bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC inhibitors modulate innate immune responses to micro-organisms relevant to chronic mucocutaneous candidiasis
Authors: Rösler B , Wang X , Keating S T , Joosten L A B , Netea M G , van de Veerdonk F L
Published: August 2018

Signal transducer and activator of transcription 1 (STAT-1) gain-of-function (GOF) mutations cause chronic mucocutaneous candidiasis (CMC), a disease associated with Candida albicans and Staphylococcus aureus infection. Patients suffer from dysegulated immune responses due to aberrant cell programming and function. We investigated the effect of inhibitory molecules targeting histone deacetylases (HDACi) on the immune responses of peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with CMC towards microbes relevant for CMC. PBMCs cells were pretreated with HDACi and challenged with C. albicans or S. aureus. Innate and adaptive cytokines were measured in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). We assessed the effect of HDAC inhibitors on T helper type 1 (Th1) and Th17 cells and measured STAT-1 and STAT-3 phosphorylation using flow cytometry. Panobinostat, a pan-HDAC inhibitor, strongly inhibits innate and adaptive cytokines upon challenge with C. albicans or S. aureus. Specific inhibitors (entinostat or RGFP966) also had a tendency to lower production of most innate cytokines in CMC patient cells. Entinostat and RGFP966 increased the production of interleukin (IL)-22 specifically after S. aureus challenge in patient cells. In healthy and control cells, entinostat and RGFP966 treatment down-regulated STAT-1 phosphorylation while pSTAT-3 levels remained stable. HDACi modulate cytokine production in response to C. albicans and S. aureus. Pan-inhibitors lower overall cytokine production, whereas specific inhibitors confer a selective effect. Entinostat and RGFP966 are promising therapeutic candidates to treat STAT-1 GOF due to their capacity to restore IL-22 production and decrease STAT-1 phosphorylation; however, their inhibition of innate cytokines poses a possible risk to secondary infections.
Roflumilast enhances cisplatin‐sensitivity and reverses cisplatin‐resistance of ovarian cancer cells via cAMP/PKA/CREB‐FtMt signalling axis
Authors: Gong Shipeng , Chen Yongning , Meng Fanliang , Zhang Yadi , Li Chanyuan , Zhang Guangping , Huan Wu , Wu Fei
Published: August 2018

Objective

We previously demonstrated the roflumilast inhibited cell proliferation and increased cell apoptosis in ovarian cancer. In this study, we aimed to investigate the roles of roflumilast in development of cisplatin (DDP)‐sensitive and ‐resistant ovarian cancer.

Methods

OVCAR3 and SKOV3 were selected and the corresponding DDP‐resistant cells were constructed. Cell viability, proliferation, apoptosis, cycle were performed. Expression cAMP, PKA, CREB, phosphorylation of CREB and FtMt were detected. The roles of roflumilast in development of DDP‐sensitive and ‐resistant ovarian cancer were confirmed by xenograft model.

Results

Roflumilast + DDP inhibited cell proliferation, and induced cell apoptosis and G0/G1 arrest in OVCAR3 and SKOV3 cells, roflumilast induced expression of FtMt, the activity of cAMP and PKA and phosphorylation of CREB in ovarian cancer cells and the above‐effect were inhibited by H89. Downregulation of CREB inhibited the roflumilast‐increased DDP sensitivity of ovarian cancer cells, and the roflumilast‐induced FtMt expression and phosphorylation of CREB. Also, roflumilast reversed cisplatin‐resistance, and induced expression of FtMt and activation of cAMP/PKA/CREB in DDP‐resistant ovarian cancer cells. Similarly, treated with H89 or downregulation of CREB inhibited the changes induced by roflumilast. In vivo, roflumilast inhibited the development of SKOV3 or SKOV3‐DDP‐R xenograft models.

Conclusions

Roflumilast enhanced DDP sensitivity and reversed the DDP resistance of ovarian cancer cells via activation of cAMP/PKA/CREB pathway and upregulation of the downstream FtMt expression, which has great promise in clinical treatment.
MicroRNA‐1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non‐small‐cell lung cancer
Authors: Jiang Wei , Wei Ke , Pan Chunfeng , Li Hong , Cao Jing , Han Xu , Tang Yu , Zhu Shichao , Yuan Weiwei , He Yaozhou , Xia Yang , Chen Liang , Chen Yijiang
Published: August 2018

Objectives

Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR‐1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR‐1258 in non‐small‐cell lung cancer remains unclear.

Methods

The differential expression of miR‐1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT‐PCR and ISH. Flow cytometry and CCK‐8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR‐1258. Potential targets of miR‐1258 were verified by dual luciferase reporter assay, qRT‐PCR, IHC and Western blotting.

