bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustaining quality in the community: trends in the performance of a structured diabetes care programme in primary care over 16 years
Authors: Riordan F. , McHugh S. M. , Harkins V. , Marsden P. , Kearney P. M.
Published: April 2018

Aim

To examine the quality of care delivered by a structured primary care‐led programme for people with Type 2 diabetes mellitus in 1999–2016.

Methods

The Midland Diabetes Structured Care Programme provides structured primary care‐led management. Trends over time in care processes were examined (using a chi‐squared trend test and age‐ and gender‐adjusted logistic regression). Screening and annual review attendance were reviewed. A composite of eight National Institute for Health and Care Excellence‐recommended processes was used as a quality indicator. Participants who were referred to diabetes nurse specialists were compared with those not referred (Student's t‐test, Pearson's chi‐squared test, Wilcoxon–Mann–Whitney test). Proportions achieving outcome targets [HbA1c ≤58 mmol/mol (7.5%), blood pressure ≤140/80 mmHg, cholesterol <5.0 mmol/l] were calculated.

Results

Data were available for people with diabetes aged ≥18 years: 1998/1999 (n=336); 2003 (n=843); 2008 (n=988); and 2016 (n=1029). Recording of some processes improved significantly over time (HbA1c, cholesterol, blood pressure, creatinine), and in 2016 exceeded 97%. Foot assessment and annual review attendance declined. In 2016, only 29% of participants had all eight National Institute for Health and Care Excellence processes recorded. A higher proportion of people with diabetes who were referred to a diabetes nurse specialist had poor glycaemic control compared with those not referred. The proportions meeting blood pressure and lipid targets increased over time.

Conclusions

Structured primary care led to improvements in the quality of care over time. Poorer recording of some processes, a decline in annual review attendance, and participants remaining at high risk suggest limits to what structured care alone can achieve. Engagement in continuous quality improvement to target other factors, including attendance and self‐management, may deliver further improvements.
Prospective evaluation of the effect of deferasirox on hematologic response in transfusion‐dependent patients with low‐risk MDS and iron overload
Authors: Rose Christian , Lenoir Caroline , Gyan Emmanuel , Hacini Maya , Amé Shanti , Corront Bernadette , Beyne‐Rauzy Odile , Adiko Didier , Loppinet Elena , Ali‐Ammar Nadia , Laribi Kamel , Wattel Eric , Dreyfus François , Roué Claire S. , Cheze Stephane
Published: May 2018

Objectives

To assess the reduction of transfusions rate in transfusion‐dependent patients with low‐risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox.

Methods

Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8‐week period). Secondary endpoints were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months.

Results

Fifty‐seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan‐Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12‐month follow‐up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI‐E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12.

Conclusion

After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low‐risk MDS. However, deferasirox could induce 31% of erythroid response during the 12‐month follow‐up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload.
The effect of enriched environment across ages: A study of anhedonia and BDNF gene induction
Authors: Dong B. E. , Xue Y. , Sakata K.
Published: May 2018

Enriched environment treatment (EET) is a potential intervention for depression by inducing brain‐derived neurotrophic factor (BDNF). However, its age dependency remains unclear. We recently found that EET during early‐life development (ED) was effective in increasing exploratory activity and anti‐despair behavior, particularly in promoter IV‐driven BDNF deficient mice (KIV), with the largest BDNF protein induction in the hippocampus and frontal cortex. Here, we further determined age dependency of EET effects on anhedonia and promoter‐specific BDNF transcription, by using the sucrose preference test and qRT‐PCR. Wild‐type (WT) and KIV mice received 2 months of EET during ED, young‐adulthood and old‐adulthood (0‐2, 2‐4 and 12‐14 months, respectively). All KIV groups showed reduced sucrose preference, which EET equally reversed regardless of age. EET increased hippocampal BDNF mRNA levels for all ages and genotypes, but increased frontal cortex BDNF mRNA levels only in ED KIV and old WT mice. Transcription by promoters I and IV was age‐dependent in the hippocampus of WT mice: more effective induction of exon IV or I during ED or old‐adulthood, respectively. Transcription by almost all 9 promoters was age‐specific in the frontal cortex, mostly observed in ED KIV mice. After discontinuance of EET, the EET effects on anti‐anhedonia and BDNF transcription in both regions persisted only in ED KIV mice. These results suggested that EET was equally effective in reversing anhedonia and inducing hippocampal BDNF transcription, but was more effective during ED in inducing frontal cortex BDNF transcription and for lasting anti‐anhedonic and BDNF effects particularly in promoter IV‐BDNF deficiency.
Targeted gene disruption by use of CRISPR/Cas9 ribonucleoprotein complexes in the water flea Daphnia pulex
Authors: Hiruta Chizue , Kakui Keiichi , Tollefsen Knut E. , Iguchi Taisen
Published: May 2018

