenesis mechanisms and to evaluate drug candidates. An important outcome of early NMO animal models was evidence for a pathogenic role of AQP4‐IgG. However, available animal models of NMO, based largely on passive transfer to rodents of AQP4‐IgG or transfer of AQP4‐sensitized T cells, often together with pro‐inflammatory maneuvers, only partially recapitulate the clinical and pathological features of human NMO, and are inherently biased toward humoral or cellular immune mechanisms. This review summarizes current progress and shortcomings in experimental animal models of seropositive NMOSD, and opines on the import of advancing animal models.
Taxing the tempted: Personal addictions, sustainable revenues and the public good
Authors: Bird Malcolm G. , Dutil Patrice , Stoney Christopher
Published: October 2019

The regulation of gaming, tobacco and alcohol is challenged by new realities. First, fewer people are convinced that government regulation of these indulgences is consistent with a rights‐based society. Second, while provincial budgets have continued to climb, the revenues drawn from “sin taxes” (excise taxes from tobacco and alcohol and revenues from gambling) have declined as a proportion of total revenues. As a result, these taxes will not cover the important social and health care costs triggered by the new permissiveness. This study contributes to budget theory by examining the changing policy landscape and sheds light on how Canadian provinces in particular have attempted to balance individual rights, social oversight and provincial revenues. It concludes by speculating on other addictive products that could soon be framed as worthy of taxation.
Risky Politics? Associations Between Adolescent Risk Preference and Political Engagement
Authors: Oosterhoff Benjamin , Wray‐Lake Laura
Published: October 2019

This study examined associations among adolescent risk preference and political engagement using nationally representative Monitoring the Future data from high school seniors (N = 109,574; modal age = 18 years) spanning 1976–2014. Greater risk preference was associated with greater past voting, donating to a campaign, writing government officials, boycotting, and protesting. Greater risk preference was also associated with higher future intentions to boycott and protest, but lower intentions to donate to or volunteer for a campaign. In general, associations between risk preference and political engagement became stronger with higher levels of political interest. Results highlight the importance of considering the adaptive role of adolescent risk preference and suggest that political engagement may be a constructive outlet for youth who pursue or are comfortable taking risks.
The Era of Adaptive Experiences: Rethinking Universal and Inclusive Design
Authors: Goto Kelly
Published: October 2019

If you’ve ever spent a day on crutches, helped a friend manage a wheelchair, or helped an aging and hearing‐impaired parent conduct a phone conversation, you’ll appreciate the beauty of universal and inclusive design. And perhaps you’ll understand when we say that these challenges, too, represent a kind of diversity.

Defining disability as diversity.
Long‐term remission rates after splenectomy in adults with Evans syndrome compared to immune thrombocytopenia: A single‐center retrospective study
Authors: Sulpizio Emilio D. , Raghunathan Vikram , Shatzel Joseph J. , Zilberman‐Rudenko Jevgenia , Worrest Tarin , Sheppard Brett C. , DeLoughery Thomas G.
Published: October 2019

Objective

Evans syndrome, the combination of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) or autoimmune neutropenia, is associated with a high rate of relapsed/refractory disease. There are limited data on the efficacy of splenectomy for this condition. We reviewed patient outcomes after splenectomy for Evans syndrome compared to ITP at our institution.

Methods

We performed a retrospective analysis of patients who underwent splenectomy for autoimmune cytopenias over a 23‐year period with the intention of comparing disease relapse rates after splenectomy in patients with Evans syndrome and in those with ITP.

Results

During the study period, 77 patients underwent splenectomy for ITP and seven underwent splenectomy for Evans syndrome. In the Evans cohort, splenectomy led to an 85.7% initial response rate with a 42.8% rate of relapse within one year and a long‐term (one‐year) response rate of 42.8%. In the ITP cohort, the initial response rate was 90.9% with a long‐term response rate of 70.1%.

Conclusion

Our data suggest that long‐term remission rates after splenectomy are lower in adults with Evans syndrome compared to those with ITP, although splenectomy may still be an acceptable treatment for certain patients with Evans syndrome. Our findings underscore the need for further research and development of additional therapeutic strategies for this patient population.
Urokinase receptor and tissue plasminogen activator as immediate‐early genes in pentylenetetrazole‐induced seizures in the mouse brain
Authors: Shmakova Anna A. , Rubina Kseniya A. , Rysenkova Karina D. , Gruzdeva Anna M. , Ivashkina Olga I. , Anokhin Konstantin V. , Tkachuk Vsevolod A. , Semina Ekaterina V.
Published: October 2019

