bluuebunny/crossref_metadata_2025 huggingface dataset:
Implant fracture failure rate and potential associated risk indicators: An up to 12‐year retrospective study of implants in 5,124 patients
Authors: Lee Dong‐Woon , Kim Na‐Hong , Lee Young , Oh Yeon‐Ah , Lee Jae‐Hong , You Hyung‐Keun
Published: January 2019

Objectives

This study investigated fracture rates and risk indicators for fractures in internal connection dental implants.

Material and Methods

We performed a retrospective analysis of 19,006 internal connection implants used in fixed restoration in 5,124 patients (4,570 males, 554 females) at the Dental Hospital of Veterans Health Service Medical Center between 2006 and 2015. Patients were followed through June 2018 (0.03–12.39 years post‐installation). Clinical factors (age, sex, implant diameter, implant length, placement site, bone graft, fixture material, cervical feature, abutment connection, microthread, and platform switching) were recorded. Kaplan–Meier survival analysis identified risk indicators associated with an implant fracture. Cox regression models elucidated potential fracture risks.

Results

One hundred and seventy‐four implants fractured in 135 patients, for an incidence rate of 0.92% after an average of 4.95 ± 2.14 years of use. Kaplan–Meier estimates showed that the 3‐, 5‐, and 10‐year survival rates of implants were 99.8%, 99.2%, and 97.7%, respectively. In the multivariable Cox regression model, the diameter, location, history of bone graft, and microthread presence were significantly correlated with implant fractures. Wide‐diameter implants had a reduced fracture risk within 90 months, after which the diameter did not correlate with fractures. Implants placed in the anterior mandible had a lower fracture risk within 90 months; mandibular premolar implants corresponded with a lower risk after 90 months. Implants without a history of bone graft or microthreads were more likely to fracture throughout the follow‐up time.

Conclusions

These results elucidate risk indicators for implant fractures and facilitate their reduction in clinical practice.
Cell cycle activation contributes to isoflurane‐induced neurotoxicity in the developing brain and the protective effect of CR8
Authors: Huang Bao‐Yi , Huang Hong‐Bing , Zhang Zhi‐Jing , Liu Zhi‐Gang , Luo Jun , Liu Min , Luo Tao
Published: January 2019

Aims

It is well established that exposure of common anesthetic isoflurane in early life can induce neuronal apoptosis and long‐lasting cognitive deficit, but the underlying mechanisms were not well understood. The cell cycle protein Cyclin B1 plays an important role in the survival of postmitotic neurons. In the present study, we investigated whether cyclin B1‐mediated cell cycle activation pathway is a contributing factor in developmental isoflurane neurotoxicity.

Methods

Postnatal day 7 mice were exposed to 1.2% isoflurane for 6 hours. CR8 (a selective inhibitor of cyclin‐dependent kinases) was applied before isoflurane treatment. Brain samples were collected 6 hours after discontinuation of isoflurane, for determination of neurodegenerative biomarkers and cell cycle biomarkers.

Results

We found that isoflurane exposure leads to upregulated expression of cell cycle‐related biomarkers Cyclin B1, Phospho‐CDK1(Thr‐161), Phospho‐n‐myc and downregulated Phospho‐CDK1 (Tyr‐15). In addition, isoflurane induced increase in Bcl‐xL phosphorylation, cytochrome c release, and caspase‐3 activation that resulted in neuronal cell death. Systemic administration of CR8 attenuated isoflurane‐induced cell cycle activation and neurodegeneration.

Conclusion

These findings suggest the role of cell cycle activation to be a pathophysiological mechanism for isoflurane‐induced apoptotic cell death and that treatment with cell cycle inhibitors may provide a possible therapeutic target for prevention of developmental anesthetic neurotoxicity.
Endorectal advancement flap for complex anal fistula: does flap configuration matter?
Authors: Yellinek S. , Krizzuk D. , Moreno Djadou T. , Lavy D. , Wexner S. D.
Published: January 2019

Aim

Treatment of complex anal fistula (CAF) is challenging, often requiring multiple operations due to a high failure rate. The plethora of options attests to the lack of a panacea. Endorectal advancement flap (ERAF) carries the advantages of no sphincter division, no contour defect to the anal canal and no perineal wound. The failure rate of this procedure ranges between 15% and 60%. Although the procedure traditionally described a rhomboid (tongue‐shaped) flap, an elliptical (curvilinear) flap was introduced to try to improve the results. This study aimed to describe the elliptical‐shaped ERAF performed by the senior authors and others and compare failure rates between elliptical and rhomboid ERAFs for CAF.

Method

A retrospective review of all patients who underwent ERAF for CAF between 2011 and 2017 was undertaken. Patients were divided into two groups based on the type of flap: rhomboid or elliptical. The main outcomes measures were postoperative persistent or recurrent fistula.

Results

Seventy‐six ERAF procedures for CAF were identified in 71 patients; 39 had a classic rhomboid flap and 37 had an elliptical configuration with mean follow‐up of 13.8 and 13.9 months, respectively. The groups were similar for demographic parameters and preoperative fistula characteristics. The overall failure rate was 37%, with a success rate of 64% in the rhomboid and 62% in the elliptical group.