Results

In vitro and in vivo gain‐ and loss‐of‐function assays suggested that miR‐1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR‐1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR‐1258. In contrast, miR‐1258 inhibitor significantly reversed si‐GRB2‐induced GRB2 down‐regulation. Mechanistically, overexpression of miR‐1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway.

Conclusions

Our results indicate that miR‐1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.
Current treatments and trials in malignant pleural mesothelioma
Authors: Bibby Anna C. , Maskell Nick A.
Published: August 2018

Objectives

This article aims to review the evidence from recent clinical trials in mesothelioma, and to provide an overview of relevant clinical trials that are currently in progress.

Data source

Ovid MEDLINE, 1946 to present.

Study Selection

Clinical trials of therapeutic interventions were considered for inclusion, regardless of phase. Of 258 papers identified in the literature search, 88 were potentially eligible based on abstract screening. Following evaluation of full‐text articles, 35 were selected for inclusion in the review.

Results

Since the original trial that demonstrated the efficacy of pemetrexed and cisplatin in mesothelioma, multiple trials have been conducted that have further informed management options. Anti‐angiogenesis agents such as bevacizumab and nintedanib appear promising as adjuncts to first‐line chemotherapy. Meanwhile, immunotherapy, anti‐mesothelin agents and molecular targeted therapies are potential areas for development, with ongoing trials promising to deliver interesting results over the next few years. Current evidence does not support surgical intervention; however, investigations are ongoing as to the role of extended pleurectomy/decortication, and surgery in the context of trapped lung. Finally radiotherapy is effective as a palliative measure for pain control, but is not indicated prophylactically to prevent the development of procedure tract metastases.

Conclusion

A large amount of high‐quality mesothelioma research has been conducted in the past decade. As a result, several new therapies are likely to become available in clinical practice in the near future. With multiple trials ongoing, the horizon for patients with mesothelioma looks brighter than ever before.
Digital mapping of a soil profile
Authors: Zhang Y. , Hartemink A. E.
Published: August 2018

Detailed information on soil profiles is required for site characterization, soil mapping, studies on pedogenesis, soil–landscape modelling and soil classification. In this study, we used digital soil mapping techniques to map the profile wall of an Alfisol (90‐cm depth × 100‐cm width). Geochemical data (sampled at 10 cm × 10 cm) and digital images (resolution 1 cm × 1 cm) were used as input data in models that predicted a range of properties across the soil profile. Fuzzy c‐means clustering was applied to the profile and colour maps, and a confusion index was calculated. The colour coordinates were strongly correlated with SOC (soil organic carbon), sand and silt contents, and weathering indices. Random forest using the RGB model (R2 = 0.57, RMSE (root mean square error) = 2.41) showed less accurate prediction of SOC content than random forest using the CIE L*a*b* (R2 = 0.84, RMSE = 1.57) and HSV, hue, saturation, chroma (R2 = 0.85, RMSE = 1.46) models. Detailed profile maps showed considerable within‐horizon variation and identified animal holes, roots and limestone fragments. Colour and profile maps of soil properties and weathering indices matched field‐delineated soil horizons. Clusters obtained by soil properties and weathering indices represented the field‐delineated horizons and had the largest overall accuracy (P = 0.85 and 0.86, respectively). The confusion index showed that the horizons had wavy and somewhat irregular boundaries. We conclude that colour coordinates are useful for predicting and mapping soil properties in soil profiles. Random forest can be used to produce high‐resolution soil profile maps, and fuzzy c‐means clustering is useful for delineating soil horizons.

Highlights

We investigated the use of digital images in soil horizon delineation and within soil horizon variation

We used various colour models to map soil profile properties and define horizons

Colour and profile maps of soil properties and weathering indices matched field delineated soil horizons.

Random forest can produce high‐resolution soil profile maps, and fuzzy c‐means clustering can delineate soil horizons
Isolation and identification of potassium‐releasing bacteria in soil and assessment of their ability to release potassium for plants
Authors: Sarikhani M. R. , Oustan S. , Ebrahimi M. , Aliasgharzad N.
Published: August 2018

The application of potassium (K)‐releasing microorganisms is a promising approach for increasing K availability in soil. The objectives of this study were to isolate and characterize the K‐releasing bacteria (KRB) and to evaluate their contribution to the solubilization of K from muscovite and biotite, and to the assimilation of released K by tomato in a pot culture experiment. Soil samples were screened in both solid and liquid Aleksandrov media to isolate bacteria with the potential to release K from biotite and muscovite. Our results fromin‐vitroexperiments revealed that more K was released in treatments with KRB than in the uninoculated media (control). Under the best conditions an increase of 188 and 127% was obtained for biotite and muscovite, respectively; among the isolates with the largest releasing ability it was 49 mg l−1. The most efficient bacteria were identified as thePseudomonasgenus. Results of the pot culture experiment showed that the concentration and content of K in plant tissue were considerably more than those in any of the controls with no living organisms present. Results revealed that significantly more biomass was accumulated and K acquired in most pots treated with bacterial strains than in the control, especially forPseudomonassp. strain S10‐3. This treatment increased K concentation and content by more than 50 and 70%, respectively, in tomato aerial tissue. Further research is necessary to examine the effects of these bacterial strains on the mobilization of K‐bearing minerals under field conditions.