Epileptogenesis progressively leads to the rearrangement of normal neuronal networks into more excitable ones and can be viewed as a form of neuroplasticity, the molecular mechanisms of which still remain obscure. Here, we studied pentylenetetrazole seizure‐induced regulation of genes for plasminogen activator system in the mouse brain. We found that expression of tissue plasminogen activator (tPA) and urokinase receptor (uPAR) mRNA was strongly increased in the mouse cerebral cortex, hippocampus, striatum and amygdala as early as 3 hr after pentylenetetrazole seizures. Such early activity‐induced expression of uPAR in the central nervous system has not been demonstrated before. uPAR mRNA accumulation was followed by elevation of uPAR protein, indicating a complete transcription–translation process. Both tPA gene induction and uPAR gene induction were independent of the protein synthesis, suggesting that they are regulated by neural activity as immediate‐early genes. In contrast to tPA and uPAR genes, the expression of which returned to the basal level 6 hr following seizures, urokinase and plasminogen activator inhibitor‐1 gene expression showed a delayed activation only at 3 days after seizures. In conclusion, our results suggest an important sensitivity of the brain plasminogen activator system to seizure activity which raises the question of its role in activity‐dependent neural tissue remodeling in pathological and normal conditions.
Hypersensitivity to DNA double‐strand breaks associated with PARG deficiency is suppressed by exo‐1 and polq‐1 mutations in Caenorhabditis elegans
Authors: Bae Woori , Park Jae Hyung , Lee Myon‐Hee , Park Hyun Woo , Koo Hyeon‐Sook
Published: October 2019

Deficiency of either of the two homologs of poly(ADP‐ribose) glycohydrolase (PARG), PARG‐1 and PARG‐2, in Caenorhabditis elegans leads to hypersensitivity to ionizing radiation (IR). In the germ cells of parg‐2 mutant worms, the dissipation of recombinase RAD‐51 foci was slower than in wild‐type (WT) cells, suggesting defects in DNA double‐strand break (DSB) repair via homologous recombination (HR). Nevertheless, RPA‐1, the large subunit of replication protein A, accumulated faster in parg‐2 worms and disappeared earlier than in WT worms. This accelerated RPA‐1 accumulation may result from the enhanced expression of exonuclease‐1 (EXO‐1) after IR treatment. Accordingly, an exo‐1 mutation reduced IR sensitivity and accumulation of RPA‐1 in parg‐2 worms. A mutation of polq‐1, encoding for a key factor in the alternative end‐joining (Alt‐EJ) pathway, suppressed the IR hypersensitivity phenotype of parg‐2 worms and normalized the kinetics of RAD‐51 dissipation. This indicates that error‐prone Alt‐EJ may mediate DSB repair in parg‐2 worms, causing hypersensitivity to IR. In summary, PARG‐2 deficiency in C. elegans causes hyperactive DSB end resection likely through EXO‐1 overproduction. DSBs with long single‐stranded DNA ends in parg‐2 worms are thought to be repaired by Alt‐EJ instead of HR, causing genomic instability.
A systematic review and meta‐analysis of randomized clinical trials comparing rotary canal instrumentation techniques with manual instrumentation techniques in primary teeth
Authors: Manchanda S. , Sardana D. , Yiu C. K. Y.
Published: October 2019

Background

Use of rotary instruments in the root canals of permanent teeth is well known; however, there are no evidence‐based recommendations on the effectiveness of rotary canal instrumentation techniques over manual instrumentation techniques during root canal treatment in primary teeth.

Aim

To appraise the current literature on the effectiveness of rotary canal preparation techniques compared to manual techniques during root canal treatment in primary teeth.

Data sources

MEDLINE, Embase, Cochrane Library, Scopus, PubMed and Web of Science (1 January 1991 to 3 January 2019).

Study eligibility criteria, participants and interventions

Population: Children with primary teeth; Intervention: Rotary canal instrumentation; Control: Manual canal instrumentation; Outcomes: Success rates (clinical and/or radiographic), quality of root filling, instrumentation and root filling time, postoperative pain, cleaning effectiveness.

Study appraisal and synthesis methods

Cochrane risk of bias tool 2.0 was used to ascertain the validity across five domains. Risk ratio (RR) for dichotomous variables and weighted mean difference for continuous variables were used as summary measures. The GRADE approach was used to assess the certainty of evidence using GRADE‐pro software.

Results

A total of 13 trials were selected of 2471 records after screening of the databases. The RR of clinical success in rotary versus manual canal preparation technique was 1.01 (95% CI: 0.91–1.12; P = 0.913) at 6 months. The RR of radiographic success in rotary versus manual techniques was 0.97 (95% CI: 0.74–1.27; P = 0.805) at 6 months. The quality of root filling was not significantly different between the two groups (P = 0.062). The weighted mean difference of instrumentation time and canal filling time was significantly less with rotary techniques (P < 0.001); however, postoperative pain was non‐significant across both techniques at 12, 24 and 72 h but significantly less with rotary techniques at 6 h (P < 0.001) and 48 h (P = 0.023).

Limitations

Inclusion of only English literature.

Conclusions and implications of key findings

Rotary canal instrumentation had a similar clinical and radiographic success rate, less postoperative pain (at 6 and 48 h), and took less instrumentation time compared to manual instrumentation techniques (moderate level of evidence).
Tadalafil is sufficiently effective for severe chronic prostatitis/chronic pelvic pain syndrome in patients with benign prostatic hyperplasia
Authors: Hiramatsu Ippei , Tsujimura Akira , Soejima Miho , Yoshiyama Azusa , Nagashima Yuki , Ishikawa Keisuke , Uesaka Yuka , Nozaki Taiji , Ogishima Tatsuya , Shirai Masato , Mitsuhashi Isao , Sugimura Sosuke , Mizuno Taiki , Noto Kensho , Shigeta Yasuhiro , Takasu Jiro , Honda Shinichi , Iwata Shinji , Horie Shigeo
Published: October 2019

Objectives

To investigate the efficacy of tadalafil for patients with benign prostatic hyperplasia and chronic prostatitis/chronic pelvic pain syndrome.

