bluuebunny/crossref_metadata_2025 huggingface dataset:
CyPA and Emmprin play a role in peri‐implantitis
Authors: Yang Lei , Zhu Qing , Gong Jingjue , Xie Ming , Jiao Ting
Published: October 2017

Background

Cyclophilin A (CyPA) and Emmprin play important roles in peri‐implantitis. However, their roles in the diagnosis and treatment of the disease are still unclear.

Purpose

The aim of this split‐mouth animal study was to describe variable trends of biomarkers during the progression of peri‐implantitis and to define relationships among CyPA, Emmprin, and peri‐implantitis.

Materials and Methods

Six male adult Labradors were used. The mandibular premolars and the first molar were extracted, and sixteen implants were placed after 3 months. Peri‐implantitis was induced around the implants on one side, which were the test group, and the implants on the other side were included in the control group. Clinical parameters such as probing depth, gingival index, and bleeding index and periapical X‐rays were recorded at weeks 0, 2, 4, 6, 8, 10, and 12. Peri‐implant crest fluid (PICF) and gingiva around the implants were collected and analyzed by ELISA and real‐time PCR, respectively.

Results

The clinical parameters of the test group indicated severe inflammation around the implants. Radiographs showed obvious bone loss beginning at week 4, and it continued over time. The concentration of CyPA in the peri‐implantitis group increased at first and then decreased beginning at week 6, and the concentration of Emmprin decreased at first and then increased beginning at week 6. Emmprin, matrix metalloproteinase‐9 and Tissue Inhibitor of Metalloproteinase‐1 showed similar changes over time. CyPA showed a consistent trend with Interleukin‐1β, but showed an opposite trend to Transforming growth factor‐β. Both the concentration of CyPA in PICF and gene expression in gingival tissue increased before bone absorption occurred.

Conclusion

Despite the limitations of this study, CyPA may be an early signal for peri‐implantitis. A CyPA‐Emmprin interaction exists in peri‐implantitis and is Emmprin‐dependent. Emmprin is related to clinical attachment loss in peri‐implantitis.
Surgical management of colonic basidiobolomycosis among adolescent and adult patients: presentation and outcome
Authors: Abd El Maksoud W. M. , Bawahab M. A. , Ashraf T. H. , Al Shehri D. M. , Mirza N. I.
Published: October 2017

Aim

The aim of this study was to review retrospectively the clinical presentations, indications for surgery and surgical outcomes of adolescent and adult patients who were diagnosed with colonic basidiobolomycosis in the last 10 years.

Method

The study was carried out in Aseer Central Hospital, Abha, Saudi Arabia by reviewing the medical files of all patients in the last 10 years who were diagnosed with colonic basidiobolomycosis and required surgical intervention.

Results

There were 22 patients. Common findings in all patients were weight loss, abdominal pain and an abdominal mass. The right colon was affected in 21 patients. The initial diagnosis was correct in seven patients while nine were thought to be malignant. All patients underwent colonic resection followed by at least 1 year of antifungal medical treatment. Intra‐operatively, all patients had moderate or dense adhesions, an abdominal mass and lymphadenopathy. Most surgeons had the impression intra‐operatively that the diagnosis was inflammatory rather than malignant. Postoperatively, three patients died within 6 months of the operation due to progression of the disease. Four patients developed severe wound infections, three of whom had abdominal dehiscence and required re‐closure.

Conclusion

Colonic basidiobolomycosis is a life‐threatening fungal infection that should be considered a surgical condition. A high index of suspicion including basidiobolomycosis in the differential diagnosis for the acute abdomen with a colonic mass is required for a proper diagnosis. Early aggressive surgical management followed by a prolonged course of itraconazole postoperatively could improve the outcome of the condition.
Enhanced gastric cancer growth potential of mesenchymal stem cells derived from gastric cancer tissues educated by CD4+ T cells
Authors: Xu Rongman , Zhao Xiangdong , Zhao Yuanyuan , Chen Bin , Sun Li , Xu Changgen , Shen Bo , Wang Mei , Xu Wenrong , Zhu Wei
Published: October 2017

Objectives

Gastric cancer mesenchymal stem cells (GC‐MSCs) can promote the development of tumour growth. The tumour‐promoting role of tumour‐associated MSCs and T cells has been demonstrated. T cells as the major immune cells may influence and induce a pro‐tumour phenotype in MSCs. This study focused on whether CD4+ T cells can affect GC‐MSCs to promote gastric cancer growth.

Materials and methods

CD4+ T cells upregulation of programmed death ligand 1 (PD‐L1) expression in GC‐MSCs through the phosphorylated signal transducer and activator of transcription (p‐STAT3) signalling pathway was confirmed by immunofluorescence, western blotting and RT‐PCR. Migration of GC cells was detected by Transwell migration assay, and apoptosis of GC cells was measured by flow cytometry using annexin V/propidium iodide double staining. CD4+ T cell‐primed GC‐MSCs promoted GC growth in a subcutaneously transplanted tumour model in BALB/c nu/nu mice.

Results

Gastric cancer mesenchymal stem cells stimulated by activated CD4+ T cells promoted migration of GC cells and enhanced GC growth potential in BALB/c nu/nu xenografts. PD‐L1 upregulation of GC‐MSCs stimulated by CD4+ T cells was mediated through the p‐STAT3 signalling pathway. CD4+ T cells‐primed GC‐MSCs have greater GC volume and growth rate‐promoting role than GC‐MSCs, with cancer cell‐intrinsic PD‐1/mammalian target of rapamycin (mTOR) signalling activation.