Conclusion

The shape of the ERAF for treatment of CAF does not appear to influence failure rate.
Modified Gant–Miwa–Thiersch procedure (mucosal plication with anal encircling) for rectal prolapse
Authors: Iida Y. , Honda K. , Saitou H. , Munemoto Y. , Tanaka H.
Published: January 2019

Aim

Rectal prolapse (RP) is usually associated with elderly women and is well recognized as having a detrimental effect on quality of life. A number of surgical procedures for RP are available, but morbidity and mortality are substantial. The Gant–Miwa–Thiersch procedure (GMT) has been frequently used for RP in Japan. However, as GMT has a high recurrence rate it is not widely used elsewhere. The aim of this study was to evaluate a modified version of GMT (mGMT) in comparison with other procedures.

Method

mGMT was performed under spinal or local anaesthesia in 187 patients with RP. No normal mucosa was left between the tags and lateral wounds were created in the Thiersch procedure. Morbidity, mortality and recurrence rates were recorded.

Results

No serious postoperative complications and no operative deaths occurred after mGMT. Eight per cent of patients suffered from infection of the strings. The overall recurrence rate after mGMT was 7.5% with a median follow‐up period of 13.8 years.

Conclusion

On the basis of these results, we consider that mGMT has a number of advantages: it is minimally invasive, does not require general anaesthesia, is technically simple to perform and is associated with satisfactory outcomes and low morbidity. mGMT should be considered an option for the treatment of RP in elderly patients.
How to Find the Right Supply Chain Strategy? An Analysis of Contingency Variables
Authors: von Falkenhausen Christian , Fleischmann Moritz , Bode Christoph
Published: January 2019

Contingency variables are characteristics of the business environment that influence the competitive priorities supply chains should pursue for maximizing profits. But which contingency variables should managers focus on when developing a supply chain strategy? On the one hand, if important variables are omitted, the selected strategy may fail to fulfill the needs of the business environment. On the other hand, considering irrelevant variables unnecessarily complicates the strategy formation process, hence preventing well‐suited strategies from being found. As a first step toward resolving this trade‐off, our study analyzes the effects hypothesized to be underlying a set of frequently cited contingency variables referred to as “DWV3” (product lifecycle Duration, delivery time Window, demand Variability, demand Volume, product Variety) as well as contribution margins. We test the hypotheses on archival data from a leading chemical manufacturer using multilevel regression. Our findings indicate that demand variability, the delivery time window, and contribution margins are important for strategy development because they indicate to what extent companies should invest in market mediation. Volume, variety, and lifecycle duration are less important for this purpose, but may instead be used for analyzing the causes of demand variability.
Impact of physical exercise on sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system in people with Type 1 diabetes: a randomized crossover trial
Authors: Moser O. , Eckstein M. L. , Mueller A. , Birnbaumer P. , Aberer F. , Koehler G. , Sourij C. , Kojzar H. , Holler P. , Simi H. , Pferschy P. , Dietz P. , Bracken R. M. , Hofmann P. , Sourij H.
Published: January 2019

Aims

To evaluate the sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system using reference blood glucose levels during moderate‐intensity exercise while on either full or reduced basal insulin dose in people with Type 1 diabetes.

Methods

Ten participants with Type 1 diabetes [four women, mean ± sd age 31.4 ± 9.0 years, BMI 25.5±3.8 kg/m2, HbA1c 55±7 mmol/mol (7.2±0.6%)] exercised on a cycle ergometer for 55 min at a moderate intensity for 5 consecutive days at the clinical research facility, while receiving either their usual or a 75% basal insulin dose. After a 4‐week washout period, participants performed the second exercise period having switched to the alternative basal insulin dose. During exercise, reference capillary blood glucose values were analysed using the fully enzymatic‐amperometric method and compared with the interstitial glucose values obtained. Intermittently viewed continuous glucose monitoring accuracy was analysed according to median (interquartile range) absolute relative difference, and Clarke error grid and Bland–Altman analysis for overall glucose levels during exercise, stratified by glycaemic range and basal insulin dosing scheme (P<0.05).

Results

A total of 845 glucose values were available during exercise to evaluate intermittently viewed continuous glucose monitoring sensor performance. The median (interquartile range) absolute relative difference between the reference values and those obtained by the sensor across the glycaemic range overall was 22 (13.9–29.7)%, and was 36.3 (24.2–45.2)% during hypoglycaemia, 22.8 (14.6–30.6)% during euglycaemia and 15.4 (9–21)% during hyperglycaemia. Usual basal insulin dose was associated with a worse sensor performance during exercise compared with the reduced (75%) basal insulin dose [median (interquartile range) absolute relative difference: 23.7 (17.2–30.7)% vs 20.5 (12–28.1)%; P<0.001).

Conclusions

The intermittently viewed continuous glucose monitoring sensor showed diminished accuracy during exercise. Absolute glucose readings derived from the sensor should be used cautiously and need confirmation by additional finger‐prick blood glucose measurements.
Caspofungin for primary antifungal prophylaxis after T‐cell–replete haploidentical stem cell transplantation with post‐transplant cyclophosphamide
Authors: Mariotti Jacopo , De Philippis Chiara , Bramanti Stefania , Sarina Barbara , Tordato Federica , Pocaterra Daria , Casari Erminia , Carlo‐Stella Carmelo , Santoro Armando , Castagna Luca
Published: January 2019

Objectives

T‐cell–replete haploidentical stem cell transplantation (Haplo‐SCT) with post‐transplant cyclophosphamide (PT‐Cy) is at high risk of invasive fungal infections (IFI), and anti‐mold–active drug is required for primary antifungal prophylaxis (PAP) according to international guidelines. No data are available on the efficacy of caspofungin as PAP in this setting.