Highlights

The aim was to determine if bacterial isolates can accelerate K release from micas for plants.

We investigated the potential of some isolated bacteria to solubilize K from muscovite and biotite.

Identification of efficient isolates showed that KRB belonged to thePseudomonasgenus.

Pseudomonassp. strain S10‐3 increased K concentration in tomato aerial tissue by more than 50%.
Regulation of 25‐hydroxyvitamin D‐1‐hydroxylase and 24‐hydroxylase in keratinocytes by PTH and FGF23
Authors: Wu Wenlin , Fan Hong , Jiang Yi , Liao Liyan , Li Lusha , Zhao Juan , Zhang Huiling , Shrestha Chandrama , Xie Zhongjian
Published: August 2018

Renal 25‐hydroxyvitamin D‐1α‐hydroxylase (1αOHase, CYP27B1) and 24‐hydroxylase (24OHase, CYP24A1) are tightly regulated. However, little is known about the regulation of 1α(OH)ase and 24(OH)ase in extrarenal tissue such as the epidermis. This study was to determine the roles of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF 23) in the regulation of 1α(OH)ase and 24(OH)ase in epidermal keratinocytes as well as epidermal keratinocyte proliferation and differentiation. The results showed that PTH increased the protein level of 1α(OH)ase in human epidermal keratinocyte cell line HaCaT, but had no effect on the level of 24(OH)ase. The effect of PTH on 1α(OH)ase was blocked by the PKC inhibitor. Treatment with FGF23 decreased mRNA and protein levels of 1α(OH)ase and increased mRNA and protein levels of 24(OH)ase in HaCaT cells. The effect of FGF23 on 1α(OH)ase and 24(OH)ase was blocked by the mitogen‐activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) inhibitor. In addition, treatment with PTH enhanced levels of differentiation markers including keratin 1, involucrin, loricrin, and filaggrin but reduced levels of BrdU incorporation in HaCaT cells. These effects were inhibited by the PKC inhibitor. FGF23 enhanced proliferation of HaCaT cells, but reduced levels of early differentiation markers including keratin 1 and involucrin and enhanced levels of the later differentiation markers including loricrin and filaggrin. These results suggest that PTH stimulates 1α(OH)ase expression and differentiation of HaCaT cells and inhibits proliferation via PKC. The data also suggest that FGF23 inhibits 1α(OH)ase expression and stimulates 24(OH)ase expression via MAPK/ERK. In addition, FGF23 enhances proliferation and late differentiation and inhibits early differentiation of HaCaT keratinocytes.
Synergism between gabapentin–tramadol in experimental diabetic neuropathic pain
Authors: Miranda Hugo F. , Sierralta Fernando , Aranda Nicolas , Poblete Paula , Noriega Viviana , Prieto Juan C.
Published: August 2018

Neuropathic pain is associated with several conditions such as surgery, cancer, and diabetes and can be induced experimentally. Among the drugs used as monotherapy are gabapentin and tramadol. The purpose of this study was to evaluate the coadministration of gabapentin and tramadol, by isobolographic analysis, in three different algesiometric assays in experimental diabetic neuropathic pain induced by streptozocin in mice. In all the behavioral tests, gabapentin or tramadol produced a dose‐dependent antinociception and their coadministration resulted in a positive interaction. This effect can be explained by principles of multimodal analgesia, whereby the different mechanisms of action of each drug contribute to the combined effect in a supra‐additive manner. The findings of the present study suggest that the combination of gabapentin and tramadol could be a useful strategy for the treatment of pain induced by diabetic neuropathy.
Structural basis for prolidase deficiency disease mechanisms
Authors: Wilk Piotr , Uehlein Monika , Piwowarczyk Rafal , Dobbek Holger , Mueller Uwe , Weiss Manfred S.
Published: August 2018

Prolidase is a metallopeptidase that cleaves iminodipeptides containing a proline (Pro) or hydroxyproline (Hyp) residue at their C‐terminal end. The disease prolidase deficiency (PD) is a rare recessive human disorder characterized by reduced prolidase activity. PD manifests itself by a wide range of severe clinical symptoms, most commonly as skin ulceration, recurrent infections of the respiratory tract, and mental retardation. Several mutations in the PEPD gene have been identified that are responsible for the loss or the reduction of prolidase activity. In contrast, the structural basis of enzyme inactivation has so far remained elusive. In this study, we present high resolution crystal structures of a number of human prolidase (HsProl) variants, in which single amino acids are either substituted by others or deleted. The observed implications of the mutations on the three‐dimensional structure of HsProl are reported and discussed and related to their enzymatic activity. The resulting structures may be divided into four groups depending on the presumed effect of the corresponding mutations on the reaction mechanism. The four possible inactivation mechanisms, which could be elucidated, are disruption of the catalytic Mn2(OH−)‐center, introduction of chain disorder along with the displacement of important active site residues, rigidification of the active site, and flexibilization of the active site.

