bluuebunny/crossref_metadata_2025 huggingface dataset:
GM-CSF and IL-4 are not involved in IVIG-mediated amelioration of ITP in mice: a role for IL-11 cannot be ruled out
Authors: Lewis B J B , Leontyev D , Neschadim A , Blacquiere M , Branch D R
Published: April 2018

Previously, we have reported that interleukin (IL)-4, granulocyte–macrophage colony-stimulating factor (GM-CSF), and IL-11, but not IL-33, are up-regulated in two strains of mice with immune thrombocytopenia (ITP) that are responsive to intravenous immunoglobulin (IVIg) treatment. Previously, IL-4 was ruled out in the mechanism of IVIg; however, other publications have suggested this cytokine as a major player in the mechanism of IVIg action. Thus, we sought to further investigate a role for IL-4 and, in addition, GM-CSF and IL-11 in the mechanism of action of IVIg using a murine model of ITP. A passive platelet antibody model was used to generate ITP in IL-4 receptor knock-out (IL-4R–/–), IL-11 receptor knock-out (IL-11Rα–/–) and GM-CSF knock-out (Csf2–/–) mice. We also used a neutralizing antibody to IL-11 and recombinant human IL-11 (rhIL-11) in addition to depleting basophils in vivo to study the effect of IVIg to ameliorate ITP. Our results showed that basophils, IL-4 and GM-CSF were unimportant in both ITP induction and its amelioration by IVIg. The role of IL-11 in these processes was less clear. Even though IL-11Rα–/– mice with ITP responded to IVIg similarly to wild-type (WT) mice, treatment of ITP WT mice with rhIL-11 instead of IVIg showed an increase in platelet numbers and WT mice administered anti-IL-11 showed a significant reduction in the ability of IVIg to ameliorate the ITP. Our findings indicate that neither IL-4, basophils or GM-CSF have roles in IVIg amelioration of ITP; however, a role for IL-11 requires further study.
Administration of activated lymphocyte-derived DNA accelerates and aggravates lupus nephritis in B6/lpr mice: a new approach to modify a lupus murine model
Authors: Zhu Y , Yue Y , Xiong S
Published: April 2018

B6/lpr mouse strain is a well-known systemic lupus erythematosus murine model characterized by uncontrolled lymphoproliferation and autoantibody production. However, it displays a delayed and mild development of lupus nephritis (LN), which is not conducive to the research of the pathogenesis and therapeutic strategies of this condition. Our previous study demonstrated that activated lymphocyte-derived DNA (ALD-DNA) could induce high urine protein levels and severe glomerulonephritis (GN) in BALB/c mice. In the present study, we tried to remedy delayed urine protein production and mild GN in B6/lpr mice via ALD-DNA immunization. We found that urine protein levels were enhanced significantly in B6/lpr mice 4 weeks after ALD-DNA immunization compared with those in unactivated lymphocyte-derived (UnALD)-DNA- and phosphate-buffered saline (PBS)-treated controls. Moreover, more serious GN and glomerular immune complex were observed in ALD-DNA-immunized B6/lpr mice. We further explored the mechanism, and found that ALD-DNA immunization promoted T helper type 17 (Th17) cell enrichment remarkably, which enhanced the proportion of autoantibody-secreting plasma cells and promoted the production of anti-dsDNA autoantibodies, leading to accelerated and aggravated LN. Our data demonstrated that ALD-DNA immunization could remedy delayed urine protein production and mild GN in B6/lpr mouse, which makes it more suitable for studies on the pathogenesis of and therapeutic strategies against LN.
The neuroprotective and antidepressant‐like effects of Hcyb1, a novel selective PDE2 inhibitor
Authors: Liu Li , Zheng Jing , Huang Xian‐Feng , Zhu Xia , Ding Shu‐Ming , Ke Heng‐Ming , O'Donnell James M. , Zhang Han‐Ting , Song Guo‐Qiang , Xu Ying
Published: April 2018

Aims

Depression is currently the most common mood disorder. Regulation of intracellular cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) signaling by phosphodiesterase (PDE) inhibition has been paid much attention for treatment of depression. This study aimed to investigate the neuroprotective effects of Hcyb1, a novel PDE2 inhibitor, in HT‐22 cells and antidepressant‐like effects in mouse models of depression.

Methods

Hcyb1 was synthesized and its selectivity upon PDE2 was tested. Moreover, HT‐22 hippocampal cells were used to determine the effects of Hcyb1 on cell viability, cyclic nucleotide levels, and the downstream molecules related to cAMP/cGMP signaling by neurochemical, enzyme‐linked immunosorbent, and immunoblot assays in vitro. The antidepressant‐like effects of Hcyb1 were also determined in the forced swimming and tail suspension tests in mice.

Results

Hcyb1 had a highly selective inhibition of PDE2A (IC50 = 0.57 ± 0.03 μmol/L) and over 250‐fold selectivity against other recombinant PDE family members. Hcyb1 at concentrations of 10−10 and 10−9 mol/L significantly increased cell viability after treatment for 24 hours. At concentrations of 10−9~10−7 mol/L, Hcyb1 also increased cGMP levels by 1.7~2.3 folds after 10‐minute treatment. Furthermore, Hcyb1 at the concentrations of 10−9 mol/L increased both cGMP and cAMP levels 24 hours after treatment. The levels of phosphorylation of CREB and BDNF were also increased by Hcyb1 treatment in HT‐22 cells for 24 hours. Finally, in the in vivo tests, Hcyb1 (0.5, 1, and 2 mg/kg, i.g.) decreased the immobility time in both forced swimming and tail suspension tests, without altering locomotor activity.