Methods

Tadalafil 5 mg was given each morning for 12 weeks to patients diagnosed as having either moderate or severe lower urinary tract symptoms. Voiding symptoms were compared between patients with a high (≥4; high group) and low (<4; low group) pain subscore of the National Institutes of Health Chronic Prostatitis Symptom Index before and after tadalafil administration. The correlation between changes in the Chronic Prostatitis Symptom Index and the International Prostate Symptom Score during treatment was also investigated.

Results

At baseline, the pain subscore of the Chronic Prostatitis Symptom Index was high (≥4) in 24 of 74 (32.4%) patients. The International Prostate Symptom Score in the group with a high pain subscore was significantly higher than that in the group with a low pain subscore. International Prostate Symptom Score, National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscore were all significantly improved after treatment. The change in the Chronic Prostatitis Symptom Index total score correlated positively with the change in the International Prostate Symptom Score. The decrease in the International Prostate Symptom Score was significantly greater in the group with high versus low pain subscore.

Conclusions

Tadalafil is sufficiently effective in the treatment of patients with benign prostatic hyperplasia and severe chronic prostatitis/chronic pelvic pain syndrome.
Minorías étnicas foráneas y determinación salarial en China
Authors: MACDONALD Andrew W. , HASMATH Reza
Published: October 2019

Si bien algunos estudios observan que las minorías étnicas urbanas en China perciben salarios más bajos que la mayoría han, otros no constatan la existencia de esa brecha. Para resolver esta contradicción, los autores proponen desglosar las experiencias laborales por grupo étnico minoritario. El análisis de las minorías étnicas sobre un amplio conjunto de datos indica que las «minorías foráneas», como los tibetanos y los grupos túrquicos, sufren una penalización salarial significativa cuando se controlan las covariables, pero no ocurre lo mismo con la totalidad de las minorías. Estas conclusiones son robustas en varias especificaciones y tienen importantes implicaciones teóricas y en materia de políticas.
Los efectos de la capacidad en el rendimiento de la sobrecalificación y la infracalificación en Malasia
Authors: WYE Chung‐Khain , ISMAIL Rahmah
Published: October 2019

El número de trabajadores con estudios superiores crece en mayor medida que el empleo calificado en Malasia. Se plantea la cuestión de hasta qué punto la acumulación de competencias, capacidades y experiencia laboral mejora la prima salarial de la sobrecalificación o atenúa la penalización salarial de la infracalificación. Los autores estiman los efectos de la capacidad sobre el rendimiento de la calificación según datos recopilados en Malasia peninsular en 2015. Concluyen que la mejora de tipos específicos de capacidad puede rectificar las deficiencias salariales resultantes de los desajustes. La educación y la formación en el empleo deben orientarse al desarrollo de recursos humanos con capacidades laborales específicas.
Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine
Authors: Hassannia Hadi , Ghasemi Chaleshtari Mitra , Atyabi Fatemeh , Nosouhian Mahshid , Masjedi Ali , Hojjat‐Farsangi Mohammad , Namdar Afshin , Azizi Gholamreza , Mohammadi Hamed , Ghalamfarsa Ghasem , Sabz Gholamabas , Hasanzadeh Sajad , Yousefi Mehdi , Jadidi‐Niaragh Farhad
Published: October 2019

Dendritic cell (DC) ‐based cancer immunotherapy is one of the most important anti‐cancer immunotherapies, and has been associated with variable efficiencies in different cancer types. It is well‐known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of programmed death ligand 1 (PD‐L1) on DCs, which interacts with PD‐1 on T cells, leads to inhibition of anti‐tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that down‐regulation of PD‐L1 in DCs in association with silencing of PD‐1 on T cells may lead to the enhancement of T‐cell priming by DCs to have efficient anti‐tumor T‐cell responses. In this study, we silenced the expression of PD‐L1 in DCs and programmed cell death protein 1 (PD‐1) in T cells by small interfering RNA (siRNA) ‐loaded chitosan–dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T‐cell functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size 77·5 nm and zeta potential of 14·3) that were associated with efficient cellular uptake and target gene silencing. Moreover, PD‐L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD‐L1‐negative DCs to PD‐1‐silenced T cells led to induction of potent T‐cell responses. Our findings imply that PD‐L1‐silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD‐1‐siRNA loaded NPs, however; further in vivo investigation is required in animal models.
Tandem host‐parasite dispersal inferred from similarities in phylogeographical patterns among Little Penguins and their ‘terrestrial’ ectoparasites
Authors: Moon Katherine L. , Chown Steven L. , Fraser Ceridwen I.
Published: October 2019

Aim

Organisms with poor intrinsic dispersal capacity, such as parasites, often rely entirely on transport with host species that have a greater dispersal capacity. Penguins, for example, are exploited by terrestrial ectoparasites when they come ashore to breed. Recent research indicates that Little Penguin (Eudyptula minor and E. novaehollandiae) hard ticks (Ixodes eudyptidis and I. kohlsi) may be capable of surviving short periods (days) at sea with their hosts, but their capacity to survive longer voyages (weeks) is not known. We here aimed to assess whether phylogeographical patterns in Little Penguins and their ticks indicate that the terrestrial ectoparasites are able to disperse long distances at sea with their swimming hosts.