Conclusions

This study showed that GC‐MSCs are plastic. The immunophenotype of GC‐MSCs stimulated by CD4+ T cells has major changes that may influence tumour cell growth. This research was based on the interaction between tumour cells, MSCs and immune cells, providing a new understanding of the development and immunotherapy of GC.
Flooding: what is the impact on pregnancy and child health?
Authors: Mallett Lea H. , Etzel Ruth A.
Published: October 2017

Floods are the most common type of natural disaster in both developed and developing countries and have led to extensive morbidity and mortality throughout the world. Worldwide, over the past 30 years, flooding has claimed the lives of more than 200,000 people and affected more than 2.8 billion others. The impact of flooding on health varies among populations and depends primarily on vulnerability and the kind of event experienced. It severely disrupts livelihoods and has a significant impact on the health of pregnant women and children. In addition, it may exacerbate a range of negative psychological and physiological child and reproductive health outcomes. Awareness‐raising, education, and the issuing of warnings appear to be key initiatives to mitigate or prevent flood morbidity and mortality, especially among people living in low‐ and middle‐income countries. Agencies responding to emergencies also need to be more cognisant of the dangers, specifically those engaged in healthcare, nutrition, and water safety programmes.
The role of social risk in an early preventative care programme for infants born very preterm: a randomized controlled trial
Authors: Spittle Alicia J , Treyvaud Karli , Lee Katherine J , Anderson Peter J , Doyle Lex W
Published: October 2017

Aim

To examine the differential effects of an early intervention programme for infants born preterm on neurodevelopment and parental mental health according to family social risk.

Method

One hundred and twenty infants born earlier than 30 weeks' gestation were randomized to early intervention (n=61) or control groups (n=59). Cognitive, language, and motor outcomes were assessed by blinded assessors at 2 years, 4 years, and 8 years, and primary caregivers completed questionnaires on their anxiety and depression. Outcomes at each time point were compared between groups using linear regression with an interaction term for social risk (higher/lower).

Results

There was evidence of interactions between intervention group and social risk for cognition at 2 years and 4 years, motor function at 4 years, and language at 8 years, with a greater intervention effect in children from higher social risk environments. In contrast, the impact of early intervention on parental depressive symptoms was greater for parents of lower social risk than for those of higher social risk.

Interpretation

Effects of early intervention on outcomes for children born preterm and their caregivers varied according to family social risk. Family social risk should be considered when implementing early intervention programmes for children born preterm and their families.

What this paper adds

Intervention is associated with better early cognitive functioning for children in higher social risk families.

Positive effects of intervention for the high risk group were not sustained at school‐age.

Intervention has a greater effect on primary caregiver mental health in the lower social risk group compared with higher social risk.
Modelling incremental benefits on complications rates when targeting lower HbA1c levels in people with Type 2 diabetes and cardiovascular disease
Authors: Mostafa S. A. , Coleman R. L. , Agbaje O. F. , Gray A. M. , Holman R. R. , Bethel M. A.
Published: October 2017

Aim

Glucose‐lowering interventions in Type 2 diabetes mellitus have demonstrated reductions in microvascular complications and modest reductions in macrovascular complications. However, the degree to which targeting different HbA1c reductions might reduce risk is unclear.

Methods

Participant‐level data for Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) participants with established cardiovascular disease were used in a Type 2 diabetes‐specific simulation model to quantify the likely impact of different HbA1c decrements on complication rates. Ten‐year micro‐ and macrovascular rates were estimated with HbA1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%) while holding other risk factors constant at their baseline levels. Cumulative relative risk reductions for each outcome were derived for each HbA1c decrement.

Results

Of 5717 participants studied, 72.0% were men and 74.2% White European, with a mean (sd) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9) mmHg, LDL‐cholesterol 2.3 (0.9) mmol/l, HDL‐cholesterol 1.13 (0.3) mmol/l and median Type 2 diabetes duration 9.6 (5.1–15.6) years. Ten‐year cumulative relative risk reductions for modelled HbA1c values of 75, 64, 53 and 42 mmol/mol, relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and 46.4% for diabetes‐related ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation; and 13.6%, 25.4%, 36.0% and 44.7 for single‐eye blindness.

Conclusions

These simulated complication rates might help inform the degree to which complications might be reduced by targeting particular HbA1c reductions in Type 2 diabetes.
Flow alteration and thermal pollution depress modelled growth rates of an iconic riverine fish, the Murray cod Maccullochella peelii
Authors: Whiterod Nick S. , Meredith Shaun N. , Humphries Paul , Sherman Bradford S. , Koehn John D. , Watts Robyn J. , Ingram Brett A. , Ryan Tom
Published: October 2017