Conclusion

These results suggest that the novel PDE2 inhibitor Hcyb1 produced neuroprotective and antidepressant‐like effects most likely mediated by cAMP/cGMP‐CREB‐BDNF signaling.
Hospital readmissions in diabetic kidney transplant recipients with peripheral vascular disease
Authors: Lubetzky Michelle , Kamal Layla , Ajaimy Maria , Akalin Enver , Kayler Liise
Published: April 2018

Background

The benefits of kidney transplantation in diabetic patients with peripheral vascular disease (PVD) are unclear. While patients may have improved survival compared to dialysis, the burden of care after transplant has not been assessed.

Methods

We performed a retrospective review of adult diabetic kidney‐only transplant recipients with and without PVD transplanted from January 2012 until June 30, 2015.

Results

Of 203 diabetic kidney transplant recipients, 56 (27.6%) had PVD and 147 (72.4%) had no PVD. At a median of 3.14 years follow‐up, there were no significant differences in 30‐, 90‐, or 1‐year readmission rates. At 1 year after transplant, PVD patients were significantly more likely to have a greater sum of unplanned inpatient days (44.6% vs 27.9% with ≥10 inpatient days, P = .03) and at least 1 reoperation (28.6% vs. 8.7%, P < .01). At 1 year post‐transplant, there were similar rates of graft‐related reoperations; however, patients with PVD had significantly increased rates of non‐graft‐related operations of which 31.2% were PVD‐related.

Conclusions

Diabetic patients with PVD utilize more resources after kidney transplant, spending more time in the hospital and undergoing more post‐transplant operations. The causes of readmission are predominantly related to progression of PVD rather than allograft complications.
Age‐related trends in cardiometabolic disease among adults with cerebral palsy
Authors: Peterson Mark D , Kamdar Neil , Hurvitz Edward A
Published: April 2018

Aim

To examine the longitudinal trends of cardiometabolic diseases in a large sample of adults with cerebral palsy (CP).

Method

The Optum Clinformatics Data Mart is a de‐identified nationwide claims database of beneficiaries from a single private payer. Beneficiaries were included if they had an International Classification of Diseases, Ninth Revision, Clinical Modification code for a diagnosis of CP. Adults with at least 3 years of continuous enrollment on a single plan between 2002 and 2009 were included in the final analyses (n=2659). We examined the longitudinal trends of incident diabetes mellitus, hypercholesterolemia, hypertension, cardiac dysrhythmias, and atherosclerosis, stratified by age categories: 18 to 39 years, 40 to 59 years, and 60 years and over. Kaplan–Meier product‐limit survival curves were compared across age categories for each of the cardiometabolic outcomes, and a Cox proportional hazards regression was run to determine adjusted hazard ratios.

Results

The cumulative incidence of each of the cardiometabolic diseases ranged from 6.0% for atherosclerosis to 34.4% for hypercholesterolemia at 3 years and over. Risk‐adjusted Cox proportional hazard models revealed that age was a robust predictor of survival for each outcome, with higher hazard ratio ranges in middle age (hazard ratio 1.41–2.72) and older adults (hazard ratio 2.20–5.93) compared with young adults.

Interpretation

Adults with CP have high rates of cardiometabolic diseases; and disease‐free survival shortens significantly with higher ages.

What this paper adds

Adults with cerebral palsy have high rates of cardiometabolic diseases.

Disease‐free survival of all cardiometabolic diseases shortens significantly with higher ages.

The highest rates were for hypercholesterolemia and hypertension.
Topical retinol attenuates stress‐induced ageing signs in human skin ex vivo, throughEGFR activation viaEGF, but notERK andAP‐1 activation
Authors: Romana‐Souza Bruna , Silva‐Xavier Welker , Monte‐Alto‐Costa Andréa
Published: April 2018

Stress‐induced oxidative damage and the inflammatory response lead to degradation of collagen and elastic fibres and wrinkle formation. Topical retinol (or vitamin A) can be a strategy to attenuate the effects of stress in skin as it promotes collagen and elastic fibre production and reduces protease synthesis. This study investigated the effect of topical retinol in stressed human skin using in vitro and ex vivo models. Human skin explants were treated with high levels of epinephrine (as observed in stressed patients) and topically with retinol for 13 days. Human dermal fibroblasts were treated with conditioned medium of ex vivo retinol‐treated and non‐stressed (without epinephrine) human skin for 24 hours. In ex vivo human skin, retinol reversed the epinephrine‐induced reduction in epidermal proliferation and differentiation, normalizing epidermal thickness. Retinol also inhibited the epinephrine‐induced reduction in elastic fibre deposition and organization, restoring dermal thickness. In addition, retinol reversed the epinephrine‐induced increase in c‐JUN protein expression, but it did not alter extracellular signal‐regulated kinase 1/2 (ERK) phosphorylation in ex vivo human skin. Conditioned medium of ex vivo retinol‐treated and non‐stressed human skin presented an increased protein expression of epidermal growth factor (EGF). In human dermal fibroblasts, conditioned medium of ex vivo retinol‐treated and non‐stressed human skin increased protein and gene expression of fibrillin‐1 and protein expression of EGF receptor (EGFR). In conclusion, topical retinol attenuates stress‐induced skin ageing signs in human skin ex vivo, probably through EGFR activation via EGF, but not by the stress‐activated ERK 1/2 and c‐JUN pathways.
The convergence theory for vitiligo: A reappraisal
Authors: Kundu Roopal V. , Mhlaba Julia M. , Rangel Stephanie M. , Le Poole I. Caroline
Published: April 2018