The microcrustacean Daphnia pulex is an important model for environmental, ecological, evolutionary and developmental genomics because its adaptive life history displays plasticity in response to environmental changes. Even though the whole‐genome sequence is available and omics data have actively accumulated for this species, the available tools for analyzing gene function have thus far been limited to RNAi (RNA interference) and TALEN (the transcription activator‐like effector nuclease) systems. The development of the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR‐associated 9) system is thus expected to further increase the genetic tractability of D. pulex and to advance the understanding of this species. In this study, we developed a genome editing system for D. pulex using CRISPR/Cas9 ribonucleoprotein complexes (Cas9 RNPs). We first assembled a CRISPR single‐guide RNA (sgRNA) specific to the Distal‐less gene (Dll), which encodes a homeodomain transcription factor essential for distal limb development in invertebrates and vertebrates. Then, we injected Cas9 RNPs into eggs and evaluated its activity in vivo by a T7 endonuclease I assay. Injected embryos showed defective formation of the second antenna and disordered development of appendages, and indel mutations were detected in Dll loci, indicating that this technique successfully knocked out the target gene.
Modelling variation in calling rates to develop a reliable monitoring method for the Australasian Bittern Botaurus poiciloptilus
Authors: Williams Emma M. , Armstrong Doug P. , O'Donnell Colin F. J.
Published: April 2018

Monitoring the abundance of cryptic species inevitably relies on the use of index methods. Unfortunately, detectability is often confounded by unidentified covariates. One such species is the critically endangered Australasian Bittern Botaurus poiciloptilus. Current monitoring relies upon the ability to count males based on the conspicuous breeding calls of males. However, as in many vocal species, calling rates vary spatially and temporally, making it necessary to account for this when using call counts to index abundance. We undertook 461 15‐min call counts of Australasian Bitterns, in a range of conditions, during two breeding seasons at Whangamarino wetland, New Zealand. We fitted a range of generalized linear mixed models to these data to determine which factors were the best predictors of calling rate per individual Bittern (CRPI), allowing us to make recommendations regarding the optimum time and conditions for monitoring. Bittern CRPI was predictable in terms of time of day, month, cloud cover, rainfall and certain moon parameters, but some spatial and temporal variation remained unexplained. Results showed that the best time to detect Australasian Bitterns was 1 h before sunrise, in September (austral spring), on a moonlit night with no cloud or rain. Such models are useful for identifying times and conditions when counts are the highest and least variable, and could be applied to any species or cue count monitoring method where detection depends on counting calling individuals. Results can be used to standardize index counts, or sensibly to adjust and compare counts from different times. Standardizing monitoring in this way can lead to the development of monitoring methods that have a greater power to show population changes across shorter time periods. Moreover, the use of modelling processes to estimate effect sizes creates potential for such methods to be applied in circumstances where monitoring conditions are rarely optimum and standardization creates logistical trade‐offs, something that is particularly common in studies of cryptic species.
Width proportion of the urethral plate to the glans can serve as an appraisal index of the urethral plate in hypospadias repair
Authors: Ru Wei , Shen Jing , Tang Daxing , Xu Shan , Wu Dehua , Tao Chang , Chen Guangjie , Gao Lei , Wang Xiaohao , Shen Yiding
Published: May 2018

Objectives

To find a new appropriate evaluation for urethral plate quality in hypospadias repair, with particular interest in the width proportion of the urethral plate to the glans, serving as an appraisal index.

Methods

Data were prospectively collected from prepubertal boys who underwent primary tubularized incised plate hypospadias repair between January 2014 and April 2016 in one center. Intrinsic parameters of the penis (meatal location, glans width, urethral plate width and curvature degree) were measured during the operation. Urethroplasty complications were recorded during follow up. The correlation between width proportion of the urethral plate to the glans and urethroplasty complications was analyzed.

Results

Primary tubularized incised plate repair was carried out in 442 patients (mean age 2.8 years, range 0.5–12 years). At mean follow up of 26 months (range 12–38 months), urethroplasty complications occurred in 59 (13.3%) patients. The width proportion of the urethral plate to the glans was weakly correlated to both the glans width and meatal location. The width proportion of the urethral plate to the glans ranged from 0.18 to 0.73, with a mean of 0.39. The cut‐off value of width proportion of the urethral plate to the glans was determined to be 0.36 by the receiver operating characteristic curve. Urethroplasty complications occurred in 17 out of 254 patients (6.7%) with width proportion of the urethral plate to the glans >0.36, and 42 out of 188 patients (22.3%) with width proportion of the urethral plate to the glans ≤0.36. The width proportion of the urethral plate to the glans ≤0.36 showed an increased odds of 4.819‐fold (95% confidence interval 2.548–9.112, P < 0.001) risk of urethroplasty complications compared with width proportion of the urethral plate to the glans >0.36. Midshaft and proximal meatal location also increased the risk of urethroplasty complications.

Conclusions

The present study highlights the value of the width proportion of the urethral plate to the glans for objectivity and accuracy in urethral plate evaluation, which in turn serves as an independent factor influencing outcomes in tubularized incised plate repair.
Dissecting the role of Krüppel homolog 1 in the metamorphosis and female reproduction of the cotton bollworm, Helicoverpa armigera
Authors: Zhang W.‐N. , Ma L. , Liu C. , Chen L. , Xiao H.‐J. , Liang G.‐M.
Published: May 2018