Location

Southern Australia and New Zealand.

Taxon

Ixodes eudyptidis and I. kohlsi ticks.

Methods

We conducted a broad‐scale genomic assessment of Little Penguin ticks from across their hosts’ ranges in Australia and New Zealand. Using genotyping by sequencing, we generated SNP data sets from ticks from 14 penguin colonies, and analysed phylogeographical structure. We included ticks from some sympatric flighted seabirds to verify host specificity.

Results

We resolved two distinct lineages of Ixodes from Little Penguins, with one restricted to Australia, and the other found throughout New Zealand and in low numbers at some eastern Australian sites. Both lineages exhibited phylogeographical structure consistent with patterns observed in their hosts, with some evidence of occasional oceanic dispersal, including across the Tasman Sea between Australia and New Zealand. Ticks from sympatric short‐tailed shearwaters (Ardenna tenuirostris), which disperse aerially, were genetically distinct from those collected from Little Penguins, supporting prior evidence of host specificity in seabird ticks.

Main conclusions

The most parsimonious explanation for our results is that ticks can travel at sea with Little Penguins. We infer that some terrestrial ectoparasites associated with aquatically dispersing hosts have evolved the capacity to survive oceanic voyages.
Observer‐independent assessment of psoriasis‐affected area using machine learning
Authors: Meienberger N. , Anzengruber F. , Amruthalingam L. , Christen R. , Koller T. , Maul J.T. , Pouly M , Djamei V. , Navarini A.A.
Published: October 2019

Background

Assessment of psoriasis severity is strongly observer‐dependent, and objective assessment tools are largely missing. The increasing number of patients receiving highly expensive therapies that are reimbursed only for moderate‐to‐severe psoriasis motivates the development of higher quality assessment tools.

Objective

To establish an accurate and objective psoriasis assessment method based on segmenting images by machine learning technology.

Methods

In this retrospective, non‐interventional, single‐centred, interdisciplinary study of diagnostic accuracy, 259 standardized photographs of Caucasian patients were assessed and typical psoriatic lesions were labelled. Two hundred and three of those were used to train and validate an assessment algorithm which was then tested on the remaining 56 photographs. The results of the algorithm assessment were compared with manually marked area, as well as with the affected area determined by trained dermatologists.

Results

Algorithm assessment achieved accuracy of more than 90% in 77% of the images and differed on average 5.9% from manually marked areas. The difference between algorithm‐predicted and photograph‐based estimated areas by physicians was 8.1% on average.

Conclusion

The study shows the potential of the evaluated technology. In contrast to the Psoriasis Area and Severity Index (PASI), it allows for objective evaluation and should therefore be developed further as an alternative method to human assessment.
Improving flood risk map accuracy using high‐density LiDAR data and the HEC‐RAS river analysis system: A case study from north‐eastern Romania
Authors: Stoleriu Cristian C. , Urzica Andrei , Mihu‐Pintilie Alin
Published: October 2019

North‐eastern Romania is frequently affected by storms that produce annual floods with catastrophic effects upon agriculture areas. The implementation of the 2007/60/ EC Directive, which aims, among other things, to assess and manage flood risk, is currently being carried out by means of rough hydrological risk maps. Additionally, the limits of the potentially floodable areas generated on digital elevation models with 30 points/m resolution (SRTM) do not correspond to the current topographic reality. Three tests (T1, T2, and T3) for modelling the floodplains and the comparative assessment of potential damages in the case of 30 localities in the study area (Başeu River basin) were carried out in this study. The results indicate that official data (T1) underestimate potential damage in the case of hydrological events with a recurrence interval probability of 1% (100‐year). The T2 [1%] (100‐year) results also highlight the role of hydro‐technical works in mitigating floods. In T3, the hydrological risk areas were generated with an accuracy of 0.5 m, evaluating the probable damage in cases of events with probabilities of 3% (33.3‐year), 1% (100‐year), and 0.1% (1,000‐year) recurrence intervals. The accuracy of the official hydrological hazard maps (T1) was improved using high‐density LiDAR data and HEC‐RAS software (T3).
Objectively Measured Physical Activity Reduces the Risk of Mortality among Brazilian Older Adults
Authors: Bielemann Renata M. , LaCroix Andrea Z. , Bertoldi Andréa D. , Tomasi Elaine , Demarco Flávio F. , Gonzalez Maria Cristina , Crespo da Silva Pedro Augusto , Wendt Andrea , Mohnsam da Silva Inácio Crochemore , Brage Soren , Ekelund Ulf , Pratt Michael
Published: October 2019

OBJECTIVES

Use of objectively measured physical activity (PA) in older adults to assess relationship between PA and risk of all‐causes mortality is scarce. This study evaluated the associations of PA based on accelerometry and a questionnaire with the risk of mortality among older adults from a city in Southern Brazil.