Vitiligo is characterized by progressive loss of skin pigmentation. The search for aetiologic factors has led to the biochemical, the neurologic and the autoimmune theory. The convergence theory was then proposed several years ago to incorporate existing theories of vitiligo development into a single overview of vitiligo aetiology. The viewpoint that vitiligo is not caused only by predisposing mutations, or only by melanocytes responding to chemical/radiation exposure, or only by hyperreactive T cells, but rather results from a combination of aetiologic factors that impact melanocyte viability, has certainly stood the test of time. New findings have since informed the description of progressive depigmentation. Understanding the relative importance of such aetiologic factors combined with a careful selection of the most targetable pathways will continue to drive the next phase in vitiligo research: the development of effective therapeutics. In that arena, it is likewise important to acknowledge that pathways affected in some patients may not be altered in others. Taken together, the convergence theory continues to provide a comprehensive viewpoint of vitiligo aetiology. The theory serves to intertwine aetiologic pathways and will help to define pathways amenable to disease intervention in individual patients.
Contribution of sea ice microbial production to Antarctic benthic communities is driven by sea ice dynamics and composition of functional guilds
Authors: Wing Stephen R. , Leichter James J. , Wing Lucy C. , Stokes Dale , Genovese Sal J. , McMullin Rebecca M. , Shatova Olya A.
Published: April 2018

Organic matter produced by the sea ice microbial community (SIMCo) is an important link between sea ice dynamics and secondary production in near‐shore food webs of Antarctica. Sea ice conditions in McMurdo Sound were quantified from time series of MODIS satellite images for Sept. 1 through Feb. 28 of 2007–2015. A predictable sea ice persistence gradient along the length of the Sound and evidence for a distinct change in sea ice dynamics in 2011 were observed. We used stable isotope analysis (δ13C and δ15N) of SIMCo, suspended particulate organic matter (SPOM) and shallow water (10–20 m) macroinvertebrates to reveal patterns in trophic structure of, and incorporation of organic matter from SIMCo into, benthic communities at eight sites distributed along the sea ice persistence gradient. Mass‐balance analysis revealed distinct trophic architecture among communities and large fluxes of SIMCo into the near‐shore food web, with the estimates ranging from 2 to 84% of organic matter derived from SIMCo for individual species. Analysis of patterns in density, and biomass of macroinvertebrate communities among sites allowed us to model net incorporation of organic matter from SIMCo, in terms of biomass per unit area (g/m2), into benthic communities. Here, organic matter derived from SIMCo supported 39 to 71 per cent of total biomass. Furthermore, for six species, we observed declines in contribution of SIMCo between years with persistent sea ice (2008–2009) and years with extensive sea ice breakout (2012–2015). Our data demonstrate the vital role of SIMCo in ecosystem function in Antarctica and strong linkages between sea ice dynamics and near‐shore secondary productivity. These results have important implications for our understanding of how benthic communities will respond to changes in sea ice dynamics associated with climate change and highlight the important role of shallow water macroinvertebrate communities as sentinels of change for the Antarctic marine ecosystem.
Multi‐Objective Optimization of Managed Aquifer Recharge
Authors: Fatkhutdinov Aybulat , Stefan Catalin
Published: April 2018

This study demonstrates the utilization of a multi‐objective hybrid global/local optimization algorithm for solving managed aquifer recharge (MAR) design problems, in which the decision variables included spatial arrangement of water injection and abstraction wells and time‐variant rates of pumping and injection. The objective of the optimization was to maximize the efficiency of the MAR scheme, which includes both quantitative and qualitative aspects. The case study used to demonstrate the capabilities of the proposed approach is based on a published report on designing a real MAR site with defined aquifer properties, chemical groundwater characteristics as well as quality and volumes of injected water. The demonstration problems include steady state and transient scenarios. The steady state scenario demonstrates optimization of spatial arrangement of multiple injection and recovery wells, whereas the transient scenario was developed with the purpose of finding optimal regimes of water injection and recovery at a single location. Both problems were defined as multi‐objective problems. The scenarios were simulated by applying coupled numerical groundwater flow and solute transport models: MODFLOW‐2005 and MT3D‐USGS. The applied optimization method was a combination of global (the non‐dominated sorting genetic algorithm [NSGA‐2]) and local (the Nelder‐Mead downhill simplex search algorithms). The analysis of the resulting Pareto optimal solutions led to the discovery of valuable patterns and dependencies between the decision variables, model properties, and problem objectives. Additionally, the performance of the traditional global and the hybrid optimization schemes were compared.
Mental accounting and behavioural hierarchy: Understanding consumer budgeting behaviour
Authors: Xiao Jing Jian , O'Neill Barbara
Published: April 2018