In insects, metamorphosis and reproduction are controlled by juvenile hormone (JH) and 20‐hydroxyecdysone (20E). Krüppel homolog 1 (Kr‐h1), a transcription factor, is regarded as a JH‐early inducible gene responsible for the repression of metamorphosis. However, the role of Kr‐h1 in reproduction of holometabolic insects is relatively less understood. In this study, we studied the role of Kr‐h1 in larvae–pupae transition and female reproduction in the major agricultural pest Helicoverpa armigera. Two HaKr‐h1 isoforms (HaKr‐h1α and HaKr‐h1ß) were identified, with HaKr‐h1α predominant in the cotton bollworm. In larvae, HaKr‐h1 was predominately expressed in the epidermis and markedly up‐regulated during the moult stage, whereas in adults HaKr‐h1 was mainly expressed in females and the highest transcription was detected in the ovaries. Considering the function of hormones in larval metamorphosis, we examined the modulation of gene expression in response to hormones, which showed that HaKr‐h1 was significantly induced by both JH analogue (JHA) and 20E. Knockdown of HaKr‐h1 in fifth‐instar larvae resulted in precocious metamorphosis from larvae to pupae. Moreover, a fluorescence immunoassay coupled with heterologous expression revealed that HaKr‐h1 was localized in the nucleus of oocyte membrane. In female adults, depletion of HaKr‐h1 severely repressed the transcription of vitellogenin, disrupted oocyte maturation and reduced the number of eggs laid, suggesting that HaKr‐h1 is required for vitellogenesis and egg production in H. armigera. The present study provides insight into the roles of HaKr‐h1 in JH‐mediated reproduction and highlights HaKr‐h1 as a target for suppression of lepidopteran pests.
Using ‘collective omics data’ for biomedical research training
Authors: Chaussabel Damien , Rinchai Darawan
Published: April 2018

Systems‐scale molecular profiling data accumulating in public repositories may constitute a useful resource for immunologists. It is for instance likely that information relevant to their chosen line of research be found among the more than 90,000 data series available in the NCBI Gene Expression Omnibus. Such ‘collective omics data’ may also be employed as source material for training purposes. This is the case when training curricula aim at the development of bioinformatics skills necessary for the analysis, interpretation or visualization of data generated on global scales. But ‘collective omics data’ may also be reused for training purposes to foster the development of the skills and ‘mental habits’ underpinning traditional reductionist science approaches. This review describes a small‐scale initiative involving investigators, for the most part immunologists, having engaged in a range of training activities relying on ‘collective omics data’.
Iterated local search and simulated annealing algorithms for the inventory routing problem
Authors: Alvarez Aldair , Munari Pedro , Morabito Reinaldo
Published: May 2018

This paper addresses the inventory routing problem (IRP), which consists in defining the customer visit schedule, the delivery quantities, and the vehicle routing plan to meet the demands of a set of customers over a given time horizon. We consider the variant with a single item, a single supplier, multiple vehicles, and a finite multiperiod planning horizon, minimizing the sum of inventory and travel costs. In addition, we address an alternative objective function that minimizes the logistic ratio, defined as the total travel cost divided by the total quantity delivered to customers. This second objective function, while more realistic in some logistics settings, poses a challenge for integer programming models and exact methods because of its nonlinearity. To our knowledge, no heuristic method has been proposed to address this objective in the IRP variant addressed in this paper. To solve this problem with each of these objective functions, we propose effective metaheuristic algorithms based on iterated local search and simulated annealing. Computational experiments show that these algorithms provide reasonably high‐quality solutions in relatively short running times for both objective functions when compared to other methods for well‐known instances from the literature. Moreover, the algorithms produce new best solutions for some of these instances.
Directing adipose‐derived stem cells into keratinocyte‐like cells: impact of medium composition and culture condition
Authors: Petry L. , Kippenberger S. , Meissner M. , Kleemann J. , Kaufmann R. , Rieger U.M. , Wellenbrock S. , Reichenbach G. , Zöller N. , Valesky E.
Published: April 2018

Background

Adipose‐derived stem cells (ASC) are known to transdifferentiate into a wide range of different cell species in vitro including along the epidermal lineage. This property makes them a promising tool for regenerative medicine to restore the epidermal barrier.

Objective

This study is dedicated to identify in vitro conditions enabling transdifferentiation to a keratinocyte‐like phenotype. In particular, the impact of different culture conditions (media compositions, 2D, 3D cultures) and extracellular matrix (ECM) molecules was evaluated.

Methods

Adipose‐derived stem cells derived from subcutaneous abdominal fat were characterized by stemness‐associated markers and subjected to different media. Epithelial differentiation in 2D cultures was monitored by pan‐cytokeratin expression using flow cytometry and immunocytochemistry. To evaluate the impact of different ECM molecules on epidermal stratification, 3D cultures were produced, lifted to the air–liquid interface (ALI) and examined by histological analysis and quantitative real‐time RT–PCR.

Results

We identified a medium composition containing retinoic acid, hydrocortisone, ascorbic acid and BMP‐4 enabling maximum pan‐cytokeratin expression in 2D cultures. Moreover, adhesion to type IV collagen further promotes the pan‐cytokeratin expression. When cultures were lifted to the ALI, significant stratification was observed, particularly in supports coated with type IV collagen or fibronectin. Moreover, epidermal differentiation markers (involucrin, cytokeratin 1 and 14) become induced.

Conclusion

Conditions with hampered wound healing such as non‐healing ulcers demand new treatment regimes. The here introduced optimized protocols for transdifferentiation of ASC into keratinocyte‐like cells may help to establish more effective treatment procedures.
Anxiety and depression in patients with moderate‐to‐severe psoriasis and comparison of change from baseline after treatment with guselkumab vs. adalimumab: results from the Phase 3 VOYAGE 2 study
Authors: Gordon K.B. , Armstrong A.W. , Han C. , Foley P. , Song M. , Wasfi Y. , You Y. , Shen Y.‐K. , Reich K.
Published: April 2018

Background

Anxiety and depression are clinically significant comorbidities associated with psoriasis. Improvements in psoriasis are known to decrease anxiety and depression. Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated efficacy and safety for the treatment of moderate‐to‐severe psoriasis.