Database

All refined structure coordinates as well as the corresponding structure factor amplitudes have been deposited in the PDB under the accession numbers 5MBY, 5MBZ, 5MC0, 5MC1, 5MC2, 5MC3, 5MC4, 5MC5, 6H2P, 6H2Q.
Micropapillary pattern in pure mucinous carcinoma of the breast – does it matter or not?
Authors: Xu Xiaoli , Bi Rui , Shui Ruohong , Yu Baohua , Cheng Yufan , Tu Xiaoyu , Yang Wentao
Published: August 2018

Aims

Pure mucinous carcinoma (PMC) of the breast is a low‐grade cancer. In this study, we aimed to elucidate the prognostic significance of micropapillary structures in breast PMC.

Methods and results

Seventy‐five patients with breast PMC were recruited. All haematoxylin and eosin (H&)‐stained slides were reviewed, and clinicopathological features including age, tumour size, growth pattern, nuclear grade, histological grade, lymph node (LN) status, immunohistochemistry (IHC) staining of hormone receptor, human epidermal growth factor receptor 2 (HER2) expression and Ki‐67 proliferation index were analysed. Fluorescence in‐situ hybridisation (FISH) was used to verify the amplification of the HER2 gene in IHC 2+ cases. Seventy‐one cases of PMC were followed‐up from 18 to 110 months (median = 68 months). All PMC patients were female, aged 31–83 years (median = 57 years). All PMCs were nuclear grades 1 or 2. Oestrogen receptor was positive in all cases (100%) and progesterone receptor was positive in 68 cases (90.7%). There was no 3+ staining or gene amplification of HER2. Four patients had axillary LN metastasis (5.7%). Micropapillae were observed in 60 cases (80%) with varied percentages, and divided into five groups: 0%, <20%, 20–49%, 50–89% and ≥90%, with 15 (20%), 15 (20%), 17 (22.7%), 17 (22.7%) and 11 (14.7%) cases in each. Follow‐up results showed that neither recurrence nor distant metastasis occurred in all PMCs. Statistical analysis revealed that only larger tumour size was correlated significantly with LN metastasis (P < 0.05).

Conclusions

The presence of nuclear grades 1 or 2 micropapillae, irrespective of the percentage, had no significant relationship with LN metastasis and patients’ survival of PMC.
Use of stainless steel crowns to restore primary molars in Germany: Questionnaire‐based cross‐sectional analysis
Authors: Santamaría Ruth Madeleyne , Pawlowitz Laura , Schmoeckel Julian , Alkilzy Mohammad , Splieth Christian Heinz
Published: August 2018

Background

Stainless steel crowns (SSCs) have shown substantial clinical success and are the restoration of choice to treat multisurface carious primary molars.

Aim

To evaluate the use of and views on SSCs for treating primary molars in Germany.

Methods

This is a questionnaire‐based cross‐sectional study, which assessed the views of dentists and dental schools on the use of SSCs (conventional and the Hall Technique [HT]) in Germany. Dentists were randomly selected (n = 267) and contacted by telephone, and a self‐administered questionnaire was sent to all German dental schools (n = 27).

Results

A total of 104 (39%) dentists agreed to participate. The majority of respondents (66%) do not use SSCs, being the main drawbacks: technique complexity (29%) and aesthetic concerns (23%). The majority of respondents (77%) were not familiar with the HT. The response rate from the universities was 85%. In 96% of the dental schools, the value of using SSCs is taught; however, in 27%, no practical training is provided. In addition, the dental schools’ questionnaire revealed that the HT was known (91%), but neither taught to nor used for most of the dental students (76%).