Budgeting is an important step in consumer finance. Budgeting behaviour is considered a desirable financial behaviour to indicate consumer financial capability. However, systematic research on budgeting behaviour with a large scale national sample is limited. The purpose of this study was to address this research gap and examine characteristics of budgeting behaviour from the perspective of a behavioural hierarchy, which is related to mental accounting. The assumption holds that consumer financial behaviours may be performed in a hierarchical manner along with an increase in economic resources. Using data from the 2015 National Financial Capability Study, evidence suggests that budgeting behaviour is at the lower end of the behavioural hierarchy. This finding has implications for consumer financial professionals.
Subungual exostosis and subungual osteochondromas: a description of 25 cases
Authors: Göktay Fatih , Atış Güldehan , Güneş Pembegül , Macit Betül , Çelik Nil Su , Gürdal Kösem Esra
Published: April 2018

Background

Subungual exostosis (SE) and subungual osteochondroma (SO) are an uncommon, benign tumor of the distal phalanx. The purpose of this retrospective study was to evaluate clinical, demographical, and radiological features; treatment modalities; and follow‐up results in SE and SO cases.

Methods

Twenty‐five cases were confirmed histopathologically as SE or SO. At the time of admission, clinical data were obtained on the age and sex of the patient, duration of symptoms, presence of pain, previous diagnoses and treatments, concomitant systemic diseases, family history, lesional localization, clinical and radiological features of the lesion, surgical treatment methods, and duration of follow‐up.

Results

There were 14 patients in the SE group and 11 patients in the SO group. There was no statistically significant difference in gender, age, duration of symptoms, or pain between the two groups. Regarding the locations of the lesions, two (14.28%) were on the hands, 12 (85.72%) lesions were on the toes, 11 (91.67%) of which were on the great toe, and one (8.33%) was on the small toe of the left foot in the SE group. All the osteochondroma lesions were located on the toes. In five (45%) cases, the lesion was on the great toe. Two patients had residual lesions in the SE group. Recurrence occurred in one case in the SO group.

Conclusions

Clinically and histopathologically, SE and SO appear to be two different entities. When diagnosed correctly and treated appropriately, the lesions have good functional and cosmetic results, as well as a very low recurrence rate.
Clinical and molecular characterization and response to acitretin in three families with Sjögren‐Larsson syndrome
Authors: Vural Seçil , Vural Atay , Akçimen Fulya , Bağci Işın S. , Tunca Ceren , Gündoğdu Eken Asli , Ruzicka Thomas , Başak A. Nazli
Published: April 2018

Introduction

Sjögren‐Larsson syndrome (SLS) is a rare congenital disorder characterized by the triad of ichthyosis, spasticity, and mental retardation. Patients are usually referred to dermatology clinics during infancy. As paraplegia becomes the most debilitating symptom of the disease within a few years, ichthyosis, although a major burden for the patient, takes a back seat. Optimum treatment of ichthyosis in these children and the effect of treatment on different aspects such as severity of the ichthyosis, pruritus, or quality of life of the patients’ and their caregivers is not well established.

Materials and Methods

Genetic background of eight patients from three families diagnosed clinically with SLS was determined with whole‐exome and Sanger sequencing. Clinical phenotypes, laboratory findings, magnetic resonance imaging (MRI), and treatment of the ichthyosis with acitretin were assessed.

Results

All patients had the classical triad of Sjögren‐Larsson syndrome. Genetic analysis revealed that one patient had a novel c.799‐1 (+/+) homozygous splicing mutation in the ALDH3A2 gene. Other patients had the c.683G>A p.R228H (NM_000382.2) mutation in the same gene. Other manifestations included skeletal anomalies, enamel hypoplasia, bilateral T2‐hyperintensities in white matter, and moderate–severe pruritus. Acitretin treatment in a maintenance dose of 0.25 mg/kg/day decreased the severity of ichthyosis in all children. It increased quality of life significantly in all of the children and their caregivers.

Conclusion

We conclude that ichthyosis can be treated effectively with low‐dose acitretin in children with Sjögren‐Larsson syndrome, and this treatment is associated with a significant improvement in the quality of life.
Decreased protein C function predicts mortality in patients with cirrhosis
Authors: Patil A. G. , Bihari C. , Shewade H. D. , Nigam N. , Sarin S. K.
Published: April 2018

Introduction

Protein C (PrC), a physiological anticoagulant, regulates inflammation and cell death and has known predictive/therapeutic roles in sepsis. Accumulating evidences suggest plasma hypercoagulability results in progression of fibrosis and formation of microclots causing end‐organ dysfunction. We investigated a possible association between natural anticoagulants—PrC, protein S (PrS) and antithrombin III (AT)—and clinical outcomes in cirrhotics.

Methods

Functional PrC, PrS and AT were analysed in 515 cirrhotic patients and compared with 229 noncirrhotics. Among those with cirrhosis, we conducted multivariable predictive model on 3‐month survival to assess the prognostic ability of anticoagulants.