DESIGN

A cohort study.

SETTING

Urban area of Pelotas, Southern Brazil.

PARTICIPANTS

A representative sample of older adults (≥60 y) from Pelotas, enrolled in 2014.

MEASUREMENTS

Overall physical activity (mg), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were estimated by raw accelerometer data. The International Physical Activity Questionnaire estimated leisure time and commuting PA. Hazard ratios (excluding deaths in the first 6 mo) stratified by sex were estimated by Cox regression analysis considering adjustment for confounders.

RESULTS

From the 1451 older adults interviewed in 2014, 145 died (10%) after a follow‐up of an average 2.6 years. Men and women in the highest tertile of overall PA had on average a 77% and 92% lower risk of mortality than their less active counterparts (95% confidence interval [CI] = .06‐.84 and 95% CI = .01‐.65, respectively). The highest tertile of LPA was also related to a lower risk of mortality in individuals of both sexes (74% and 91% lower risk among men and women, respectively). MVPA statistically reduced the risk of mortality only among women (hazard ratio [HR] = .30 and HR = .07 in the second and third tertiles). Self‐reported leisure‐time PA was statistically associated with a lower risk of mortality only among men. Women in the highest tertiles of commuting PA showed a lower risk of mortality than those in the reference group.

CONCLUSION

Accelerometry‐based PA was associated with a lower risk of mortality among Brazilian older adults. Older individuals should practice any type of PA. J Am Geriatr Soc 68:137–146, 2019
Phosphatidylserine is critical for vesicle fission during clathrin‐mediated endocytosis
Authors: Varga Kelly , Jiang Zhong-Jiao , Gong Liang‐Wei
Published: October 2019

Phosphatidylserine (PS), a negatively charged phospholipid present predominantly at the inner leaflet of the plasma membrane, has been widely implicated in many cellular processes including membrane trafficking. Along this line, PS has been demonstrated to be important for endocytosis, however, the involved mechanisms remain uncertain. By monitoring clathrin‐mediated endocytosis (CME) of single vesicles in mouse chromaffin cells using cell‐attached capacitance measurements that offer millisecond time resolution, we demonstrate in the present study that the fission‐pore duration is reduced by PS addition, indicating a stimulatory role of PS in regulating the dynamics of vesicle fission during CME. Furthermore, our results show that the PS‐mediated effect on the fission‐pore duration is Ca2+‐dependent and abolished in the absence of synaptotagmin 1 (Syt1), implying that Syt1 is necessary for the stimulatory role of PS in vesicle fission during CME. Consistently, a Syt1 mutant with a defective PS–Syt1 interaction increases the fission‐pore duration. Taken together, our study suggests that PS–Syt1 interaction may be critical in regulating fission dynamics during CME.

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Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer
Authors: Norlin Maria
Published: October 2019

The active vitamin D hormone, 1,25‐dihydroxyvitamin D3, exerts many physiological actions in the body, including effects on the nervous system. Studies of steroidogenesis in cells of the nervous system and elsewhere not only indicate that 1,25‐dihydroxyvitamin D3 affects steroidogenic pathways but also suggest varying responses in different cell types. For example, 1,25‐dihydroxyvitamin D3 stimulates the expression of aromatase in human glioma but not in human neuroblastoma cells or rat astrocytes. However, in astrocytes, 1,25‐dihydroxyvitamin D3 suppresses 3β‐hydroxysteroid dehydrogenase and steroid 17‐hydroxylase/lyase. Other studies indicate cross‐talk between vitamin D signalling and signalling of oestrogens, progesterone or glucocorticoids. Reported data indicate synergistic effects of combinations of 1,25‐dihydroxyvitamin D3 and other steroid hormones on neuroinflammation, neurite outgrowth and neuroprotection. Also, dysregulation of steroid pathways affecting brain cells is found in vitamin D deficiency. Thus, several studies suggest that active vitamin D may affect steroid hormone synthesis and/or signalling in the nervous system, although the potential mechanisms for these responses remain unclear. 1,25‐Dihydroxyvitamin D3 suppresses proliferation in several cell types and is therefore of interest in cancer treatment. Also, epidemiological studies associate vitamin D levels with cancer risk or outcomes. Reported data on tumours of the nervous system are mainly on glioma, a common type of brain cancer. Expression of the vitamin D receptor in glioma tumours is associated with improved survival. Several studies show that 1,25‐dihydroxyvitamin D3 and vitamin D analogues (synthetic vitamin D‐like compounds) suppress proliferation and migration in human vitamin D receptor‐expressing glioma cell lines. Studies on mechanisms for actions of 1,25‐dihydroxyvitamin D3 or its analogues indicate regulation of cell cycle proteins and senescence markers. These compounds also show synergism in combination with other cancer therapies treating glioma. From the data available, vitamin D analogues emerge as interesting candidates for the future improved treatment of human glioma and possibly also other cancers of the nervous system.
Clinical diagnosis of sensory neuropathy in HIV patients treated with tenofovir: A 6‐month follow‐up study
Authors: Pillay Prinisha , Wadley Antonia L. , Cherry Catherine L. , Karstaedt Alan S. , Kamerman Peter R.
Published: October 2019

Background

Sensory neuropathy (SN) is a common and often painful neurological condition associated with HIV‐infection and its treatment. However, data on the incidence of SN in neuropathy‐free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking.