Conclusion

Independent of the technique used, SSCs are considerably underutilized in the dental practice in Germany, although SSCs are well accepted by the universities, however, predominantly using the conventional approach.
Fabrication of 0.24Pb(In1/2Nb1/2)O3‐0.42Pb(Mg1/3Nb2/3)O3‐0.34PbTiO3 transparent ceramics by conventional sintering technique
Authors: Fujii Ichiro , Nakashima Saki , Wada Takahiro
Published: August 2018

0.24Pb(In1/2Nb1/2)O3‐0.42Pb(Mg1/3Nb2/3)O3‐0.34PbTiO3 transparent ceramics were fabricated by a conventional sintering technique. Through optimization of sintering conditions of calcination and sintering temperatures and time, the obtained ceramics showed high optical transmittance of 53% and 71% at light wavelengths of 1300 and 2000 nm, respectively. The ceramics showed a rhombohedral to tetragonal phase transition at ~120°C and a tetragonal to cubic phase transition at 222°C. These transition temperatures were higher than those of 0.67Pb(Mg1/3Nb2/3)‐0.33PbTiO3 ceramics. In addition, the ceramics had a ferroelectric hysteresis loop, a large piezoelectric constant d33 of 407 pC/N, and a planar electromechanical coupling factor kp of 52%. These results suggest that the transparent ceramics may be used as a temperature‐stable, linear electro‐optic material.
Evolutionary and ecological success is decoupled in mammals
Authors: Faurby Søren , Antonelli Alexandre
Published: August 2018

Aim

To identify which factors distinguish ecologically successful mammalian clades (i.e., clades with a large combined range size) from less successful ones.

Location

Global.

Methods

We estimated the total range sizes for each individual mammalian subfamily and used phylogenetic regressions to identify the relative importance of factors related to colonization ability (body size and niche width) and adaptability (rate of evolution of body size and rate of evolution of climatic preference) in determining these ranges. We then estimated the importance of the same factors on the variation in diversification rate within mammals.

Results

We found strong support for a link between total range size and traits related to colonization ability. In particular, we found larger total range sizes among clades containing larger bodied species and clades with wider climatic niche width, while we did not find support for any predictors related to adaptability being linked to total range size. We also found that traits related to increased range size were associated with reduced diversification rate.

Main Conclusions

Range size for mammalian clades is mainly predicted by colonization ability, suggesting that most clades are limited by dispersal rather than their ability to adapt to new environments. The most ecologically successful (i.e., most widespread) mammalian clades tend to possess traits that reduce geographical isolation among populations, but the same traits tend to decrease diversification rates. Our results unveil a decoupling between evolutionary and ecological success in mammals.
microRNA Let‐7b: A Novel treatment for endometriosis
Authors: Sahin Cagdas , Mamillapalli Ramanaiah , Yi Kyong W. , Taylor Hugh S.
Published: August 2018

Endometriosis is an oestrogen‐dependent, chronic inflammatory disease that affects 10% of reproductive‐aged women. Current treatment options depend on female sex steroid hormone modulation; however, all have side effects and are not useful in women who want to conceive. microRNAs treatments have provided promising results for some chronic diseases and cancers. We have previously shown the microRNA Let‐7b is repressed in endometriosis and that loss of Let‐7 contributes to the pathophysiology of the disease. Here, we propose using microRNA Let‐7b for the treatment of endometriosis in a murine model. Endometriosis was treated using microRNA Let‐7b or a scrambled control microRNA. Let‐7b treatment resulted in reduced endometriosis lesion size. Decreased gene expression was noted in several genes known to promote endometriosis growth including ER‐α, ER‐ß, Cyp19a, KRAS 4A, KRAS 4B and IL‐6. These results indicate that microRNA Let‐7b has a pleiotropic role in endometriosis pathophysiology affecting oestrogen signalling, inflammation and growth factor receptors. Local treatment of endometriosis with Let‐7b is a promising therapy for endometriosis that simultaneously affects multiple pathways driving endometriosis without systemic hormonal side effects.
Impact of spinal needle type on postdural puncture headache among women undergoing Cesarean section surgery under spinal anesthesia: A meta‐analysis
Authors: Lee Sang IL , Sandhu Shabaaz , Djulbegovic Benjamin , Mhaskar Rahul S
Published: August 2018

Objective

Spinal anesthesia is the most frequently performed anesthesia for cesarean section. The American Society of Anesthesiology recommends using pencil‐point spinal needles (SNs) over cutting‐bevel SNs to reduce postdural puncture headache (PDPH) in their practice guidelines for obstetric anesthesia. However, there is no meta‐analysis addressing the impact of the type of SNs on PDPH among women undergoing Cesarean section surgery.

Methods

We conducted a systematic review and meta‐analysis including randomized controlled trials comparing the incidence of PDPH of pencil‐point SNs with cutting‐bevel SNs in patients undergoing Cesarean section with spinal anesthesia. A comprehensive search of PubMed, Cochrane Library, EMBASE, and CINAHL without using any language and time restrictions were performed.

Results

A total of 4936 patients from 20 studies (31 comparisons) were included. Pencil‐point SN leads to reduced PDPH (risk ratio [RR] 0.33, 95% confidence intervals [CI] 0.25 to 0.45) and reduced requirement of epidural blood patch (RR = 0.21, 95% CI 0.09 to 0.51) compared to cutting‐bevel SN. The incidence of anesthesia failure, non‐PDPH, backache, and other adverse effects was not statistically significantly difference between the two SNs. Overall quality of evidence was moderate to low.