Methods

Here, we report our retrospective experience with 103 consecutive patients treated with caspofungin as PAP after Haplo‐SCT. Caspofungin was administered only during the pre‐engraftment phase.

Results

Hundred‐day cumulative incidence of proven‐probable IFI (PP‐IFI) was 8.7% and median day of onset was 19 post‐SCT. No patient died of PP‐IFI, and overall survival (OS) and non‐relapse mortality (NRM) hazard ratio (HR) for patients experiencing IFI were 1.02 (P = 0.9) and 0.7 (P = 0.7), respectively. Three‐year overall survival (OS) and 1‐year non‐relapse mortality (NRM) were 55% and 19%, respectively. By univariate analysis, duration of neutropenic phase and partial remission pre‐transplant disease status were associated with increased incidence of IFI, but were not confirmed by multivariate analysis.

Conclusion

In summary, PAP with caspofungin is an effective strategy for preventing IFI in the context of Haplo‐SCT with PT‐Cy. Further efforts are required in order to identify more potent strategies able to avoid the occurrence of breakthrough infections.
The proper application of the wooden shoe: An overview
Authors: O'Grady S. E.
Published: January 2019

The wooden shoe provides the clinician with an alternative option to conventional farriery when treating a variety of foot problems such as acute/chronic laminitis, white line disease, distal phalanx fractures and poor‐quality hoof capsules. The wooden shoe provides a simplified method to apply many of the principles of therapeutic farriery which include redistributing the load or forces on the foot, repositioning breakover and providing heel elevation when necessary. Understanding the biomechanics of the wooden shoe along with understanding good basic farriery which include the appropriate foot trim, proper size, fit and placement of the wooden shoe on the foot combined with the appropriate application are essential for consistent success. This paper outlines what is considered to be the proper application of the wooden shoe.
New maps of struggle for gender justice: Rethinking feminist research on organizations and work
Authors: Connell Raewyn
Published: January 2019

The 2018 Gender, Work and Organization conference was held in Sydney. That fact is relevant to the issues now facing feminist organization research. The journal was launched in 1994 in the global North, in the wake of the women's liberation movement but after a first wave of neoliberal politics. Gender studies has changed since then, especially with growing recognition of feminist thought and activism in the global South. There have been changes in the object of knowledge ‐ that is, work and organization ‐ especially managerial transformation of organizations and global economic restructuring. There are related changes in the political arena, most recently the rise of an authoritarian populism with new patterns of masculinity politics. Proposals are made for an agenda of feminist research in this field, relevant to the new circumstances and the continuing struggles for gender equality.
Impact of tumour budding grade in 310 patients who underwent surgical resection for extrahepatic cholangiocarcinoma
Authors: Ogino Mariko , Nakanishi Yoshitsugu , Mitsuhashi Tomoko , Hatanaka Yutaka , Amano Toraji , Marukawa Katsuji , Nitta Takeo , Ueno Takashi , Ono Masato , Kuwabara Shota , Yamada Tooru , Hirano Satoshi
Published: January 2019

Aims

Tumour budding is a risk factor for poor prognosis in various cancers. Tumour buds may present an epithelial–mesenchymal transition (EMT) morphological phenotype. This study aimed to elucidate the prognostic impact of tumour budding grade and its association with clinicopathological and EMT‐related features in perihilar cholangiocarcinoma (PHCC) or distal cholangiocarcinoma (DCC).

Methods and results

Subjects included 195 PHCC and 115 DCC patients. The numbers of tumour buds in different patients were stratified for postoperative survival using the recursive partitioning technique. Consequently, the numbers of tumour buds in PHCC patients were classified into three grades; namely, low (0–4 buds); intermediate (5–11 buds); and high (≥12 buds); those of DCC patients were classified into two grades; namely, low (0–4 buds) and high (≥5 buds). In both PHCC and DCC patients, high tumour budding grade was associated with poor histological differentiation, higher pT factor, presence of lymphatic, venous, perineural invasion and regional lymph node metastasis. In PHCC patients, residual invasive tumour in the resected margin was also associated with high tumour budding grade. For both PHCC and DCC patients, high tumour budding grade was an independent adverse prognostic factor in multivariate analysis (P < 0001 and P = 0.046, respectively). Immunohistochemical examination revealed that the number of tumour buds increased in patients with tumours showing a mesenchymal profile (negative for E‐cadherin and positive for vimentin).

Conclusions

Higher tumour budding grade is associated with invasive clinicopathological features, adverse postoperative prognosis and EMT status in extrahepatic cholangiocarcinoma.
Endodontics and diabetes: association versus causation
Authors: Segura‐Egea J. J. , Cabanillas‐Balsera D. , Jiménez‐Sánchez M. C. , Martín‐González J.
Published: January 2019