The serial discontinuity concept (SDC) proposes that hypolimnetic‐releasing impoundments cause major disruptions to the naturally occurring physical, chemical and biological gradients of rivers but that this impact diminishes with distance downstream. Such a gradient in discharge, flow velocity and temperature regime occurs below a large hypolimnetic‐releasing impoundment, the Hume Dam, on the River Murray in south‐eastern Australia. To examine the effects of this disturbance gradient on a warm‐water large‐bodied freshwater fish, the Murray cod (Maccullochella peelii), a bioenergetics model was developed and calibrated to explore energy expended under differing water velocities and temperature regimes. Model simulations predicted negative growth of juveniles directly downstream of the impoundment, due largely to the energetic costs associated with active and, to a lesser extent, standard metabolism outweighing the achievable energetic gains through food consumption. As flow velocity and temperature regimes became more favourable downstream, so did the simulated growth of the species. It was not until +239 km downstream of the impoundment that the model predicted that flow velocity and temperature regimes were suitable for greater weight gains. The modelled growth responses of juvenile Murray cod are consistent with the predictions of the SDC, emphasising that changes in the bioenergetics of individuals are likely to be reflected in reduced growth rates under the changed flow velocity and temperature regimes imposed by disturbance gradients. This research represents a valuable step in the biological understanding of Murray cod within variable riverine environments and emphasises the urgency required to mitigate impacts associated with hypolimnetic impoundments.
Diminished socially selective neural processing in 5‐month‐old infants at high familial risk of autism
Authors: Braukmann Ricarda , Lloyd‐Fox Sarah , Blasi Anna , Johnson Mark H. , Bekkering Harold , Buitelaar Jan K. , Hunnius Sabine
Published: October 2017

The social and communicative difficulties that characterize autism spectrum disorder (ASD) are considered the most striking feature of the disorder. Research has reported that individuals with ASD show abnormalities in the brain regions associated with the processing of social information. Importantly, a recent study using functional near‐infrared spectroscopy (fNIRS) found the first evidence of atypicalities in the neural processing of social information in 4‐ to 6‐month‐old infants at high familial risk of ASD. These findings provide an important step in the search for early markers of ASD and highlight the potential for neuroimaging techniques to detect atypical patterns of neural activity prior to the manifestation of most behavioural symptoms. This study aimed to extend the findings of reduced neural sensitivity to social stimuli in an independent cohort. Twenty‐nine 5‐month‐old infants (13 low‐risk infants, 16 high‐risk infants) were presented with social and non‐social visual stimuli, similar to the previous experiment. Importantly, a non‐social dynamic motion control condition was introduced allowing the comparison between social dynamic and non‐social, static, as well as dynamic stimuli. We found that while low‐risk infants showed activation to social stimuli in the right posterior temporal cortex, this activation was reduced in infants at high risk of ASD. Although the current sample size was relatively small, our results replicate and extend previous work and provide evidence for a social processing difference in infants at risk of autism. Future research will determine whether these differences relate to an eventual ASD diagnosis or may rather reflect the broader autism phenotype.
Lobular patterns of cerebellar resting‐state connectivity in adults with Autism Spectrum Disorder
Authors: Olivito Giusy , Lupo Michela , Laghi Fiorenzo , Clausi Silvia , Baiocco Roberto , Cercignani Mara , Bozzali Marco , Leggio Maria
Published: October 2017

Autism spectrum disorder is a neurodevelopmental disorder characterized by core deficits in social functioning. Core autistics traits refer to poor social and imagination skills, poor attention‐switching/strong focus of attention, exceptional attention to detail, as expressed by the autism‐spectrum quotient. Over the years, the importance of the cerebellum in the aetiology of autism spectrum disorder has been acknowledged. Neuroimaging studies have provided a strong support to this view, showing both structural and functional connectivity alterations to affect the cerebellum in autism spectrum disorder. According to the underconnectivity theory, disrupted connectivity within cerebello‐cerebral networks has been specifically implicated in the aetiology of autism spectrum disorder. However, inconsistent results have been generated across studies. In this study, an integrated approach has been used in a selected population of adults with autism spectrum disorder to analyse both cerebellar morphometry and functional connectivity. In individuals with autism spectrum disorder, a decreased cerebellar grey matter volume affected the right Crus II, a region showing extensive connections with cerebral areas related to social functions. This grey matter reduction correlates with the degree of autistic traits as measured by autism‐spectrum quotient. Interestingly, altered functional connectivity was found between the reduced cerebellar Crus II and contralateral cerebral regions, such as frontal and temporal areas. Overall, the present data suggest that adults with autism spectrum disorder present with specific cerebellar structural alterations that may affect functional connectivity within cerebello‐cerebral modules relevant to social processing and account for core autistics traits.
The spatio‐temporal profile of multisensory integration
Authors: Starke Johanna , Ball Felix , Heinze Hans‐Jochen , Noesselt Toemme
Published: October 2017

Task‐irrelevant visual stimuli can enhance auditory perception. However, while there is some neurophysiological evidence for mechanisms that underlie the phenomenon, the neural basis of visually induced effects on auditory perception remains unknown. Combining fMRI and EEG with psychophysical measurements in two independent studies, we identified the neural underpinnings and temporal dynamics of visually induced auditory enhancement. Lower‐ and higher‐intensity sounds were paired with a non‐informative visual stimulus, while participants performed an auditory detection task. Behaviourally, visual co‐stimulation enhanced auditory sensitivity. Using fMRI, enhanced BOLD signals were observed in primary auditory cortex for low‐intensity audiovisual stimuli which scaled with subject‐specific enhancement in perceptual sensitivity. Concordantly, a modulation of event‐related potentials could already be observed over frontal electrodes at an early latency (30–80 ms), which again scaled with subject‐specific behavioural benefits. Later modulations starting around 280 ms, that is in the time range of the P3, did not fit this pattern of brain‐behaviour correspondence. Hence, the latency of the corresponding fMRI‐EEG brain‐behaviour modulation points at an early interplay of visual and auditory signals in low‐level auditory cortex, potentially mediated by crosstalk at the level of the thalamus. However, fMRI signals in primary auditory cortex, auditory thalamus and the P50 for higher‐intensity auditory stimuli were also elevated by visual co‐stimulation (in the absence of any behavioural effect) suggesting a general, intensity‐independent integration mechanism. We propose that this automatic interaction occurs at the level of the thalamus and might signify a first step of audiovisual interplay necessary for visually induced perceptual enhancement of auditory perception.
Discounting methods and personal taxes
Authors: Dempsey Michael
Published: October 2017