Objective

Assess improvements in anxiety and depression with guselkumab vs. placebo and adalimumab using the Hospital Anxiety and Depression Scale (HADS).

Methods

In VOYAGE 2, a Phase 3, randomized, double‐blind, placebo‐ and adalimumab‐controlled study, patients received placebo (through week 16 followed by crossover to guselkumab), guselkumab, or adalimumab through week 24. HADS consists of two subscales measuring anxiety (HADS‐A) and depression (HADS‐D), with scores ranging from 0 to 21 and higher scores indicating more severe symptoms. Scores ≥8 indicate instrument‐defined anxiety or depression. Severity of psoriasis was assessed using the Psoriasis Area and Severity Index (PASI).

Results

Among 989 patients randomized (with baseline HADS measurements), mean HADS‐A and HADS‐D scores were 6.8 ± 4.2 and 5.3 ± 4.2, respectively; 38.6% of patients reported HADS‐A ≥8 and 27.7% HADS‐D ≥8 at baseline. At week 16, a significantly greater proportion of guselkumab patients with baseline HADS‐A or HADS‐D ≥8 reported HADS‐A <8 (51.4% vs. 25.9%; P < 0.001) or HADS‐D <8 (59.2% vs. 27.0%; P < 0.001) vs. placebo patients. At week 24, a greater proportion of guselkumab patients with baseline HADS‐A or HADS‐D ≥8 reported HADS‐A <8 (58.4% vs. 42.9%; P = 0.028) or HADS‐D <8 (59.8% vs. 46.4%; P = 0.079) vs. adalimumab patients. PASI improvements correlated with improvement in anxiety (r = 0.27; P < 0.0001) and depression (r = 0.25; P < 0.0001) scores in patients with baseline HADS‐A or HADS‐D ≥8. Greater improvements in HADS were also observed at week 16 in guselkumab‐treated patients vs. placebo using a more stringent cut‐off of HADS ≥11.

Conclusion

Guselkumab treatment was associated with greater improvements in symptoms of anxiety and depression scores in patients with psoriasis compared with placebo and adalimumab.
Longitudinal subungual acanthoma: one denomination for various clinical presentations
Authors: Baran R. , Moulonguet I. , Goettmann‐Bonvallot S. , Encaoua R. , Robert C.
Published: April 2018

Background

Benign subungual proliferation of the distal nail matrix and bed such as longitudinal keratosis, seborrhoeic keratosis or onychocytic matricoma should belong to a single spectrum of diseases.

Objective

This article intends to demonstrate clinically and histologically the different facets of Nail unit longitudinal acanthoma.

Methods

We report three new cases that present as a longitudinal melanonychia with thickening of the nail plate in two of them and as leukoxanthonychia in the third one. We compared them with the two original cases we described in 1999, reminiscent of seborrhoeic keratosis and all the new cases published since then.

Results

We therefore consider that all these tumours belong to a single spectrum of diseases, we have called ‘nail unit longitudinal acanthoma’ which describes a histopathological process. The distinct clinical features of these tumours, melanonychia or leukoxanthonychia may be linked to their variable anatomic locations in different zones of the nail unit.
Long‐term real‐life safety profile and effectiveness of fumaric acid esters in psoriasis patients: a single‐centre, retrospective, observational study
Authors: Dickel H. , Bruckner T. , Altmeyer P.
Published: April 2018

Background

Fumaric acid esters (FAEs) are an established systemic treatment for moderate‐to‐severe psoriasis. However, the long‐term clinical safety and effectiveness of continuous FAE monotherapy and combination therapy have not been established.

Objective

To examine the long‐term safety and effectiveness of FAEs as monotherapy and in combination with phototherapy or methotrexate in patients with psoriasis treated at a single centre in Germany.

Methods

This monocentric, retrospective observational study, with a follow‐up period of up to 32.5 years, included 859 patients: 626 received FAE monotherapy, 123 received FAEs with concomitant phototherapy and 110 received FAEs with methotrexate.

Results

Approximately half of patients (49.0%) reported adverse events (566 total events), most of which involved the gastrointestinal tract. Serious adverse events were reported in 2.3% of patients, but none were deemed to have a causal relationship with any of the treatment regimens. Adverse events leading to treatment discontinuation were observed in 12.9% of patients. A median duration of 1 year was observed in all three treatment subcohorts (P = 0.70) from initiation of FAE treatment to a 50% response rate, where response was defined as achieving a cumulative static Physician's Global Assessment (PGA) score of ‘light’ and at least a 2‐point reduction in baseline PGA. A 50% response rate for the cumulative Psoriasis Area and Severity Index 75 was achieved in the FAE monotherapy subcohort after a median of 3 years of treatment, in the FAEs + phototherapy subcohort after 6.7 years and in the FAEs + methotrexate subcohort after 8.1 years (P = 0.001).