Endodontic Medicine has gained more attention and is becoming a more important issue in Endodontics. As an example, more than one hundred articles on this topic have been published in the last eight years. Several of these studies have found an association between endodontic variables, that is the prevalence of apical periodontitis, the prevalence of root canal treatment (RCT) and the outcome of RCT assessed as root filled teeth (RFT) with radiolucent periapical lesions (RPL) or non‐retained RFT, and several systemic diseases, such as diabetes, cardiovascular disease, smoking habits, osteoporosis, inherited coagulopaties, biological medications, low birth weight or physical fitness. However, the demonstration of association does not prove by itself the existence of a cause–effect relationship. Two variables can be related statistically to each other without either variable directly affecting the values of the other thus resulting in a non‐causal relationship. Causality is assumed when one variable is shown to contribute to the development of the other, and its removal is shown to reduce the frequency of disease. Therefore, once a significant statistical association has been found between two variables, it is necessary to exclude the presence of bias, which would imply that the association is artefactual, and to analyse if the causation criteria defined by Hill (Proceedings of the Royal Society of Medicine 1965; 58: 295‐300) are fulfilled to establish a causal relationship. Only if they are satisfied, can it be concluded that the association is causal. The aim of this study was to analyse the difference between association and causation, applying the criteria of causality to the specific case of the association between endodontic disease and diabetes mellitus.
Effect of birth plans on childbirth experience: A systematic review
Authors: Mirghafourvand Mojgan , Mohammad Alizadeh Charandabi Sakineh , Ghanbari‐Homayi Solmaz , Jahangiry Leila , Nahaee Jila , Hadian Tahereh
Published: January 2019

Aim

The birth plans were developed as an approach for pregnant women to present their expectations for labour and childbirth. The aim of this study was to assess whether birth plans (a written document in which pregnant women describe preferences about their care during labour and childbearing) compared with standard or routine approach (supine position, continuous fetal monitoring, enema, episiotomy) affect the birth experience (woman's perception of labour and childbirth as positive or negative experience) or satisfaction with birth.

Methods

This systematic review was performed by searching several databases, including Cochrane Library, Web of Science, MEDLINE, Embase, CINAHL, Scopus, PsycINFO, ACP Journal Club, Google Scholar, and Persian databases (SID, Magiran, and Barakat) up to February 10, 2018.

Results

By searching the databases, 1006 published articles were found, of which 480 and 114 articles were excluded by review of the titles and the abstracts, respectively. Finally, we included three clinical trials (1132 women) in the review. The results of two study showed that the mean score of birth experience in the birth plan group was significantly higher than the control group (P ≤ 0.01). However, the results of a study showed that there were no statistically significant differences between birth plan and control groups (P > 0.05). Quality of included studies was very low.

Conclusions

There is not enough evidence to support or refute that birth plan can improve the birth experience or satisfaction with birth.
Price discount facility in an EOQ model for deteriorating items with stock‐dependent demand and partial backlogging
Authors: Shaikh Ali Akbar , Khan Md. Al‐Amin , Panda Gobinda Chandra , Konstantaras Ioannis
Published: January 2019

All‐units discount facilities are one of the attractive features in the competitive business situation. Due to the globalization of the marketing policy, all‐units discount facilities play an important role in the competitive business. Typical economic order quantity (EOQ) models are cloistered by considering as constant not only the purchase cost (irrespective of the order size of the product) but also the carrying cost during the entire cycle period. However, the unit purchase cost has an antagonistic relationship with the order size, and the carrying cost has a commensurate relationship with the storage time‐period of the product, that is, the higher the order size, the lower the unit purchase cost, and the longer the storage time‐period, the greater carrying cost per unit. Also deterioration is another imperative issue in inventory analysis as it has a huge impact on profit or cost of the inventory system. Considering all of the above‐mentioned factors, we study two different inventory models, namely (a) inventory model for zero‐ending case and (b) inventory model for shortages case. The demand for both models is considered as price and stock dependent, whereas shortages are partially backlogged at a rate with the length of the waiting time to the arrivals of the next lot. The existence and uniqueness of the optimal solution for both models are examined theoretically and the solution procedures are discussed along with two proposed algorithms for minimizing the total cost. Finally, we perform sensitivity analyses for both models and make a fruitful conclusion regarding the proposed work.
Systematic review and meta‐analysis of experimental studies: In‐hospital mobilization for patients admitted for medical treatment
Authors: Cortes Olga L. , Delgado Sandra , Esparza Maribel
Published: January 2019

Aim

To determine the impact of strategies to promote mobilization on physical function in hospitalized adults with medical conditions.

Background

Slow progress is noted on the promotion of mobilization during hospitalization for adult patients admitted for medical conditions. This may reflect the limited evidence on the evaluation of the impact of progressive mobilization activities on clinical endpoints in adult patients throughout hospitalization.

Design

A systematic review and meta‐analysis of published randomized controlled trials in any language.

Data resources

The literature search was performed in the MEDLINE, CINAHL online, HealthStar, EMBASE, the Cochrane Library Controlled Trials Registry and LILACS databases (January 2000–February 2017).

Review methods

Two authors independently identified randomized trials meeting inclusion criteria, assessed their quality and extracted relevant data. Outcomes assessed were the changes in physical function evaluated by scales measuring either the aerobic (metres walked/second) or the balance domain (using the Time Up and Go test, in seconds), length of hospital stay (days), and adverse clinical events. We calculated pooled mean differences or Mantel–Haenszel odds ratios and 95% confidence intervals for continuous or dichotomous outcome data and obtained heterogeneity statistics across studies.

Results

Thirteen studies, including in total 2,703 participants, met our eligibility criteria. Patients in the intervention group showed significant improvement in physical function (aerobic domain), reduced length of stay, and a reduction of pulmonary embolism.