Results

Protein C (P < .001), PrS (P < .001) and AT (P < .001) levels were lower in cirrhotics compared with noncirrhotics. In addition, patients with Child‐Pugh (CP)‐C had significantly lower (P < .05) functional PrC, PrS and AT levels than CP‐B, CP‐A and noncirrhotic patients. Low PrC function correlated with markers of liver dysfunction and inflammation: INR(r = −.72, P < .001), bilirubin (r = −.620, P < .001), albumin (r = .539, P < .001), creatinine (r = −.417, P < .001), ferritin (r = −.68, P = .035), procalcitonin (r = −.79, P = .01), raised ESR (r = .56, P < .001) and liver fibrosis (r = −.840, P < .001). Patients who died (n = 160) had significantly lower median PrC function (23.8%, 16.3‐33.0]) compared with those who remained alive (74.9%, [59.7‐92.5]); P < .001. In a multivariable predictive model using PrC, and MELD score, we found a significant impact of low PrC levels on survival (P < .001, IRR = 0.97, 95% CI = 0.96‐0.98). Receiver operating characteristic (ROC) curve analysis revealed that functional PrC levels <52% were associated with increased mortality (P < .001).

Conclusion

Low functional protein C level correlated with markers of liver dysfunction, inflammation and sepsis and independently predicted mortality at 3 months in cirrhotics, especially if functional levels were <52%.
Establishment of new complete blood count reference values for healthy Thai adults
Authors: Wongkrajang P. , Chinswangwatanakul W. , Mokkhamakkun C. , Chuangsuwanich N. , Wesarachkitti B. , Thaowto B. , Laiwejpithaya S. , Komkhum O.
Published: April 2018

Introduction

Laboratory reference ranges are essential for diagnostic orientation and treatment decision. As complete blood count parameters are influenced by various factors, including gender, geographic origin, and ethnic origin, it is important to establish specific hematologic reference values for specific populations.

Methods

This study was conducted at the Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Blood samples were taken from healthy adults aged 18‐60 years that attended a health check‐up program at our hospital during February 2015 to July 2015. Hematologic and routine chemistry analysis were performed. Participants were determined to be healthy based on medical history and routine medical examinations. Serum vitamin B12, folate, ferritin, and hemoglobin typing were also analyzed to exclude the possible presence of anemia.

Results

A statistically significant difference was observed between males and females for Hb level, hematocrit level, red blood cell count, mean corpuscular hemoglobin concentration, percentage neutrophils, monocytes and eosinophils, and absolute neutrophil, lymphocyte, basophil, and platelet counts. Accordingly, gender‐specific reference intervals were established for all complete blood count parameters in healthy Thai adult population.

Conclusions

The reference value ranges established in this study reflect significant differences between genders. It is possible that these reference ranges may be generalizable to adults living in Thailand. The findings of this study emphasize the importance of establishing specific hematologic reference values for specific populations.
Development of GMP‐1 a molecular chaperone network modulator protecting mitochondrial function and its assessment in fly and mice models of Alzheimer's disease
Authors: Pavlov Pavel F. , Hutter‐Paier Birgit , Havas Daniel , Windisch Manfred , Winblad Bengt
Published: April 2018

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and may play an important role in the pathogenesis of disease. It has been shown that amyloid beta peptide (Aβ) and amyloid precursor protein (APP) interact with mitochondria contributing to the mitochondrial dysfunction in AD. Prevention of abnormal protein targeting to mitochondria can protect normal mitochondrial function, increase neuronal survival and at the end, ameliorate symptoms of AD and other neurodegenerative disorders. First steps of mitochondrial protein import are coordinated by molecular chaperones Hsp70 and Hsp90 that bind to the newly synthesized mitochondria‐destined proteins and deliver them to the protein import receptors on the surface of organelle. Here, we have described the development of a novel compound named GMP‐1 that disrupts interactions between Hsp70/Hsp90 molecular chaperones and protein import receptor Tom70. GMP‐1 treatment of SH‐SY5Y cells results in decrease in mitochondria‐associated APP and protects SH‐SY5Y cells from toxic effect of Aβ1‐42 exposure. Experiments in drosophila and mice models of AD demonstrated neuroprotective effect of GMP‐1 treatment, improvement in memory and behaviour tests as well as restoration of mitochondrial function.
Comments to: skin findings of twenty‐first‐century movie response
Authors: Ishida Y. , Otsuka A. , Kabashima K.
Published: April 2018

Linked article: This article is commented on by V. Reese et al., pp. e424–e425 in this issue. To view this article visit https://doi.org/10.1111/jdv.15015
Tretinoin (0.05% cream vs. 5% peel) for photoaging and field cancerization of the forearms: randomized, evaluator‐blinded, clinical trial
Authors: Sumita J.M. , Miot H.A. , Soares J.L.M. , Raminelli A.C.P. , Pereira S.M. , Ogawa M.M. , Picosse F.R. , Guadanhim L.R.S. , Enokihara M.M.S.S. , Leonardi G.R. , Bagatin E.
Published: April 2018

Background

Topical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness.

Objective

To compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms.

Methods

Clinical trial with therapeutic intervention, prospective, randomized (computer‐generated randomization list), parallel, comparative (intrasubject) and evaluator‐blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high‐frequency ultrasound, histology (haematoxylin–eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl‐2, Ki67 and collagen I) were assessed.