Conclusion

According to our data, FAEs as monotherapy or in combination with phototherapy or methotrexate are safe and beneficial for long‐term clinical use. However, multicentre, randomized controlled trials are required to establish the clinical value of monotherapy versus combination therapy and the optimal treatment duration.
Cutaneous melanoma in France in 2015 attributable to solar ultraviolet radiation and the use of sunbeds
Authors: Arnold M. , Kvaskoff M. , Thuret A. , Guénel P. , Bray F. , Soerjomataram I.
Published: April 2018

Background

Exposure to solar ultraviolet radiation (UVR) and the use of UV‐emitting tanning devices are associated with cutaneous malignant melanoma occurrence.

Objective

The aim of this study was to quantify the proportion and number of melanoma cases attributable to solar UVR exposure and sunbed use in France in 2015.

Methods

Population attributable fractions (PAFs) and numbers of melanoma cases attributable to solar UVR exposure were estimated by age and sex using the incidence rates of a 1903 birth cohort as the primary reference. Further analyses were performed using the following: (i) contemporary melanoma incidence rates in low‐incidence regions within France and (ii) national melanoma incidence rates for the year 1980, as additional references. Assuming a 15‐year lag period, PAF and melanoma cases attributable to sunbed use were calculated using prevalence estimates from a cross‐sectional population survey and published relative risk estimates.

Results

In 2015, an estimated 10 340 melanoma cases diagnosed in French adults were attributable to solar UVR exposure, corresponding to 83% of all melanomas and 3% of all cancer cases in that year. PAFs for melanoma were highest in the youngest age group (30–49 years) and higher in men than in women (89% vs. 79%). A total of 382 melanoma cases occurring in French adults in 2015 were attributed to the use of sunbeds, equivalent to 1.5% and 4.6% of all melanoma cases in men and women, respectively.

Conclusions

A considerable proportion of melanoma cases in France in 2015 were attributable to solar UVR exposure, suggesting that targeted prevention strategies need to be implemented.
The effects of season and weather on healthcare utilization among patients with atopic dermatitis
Authors: Hamann C.R. , Andersen Y.M.F. , Engebretsen K.A. , Skov L. , Silverberg J.I. , Egeberg A. , Thyssen J.P.
Published: April 2018

Background

Patient‐reported triggers for atopic dermatitis (AD) flares include changes in ultraviolet irradiation, humidity and temperature.

Objectives

To identify the relationships between weather data and healthcare utilization in AD patients.

Methods

Using nationwide healthcare registries, clinic (1994–2012) and hospital visits (1977–2012) for AD treatment were calculated as well as monthly totals of topical corticosteroid (TCS) (1996–2012) and calcineurin inhibitor (TCI) prescriptions (2003–20012) filled by AD patients. We calculated monthly averages of temperature, atmospheric pressure, cloud cover and hours of bright sunlight and compared these variables to healthcare utilization endpoints, for the years 2000–2012 (n = 156 months), using linear regression models.

Results

In Denmark, between the year 2000 and 2012, mean monthly totals of AD emergency room visits were 6, AD hospitalizations 32, AD outpatient visits 170, TCS prescriptions filled by AD patients 3811 and TCI prescriptions 2552. Healthcare utilization among AD patients was highest in winter/spring. Temperature was the environmental variable that had the strongest association with healthcare utilization: per 1°C lower monthly temperature, 2 more (95% confidence interval [CI] 1–4) AD clinic/hospital visits hospitalizations were observed, 18 (95% CI 9–26) more TCS prescriptions and 53 (95% CI 36–70) more TCI prescriptions were filled by patients with AD. Environmental variables were highly correlated. Associations between AD healthcare utilization and hours of cloud cover were generally positive, while those with hours of bright sunlight were generally inverse.

Conclusions

AD healthcare utilization markers changed significantly with season. A decline in temperature correlated well with AD patients’ healthcare utilization, but a causative role could not be determined with certainty.
Subclinical enthesopathy of extensor digitorum tendon is highly prevalent and associated with clinical and ultrasound alterations of the adjacent fingernails in patients with psoriatic disease
Authors: Moya Alvarado P. , Roé Crespo E. , Muñoz‐Garza F.Z. , López‐Ferrer A. , Laiz Alonso A. , Vilarrassa Rull E. , Casademont i Pou J. , Puig Sanz L.
Published: April 2018

Background

Nail psoriasis disease is associated with an increased probability of psoriatic arthritis, and its clinical signs may have different correlates with the pathogenesis of adjacent bone destruction and have different prognostic value. Recent publications about psoriasis and nail psoriatic disease describe different ultrasonographic findings but the relationship between these ungueal alterations measured by ultrasonography and the presence of enthesopathy of the extensor digitorum has yet to be discovered.

Objective

To describe which ultrasonographic characteristics of nail psoriasis are associated with the presence of subclinical enthesopathy in patients with PsO and asymptomatic PsA.

Methods

Patients with psoriasis and asymptomatic psoriatic arthritis were included in the prospective study. Demographic, clinical data and PASI and NAPSI indexes were recorded of all the patients in the assessment visit. The US assessment included Achilles tendon, extensor digitorum tendon and US scan of the nail plate, nail matrix, nail bed and adjacent skin over nail matrix of the five nails of each hand.