Conclusion

Patients and health providers should consider a course of therapy that enhances the functional capacity of medical patients during hospitalization.
Predicting contemporary range‐wide genomic variation using climatic, phylogeographic and morphological knowledge in an ancient, unglaciated landscape
Authors: Binks Rachel M. , Gibson Neil , Ottewell Kym M. , Macdonald Bronwyn , Byrne Margaret
Published: January 2019

Aim

Understanding the spatial distribution of genetic variation across a species’ range is a central tenet in evolutionary biology and the ability to predict such patterns is valuable to conservation management. Genetic diversity and differentiation may be explained by present‐day niche centrality, historical processes, or morphological variation across a species’ range, yet few studies evaluate these factors concurrently. Moreover, there is a particular lack of knowledge of the influence of these factors in ancient, unglaciated landscapes of the Southern Hemisphere. We investigate these concepts for their influence upon spatial patterns of genetic variation in a widespread plant species in a southern biodiversity hotspot.

Location

South‐western Australia.

Taxon

Calothamnus quadrifidus.

Methods

We use genotyping‐by‐sequencing to assess genome‐wide diversity and differentiation across the range of Calothamnus quadrifidus, a morphologically variable species that occurs over a wide geographic range in an ancient, unglaciated landscape. We correlated the patterns of genetic diversity and differentiation with those predicted under four hypotheses regarding effects of geographic centrality, climatic centrality, historical phylogeography and morphological subspecies.

Results

We found spatial variation in genetic diversity and strong population structuring, and while each hypothesis was consistent with some of these patterns, no hypothesis predicted the full extent of genetic diversity or structure in C. quadrifidus.

Main conclusions

Our results are indicative of a complex evolutionary history, with multiple factors shaping contemporary genetic variation in C. quadrifidus over time, rather than any one major driving factor. This is enabled by the greater capacity to build complex evolutionary signals in ancient, more stable landscapes like the southwest of Western Australia that are not as predictable as those within the younger, post‐glacial landscapes of the Northern Hemisphere. Finally, our study demonstrates the importance of using an interdisciplinary approach to understanding the spatial patterns of genetic variation across species’ ranges and the influence of ecological, geographical and historical factors.
Effect of antihypertensive medications on thrombolysis therapy and outcomes in acute ischemic stroke patients
Authors: Fleming Tyler , Blum Brice , Averkamp Benjamin , Sullivan James , Nathaniel Thomas
Published: January 2019

There are concerns that specific risk factors may alter the benefits of thrombolysis in stroke patients with controlled contraindications including hypertension. The objective of this study was to evaluate the association between clinical risk factors and outcomes in ischemic stroke patients that received thrombolysis therapy pretreated with antihypertensive medications. Using data obtained from a stroke registry, a non‐randomized retrospective data analysis was conducted on patients with the primary diagnosis of acute ischemic stroke with hypertension pretreated with antihypertensive medications. The association between clinical risk factors and functional ambulatory outcome was determined using logistic regression while odd ratios (OR) were used to predict the odds of achieving improved ambulatory outcome in thrombolysis treatment status. Improved or poor functional ambulatory outcome was considered as the end point in our analysis. A total of 4665 acute ischemic stroke patients were identified, of whom 1446 (31.0%) were eligible for thrombolysis, while 3219 were not, and 595 received rtPA, of whom 288 were on antihypertensive medications, while 233 were not. In the rtPA group with antihypertensive (anti‐HTN) medication, only NIHSS score (OR = 1.094, 95% CI, 1.094‐1.000, P = 0.005) was associated with improved functional outcome while patients with congestive heart failure (OR = 0.385, 95% CI, 0.385‐0.159, P = 0.035) and patients with a history of previous TIA (OR = 0.302, 95% CI, 0.302‐0.113, P = 0.017) were more likely to be associated with poor functional outcomes. Congestive heart failure and TIA are independent predictors of functional outcomes in stroke patients pretreated with antihypertensive medications prior to thrombolysis therapy.
An integrative systems approach identifies novel candidates in Marfan syndrome‐related pathophysiology
Authors: Bhushan Raghu , Altinbas Lukas , Jäger Marten , Zaradzki Marcin , Lehmann Daniel , Timmermann Bernd , Clayton Nicholas P. , Zhu Yunxiang , Kallenbach Klaus , Kararigas Georgios , Robinson Peter N.
Published: January 2019

Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in the FBN1 gene. Although many peripheral tissues are affected, aortic complications, such as dilation, dissection and rupture, are the leading causes of MFS‐related mortality. Aberrant TGF‐beta signalling plays a major role in the pathophysiology of MFS. However, the contributing mechanisms are still poorly understood. Here, we aimed at identifying novel aorta‐specific pathways involved in the pathophysiology of MFS. For this purpose, we employed the Fbn1 under‐expressing mgR/mgR mouse model of MFS. We performed RNA‐sequencing of aortic tissues of 9‐week‐old mgR/mgR mice compared with wild‐type (WT) mice. With a false discovery rate <5%, our analysis revealed 248 genes to be differentially regulated including 20 genes previously unrelated with MFS‐related pathology. Among these, we identified Igfbp2, Ccl8, Spp1, Mylk2, Mfap4, Dsp and H19. We confirmed the expression of regulated genes by quantitative real‐time PCR. Pathway classification revealed transcript signatures involved in chemokine signalling, cardiac muscle contraction, dilated and hypertrophic cardiomyopathy. Furthermore, our immunoblot analysis of aortic tissues revealed altered regulation of pSmad2 signalling, Perk1/2, Igfbp2, Mfap4, Ccl8 and Mylk2 protein levels in mgR/mgR vs WT mice. Together, our integrative systems approach identified several novel factors associated with MFS‐aortic‐specific pathophysiology that might offer potential novel therapeutic targets for MFS.
Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats
Authors: Zhang Jie , Wang Liang , Cao He , Chen Nan , Yan Bin , Ao Xiang , Zhao Huiyu , Chu Jun , Huang Minjun , Zhang Zhongmin
Published: January 2019