Conclusions

Using pencil‐point SN appears to be beneficial for preventing PDPH in patients undergoing Cesarean section without increasing any potential adverse effects. Further research addressing the specific gauge of pencil‐point SNs, which might further reduce the incidence of PDPH is highly desired.
The case for a meta‐nosological investigation of pragmatic disease definition and classification
Authors: Livingstone‐Banks Jonathan
Published: August 2018

Nosology is the science of defining and classifying diseases. Meta‐nosology is the study of how we do this, on what principles nosological practices are based, the quality of the resulting medical taxonomy, and primarily whether/how diseases can be defined better than they are now. In modern Western medicine, there are a wide variety of ways in which diseases are defined and categorized. Examples include by the symptoms they present with (syndromic), their underlying causes (etiological), the biological mechanisms involved (pathogenetic), available treatments, historical precedent, and through diagnostic exclusion. Here, I explore the hypothesis that how we define diseases has an impact on how (and how effectively) we research and treat them. I explore the philosophical implications of this thesis and suggest a direction that the underlying metaphysics of disease definition might follow. I conclude that further research is warranted into whether our current disease definitions could be improved upon.
Body shape and robustness response to water flow during development of brown trout Salmo trutta parr
Authors: Fenkes Miriam , Shiels Holly A. , Nudds Robert L.
Published: August 2018

Domesticated brown trout Salmo trutta parr were subjected to increased, variable flow under controlled experimental conditions. Using geometric morphometric analyses, (a mass–length index) and caudal fin area–body length ratio, this study assessed morphological responses in lateral body depth, growth and robustness and propulsive potential, respectively, of parr over the course of 32 weeks. Geometric morphometric analyses did not reveal an effect of exercise on either lateral body depth or caudal fin area. However, improved overall robustness and growth trajectories in exercised parr showed a positive adaptive response to the enriched habitat. Exercise and habitat heterogeneity thus have the potential to improve survivability of domesticated salmonids in the wild.
Gamma‐aminobutyric acid receptor type B agonist baclofen inhibits acid‐induced excitation of secondary peristalsis but not heartburn sensation
Authors: Wong Ming‐Wun , Hung Jui‐Sheng , Liu Tso‐Tsai , Yi Chih‐Hsun , Lei Wei‐Yi , Chen Chien‐Lin
Published: August 2018

Background and Aim

Acute esophageal acid infusion promotes distension‐induced secondary peristalsis. The gamma‐aminobutyric acid receptor type B (GABA‐B) receptors activation inhibits secondary peristalsis. This study aimed to test the hypothesis whether acid excitation of secondary peristalsis can be influenced by baclofen.

Methods

Secondary peristalsis was performed with intra‐esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1 N HCl following pretreatment with placebo or baclofen was randomly performed at least 1 week apart. Symptom intensity, distension thresholds, and peristaltic parameters were determined and compared between each study protocol.

Results

The intensity of heartburn symptom in response to esophageal acid infusion was significantly greater with baclofen than the placebo (P = 0.002). The threshold volume of secondary peristalsis during slow air injections in response to acid infusion was significantly greater with baclofen than the placebo (P = 0.001). Baclofen significantly increased the threshold volume of secondary peristalsis during rapid air injections in response to acid infusion (P = 0.001). The frequency of secondary peristalsis in response to acid infusion was significantly decreased by baclofen as compared with the placebo (P = 0.001). Baclofen significantly decreased peristaltic amplitudes in response to acid infusion during rapid air injections (P = 0.007).

Conclusions

Gamma‐aminobutyric acid receptor type B agonist baclofen inhibits acid excitation of secondary peristalsis in human esophagus, which is probably mediated by both muscular and mucosal mechanoreceptors. This work supports the evidence of potential involvement of GABA‐B receptors in negative modulation of acid excitation of esophageal perception as well as secondary peristalsis.
Preliminary randomized controlled trial of antiaging effects of l‐ascorbic acid applied in combination with no‐needle and microneedle mesotherapy
Authors: Zasada Malwina , Markiewicz Agata , Drożdż Zuzanna , Mosińska Paula , Erkiert‐Polguj Anna , Budzisz Elżbieta
Published: August 2018

Background

The epidermis is keratinized stratified squamous epithelium covered by hydro‐lipid barrier. Vitamin C is a water‐soluble antioxidant which protects skin from oxidative damage and rejuvenates photo‐aged skin. There are different options of improving active substance penetration through the stratum corneum of the epidermis. One of them is noneedle mesotherapy which is a non‐invasive rejuvenation technique involving electric pulses, electroporation, and ultrasounds. The use of these physicals factors results in deeper penetration of active ingredients. The other one is micro‐needle mesotherapy which is nonsurgical therapy, which could cause the controlled inflammation. Micro channels are formed by needles during the skin puncture, that facilitate penetration of the active ingredients.