Results

Forty‐eight patients were included in the study; 33 of them presented ultrasound evidence of extensor digitorum tendon enthesopathy. Nails of the patients with subclinical enthesopathy had a higher NAPSI and skin thickness than the nails of the patients without subclinical enthesopathy (P = 0.047). Patients with asymptomatic enthesopathy had significantly thicker proximal nail folds (1.44 ± 0.312 vs. 1.23 ± 0.27, P = 0.023). Nail beds and matrices were also thicker but the differences were not statistically significant (1.77 ± 0.27 vs. 1.74 ± 0.21, P = 0.66, and 1.79 ± 0.28 vs. 1.67 ± 0.19, P = 0.10, respectively). No statistically significant differences in the trilaminar structure were found between both groups. Patients with and without asymptomatic enthesopathy of extensor digitorum tendons did not statistically differ as regards ultrasonographic alterations of the Achilles tendons (60.6% vs. 46.4%, P 0.368).

Conclusion

Enthesopathy abnormalities can be detected by US in patients with psoriasis without musculoskeletal complaints frequently. There is a close relationship between subclinical enthesopathy of the extensor digitorum tendon and the presence of nail alterations. Further studies are required to research what implications have the presence of these ungual alterations measured by US, and how it affects later development of a PsA.
Mohs micrographic surgery for nail unit tumours: an update and a critical review of the literature
Authors: Lambertini M. , Piraccini B.M. , Fanti P.A. , Dika E.
Published: April 2018

Mohs micrographic surgery (MMS) is a good treatment option for epithelial neoplasms, especially when localized in areas where tissue conservation is crucial, such as the nail unit (NU). MMS is a method of radical excision offering high cure rates due to the margin control and functional preservation. Our aim is to provide a review on the use of MMS for the treatment of the most common nail tumours. We revised the current literature on the use of MMS to treat malignant neoplasms (Bowen's disease, squamous cell carcinoma, melanoma, basal cell carcinoma, keratoacanthoma, carcinoma cuniculatum) and benign neoplasms (onychomatricoma and glomus tumour). MMS represents a successful surgical option for nail tumours, firstly in terms of tissue conservation: the NU anatomy is complex and the preservation of the component structures is imperative for its functionality. Secondly, due to the surgical radicality, which is essential not only for the clearing of malignant tumours, but also for benign cases, in order to reduce recurrences. Although a conservative treatment of NU melanoma with MMS has been proposed, in our experience, the conservative approach with functional surgery is a good option for the treatment of non‐invasive melanoma (in situ and Ia).
Emerging concepts on the role of epigenetics in the relationships between nutrition and health
Authors: Stover P. J. , James W. P. T. , Krook A. , Garza C.
Published: April 2018

Understanding the physiological and metabolic underpinnings that confer individual differences in responses to diet and diet‐related chronic disease is essential to advance the field of nutrition. This includes elucidating the differences in gene expression that are mediated through programming of the genome through epigenetic chromatin modifications. Epigenetic landscapes are influenced by age, genetics, toxins and other environmental factors, including dietary exposures and nutritional status. Epigenetic modifications influence transcription and genome stability are established during development with life‐long consequences. They can be inherited from one generation to the next. The covalent modifications of chromatin, which include methylation and acetylation, on DNA nucleotide bases, histone proteins and RNA are derived from intermediates of one‐carbon metabolism and central metabolism. They influence key physiological processes throughout life, and together with inherited DNA primary sequence, contribute to responsiveness to environmental stresses, diet and risk for age‐related chronic disease. Revealing diet–epigenetic relationships has the potential to transform nutrition science by increasing our fundamental understanding of: (i) the role of nutrients in biological systems, (ii) the resilience of living organisms in responding to environmental perturbations, and (iii) the development of dietary patterns that programme physiology for life‐long health. Epigenetics may also enable the classification of individuals with chronic disease for specific dietary management and/or for efficacious diet‐pharmaceutical combination therapies. These new emerging concepts at the interface of nutrition and epigenetics were discussed, and future research needs identified by leading experts at the 26th Marabou Symposium entitled ‘Nutrition, Epigenetics, Genetics: Impact on Health and Disease’.

For a compilation of the general discussion at the marabou symposium, click here http://www.marabousymposium.org/.
Effects of concentrate‐to‐forage ratios and 2‐methylbutyrate supplementation on ruminal fermentation, bacteria abundance and urinary excretion of purine derivatives in Chinese Simmental steers
Authors: Wang C. , Liu Q. , Guo G. , Huo W. J. , Pei C. X. , Zhang S. L. , Wang H.
Published: May 2018

This study evaluated the effects of dietary concentrate levels and 2‐methylbutyrate (2MB) supplementation on performance, ruminal fermentation, bacteria abundance, microbial enzyme activity and urinary excretion of purine derivatives (PD) in steers. Eight ruminally cannulated Simmental steers (12 months of age; 389 ± 3.7 kg of body weight) were used in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement. Moderate‐concentrate (400 g/kg diet [MC]) or high‐concentrate (600 g/kg diet [HC]) diets were fed with or without 2MB (0 g/day [2MB−] or 15.0 g/day [2MB+]). Dry matter intake and average daily gain increased, but feed conversion ratio decreased with the HC diet or 2MB supplementation. Ruminal pH decreased, but total volatile fatty acid increased with the HC diet or 2MB supplementation. Molar proportion of acetate and acetate‐to‐propionate ratio decreased with the HC diet, but increased with 2MB supplementation. Propionate molar proportion and ruminal NH3‐N content increased with the HC diet, but decreased with 2MB supplementation. Neutral detergent fibre degradability decreased with the HC diet, but increased with 2MB supplementation. Crude protein degradability increased with the HC diet or 2MB supplementation. Abundance of Ruminococcus albus, Ruminococcus flavefaciens, Fibrobacter succinogenes and Bufyrivibrio fibrisolvens as well as activities of carboxymethyl cellulase, cellobiase, xylanase and pectinase decreased with the HC diet, but increased with 2MB supplementation. However, abundance of Prevotella ruminicola and Ruminobacter amylophilus as well as activities of α‐amylase and protease increased with the HC diet or 2MB supplementation. Total PD excretion also increased with the HC diet or 2MB supplementation. The results suggested that growth performance, ruminal fermentation, CP degradability and total PD excretion increased with increasing dietary concentrate level from 40% to 60% or 2MB supplementation. The observed diet × 2MB interaction indicated that supplementation of 2MB was more efficacious for improving growth performance, ruminal fermentation and total PD excretion with promoted ruminal bacteria abundance and enzyme activity in the MC diet than in the HC diet.
Sex‐specific dietary specialization in a terrestrial apex predator, the leopard, revealed by stable isotope analysis
Authors: Voigt C. C. , Krofel M. , Menges V. , Wachter B. , Melzheimer J.
Published: April 2018