Aims

We investigated the 6‐month incidence of SN in ART naïve individuals initiating tenofovir (TDF)‐based cART, and the clinical factors associated with the development of SN.

Methods

120 neuropathy‐free and ART naïve individuals initiating cART at a single center in Johannesburg, South Africa were enrolled. Participants were screened for SN using clinical signs and symptoms at study enrolment and approximately every 2‐months for a period of ~6‐months. Diagnostic criteria for symptomatic SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin‐prick hypoaesthesia). Diagnostic criteria for asymptomatic SN required at least two clinical signs only (as above).

Results

A total of 88% of the cohort completed three visits within the 6‐month period. The 6‐month cumulative incidence of neuropathy was 140 cases per 1000 patients (95% CI: 80‐210) at an incidence rate of 0.37 (95% CI: 0.2‐0.5) per person year. Height and active tuberculosis (TB) disease were independently associated with the risk of developing SN (P < .05).

Interpretation

We found that within the first 6 months of starting cART, incident SN persists in the post‐stavudine era, with 11 (9%) of individuals developing asymptomatic SN, and 9 (8%) developing symptomatic SN.
Acne treatment efficacy of intense pulsed light photodynamic therapy with topical licochalcone A, l‐carnitine, and decanediol: A spilt‐face, double‐blind, randomized controlled trial
Authors: Wanitphakdeedecha Rungsima , Tavechodperathum Nudpanuda , Tantrapornpong Ploypailin , Suphatsathienkul Panittra , Techapichetvanich Thanya , Eimpunth Sasima , Manuskiatti Woraphong
Published: October 2019

Background

Depending on disease severity, standard acne treatments can vary from topical to systemic therapy. However, poor compliance caused by adverse events and antibiotic resistance is a major cause of treatment failure.

Aims

To determine the effectiveness of photodynamic therapy (PDT) with intense pulsed light (IPL) in the treatment of acne when combined with a cream containing licochalcone A, L‐carnitine and decanediol (so‐called, ‘active formulation’) versus PDT alone.

Patients/Methods

Twenty‐nine volunteers, aged 21‐39 years (26 women and 3 men, mean age 29.41 ± 5.24 years), with mild to severe facial acne, were enrolled. Each subject’s face sides were randomized in a split‐face manner to either receive PDT (IPL with a 400‐720 nm cut‐off filter, at 4 sessions with two‐week intervals) combined with the active formulation cream twice daily for 10 weeks on one face side; or PDT and the vehicle cream on the other side, with the same treatment protocol. Reduction in acne quantity, melanin index and erythema index were assessed 2 weeks after the second treatment (day 28), 1 week after the fourth treatment (day 49), and 1 month after the fourth treatment (day 70).

Results

Compared to baseline, patients in the active formulation group demonstrated a faster onset of reduction in the number of lesions at 2 weeks after the second treatment (p=0.010 for inflammatory acne and p=0.001 for non‐inflammatory acne). A significantly greater reduction in lesion count was observed in the active formulation group compared with the vehicle group at all timepoints of evaluation for noninflammatory acne (day 28, day 49, and day 70; p=0.003, 0.005 and 0.002 respectively), and at 1 month after the fourth treatment for inflammatory acne (p=0.036). Compared to the vehicle group, the melanin index of the active formulation group decreased significantly at 1 month after the fourth treatment (p=0.015).

Conclusion

PDT is more effective in treating acne when combined with a topical cream containing licochalcone A, L‐carnitine and decanediol, than PDT alone. Significant acne reduction and improvements in post‐inflammatory hyperpigmentation were observed, which offers acne patients a better therapeutic option. It is a safe and effective combination treatment for patients with moderate and severe acne
Higher frequency of hospitalization but lower relative mortality for pandemic influenza in people with type 2 diabetes
Authors: Ruiz P. L. D. , Bakken I. J. , Håberg S. E. , Tapia G. , Hauge S. H. , Birkeland K. I. , Gulseth H. L. , Stene L. C.
Published: October 2019

Background

There is limited evidence linking type 2 diabetes (T2D) to influenza‐related complications.

Objectives

To test a set of research questions relating to pandemic influenza vaccination, hospitalization and mortality in people with and without T2D.

Methods

In this population‐based cohort study, we linked individual‐level data from several national registers for all Norwegian residents aged 30 years or more as of January 2009. People with or without T2D at baseline (n = 2 992 228) were followed until December 2013. We used Cox regression to estimate adjusted hazard ratios (aHRs).