Results

One participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens.

Conclusion

Tretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.
Alitretinoin can be a good treatment option for idiopathic recalcitrant trachyonychia in adults: an open‐label study
Authors: Shin K. , Kim T.‐W. , Park S.‐M. , Lee H.‐J. , Jin H. , You H.‐S. , Shim W.‐H. , Kim G.‐W. , Kim H.‐S. , Ko H.‐C. , Kim B.‐S. , Kim M.‐B.
Published: April 2018

Background

Trachyonychia can be refractory to conventional treatments including topical, intralesional or systemic corticosteroids, as well as cyclosporine and retinoids. Therefore, new treatment options are needed for recalcitrant trachyonychia.

Objective

To evaluate the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia.

Methods

A total of 21 adult patients with 210 nails affected by idiopathic recalcitrant trachyonychia were evaluated in this open‐label prospective study. All patients took 30 mg of alitretinoin daily for at least 3 months. Clinical outcomes were assessed using the Physician Global Assessment (PGA) scale proposed by Park et al. (degree of roughness: 0, clear; 1, mild; 2, moderate; 3, marked; 4, severe) at baseline and 1, 3 and 6 months after treatment.

Results

After 1, 3 and 6 months of treatment, 74.3% (123/210), 98.1% (206/210) and 99.2% (119/120) of nails showed clinical improvement, respectively; 0% (0/210), 22.9% (48/210) and 69.2% (83/120) were completely free from nail abnormalities. The mean PGA score at baseline was 3.4, decreasing significantly to 2.7, 1.3 and 0.7 at 1, 3 and 6 months following treatment, respectively.

Limitations

A small number of participants and lack of a control group were limitations.

Conclusions

For the first time, this study evaluated the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia in adults. The results suggest that oral alitretinoin can be a good treatment option for adult patients with recalcitrant trachyonychia.
Katharsis of the skin: peeling applications and agents of chemical peelings in Greek medical textbooks of Graeco‐Roman antiquity
Authors: Ursin F. , Steger F. , Borelli C.
Published: April 2018

Background

Recipes for peelings date back to medical texts of old Egypt. The oldest medical papyri contain recipes for ‘improving beauty of the skin’ and ‘removing wrinkles’ by use of agents such as salt and soda. The Egyptian Queen Cleopatra (69–30 BC) is said to have taken bathes in donkey's milk to improve the beauty of her skin. However, little is known about other agents and peeling applications in later Greek medical textbooks.

Objective

We will discover new agents and describe ancient peeling applications. First, we will have to identify ancient Greek medical terms for the modern terms ‘peeling’ and ‘chemical peeling’. Second, on the basis of the identified terms, we will perform a systematic full‐text search for agents in original sources. Third, we will categorize the results into three peeling applications: (i) cleansing, (ii) aesthetical improvement of the skin and (iii) therapy of dermatological diseases.

Methods

We performed a full systematic keyword search with the identified Greek terms in databases of ancient Greek texts. Our keywords for peeling and chemical peeling are ‘smēxis’ and ‘trīpsis’. Our keywords for agents of peeling and chemical peeling are ‘smégmata’, ‘rhýmmata’, ‘kathartiká’ and ‘trímmata’.

Results

Diocles (4th century BC) was the first one who mentioned ‘smēxis’ and ‘trīpsis’ as parts of daily cleansing routine. Criton (2nd century AD) wrote about peeling applications, but any reference to the agents is lost. Antyllus (2nd century AD) composed three lists of peeling applications including their agents.

Conclusion

Greek medical textbooks of Graeco‐Roman antiquity report several peeling applications such as cleansing, brightening, darkening, softening and aesthetical improvement of the skin by use of peeling and chemical peeling, as well as therapy of dermatological diseases. There are 27 ancient agents for what is contemporarily called peeling and chemical peeling. We discovered more specific agents than hitherto known to research.
Comparison of PCR‐based methods for the diagnosis of cutaneous leishmaniasis in two different epidemiological scenarios: Spain and Morocco
Authors: Merino‐Espinosa G. , Rodríguez‐Granger J. , Morillas‐Márquez F. , Tercedor J. , Corpas‐López V. , Chiheb S. , Alcalde‐Alonso M. , Azaña‐Defez J.M. , Riyad M. , Díaz‐Sáez V. , Martín‐Sánchez J.
Published: April 2018

Background

Cutaneous leishmaniasis (CL) is a disfiguring and stigmatising disease occurring in more than 70 countries across the world including Spain and Morocco. The use of sensitive tests that can differentiate Leishmania species is advised.

Objective

To evaluate the influence of the epidemiological scenario on the reliability of the PCR techniques and contribute to the selection of the most efficient one for CL diagnosis.

Methods

The sensitivities of parasitological methods and four PCRs were compared in cutaneous samples from 77 patients from Spanish (PSH) and Moroccan hospitals (PMH). Exudates and fresh or paraffin‐embedded tissue biopsies were used.