Apex predators in terrestrial ecosystems, such as leopards in the African savanna, feed on a wide variety of prey species, yet it is unknown whether individuals specialize on certain prey, and whether specialization changes with body traits. Here, we asked whether individual specialization of adult leopards (Panthera pardus) varies with sex, body mass, body length and age classes. We used the variation of stable carbon and nitrogen isotope ratios in 643 segments of whiskers as a temporal record of past diets and established isotopic dietary niches for 36 adult leopards (18 males, 18 females). Based on a variance analysis for stable carbon isotope ratios, we found that between‐individual variation was larger than within‐individual variation, indicating a high degree of overall specialization within the studied leopards. Female adult leopards exhibited larger isotopic dietary niche widths than male adult leopards. Isotopic niche width did not vary with body mass, body length or age. Our data suggest a difference in the level of specialization between the sexes, which might be explained by more opportunistic feeding of small‐sized female leopards, most likely connected with a higher use of small prey species of different isotopic composition. Inter‐sexual resource partitioning likely facilitates territory sharing between the sexes.
Prevalence and risk factors for chronic kidney disease in primary health care in the southern region of New Zealand
Authors: Lloyd Hywel , Li Grace , Tomlin Andrew , Tilyard Murray W , Walker Robert , Schollum John
Published: May 2018

Aim

While the prevalence of end stage kidney disease in New Zealand (NZ) is well defined, the prevalence of chronic kidney disease (CKD) in NZ is unknown. To estimate the prevalence of and risk factors for CKD in the southern region of New Zealand.

Methods

A retrospective electronic health record cohort study using data from the Southern Primary Care register covering 94% of the population. Patients, 20 years or older were identified and linked to laboratory results for serum creatinine and urinary albumin excretion. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2 (G3‐5) or the presence of albuminuria of greater than 3 mg/mmol (A2‐3). Diabetes was identified from a national virtual diabetes database. From this, we estimated the prevalence of CKD by age, gender, ethnicity, deprivation and the presence of diabetes mellitus.

Results

Of a total adult population of 211 980, 159 799 had a serum creatinine checked and 27 905 had an estimate of albuminuria. The estimated prevalence of CKD was 11.8%. 6.3% of total population had CKD stage G3a, 2.4% G3b, 0.8% G4, 0.2% G5, 1.8% A2 albuminuria and 0.3% A3 albuminuria. Increasing age, female sex, ethnic group, social deprivation and diabetes mellitus were associated with an increased risk of CKD. 11 351 patients had a diagnosis of diabetes mellitus and were almost universally tested (99.3%) for CKD. The presence of albuminuria was strongly correlated with ethnic group, male sex and living in a deprived area. The retrospective electronic health record study with associated selection and testing bias are potential limitations of the present study.

Conclusion

Chronic kidney disease prevalence in this region appears to be similar to other reported populations. The majority of those at risk for CKD were tested for reduced eGFR. The presence of albuminuria, an integral component of CKD diagnostic criteria, was under utilized in the non‐diabetic population.
Human papillomavirus prevalence in a Mid‐European oral squamous cell cancer population: A cohort study
Authors: Dalla Torre Daniel , Burtscher Doris , Soelder Elisabeth , Offermanns Vincent , Rasse Michael , Puelacher Wolfgang
Published: April 2018

Objectives

Human papillomavirus infection has been investigated intensively regarding oropharyngeal carcinoma. However, there is still lack of knowledge about the impact of oral HPV infections concerning oral squamous cell carcinoma. This study investigates the prevalence of oral HPV infection in such patients, identifying possible differences between HPV+ and HPV– patients.

Subjects and Methods

One hundred and six consequent patients were investigated. After completion of a study questionnaire regarding risk factors, a brush smear sample was taken in each subject to identify the individual oral HPV status (overall/low risk/high risk).

Results

About 35.8% of the patients were tested positive for HPV in the oral cavity (14% low risk, 28.3% high risk). Patients with oral HPV infection and high‐risk HPV infection were significantly younger (p < 0.001) and had a higher alcohol consumption (p = 0.0075 resp. p = 0.0022). A high number of different sexual partners were significantly correlated with any type of HPV infection. At last, patients with high‐risk oral HPV infection had experienced more tooth extractions during their lifetime.