Aims

The aim of the study was to assess the efficacy of L‐ascorbic acid applied in combination with no‐needle and micro‐needle mesotherapy in anti‐aging therapy.

Materials and Methods

This study involved 17 healthy volunteers, 2.5 ml of serum containing 20% L‐ascorbic acid with hydrate from strawberries was used topically in every of 4 treatments. No‐needle mesotherapy was applied on the left half of the face while microneedle mesotherapy in combination with the same serum was performed on the right half of face.

Results

In vivo studies confirmed the effectiveness of both methods.

Conclusion

The impact of active substance on skin firmness and elasticity as well as the degree of hydration and skin tone was more efficient after micro‐needle mesotherapy.
Case for a role of the microbiome in gynecologic cancers: Clinician's perspective
Authors: Mert Ismail , Walther‐Antonio Marina , Mariani Andrea
Published: August 2018

In this review, we aimed to provide insight into the microbiome and its association with endometrial and ovarian cancer and their risk factors. We reviewed the literature focusing on the relationship between the microbiome and cancer, as well as the relationship between gynecologic diseases and cancers. The human body contains different kinds of microorganisms in various body parts, which is termed the microbiome. The number of microorganisms that live in and on the human body is greater than that of the human germ and somatic cells by 10‐fold. The relationship between a human and their microbiome is complex; it is also one of the most important components of homeostasis. Impairment of microbiome–host homeostasis has been associated with obesity, several cancers, preterm labor, inflammatory and allergic conditions and neurodevelopmental disorders. Direct and strong causal relationships have been established for several cancers and microorganisms, such as gastric lymphoma and Helicobacter pylori infection. Interestingly, eradication of the infectious agents has also been shown to be therapeutic. The association between cancer and the microbiome, however, is more complicated than a 1 bacteria–1 cancer model, and a shift in a healthy microbiome can result in various cancers via inflammation, change in microenvironment or DNA‐damaging toxins. The human microbiome is an integral part of homeostasis. Understanding the mechanisms that cause dysbiosis will enable us to elucidate the pathways that result in malignancy and investigate new treatment modalities.
The ‘First Generation’ in Historical Perspective: Canadian Students in the 1960s
Authors: Grayson J. P.
Published: August 2018

Over the past few years a number of studies have focused on the disadvantages confronted by students who are the first in their families to attend university. Their liabilities include relatively low levels of preparedness, a lack of involvement in campus activities, and low levels of academic achievement. Rather than accepting the universality of this characterization, in this article, these negative characteristics and experiences were viewed as one ‘ideal type.’ Using this ideal type as a reference point, the current study focused on a period in Canadian history in which first generation students were the norm. In an examination of Glendon College, York University, located in Toronto Canada, in the mid 1960s, it was found that the experiences of the first generation did not fit the ideal type. Those who likely were the first in their families to attend university were prepared for their studies, involved in campus activities, and earned good grades. Possible explanations for this deviation from the ideal type include the buoyancy of the economy in the mid‐sixties, an expanding university sector, the size and relative intimacy of the College, the way in which high schools prepared students for university, and stringent admission requirements.
Mini‐ versus classical kissing balloon inflation in provisional technique for bifurcation intervention
Authors: Liu Jia , Chen Shaoliang , Wei Jianrui , Zeng Fang , Li Li
Published: August 2018

Objectives

We compared the potential benefits of mini‐KBI (M‐KBI), an optimized kissing balloon inflation (KBI), and classical KBI (C‐KBI) in provisional bifurcation stenting.

Background

The long‐term clinical outcomes of C‐KBI in a provisional stenting strategy continue to be under debate due to main vessel (MV) stent deformation and overexpansion.

Methods

Twelve stents were deployed in a silicone coronary bifurcation model using a provisional stenting strategy: C‐KBI (two non‐compliant balloons juxtaposed within the MV stent) was performed in six cases, and M‐KBI (the side branch (SB) balloon protruded only into the MV at the upper edge of the SB ostium) was performed in the remaining six cases, all of which were followed by proximal optimization technique POT. Stent geometry was evaluated by bench photos, videoscope, micro‐CT, microscopy, and intravascular ultrasound (IVUS).

Results

C‐KBI rectified the MV stent malapposition, but resulted in stent deformation, overexpansion and the “bottleneck” effect, which could not be rectified by POT. M‐KBI also rectified the MV stent malapposition, without notable stent deformation, overexpansion, or the “bottleneck” effect. POT optimized the MV strut apposition.