Results

Pandemic influenza hospitalization was more common in individuals with T2D (aHR = 2.46, 95% CI 2.04–2.98). The mortality hazard ratio associated with hospitalization for pandemic influenza was lower in people with T2D (aHR = 1.82, 95% CI 1.21–2.74) than in those without T2D (aHR = 3.89, 95% CI 3.27–4.62). The same pattern was observed when restricting to 90‐day mortality (aHR = 3.89, 95% CI 1.25–12.06 amongst those with T2D and aHR = 10.79, 95% CI 7.23–16.10 amongst those without T2D). The rate of hospitalization for pandemic influenza was 78% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR = 0.22, 95% CI 0.11–0.39), whilst the corresponding estimate for those without T2D was 59% lower (aHR = 0.41, 95% CI 0.33–0.52). Mortality was 25% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR = 0.75, 95% CI 0.73–0.77), whilst the corresponding estimate for those without T2D was 9% (aHR = 0.91, 95% CI 0.90–0.92).

Conclusions

There may have been a lower threshold for pandemic influenza hospitalization for people with T2D, rather than more severe influenza infection. Our combined results support the importance of influenza vaccination amongst people with T2D, especially during pandemics.
Association between mandibular advancement device therapy and reduction of excessive daytime sleepiness due to obstructive sleep apnoea
Authors: Silva Gomes Ribeiro Cynthia Valeria , Ribeiro‐Sobrinho Djalma , Muñoz Lora Victor Ricardo Manuel , Morais Dornelas Bezerra Louise , Del Bel Cury Altair Antoninha
Published: October 2019

Background

Excessive daytime sleepiness (EDS) is frequently reported as a symptom for obstructive sleep apnoea (OSA), leading to problems with concentration, mood and memory. Mandibular advance device (MAD) is considered as an effective therapy to control OSA, reducing EDS and improving sleep quality.

Objectives

The present study aimed to investigate the effects MAD therapy on EDS of patients diagnosed with OSA.

Methods

Ten patients from the Sleep Medicine Service of the “Hospital Geral Sanatório” (Maceió, Alagoas, Brazil) were diagnosed with EDS, and a personalised MAD was made for each one of them. Nocturnal polysomnography (NPSG) and maintenance of wakefulness test (MWT) were applied before (baseline) and 3 months after the continuous use of the MAD. The number of arousals and micro‐arousals at baseline and after treatment was also evaluated.

Results

All 10 patients completed the investigation. A significant decrease in the number of arousals and micro‐arousals per night of sleep was observed after the use of MAD for three consecutive months (P = 0.0078; Wilcoxon signed‐rank test). Also, there was a significant reduction on the apnoea/hypopnea index between baseline and post‐treatment values (P = 0.0001; paired t test), as well as an increase in the mean latency for the onset of sleep (MSL) in the MTW (P = 0.0047; paired t test), indicating a significant difference among baseline and after treatment.

Conclusion

We conclude that the improvement on EDS is associated with the used of MAD in patients diagnosed with OSA, improving their quality of sleep.
Extra‐pair paternity in birds
Authors: Brouwer Lyanne , Griffith Simon C.
Published: October 2019

Since the first molecular study providing evidence for mating outside the pair bond in birds over 30 years ago, >500 studies have reported rates of extra‐pair paternity (EPP) in >300 bird species. Here, we give a detailed overview of the current literature reporting EPP in birds and highlight the sampling biases and patterns in the data set with respect to taxonomy, avian phylogeny and global regions, knowledge of which will be crucial for correct interpretation of results in future comparative studies. Subsequently, we use this comprehensive dataset to simultaneously test the role of several ecological and life history variables. We do not find clear evidence that variation in EPP across socially monogamous species can be explained by latitude, density (coloniality), migration, generation length, genetic structuring (dispersal distance), or climatic variability, after accounting for phylogeny. These results contrast previous studies, most likely due to the large heterogeneity within species in both EPP and the predictor of interest, indicating that using species averages might be unreliable. Despite the absence of broadscale ecological drivers in explaining interspecific variation in EPP, we suggest that certain behaviours and ecological variables might facilitate or constrain EPP, as indicated by our finding that EPP was negatively associated with latitude within noncolonial species, suggesting a role of breeding synchrony. Thus, rather than focussing on general explanations for variation in EPP across all species, a future focus should be on how various aspects of ecology or life history might have driven variation in EPP among groups of species or populations of the same species. Hence, we argue that variation in EPP can be partly explained when taking the right perspective. This comprehensive overview, and particularly the dataset provided herein will create a foundation for further studies.
Urbanization impacts apex predator gene flow but not genetic diversity across an urban‐rural divide
Authors: Trumbo Daryl R. , Salerno Patricia E. , Logan Kenneth A. , Alldredge Mathew W. , Gagne Roderick B. , Kozakiewicz Christopher P. , Kraberger Simona , Fountain‐Jones Nicholas M. , Craft Meggan E. , Carver Scott , Ernest Holly B. , Crooks Kevin R. , VandeWoude Sue , Funk W. Chris
Published: October 2019