We advance models of valuation that incorporate personal taxes. The models are general in allowing for uneven cash flows, changes in debt levels, and changes in the costs of equity and debt. The models are mutually consistent, are consistent with the CAPM, and are consistent with the Modigliani and Miller propositions allowing personal taxes.
Shared Residence Among Parents Living Apart in Norway
Authors: Kitterød Ragni Hege , Wiik Kenneth Aarskaug
Published: October 2017

Over the last decade there has been a dramatic increase in shared residence for children among parents living apart in Norway, and a related shift away from mother sole custody. Currently, 3 in 10 children in separated families have shared residence, compared to less than 10% at the beginning of the century. This likely reflects several factors, including more symmetrical parenting practices in intact families in Norway and policy measures that promote a more equal division of practical care and economic provision among separated parents. Shared residence is most widespread among those from high socioeconomic backgrounds. Parents with shared residence generally report better cooperation and less conflict than sole custody parents and also more gender‐equal caring practices prior to separation.
Geomorphic influence on intraspecific genetic differentiation and diversity along hyporheic corridors
Authors: Malard Florian , Capderrey Cécile , Churcheward Benjamin , Eme David , Kaufmann Bernard , Konecny‐Dupré Lara , Léna Jean‐Paul , Liébault Frédéric , Douady Christophe J.
Published: October 2017

The hyporheic zone of rivers potentially acts as a dispersal corridor for groundwater organisms because it provides a spatially continuous interstitial habitat between isolated aquifers. Yet, the degree to which it can facilitate the movement of organisms has been hypothesized to vary in response to change in sediment regime, which determines channel morphology.

In this study, we used microsatellite markers to test for a relationship between the genetic structure and diversity of the minute interstitial isopod Proasellus walteri and channel morphology along three nearby hyporheic corridors differing widely in their sediment regime. We predicted that genetic diversity would decrease and genetic structuring would increase as sediment supply‐limited channels would become prominent features in the river corridor. The reason is that such channels have fewer and less suitable sedimentary habitats for migration because they lack large depositional bedforms such as gravel bars.

Using genotypic data from seven microsatellite loci for a total of 713 individuals distributed among 25 demes, we found that demes had on average more alleles and were less differentiated in the river showing the most extensive alluvial deposits and shortest length of sediment supply‐limited channels. Population clusters were also of greater size, reaching up to 30 km in length. The longitudinal pattern of genetic differentiation in this sediment‐rich river was best explained by hydrologic distance and the longitudinal pattern of allelic richness was bell‐shaped, as expected under a stepping‐stone model with symmetrical migration.

The length of sediment supply‐channels was more important than hydrologic distance in explaining the longitudinal distribution of genetic differentiation in the two other corridors facing a sediment shortage. Allelic richness decreased monotonically upstream in the most sediment‐poor river. This correlates with the expansion further downstream of sediment supply‐limited channels in this river, which is likely to decrease animal movement and hence gene flow among demes.

This study provides the first evidence that the degree to which the hyporheic zone facilitates the movement of groundwater organisms varies greatly among rivers of contrasted geomorphology. Extending the application of riverscape genetics across a range of interstitial taxa and geomorphic settings holds much promise for assessing the contribution of the hyporheic zone to the dispersal of groundwater organisms.
Mining, meaning and memory in the Andes
Authors: Perreault Tom
Published: October 2017

This paper examines the relationship between mining, memory and environmental suffering on the Bolivian Altiplano (Andean plateau). Mining activity has had a long and well documented role in transforming landscapes throughout the Andean region, and Bolivia provides some of South America's starkest examples of mine‐related water and soil contamination. In Bolivia, mining is publicly memorialised as central to the collective national experience, and public murals and monuments help construct a national identity as apaís minero(mining country). Memory is similarly important, though less public, for populations impacted by mine‐related pollution and their demands for remediation and reparation. In discussing these conditions, residents of the region draw on memories of past landscapes and waterscapes, which they often represent as verdant and bountiful. Such memory narratives are less important for what they tell us about the former landscapes – which were likely less pristine than reported – than what they tell us about contemporary conditions. Drawing on ethnographic research, I argue that memory – as represented in stories told about past experience – necessarily requires selective remembering and selective forgetting, and may function as a political and ideological resource in its own right. In this sense, memory can be mobilised in various forms and at a range of scales, from the individual to the national. As a representation of the past, memory is always also a representation of the present, and a reflection of contemporary realities, which in turn informs political demands. The paper ends by considering the potential and limitations of memory as a conceptual tool for envisioning environmentally just futures.
ALK‐positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature
Authors: Geller Shamir , Canavan Theresa N. , Pulitzer Melissa , Moskowitz Alison J. , Myskowski Patricia L.
Published: October 2017