Despite the fact that extensive studies have focused on heterotopic ossification (HO), its molecular mechanism remains unclear. The endothelial‐mesenchymal transition (EndMT), which may be partially modulated by neuroendocrine cytokines is thought to play a major role in HO. Neurotrophin‐3 (NT‐3), which has neuroendocrine characteristics is believed to promote skeletal remodeling. Herein, we suggest that that NT‐3 may promote HO formation through regulation of EndMT. Here, we used an in vivo model of HO and an in vitro model of EndMT induction to elucidate the effect and underlying mechanism of NT‐3 on EndMT in HO. Our results showed that heterotopic bone and cartilage arose from EndMT and NT‐3 promoted HO formation in vivo. Our in vitro results showed that NT‐3 up‐regulated mesenchymal markers (FSP‐1, α‐SMA and N‐cadherin) and mesenchymal stem cell (MSC) markers (STRO‐1, CD44 and CD90) and down‐regulated endothelial markers (Tie‐1, VE‐cadherin and CD31). Moreover, NT‐3 enhanced a chondrogenesis marker (Sox9) and osteogenesis markers (OCN and Runx2) via activation of EndMT. However, both EndMT specific inhibitor and tropomyosin‐related kinase C (TrkC) specific inhibitor rescued NT‐3‐induced HO formation and EndMT induction in vivo and in vitro. In conclusion, our findings demonstrate that NT‐3 promotes HO formation via modulation of EndMT both in vivo and in vitro, which offers a new potential target for the prevention and therapy of HO.
Crystal toxins and the volunteer's dilemma in bacteria
Authors: Patel Matishalin , Raymond Ben , Bonsall Michael B. , West Stuart A.
Published: January 2019

The growth and virulence of the bacteria Bacillus thuringiensis depend on the production of Cry toxins, which are used to perforate the gut of its host. Successful invasion of the host relies on producing a threshold amount of toxin, after which there is no benefit from producing more toxin. Consequently, the production of Cry toxin appears to be a different type of social problem compared with the public goods scenarios that bacteria usually encounter. We show that selection for toxin production is a volunteer's dilemma. We make specific predictions that (a) selection for toxin production depends upon an interplay between the number of bacterial cells that each host ingests and the genetic relatedness between those cells; (b) cheats that do not produce toxin gain an advantage when at low frequencies, and at high bacterial density, allowing them to be maintained in a population alongside toxin‐producing cells. More generally, our results emphasize the diversity of the social games that bacteria play.
Oxynoemacheilus cemali, a new species of stone loach (Teleostei: Nemacheilidae) from the Çoruh River drainage, Turkey
Authors: Turan Davut , Kaya Cüneyt , Kalayci Gökhan , Bayçelebi Esra , Aksu İsmail
Published: January 2019

Oxynoemacheilus cemali sp. nov. is described from the Çoruh River drainage in the eastern Black Sea basin. One molecular marker (coI), 25 morphometric and four meristic characters were analysed. Oxynoemacheilus cemali is distinguished from O. kosswigi, O. banarescui, O. samanticus and O. angorae in the Black Sea basin by having a suborbital groove in males, an axillary lobe at the pelvic‐fin base, no dorsal adipose crest on the caudal peduncle, a slightly‐forked caudal fin and 7–15 dark grey dorsal saddles. Morever, Oxynoemacheilus cemali is distinguished by commonly having 9–15 irregularly‐shaped dark‐grey bars on the flank posterior to the dorsal‐fin origin or, rarely having a mottled pattern or 4–6 irregularly shaped dark‐grey bars on the flank posterior to the dorsal‐fin origin. Oxynoemacheilus cemali is also distinguished from the closely related species O. araxensis and O. cyri, distributed outside the Black Sea basin, by having 15 and 31 diagnostic nucleotide substitutions in the coI barcode region, respectively.
Clinical features of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without advanced fibrosis
Authors: Kodama Kazuhisa , Kawaguchi Takumi , Hyogo Hideyuki , Nakajima Tomoaki , Ono Masafumi , Seike Masataka , Takahashi Hirokazu , Nozaki Yuichi , Kawanaka Miwa , Tanaka Saiyu , Imajo Kento , Sumida Yoshio , Kamada Yoshihiro , Fujii Hideki , Seko Yuya , Takehara Tetsuo , Itoh Yoshito , Nakajima Atsushi , Masaki Naohiko , Torimura Takuji , Saibara Toshiji , Karino Yoshiyasu , Chayama Kazuaki , Tokushige Katsutoshi
Published: January 2019

Background and Aim

The prevalence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD‐HCC) is increasing. Unfortunately, NAFLD frequently develops into HCC without liver cirrhosis. Therefore, we investigated the clinical features of HCC in NAFLD patients without advanced fibrosis.

Methods

We compared clinical characteristics, survival rates, and recurrence rates between 104 NAFLD‐HCC patients diagnosed between January 2000 and December 2016, including 35 without (F0–2) and 69 with advanced fibrosis (F3–F4). Risk factors associated with survival and recurrence were evaluated.