Results

None of the PCRs used in this study allowed the diagnosis of all CL cases, showing also some drawbacks. Lmj4/Uni21‐PCR displayed the best sensitivity with PMH, but it did not provide positive results in PSH with CL confirmed by other PCRs. Conversely, JW13/JW14‐PCR and L. infantum‐PCR‐ELISA displayed good sensitivities with PSH that were not achieved with PMH. Nested‐ITS‐1‐PCR did not show enough sensitivity with paraffin‐embedded tissue biopsies. False‐negative results were obtained in 19% of PSH due to unspecific hybridizations of ITS‐1 primers with human chromosome1.

Conclusions

PCR should be routinely used in patients with cutaneous lesions compatible with CL and furthermore, the combination of two PCR techniques is advisable. The selection of these PCRs will be influenced by the epidemiological scenario: In areas where L. infantum is endemic, the use of the PCR‐ELISA joint with JW13/JW14‐PCR seems an appropriate choice, whereas in areas such as Morocco, Lmj4/Uni21 and ITS‐1 provide satisfactory results.
Leaf stage‐associated resistance is correlated with phytohormones in a pathosystem‐dependent manner
Authors: Xu You‐Ping , Lv Lin‐Hui , Xu Ya‐Jing , Yang Juan , Cao Jia‐Yi , Cai Xin‐Zhong
Published: April 2018

It has been reported in several pathosystems that disease resistance can vary in leaves at different stages. However, how general this leaf stage‐associated resistance is, and the molecular mechanism(s) underlying it, remain largely unknown. Here, we investigated the effect of leaf stage on basal resistance, effector‐triggered immunity (ETI) and nonhost resistance, using eight pathosystems involving the hosts Arabidopsis thaliana, Nicotiana tabacum, and N. benthamiana and the pathogens Sclerotinia sclerotiorum, Pseudomonas syringae pv. tabaci, P. syringae pv. tomato DC3000, and Xanthomonas oryzae pv. oryzae (Xoo). We show evidence that leaf stage‐associated resistance exists ubiquitously in plants, but with varying intensity at different stages in diverse pathosystems. Microarray expression profiling assays demonstrated that hundreds of genes involved in defense responses, phytohormone biosynthesis and signaling, and calcium signaling, were differentially expressed between leaves at different stages. The Arabidopsis mutants sid1, sid2‐3, ein2, jar1‐1, aba1 and aao3 lost leaf stage‐associated resistance to S. sclerotiorum, and the mutants aba1 and sid2‐3 were affected in leaf stage‐associated RPS2/AvrRpt2+‐conferred ETI, whereas only the mutant sid2‐3 influenced leaf stage‐associated nonhost resistance to Xoo. Our results reveal that the phytohormones salicylic acid, ethylene, jasmonic acid and abscisic acid likely play an essential, but pathosystem‐dependent, role in leaf stage‐associated resistance.
Calcium/calmodulin‐dependent kinase II and memory destabilization: a new role in memory maintenance
Authors: Vigil Fabio Antonio , Giese Karl Peter
Published: April 2018

In this review, we discuss the poorly explored role of calcium/calmodulin‐dependent protein kinase II (CaMKII) in memory maintenance, and its influence on memory destabilization. After a brief review on CaMKII and memory destabilization, we present critical pieces of evidence suggesting that CaMKII activity increases retrieval‐induced memory destabilization. We then proceed to propose two potential molecular pathways to explain the association between CaMKII activation and increased memory destabilization. This review will pinpoint gaps in our knowledge and discuss some ‘controversial’ observations, establishing the basis for new experiments on the role of CaMKII in memory reconsolidation. The role of CaMKII in memory destabilization is of great clinical relevance. Still, because of the lack of scientific literature on the subject, more basic science research is necessary to pursue this pathway as a clinical tool.

image
The role of corticostriatal–hypothalamic neural circuits in feeding behaviour: implications for obesity
Authors: Clarke Rachel E. , Verdejo‐Garcia Antonio , Andrews Zane B.
Published: April 2018

Emerging evidence from human imaging studies suggests that obese individuals have altered connectivity between the hypothalamus, the key brain region controlling energy homeostasis, and cortical regions involved in decision‐making and reward processing. Historically, animal studies have demonstrated that the lateral hypothalamus is the key hypothalamic region involved in feeding and reward. The lateral hypothalamus is a heterogeneous structure comprised of several distinct types of neurons which are scattered throughout. In addition, the lateral hypothalamus receives inputs from a number of cortical brain regions suggesting that it is uniquely positioned to be a key integrator of cortical information and metabolic feedback. In this review, we summarize how human brain imaging can inform detailed animal studies to investigate neural pathways connecting cortical regions and the hypothalamus. Here, we discuss key cortical brain regions that are reciprocally connected to the lateral hypothalamus and are implicated in decision‐making processes surrounding food.

image
Are reflective models appropriate for very short scales? Proofs of concept of formative models using the Ten‐Item Personality Inventory
Authors: Myszkowski Nils , Storme Martin , Tavani Jean‐Louis
Published: April 2018

Objective

Because of their length and objective of broad content coverage, very short scales can show limited internal consistency and structural validity. We argue that it is because their objectives may be better aligned with formative investigations than with reflective measurement methods that capitalize on content overlap. As proofs of concept of formative investigations of short scales, we investigate the Ten‐Item Personality Inventory (TIPI).