Anaplastic large cell lymphoma (ALCL) limited to the skin is a distinct disease that is designated primary cutaneous ALCL (pcALCL). It has an indolent course with a significantly better prognosis compared to systemic ALCL (sALCL). Anaplastic lymphoma kinase (ALK) expression in lesions of cutaneous ALCL is classically considered to be a marker for skin involvement by sALCL. However, recent reports of patients with ALK‐positive pcALCL challenge this concept and raise prognostic and therapeutic dilemmas. Herein, we report a case of ALK‐positive pcALCL in a 45‐year‐old woman who was treated with local radiotherapy. We review previously reported cases in the literature to better characterize this rare variant. Overall, the rates of cutaneous recurrence, systemic dissemination, and disease‐related mortality in ALK‐positive pcALCL do not differ from those previously reported in pcALCL. ALK‐positive pcALCL is diagnosed at younger age and has a better disease course in children compared to adults with lower incidences of skin recurrence and progression to systemic disease. We conclude that ALK‐positivity in cutaneous ALCL does not necessarily imply systemic disease. ALK‐positive pcALCL has an excellent prognosis and should be treated by excision and/or radiotherapy. However, patients must remain under close long‐term follow‐up as recurrence and progression to systemic disease may occur.
Current immunogenetic predisposition to tuberculosis in the Moroccan population
Authors: Qrafli M. , Najimi M. , Elaouad R. , Sadki K.
Published: October 2017

Tuberculosis (TB) is a serious infectious disease that kills approximately two million people per year, particularly in low‐ and middle‐income countries. Numerous genetic epidemiology studies have been conducted of many ethnic groups worldwide and have highlighted the critical impact of the genetic environment on TB distribution. Many candidate genes associated with resistance or susceptibility to TB have been identified. In Morocco, where TB is still a major public health problem, various observations of clinical, microbiological and incidence distribution are heavily affected by genetic background and external environment. Morocco has almost the same clinical profile as do other North African countries, mainly the increase in more extrapulmonary than pulmonary forms of the diseases, when compared to European, Asian or American populations. In addition, a linkage analysis study that examined Moroccan TB patients identified a unique chromosome region that had a strong association with the risk of contracting TB. Other genes in the Moroccan population that were found to be associated seem to be involved predominantly in modulating the innate immunity. In this review, we appraise the major candidate genes that have been reported in Moroccan immunogenetic studies and discuss their updated role in TB, particularly during the first phase of the immune response to Mycobacterium tuberculosis (Mtb) infection.
Marketisation policies in different contexts: Consequences for home‐care workers in Germany, Japan and Sweden
Authors: Theobald Hildegard , Szebehely Marta , Saito Yayoi , Ishiguro Nobu
Published: October 2017

Market‐oriented restructurings of long‐term care policies contribute significantly to the aggravation of care workers’ situations. This article focuses on the effects of broader long‐term care policy developments on market‐oriented reforms. Germany, Japan and Sweden are three countries that have introduced market‐oriented reforms into home‐based care provision embedded in distinct long‐term care policy developments. Conceptually, this article draws on comparative research on care to define the institutional dimensions of long‐term care policies. Empirically, the research is based on policy analyses, as well as on national statistics and a comparative research project on home‐care workers in the aforementioned countries. The findings reveal the mediating impact of the extension and decline of long‐term public care support and the corresponding development of the care infrastructure on both the restructuring of care work and the assessments of the care workers themselves.
Exploring the genomic basis of early childhood caries: a pilot study
Authors: Ballantine Jami L. , Carlson Jenna C. , Ferreira Zandoná Andrea G. , Agler Cary , Zeldin Leslie P. , Rozier Richard Gary , Roberts Michael W. , Basta Patricia V. , Luo Jason , Antonio‐Obese Mikafui E. , McNeil Daniel W. , Weyant Robert J. , Crout Richard J. , Slayton Rebecca L. , Levy Steven M. , Shaffer John R. , Marazita Mary L. , North Kari E. , Divaris Kimon
Published: October 2017

Objective

A genetic component in early childhood caries (ECC) is theorized, but no genome‐wide investigations of ECC have been conducted. This pilot study is part of a long‐term research program aimed to: (1) determine the proportion of ECC variance attributable to the human genome and (2) identify ECC‐associated genetic loci.

Methods

The study's community‐based sample comprised 212 children (mean age=39 months; range = 30–52 months; males = 55%; Hispanic/Latino = 35%, African‐American = 32%; American Academy of Pediatric Dentistry definition of ECC prevalence = 38%). Approximately 2.4 million single nucleotide polymorphisms (SNPs) were genotyped using DNA purified from saliva. A P < 5 × 10−8 criterion was used for genome‐wide significance. SNPs with P < 5 × 10−5 were followed‐up in three independent cohorts of 921 preschool‐age children with similar ECC prevalence.

Results

SNPs with minor allele frequency ≥5% explained 52% (standard error = 54%) of ECC variance (one‐sided P = 0.03). Unsurprisingly, given the pilot's small sample size, no genome‐wide significant associations were found. An intergenic locus on 4q32 (rs4690994) displayed the strongest association with ECC [P = 2.3 × 10−6; odds ratio (OR) = 3.5; 95% confidence interval (CI) = 2.1–5.9]. Thirteen loci with suggestive associations were followed‐up – none showed evidence of association in the replication samples.