Apex predators are important indicators of intact natural ecosystems. They are also sensitive to urbanization because they require broad home ranges and extensive contiguous habitat to support their prey base. Pumas (Puma concolor) can persist near human developed areas, but urbanization may be detrimental to their movement ecology, population structure, and genetic diversity. To investigate potential effects of urbanization in population connectivity of pumas, we performed a landscape genomics study of 130 pumas on the rural Western Slope and more urbanized Front Range of Colorado, USA. Over 12,000 single nucleotide polymorphisms (SNPs) were genotyped using double‐digest, restriction site‐associated DNA sequencing (ddRADseq). We investigated patterns of gene flow and genetic diversity, and tested for correlations between key landscape variables and genetic distance to assess the effects of urbanization and other landscape factors on gene flow. Levels of genetic diversity were similar for the Western Slope and Front Range, but effective population sizes were smaller, genetic distances were higher, and there was more admixture in the more urbanized Front Range. Forest cover was strongly positively associated with puma gene flow on the Western Slope, while impervious surfaces restricted gene flow and more open, natural habitats enhanced gene flow on the Front Range. Landscape genomic analyses revealed differences in puma movement and gene flow patterns in rural versus urban settings. Our results highlight the utility of dense, genome‐scale markers to document subtle impacts of urbanization on a wide‐ranging carnivore living near a large urban center.
Time and Measures of Success: Interpreting and Implementing Laudato Si’
Authors: Grey Carmody Teresa Sinclair
Published: October 2019

Laudato Si’ contains a prophetic vision of what time is and is for. It challenges development organisations to think critically about the way they conceive ‘progress’, the way they measure their ‘success’. In doing so, it invites them to ask how they express in their activity a particular conception of the meaning of time. This paper argues that Laudato Si’ proposes a vision of time which is theological, teleological, dialectical and contemplative, and that it is this vision which underpins its contrast between true and false notions of progress. The paper seeks to articulate a foundation for the formulation of authentic ‘measures of success’ that are expressive of this understanding of time, and to imagine what the organisational implications of such measures might be.
Hylomorphism, Intentionality, and Prior's Puzzle
Authors: Younan Andrew
Published: October 2019

In this paper I intend to discuss the question in philosophy of mind called “Prior's Puzzle” within a hylomorphic, that is, a broadly Aristotelian-Thomistic, context. After laying the groundwork explaining hylomorphism in natural philosophy and basic psychology in Part I, I will examine Prior's puzzle about nonexistent mental objects in Part II. The connection between these two issues will become clear as the paper progresses, but the fundamental principle that will guide my presentation is that of intentionality, or “directedness.”
Analogy, Synergy, Revelation: Divine-Humanity in John Milbank's Poetic Theology
Authors: Tromans Oliver
Published: October 2019

This article builds upon the analogical reflections of John Milbank – taking his work in a distinctly “projectionist” direction. It is argued that analogy (as Milbank understands it) allows us to talk of “projection” in theology without succumbing to Feuerbach's anthropological reductionism. In my discussion of Milbank's work, what is emphasized is the “poetic” nature of theological analogy, in which the divine and human creations intersect. God is revealed in and through the human, through the things we make. In its development of projectionist themes, Milbank's work, it is shown, demonstrates several potentials for feminist theology and philosophy of religion. In particular, his analogical vision helps to overcome any sort of dichotomy between human and divine, “projection” and “truth”. Crucially in this regard, Milbank's analogy stresses the importance, not only of our “makings”, but also of the divine initiative.
Lead us not into Temptation: On the Proposed Revision of the Our Father
Authors: Hewitt Simon
Published: October 2019

Recently a change to the Italian text of the Pater Noster has been proposed. Motivation for this change centers on worries about the suggestion that God leads us into temptation. This paper argues that these worries issue from a confused picture of the relationship between God and creaturely freedom. More fundamentally, however, the suggestion that these kind of worries ought to precipitate revision of liturgical texts fails to take seriously the nature of the liturgy as prayer, rather than simply a means of communicating information. Drawing on Wittgenstein, the sui generis nature of prayer is laid out before the paper concludes with some comments on the distinctive values of both scholarship and prayer.
Looking to the future: key points for sustainable management of northern Great Plains grasslands
Authors: Perkins Lora B. , Ahlering Marissa , Larson Diane L.
Published: October 2019

The grasslands of the northern Great Plains (NGP) region of North America are considered endangered ecosystems and priority conservation areas yet have great ecological and economic importance. Grasslands in the NGP are no longer self‐regulating adaptive systems. The challenges to these grasslands are widespread and serious (e.g. climate change, invasive species, fragmentation, altered disturbance regimes, and anthropogenic chemical loads). Because the challenges facing the region are dynamic, complex, and persistent, a paradigm shift in how we approach restoration and management of the grasslands in the NGP is imperative. The goal of this article is to highlight four key points for land managers and restoration practitioners to consider when planning management or restoration actions. First, we discuss the appropriateness of using historical fidelity as a restoration or management target because of changing climate, widespread pervasiveness of invasive species, the high level of fragmentation, and altered disturbance regimes. Second, we highlight ecosystem resilience and long‐term population persistence as alternative targets. Third, because the NGP is so heavily impacted with anthropogenic chemical loading, we discuss the risks of ecological traps and extinction debt. Finally, we highlight the importance of using adaptive management and having patience during restoration and management. Consideration of these four points will help management and restoration of grasslands move toward a more successful and sustainable future. Although we specifically focus on the NGP of North America, these same issues and considerations apply to grasslands and many other ecosystems globally.