Method

In Study 1, we administered the TIPI and the Big Five Inventory (BFI) to 938 adults and fitted a formative Multiple Indicators Multiple Causes model, which consisted of the TIPI items forming five latent variables, which in turn predicted the five BFI scores. These results were replicated in Study 2 on a sample of 759 adults, but this time with the Revised NEO Personality Inventory (NEO‐PI‐R) as the external criterion.

Results

The models fit the data adequately, and moderate to strong significant effects (.37 < |β| < .69, all ps < .001) of all five latent formative variables on their corresponding BFI and NEO‐PI‐R scores were observed.

Conclusions

This study presents a formative approach that we propose to be more consistent with the aims of scales with broad content and short length like the TIPI.
Potential role of periodontal pathogens in compromising epithelial barrier function by inducing epithelial‐mesenchymal transition
Authors: Abdulkareem A. A. , Shelton R. M. , Landini G. , Cooper P. R. , Milward M. R.
Published: April 2018

Background and Objective

Epithelial‐mesenchymal transition (EMT) is a process by which epithelial cells acquire a mesenchymal‐like phenotype and this may be induced by exposure to gram‐negative bacteria. It has been proposed that EMT is responsible for compromising epithelial barrier function in the pathogenesis of several diseases. However, the possible role of EMT in the pathogenesis of periodontitis has not previously been investigated. The aim of this study therefore was to investigate whether gram‐negative, anaerobic periodontal pathogens could trigger EMT in primary oral keratinocytes in vitro.

Material and Methods

Primary oral keratinocytes were harvested from labial mandibular mucosa of Wistar Han rats. Cells were exposed to heat‐killed Fusobacterium nucleatum and Porphyromonas gingivalis (100 bacteria/epithelial cell) and to 20 μg/mL of Escherichia coli lipopolysaccharide over an 8‐day period. Exposure to bacteria did not significantly change epithelial cell number or vitality in comparison with unstimulated controls at the majority of time‐points examined. Expression of EMT marker genes was determined by semiquantitative RT‐PCR at 1, 5, and 8 days following stimulation. The expression of EMT markers was also assessed by immunofluorescence (E‐cadherin and vimentin) and using immunocytochemistry to determine Snail activation. The loss of epithelial monolayer coherence, in response to bacterial challenge, was determined by measuring trans‐epithelial electrical resistance. The induction of a migratory phenotype was investigated using scratch‐wound and transwell migration assays.

Results

Exposure of primary epithelial cell cultures to periodontal pathogens was associated with a significant decrease in transcription (~3‐fold) of E‐cadherin and the upregulation of N‐cadherin, vimentin, Snail, matrix metalloproteinase‐2 (~3‐5 fold) and toll‐like receptor 4. Bacterial stimulation (for 8 days) also resulted in an increased percentage of vimentin‐positive cells (an increase of 20% after stimulation with P. gingivalis and an increase of 30% after stimulation with F. nucleatum, compared with controls). Furthermore, periodontal pathogens significantly increased the activation of Snail (60%) and cultures exhibited a decrease in electrical impedance (P < .001) in comparison with unexposed controls. The migratory ability of the cells increased significantly in response to bacterial stimulation, as shown by both the number of migrated cells and scratch‐wound closure rates.

Conclusion

Prolonged exposure of primary rat oral keratinocyte cultures to periodontal pathogens generated EMT‐like features, which introduces the possibility that this process may be involved in loss of epithelial integrity during periodontitis.
Cementum protein 1 transfection does not lead to ultrastructural changes in nucleolar organization of human gingival fibroblasts
Authors: Villegas‐Mercado C. E. , Agredano‐Moreno L. T. , Bermúdez M. , Segura‐Valdez M. L. , Arzate H. , Del Toro‐Rangel E. F. , Jiménez‐García L. F.
Published: April 2018

Background and Objective

Transfection of cementum protein 1 (CEMP1) into human gingival fibroblasts (HGFs) notably increases cell metabolism and results in overexpression of molecules related to biomineralization at transcriptional and protein levels. Therefore, HGF‐CEMP1 cells are considered as putative cementoblasts. This represents a significant advance in periodontal research because cementum neoformation is a key event in periodontal regeneration. In addition, it is well known that important changes in cell metabolism and protein expression are related to nucleolar structure and the function of this organelle, which is implicated in ribosome biogenesis. The aim of this study was to determine the effect of transfecting CEMP1 gene in human HGF on the ultrastructure of the nucleolus.

Material and Methods

Cells were processed using the conventional technique for transmission electron microscopy, fixed with glutaraldehyde, postfixed with osmium tetraoxide, and embedded in epoxy resin. Semi‐thin sections were stained with Toluidine blue and observed by light microscopy. Thin sections were stained with uranyl acetate and lead citrate. For ribonucleoprotein detection, the staining method based on the regressive effect of EDTA was used. In addition, the osmium ammine technique was used for specific staining of DNA.

Results

The results obtained in this study suggest that transfection of CEMP1 into HGFs does not produce changes in the general nucleolar ultrastructure because the different components of the organelle are present as fibrillary centers, and dense fibrillar and granular components compared with the control.

Conclusion

The transfection of CEMP1 into HGFs allows these cells to perform cementoblast‐like functions without alteration of the ultrastructure of the nucleolus, evaluated by the presence of the different compartments of this organelle involved in ribosomal biogenesis.