Conclusion

This study's findings support a heritable component of ECC and demonstrate the feasibility of conducting genomics studies among preschool‐age children.
The efficacy of removable devices to offload and heal neuropathic plantar forefoot ulcers in people with diabetes: a single‐blinded multicentre randomised controlled trial
Authors: Bus Sicco A , van Netten Jaap J , Kottink Anke IR , Manning Erik A , Spraul Maximilian , Woittiez Arend‐Jan , van Baal Jeff G
Published: October 2017

Non‐removable offloading is the ‘gold standard’ treatment for neuropathic diabetic plantar forefoot ulcers. However, removable offloading is the common ‘standard of care’. We compared three removable offloading devices for ulcer healing efficacy. In this multicentre, randomised controlled trial, 60 persons with neuropathic diabetic plantar forefoot ulcers were randomly assigned to wear a custom‐made knee‐high cast [BTCC (bivalved TCC)], custom‐made ankle‐high cast shoe or a prefabricated ankle‐high forefoot‐offloading shoe (FOS). Primary outcome was healing at 12 weeks. Dynamic plantar pressures, daily stride count and treatment adherence were assessed on a randomly selected subset (n = 35). According to intention‐to‐treat analysis, 58% of patients healed with BTCC [OR 0·77 (95% CI 0·41–1·45) versus FOS], 60% with cast shoe [OR 0·81 (95% CI 0·44–1·49) versus FOS] and 70% with FOS (P = 0·70). Mean ± SD peak pressure in kPa at the ulcer site was 81 ± 55 for BTCC, 176 ± 80 for cast shoe and 107 ± 52 for FOS (P = 0·005); stride count was 4150 ± 1626, 3514 ± 1380 and 4447 ± 3190, respectively (P = 0·71); percentage of 2‐week intervals that patients wore the device <50% of time was 17·3%, 5·2% and 4·9%, respectively. Non‐significant differences in healing efficacy between the three devices suggest that, when non‐removable offloading is contraindicated or not available, each can be used for plantar forefoot ulcer offloading. Efficacy is lower than previously found for non‐removable offloading maybe because suboptimal adherence and high stride count expose the patient to high repetitive stresses. These factors should be carefully considered in decision making regarding ulcer treatment.
Jasmonate signaling makes flowers attractive to pollinators and repellant to florivores in nature
Authors: Li Ran , Schuman Meredith C. , Wang Yang , Llorca Lucas Cortés , Bing Julia , Bennion Anne , Halitschke Rayko , Baldwin Ian T.
Published: October 2017

Flowers are required for the Darwinian fitness of flowering plants, but flowers’ advertisements for pollination services can attract florivores. Previous glasshouse work with Nicotiana attenuata revealed the role of jasmonate (JA) signaling in flower development, advertisement and defense. However, whether JA signaling mediates flowers’ filtering of floral visitors in nature remained unknown. This field study revealed that silencing JA signaling resulted in flowers that produce less nectar and benzyl acetone, two pollinator‐attractive traits. Meanwhile, flowers of defenseless plants were highly attacked by a suite of native herbivores, and damage to buds in native plants correlated negatively with their JA‐Ile levels.
Porphyromonas gingivalis lipopolysaccharide induces over production of CC chemokine ligand 2 via toll‐like receptor‐4 in oral lichen planus
Authors: Zeng Qi , Yang Xi , Chen Xiaobing , Xia Juan , Cheng Bin , Tao Xiaoan
Published: October 2017

Background

We recently reported that the CC chemokine ligand 2 (CCL2)‐CC receptor 2 (CCR2) axis was involved in the pathogenesis of oral lichen planus (OLP). However, the exact mechanism for the high expression of CCL2 in OLP specimens is not clear. Therefore, this study was designed to investigate the potential role of the toll‐like receptor 4 (TLR‐4) pathway in overproduction of CCL2 in OLP lesions.

Methods

Immunohistochemical staining and real‐time RT‐PCR were used to detect TLR‐4, CCL2, and CCR2 expression in OLP lesions. Then, gingival epithelial cells from OLP lesions were established and treated with Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). CCL2 expression in epithelial cells was determined by Western blotting and real‐time RT‐PCR. In some experiments, TAK‐242, a specific inhibitor of TLR‐4, was used to block the TLR‐4 pathway before cells were stimulated with LPS.

Results

We found that TLR‐4 was significantly increased in the epithelium of OLP specimens, compared with controls. Moreover, LPS can induce the over production of CCL2 in epithelial cells of OLP, in vitro. TAK‐242 effectively eliminated the increase in CCL2 expression induced by LPS by blocking the TLR‐4/NF‐κB pathway. In addition, we again confirmed that expression of CCL2 and CCR2 was increased in OLP specimens.

Conclusion

Increased TLR‐4 expression contributes to the upregulated expression of CCL2 in the epithelium of OLP lesions, which suggests that oral bacteria participate in the pathogenesis of OLP via the TLR‐4 pathway.
Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives
Authors: Bahreyni Amirhossein , Khazaei Majid , Rajabian Majid , Ryzhikov Mikhail , Avan Amir , Hassanian Seyed M
Published: October 2017

Objectives

Adenosine concentration significantly increases in tumour microenvironment contributing to tumorigenic processes including cell proliferation, survival, invasion and of special interest in this review angiogenesis.