Results

In total, 66.3% of those diagnosed had advanced fibrosis, 58.8% in men and 80.5% in women (men vs women, P = 0.03). In NAFLD‐HCC without advanced fibrosis, tumor size was significantly larger and liver histological activity was lower than those in patients with advanced fibrosis. Survival rates between the two groups did not differ. Among those achieving curative treatment, the recurrence rate was significantly lower in NAFLD‐HCC without advanced fibrosis (P < 0.01). Risk factors of recurrence were male gender, lower serum albumin, and advanced fibrosis.

Conclusions

In men, HCC tended to develop from NAFLD without advanced fibrosis. Although tumor size in NAFLD‐HCC without advanced fibrosis is significantly larger, the recurrence rate is significantly lower. Surgical therapy should be strongly considered in these cases.
Comparative Effectiveness of Medication Therapy Management Eligibility Criteria Across Racial/Ethnic Groups
Authors: Spivey Christina A. , Qiao Yanru , Wang Junling , Shih Ya‐Chen Tina , Wan Jim Y. , Dagogo‐Jack Samuel , Cushman William C. , Hines Lisa E. , Chisholm‐Burns Marie A.
Published: January 2019

BACKGROUND/OBJECTIVES

Previous research indicates that eligibility criteria for medication therapy management (MTM) services in Medicare prescription drug (Part D) plans, defined under the Medicare Modernization Act (MMA), are associated with racial/ethnic disparities and ineffective in identifying individuals with medication utilization issues. Our study's objective was to determine the comparative effectiveness of MTM eligibility criteria under MMA and in the Affordable Care Act (ACA) in identifying patients with medication utilization issues across racial/ethnic groups.

DESIGN

ACA and MMA MTM eligibility criteria were compared on proportions of eligible individuals among patients with medication utilization issues. Multinomial logistic regression was conducted to control for patient/community characteristics. Need‐based and demand‐based analyses were used to determine disparities due to need and demand for healthcare. Main/sensitivity analyses were conducted for the range of eligibility thresholds.

SETTING

Medicare data (2012‐2013) linked to Area Health Resources Files.

PARTICIPANTS

A total of 964 610 patients 65 years or older.

MEASUREMENTS

Medication safety/adherence measures, developed primarily by the Pharmacy Quality Alliance, were used to determine medication utilization issues.

RESULTS

Higher proportions of patients were eligible based on ACA than MMA MTM eligibility criteria. For example, in 2013, proportions based on ACA and MMA MTM eligibility criteria would be 99.7% and 26.2%, respectively, in the main analysis (p < .001); in the demand‐based main analysis, ACA criteria were associated with 13.6% and 9.8%, respectively, higher effectiveness than MMA criteria among non‐Hispanic blacks and Hispanics than non‐Hispanic whites.

CONCLUSION

ACA MTM eligibility criteria are more effective than MMA criteria in identifying older patients needing MTM, particularly among minorities. J Am Geriatr Soc 67:581–587, 2019.
Noise footprint from personal land‐based mobility
Authors: Cucurachi Stefano , Schiess Samuel , Froemelt Andreas , Hellweg Stefanie
Published: January 2019

A large part of the world population is exposed to noise levels that are unhealthy. Yet noise is often neglected when impact assessment studies are conducted and when policy interventions are designed. In this study, we provide a way to calculate the noise footprint of citizens directly determined by their use of private and public transport on land. The study combines the results of the large transport simulation model MATSim applied to Switzerland, with a noise characterization model, N‐LCA, developed in the context of life cycle assessment. MATSim results allow tracking the use of private and public transportation by agents in the model. The results after characterization provide a consumption‐based noise footprint, thus the total noise and impacts that are caused by the private mobility demand of the citizens of Switzerland. Our results confirm that road transportation is the largest contributor to the total noise footprint of land‐based mobility. We also included a scenario with a full transition to an electrified car fleet, which showed the potential for the reduction of impacts, particularly in urban areas, by about 55% as compared to the modeled regime with combustion engines.
Integrated self‐management program effects on hemodialysis patients: A quasi‐experimental study
Authors: Park Ok Lae , Kim Sung Reul
Published: January 2019

Aim

To evaluate the effects of an integrated self‐management program using a mobile application, a short message service using a smartphone, and face‐to‐face counseling and education among hemodialysis patients.

Methods

A quasi‐experimental study design was used. The participants of this study were 84 hemodialysis patients (42 in the experimental group and 42 in the control group). The experimental group received the integrated self‐management program for 8 weeks. The data were analyzed by using the independent t‐test and Mann–Whitney U test to identify differences in self‐efficacy, treatment compliance, the ratio of interdialytic weight gain to dry weight, and serum potassium and phosphorus levels between the experimental group and the control group at the end of the program.

Results

The scores for self‐efficacy and treatment compliance were significantly higher in the experimental group than in the control group. The ratio of interdialytic weight gain to dry weight significantly decreased in the experimental group, compared to the control group. The serum potassium and phosphorus levels in the experimental group were not significantly lower than those of the control group.