Conclusion

Oral HPV infections may influence the course of disease of oral squamous cell carcinoma as HPV+ patients are about 10 years younger. It seems that high alcohol consumption facilitates high‐risk HPV infection. It may be presumed that both alcohol consumption and high‐risk oral HPV infection act synergistically, explaining earlier cancer onset.
Effect of Ovar‐DRA and Ovar‐DRB1 genotype in small ruminants with haemonchosis
Authors: Estrada‐Reyes Z. M. , Tsukahara Y. , Goetsch A. L. , Gipson T. A. , Sahlu T. , Puchala R. , Wang Z. , Hart S. P. , Mateescu R. G.
Published: May 2018

The effect of Ovar‐DRA and Ovar‐DRB1 genotypes on faecal egg count (FEC) was determined in sheep and goats infected with Haemonchus contortus. One hundred and forty‐three sheep from 3 different breeds (St. Croix, Katahdin and Dorper) and 150 goats from three different breeds (Spanish, Boer and Kiko) were used. Parasitological (FEC), haematological (packed cell volume) and immunological (IgA, IgG and IgM) parameters were measured. Sheep populations showed a higher FEC and humoural response than goat breeds. Genotypes were determined by high‐resolution melting assays and by conventional PCR. For Ovar‐DRA, sheep and goats carrying the AA genotype showed significant lower FEC than AG and GG genotypes. The additive effect was found to be 115.35 less eggs per gram of faeces for the A allele for goats. For Ovar‐DRB1, only in sheep, the GC genotype was associated with low FEC. The additive effect was 316.48 less eggs per gram of faeces for the G allele, and the dominance effect was 538.70 less eggs per gram of faeces. The results indicate that single nucleotide polymorphisms within Ovar‐DRA and Ovar‐DRB1 could be potential markers to be used in selection programmes for improving resistance to Haemonchus contortus infection.
Zinc deficiency tolerance in maize is associated with the up‐regulation of Zn transporter genes and antioxidant activities
Authors: Khatun M. A. , Hossain M. M. , Bari M. A. , Abdullahil K. M. , Parvez M. S. , Alam M. F. , Kabir A. H.
Published: May 2018

Zinc (Zn) is an essential micronutrient for the growth and development of plants. However, Zn deficiency is a common abiotic stress causing yield loss in crop plants. This study elucidates the mechanisms of Zn deficiency tolerance in maize through physiological and molecular techniques.

Maize lines tolerant (PAC) and sensitive (DAC) to Zn deficiency were examined physiologically and by atomic absorption spectrometry (AAS). Proteins, H2O2, SOD, POD, membrane permeability and gene expression (using real‐time PCR) of roots and shoots of both maize lines were assessed.

Zn deficiency had no significant effect on root parameters compared with control plants in PAC and DAC but showed a substantial reduction in shoot parameters in DAC. AAS showed a significant decrease in Zn concentrations in both roots and shoots of DAC but not PAC under Zn deficiency, implying that Zn deficiency tolerance mechanisms exist in PAC. Consistently, total protein and membrane permeability were significantly reduced in DAC but not PAC in both roots and shoots under Zn deficiency in comparison with Zn‐sufficient plants. Real‐time PCR showed that expression of ZmZIP1, ZmZIP4 and ZmIRT1 transporter genes significantly increased in roots of PAC, but not in DAC due to Zn deficiency compared with controls. The H2O2 concentration dramatically increased in roots of DAC but not PAC. Moreover, tolerant PAC showed a significant increase in POD and SOD activity due to Zn deficiency, suggesting that POD‐ and SOD‐mediated antioxidant defence might provide tolerance, at least in part, under Zn deficiency in PAC.

This study provides an essential background for improving Zn biofortification of maize.
Tripartite motif‐containing proteins precisely and positively affect host antiviral immune response
Authors: Wei Y. , Chen S. , Wang M. , Cheng A.
Published: April 2018

The tripartite motif‐containing proteins (TRIMs) comprise a large family of proteins with over 70 members in humans. Recent studies have shown that TRIMs play unexpected roles in the antiviral immune responses to infections by HIV, MLV, EMCV, AIV and other viruses. There are two mechanisms used by TRIMs in the inhibition of virus infections: (1) TRIMs target the produced viruses for ubiquitination, which induces proteasome‐dependent degradation, or they interact with host proteins to inhibit viral infection in various periods of the viral life cycle. (2) TRIMs activate innate immune signalling pathways, such as RLR and TLR, which induce IFN production. In this study, we will review recent studies regarding the means by which TRIMs function as inhibitors in viral infection through the mechanisms described above.
Germline V repertoires: Origin, maintenance, diversification
Authors: Steele E. J. , Lindley R. A.
Published: April 2018

In our view, Melvin Cohn (Scand J Immunol. 2018;87:e12640) has set out the logical guidelines towards a resolution of the very real enigma of the selectability of vertebrate germline Ig V repertoires under the current evolutionary paradigm…” A somatically derived repertoire scrambles this (germline VL + VH) substrate so that its specificities are lost, making it un‐selectable in the germline. Consequently, evolution faced an incompatibility.” It is argued here in Reply that a reverse transcriptase‐based soma‐to‐germline process (S‐>G) targeting germline V segment arrays goes some considerable way to resolving fundamental contradictions on the origin, maintenance and then real‐time adaptive diversification of these limited sets of V segments encoded within various V repertoire arrays.