Key findings

This review summarizes the role of pharmacological adenosine receptor agonist and antagonist in regulating angiogenesis for a better understanding and hence a better management of angiogenesis-associated disorders.

Depending upon the pharmacological characteristics of adenosine receptor subtypes, adenosine elicits anti- or pro-angiogenic responses in stimulated cells. Inhibition of the stimulatory effect of adenosine signalling on angiogenesis using specific pharmacological adenosine receptor agonist, and antagonist is a potentially novel strategy to suppress angiogenesis in tumours.
Identifying Variability in Patient Characteristics and Prevalence of Emergency Department Utilization for Mental Health Diagnoses in Rural and Urban Communities
Authors: Schroeder Shawnda M. , Peterson Mandi‐Leigh
Published: October 2017

Purpose

In order to redirect at‐risk patients to more appropriate, cost‐effective behavioral health care, research must identify the prevalence, and common characteristics, of patients presenting to the emergency department (ED) for mental disorders. Question: Are large, small, and/or isolated rural patients presenting to the ED for mental disorders in greater proportion than urban ED patients?

Methods

Analyses included data from the Health Care Cost and Utilization Project State Emergency Department Databases (2013) provided by 7 states, covering all Census regions. Variables included patient demographics, ZIP code, and primary and secondary ED diagnoses. ZIP codes were linked to the Rural‐Urban Commuting Areas, aggregating into 4 categories. Prevalence rates were compared within and between groups (P < .05).

Findings

Nearly 1 in 20 ED visits carried a primary/secondary diagnosis of mental disorder. Large, small, and isolated rural patients were not more likely than urban patients to present to the ED for mental disorders. Large, small, and isolated rural residents diagnosed with a primary/secondary mental disorder in the ED were more likely than urban to be female, 65 years of age or older, covered by Medicaid or Medicare, and dual eligible. The top 3 diagnoses for mental disorders in the ED were anxiety‐state, unspecified; depressive disorder; and suicidal ideation.

Conclusions

EDs treating large, small, or isolated rural patients with mental disorders are more likely to treat populations identified in the literature at greater risk of preventable visits, readmitting, and more costly care. Recommendations are made for policy, community interventions, workforce, and training.
Evaluation of the safety of daily administration of capromorelin in cats
Authors: Wofford J. A. , Zollers B. , Rhodes L. , Bell M. , Heinen E.
Published: October 2017

Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite stimulation in dogs. The objective of this study was to evaluate the safety of daily oral administration of capromorelin to cats over a range of doses and for an extended period. Two randomized, controlled studies were conducted: in Study 1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30 or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at 6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated using clinical observations and clinical pathology test results for both studies, with the addition of postmortem examination in Study 1 and measurements of growth hormone and insulin‐like growth factor 1 in Study 2. Abnormal clinical observations were limited to emesis, hypersalivation, lethargy/depression, head shaking and lip smacking, which occurred more frequently in the capromorelin‐treated groups than in the placebo group. There were no clinically relevant differences in clinical pathology test results between the capromorelin and placebo groups in either study.
A medical device containing purified bovine colostrum (Monurelle Biogel) in the treatment of vulvovaginal atrophy in postmenopausal women: Retrospective analysis of urinary symptoms, sexual function, and quality of life
Authors: Schiavi M. C. , Di Tucci C. , Colagiovanni V. , Faiano P. , Giannini A. , D’Oria O. , Prata G. , Perniola G. , Monti M. , Zullo M. A. , Muzii L. , Benedetti Panici P.
Published: October 2017

Objective

This study assessed the effectiveness and safety of a medical device containing purified bovine colostrum (Monurelle Biogel; Zambon, Bresso, Italy) in improving vulvovaginal atrophy (VVA), sexual function, urinary symptoms, and quality of life (QoL) in postmenopausal women.

Methods

In all, 172 postmenopausal women with VVA were included in the study. All women were treated with vaginal Monurelle Biogel daily for 12 weeks. Patients underwent clinical examinations, completed a 3‐day voiding diary, and had VVA graded using the Vaginal Health Index (VHI) at baseline and 12 weeks. Patients also completed the Female Sexual Function Index (FSFI), overactive bladder questionnaire (OAB‐Q), and the Urogenital Distress Inventory (UDI‐6), among others.

Results

After 12 weeks, there were significant increases in mean (± SD) VHI (12.53 ± 3.67 vs. 19.31 ± 3.49; P < .0001), the number of patients engaging in regular sexual activity 102 (59.3%) vs. 144 (83.7%), and in the total FSFI score (21.64 ± 2.99 vs. 28.16 ± 1.93; P < .0001) compared with baseline. In addition, there were significant reductions in the mean number of 24‐hour voids (9.57 ± 2.12 vs. 7.13 ± 1.22; P < .0001), urgent micturition episodes per 24 hours (1.75 ± 0.76 vs. 1.14 ± 0.87; P = .001), nocturia episodes (1.58 ± 0.85 vs. 0.97 ± 1.18; P = .0002), and urinary incontinence episodes per 24 hours (0.74 ± 0.59 vs. 0.28 ± 0.52; P = .003). Finally, after 12 weeks treatment, there were significant differences in UDI‐6 (7.85 ± 0.81 vs. 5.56 ± 1.40), OAB‐Q symptom (53.60 ± 12.57 vs. 22.08 ± 9.63), and OAB‐Q health‐related QoL (21.75 ± 8.51 vs. 69.34 ± 14.59) scores compared with baseline (P < .0001 for all). The Patient Impression of Global Improvement scale revealed global improvement in 143 women (83.14%).