Conclusion

The findings suggest that the integrated self‐management program that was implemented in this study could be a potentially effective intervention to improve the self‐management of hemodialysis patients. Further research on various nursing intervention programs is warranted, including a mobile application program to improve hemodialysis patients’ self‐management.
Effects of HIV‐1 Tat on oligodendrocyte viability are mediated by CaMKIIβ–GSK3β interactions
Authors: Zou Shiping , Balinang Joyce M. , Paris Jason J. , Hauser Kurt F. , Fuss Babette , Knapp Pamela E.
Published: January 2019

Myelin disruptions are frequently reported in human immunodeficiency virus (HIV)‐infected individuals and can occur in the CNS very early in the disease process. Immature oligodendrocytes (OLs) are quite sensitive to toxic increases in [Ca2+]i caused by exposure to HIV‐1 Tat (transactivator of transcription, a protein essential for HIV replication and gene expression), but sensitivity to Tat‐induced [Ca2+]i is reduced in mature OLs. Tat exposure also increased the activity of Ca2+/calmodulin‐dependent kinase IIβ (CaMKIIβ), the major isoform of CaMKII expressed by OLs, in both immature and mature OLs. Since CaMKIIβ is reported to interact with glycogen synthase kinase 3β (GSK3β), and GSK3β activity is implicated in OL apoptosis as well as HIV neuropathology, we hypothesized that disparate effects of Tat on OL viability with maturity might be because of an altered balance of CaMKIIβ–GSK3β activities. Tat expression in vivo led to increased CaMKIIβ and GSK3β activity in multiple brain regions in transgenic mice. In vitro, immature murine OLs expressed higher levels of GSK3β, but much lower levels of CaMKIIβ, than did mature OLs. Exogenous Tat up‐regulated GSK3β activity in immature, but not mature, OLs. Tat‐induced death of immature OLs was rescued by the GSK3β inhibitors valproic acid or SB415286, supporting involvement of GSK3β signaling. Pharmacologically inhibiting CaMKIIβ increased GSK3β activity in Tat‐treated OLs, and genetically knocking down CaMKIIβ promoted death in mature OL cultures treated with Tat. Together, these results suggest that the effects of Tat on OL viability are dependent on CaMKIIβ–GSK3β interactions, and that increasing CaMKIIβ activity is a potential approach for limiting OL/myelin injury with HIV infection.

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Preferring to manage by myself: A qualitative study of the perspectives of hardly reached people with type 2 diabetes on social support for diabetes management
Authors: Bech Laura K. , Borch Jacobsen Camilla , Mathiesen Anne Sophie , Thomsen Thordis
Published: January 2019

Aims and objectives

To explore the perspectives of hardly reached people with type 2 diabetes on social support for diabetes management from their formal and informal networks.

Background

People with low socioeconomic status and poorly controlled type 2 diabetes may be categorised as hardly reached. Social support is increasingly perceived to be a cornerstone in the management of type 2 diabetes. Few studies have, however, explored social support for diabetes management from the perspective of hardly reached people.

Methods

A qualitative design with individual semi‐structured interviews captured the unique perspectives of hardly reached people. Data from 14 participants were analysed using conventional content analysis. The article adheres to the COREQ guidelines for reporting qualitative research.

Results

Participants preferred not to involve family and friends (the informal network) in diabetes management due to dysfunctional or lacking networks, existing norms and not wanting to burden vulnerable relationships. Others simply did not perceive themselves as sick and therefore saw no need for support. Opposed to this, participants wished for continuity and a personalised relationship with health professionals (the formal network). This entailed consultations that facilitated discussion of issues of importance to the participants.

Conclusions

Hardly reached people with type 2 diabetes preferred to spare their informal networks from diabetes management. Instead, they wished for more presence and individualised support from health professionals.

Relevance to Clinical practice

It appears timely to rethink the current “one‐size‐fits‐all” approach for people with type 2 diabetes in order to allocate resources to those most in need. It is important that health professionals elicit perceptions of support needs and potential sources of support in hardly reached people with type 2 diabetes both from the formal and from informal networks in regard to managing their diabetes. To better reach hardly reached people with type 2 diabetes, specialised education of health professionals may be necessary to capture the complex underlying dynamics influencing disease management.
Assessment of Interleukin‐18 gene polymorphism and serum levels in oral lichen planus in an Indian population
Authors: Negi Deepika , Urs Aadithya B. , Kumar Priya , Mahajan Bhawna , Singh Hanspal , Polipalli Sunil K. , Kapoor Seema
Published: January 2019

Background

Oral lichen planus (OLP) is a chronic, inflammatory disease with uncertain etiology. The aim of this study was to assess Interleukin‐18 (IL‐18) gene polymorphism and serum levels in OLP cases of Indian origin and to compare them with a control population of similar background.

Methods

The assessment of single‐nucleotide polymorphisms (SNPs) of IL‐18 gene at promoter regions −137(G/C) and −607(C/A) was done in 70 OLP cases and 70 healthy controls using sequence‐specific primer‐polymerase chain reaction (SSP‐PCR). In a subset of this cohort, comprising of 41 OLP cases and 41 controls, serum IL‐18 levels were assessed using enzyme‐linked immunosorbent assay (ELISA).

Results

Mean serum levels of IL‐18 among OLP cases were significantly higher when compared to controls. Genotypic and allelic frequencies of IL‐18 at position −137(G/C) showed that GG genotype and allele G was significantly higher in OLP cases, whereas, GC genotype and C allele was high in the control group. Polymorphism of IL‐18 at position −607(C/A) showed no significant differences.

Conclusions

Gene polymorphism at −137GG genotype and allele G seems to be associated with genetic susceptibility to OLP whereas −137GC and allele C may have a protective role against its development. However, our study lacks clear statistical correlation, the differences observed could be caused by sampling problems and the results could not be fully representative of Indian patients with OLP. Further studies are warranted to explore the role of IL‐18 genetic polymorphisms in OLP development.