Conclusions

Monurelle Biogel is an effective treatment for VVA in postmenopausal women, improving sexual life, urinary symptoms, and QoL.
Interplay between silica deposition and viability during the life span of sorghum silica cells
Authors: Kumar Santosh , Elbaum Rivka
Published: October 2017

Silica cells are specialized epidermal cells found on both surfaces of grass leaves, with almost the entire lumen filled with solid silica. The mechanism precipitating silicic acid into silica is not known. Here we investigate this process in sorghum (Sorghum bicolor) leaves.

Using fluorescent confocal microscopy, we followed silica cells’ ontogeny, aiming to understand the fate of vacuoles and nuclei. Correlating the confocal and scanning electron microscopy, we timed the initiation of silica deposition in relation to cell's viability.

Contrary to earlier reports, silica cells did not lose their nucleus before silica deposition. Vacuoles in silica cells did not concentrate silicic acid. Instead, postmaturation silicification initiated at the cell periphery in live cells. Less than 1% silica cells showed characteristics of programmed cell death in the cell maturation zone. In fully elongated mature leaves, 2.4% of silica cells were nonsilicified and 1.6% were partially silicified.

Silica deposition occurs in the paramural space of live silica cells. The mineral does not kill the cells. Instead, silica cells are genetically programmed to undergo cell death independent of silicification. Fully silicified cells seem to have nonsilicified voids containing membrane remains after the completion of the cell death processes.
You don’t belong here: explaining the excess of rare species in terms of habitat, space and time
Authors: Sgarbi Luciano F. , Melo Adriano S.
Published: October 2017

Ecological communities are composed of a few common and several rare species. Many studies have evaluated the shape of abundance distribution curves, but few studies have assessed the causes of rarity. Using a dataset of stream macroinvertebrates, we investigated whether the excess of rare species in three focal communities of stones in riffles were common 1) in other habitats at the same stream site and period of sampling (environment), 2) in other stream sites in the same habitat and period of sampling (space), and 3) in other years in the same stream site and habitat (time). We observed that around 28% of the rare species were common in other habitats (environment), stream sites (space) or years (time). Among the three factors, rarity was mostly explained by habitat type, whereas a significant portion of the rare species in riffles were common in pools, submerged roots of terrestrial plants or in partially submerged moss patches. This result suggests that the presence in non‐optimum habitat is a strong determinant of the rarity observed in natural communities and most rare species are due to sampling artifacts or accidentally sampled transient species.
Cope's rule and the adaptive landscape of dinosaur body size evolution
Authors: Benson Roger B. J. , Hunt Gene , Carrano Matthew T. , Campione Nicolás
Published: October 2017

The largest known dinosaurs weighed at least 20 million times as much as the smallest, indicating exceptional phenotypic divergence. Previous studies have focused on extreme giant sizes, tests of Cope's rule, and miniaturization on the line leading to birds. We use non‐uniform macroevolutionary models based on Ornstein–Uhlenbeck and trend processes to unify these observations, asking: what patterns of evolutionary rates, directionality and constraint explain the diversification of dinosaur body mass? We find that dinosaur evolution is constrained by attraction to discrete body size optima that undergo rare, but abrupt, evolutionary shifts. This model explains both the rarity of multi‐lineage directional trends, and the occurrence of abrupt directional excursions during the origins of groups such as tiny pygostylian birds and giant sauropods. Most expansion of trait space results from rare, constraint‐breaking innovations in just a small number of lineages. These lineages shifted rapidly into novel regions of trait space, occasionally to small sizes, but most often to large or giant sizes. As with Cenozoic mammals, intermediate body sizes were typically attained only transiently by lineages on a trajectory from small to large size. This demonstrates that bimodality in the macroevolutionary adaptive landscape for land vertebrates has existed for more than 200 million years.
Inheritance and characterization of the new and rare gene Rph25 conferring seedling resistance in Hordeum vulgare against Puccinia hordei
Authors: Kavanagh Paul J. , Singh Davinder , Bansal Urmil K. , Park Robert F.
Published: October 2017

In this study, we characterized and mapped a new and rare resistance gene (RphFT) in the Chinese barley variety ‘Fong Tien’. RphFT, a dominant gene, was mapped to chromosome 5HL at a genetic position of 142.1 cM using DArT‐seq markers. The gene was also confirmed to be present in Australian cultivar ‘Yagan’ based on allelic tests, and likely ‘Lockyer’ based on multipathotype tests. The genetic studies also confirmed the presence of Rph12 in Australian cultivar ‘Baudin’. Rph12 is also located on chromosome 5HL close to RphFT, and the two loci were confirmed to be independent. Gene RphFT is of limited breeding value because it is effective to only one pathotype of P. hordei, 220P+ +Rph13 in Australia; nevertheless, it may play a role in controlling leaf rust if used in combination with other Rph genes. The locus symbol Rph25 is recommended for RphFT in accordance with the rules and numbering system of barley gene nomenclature.