Conclusions

M‐KBI, an optimized KBI, is recommended to prevent stent deformation and overexpansion and to optimize stent deployment in a provisional stenting strategy.
Sleep disorders, depression and anxiety are associated with adverse safety outcomes in healthcare workers: A prospective cohort study
Authors: Weaver Matthew D. , Vetter Céline , Rajaratnam Shantha M.W. , O’Brien Conor S. , Qadri Salim , Benca Ruth M. , Rogers Ann E. , Leary Eileen B. , Walsh James K. , Czeisler Charles A. , Barger Laura K.
Published: August 2018

The objective of the study was to determine if sleep disorder, depression or anxiety screening status was associated with safety outcomes in a diverse population of hospital workers. A sample of shift workers at four hospitals participated in a prospective cohort study. Participants were screened for five sleep disorders, depression and anxiety at baseline, then completed prospective monthly surveys for the next 6 months to capture motor vehicle crashes, near‐miss crashes, occupational exposures and medical errors. We tested the associations between sleep disorders, depression and anxiety and adverse safety outcomes using incidence rate ratios adjusted for potentially confounding factors in a multivariable negative binomial regression model. Of the 416 hospital workers who participated, two in five (40.9%) screened positive for a sleep disorder and 21.6% screened positive for depression or anxiety. After multivariable adjustment, screening positive for a sleep disorder was associated with 83% increased incidence of adverse safety outcomes. Screening positive for depression or anxiety increased the risk by 63%. Sleep disorders and mood disorders were independently associated with adverse outcomes and contributed additively to risk. Our findings suggest that screening for sleep disorders and mental health screening can help identify individuals who are vulnerable to adverse safety outcomes. Future research should evaluate sleep and mental health screening, evaluation and treatment programmes that may improve safety.
Neurocognitive performance in insomnia disorder: The impact of hyperarousal and short sleep duration
Authors: Khassawneh Basheer Y. , Bathgate Christina J. , Tsai Sheila C. , Edinger Jack D.
Published: August 2018

Given the recent evidence on the association between hyperarousal in insomnia disorder and neurocognitive deficits, we aimed to examine the effect of short sleep duration on neurocognitive reaction time tests in insomnia disorder sufferers. We recruited subjects with insomnia disorder (n = 35, mean age = 40.6 years) who scored ≥29 on a Hyperarousal Scale, and a group of controls (n = 54, mean age = 31.5 years) who had no sleep disorders and scored <26 on the Hyperarousal Scale. Participants completed two in‐home polysomnograms and four daytime trials of neurocognitive tests, including simple reaction time, choice reaction time, big circle–little circle, rapid visual information processing, attention switching task, and spatial working memory tests. Total sleep time divided study cohorts into subgroups of short (total sleep time <6 hr) and normal (total sleep time ≥6 hr) sleepers. ANCOVA showed a significant interaction between participant type (insomnia disorder versus controls) and sleep duration (short versus normal) for spatial working memory‐latency (p = 0.020) and spatial working memory‐errors (p = 0.025). The short‐sleeping insomnia disorder group had longer spatial working memory‐latencies and more spatial working memory‐errors than did normal‐sleeping controls. Regardless of sleep duration, those with insomnia disorder had more attentional deficits with longer attention switching task‐latency (p = 0.011) and more attention switching task‐incorrect trials (p = 0.015) than the control group. Normal‐sleepers only had longer attention switching task‐latency than short‐sleepers (p = 0.004). A phenotype of insomnia disorder with hyperarousal and short sleep duration is associated with daytime cognitive deficits in complex attentional and spatial working memory tasks.
Clinicopathological features of He Shou Wu‐induced liver injury: This ancient anti‐aging therapy is not liver‐friendly
Authors: Wang Yan , Wang Lan , Saxena Romil , Wee Aileen , Yang Ruiyuan , Tian Qiuju , Zhang Jiping , Zhao Xinyan , Jia Jidong
Published: August 2018

Background & Aims

Polygonum Multiflorum Thumb (PMT), an ancient anti‐aging Chinese herb known traditionally as He Shou Wu, has side effects of liver toxicity. To determine the main clinical and pathological characteristics of liver toxicity induced by PMT and the clinical course after its cessation.

Methods

Data of patients, diagnosed as drug‐induced liver injury and hospitalised in Beijing Friendship Hospital from August 2005 to August 2017, were retrospectively reviewed. Clinical, pathological data and outcome after cessation of He Shou Wu were obtained and analysed. Kruskal‐Wallis and Chi‐square (χ2) tests were performed.

Results

Twenty‐nine patients with He Shou Wu‐induced liver injury were enrolled. The median age was 53 years (range 15‐74) and 75.9% (22/29) were women. The most common symptom was jaundice (79.3%, 23/29). Of nine patients with liver biopsies, six showed acute cholestatic hepatitis, two acute, and one chronic hepatocellular injury pattern. The latency, liver chemistries and outcomes were comparable between pure He Shou Wu (5 patients) and its compounds (24 patients). Twenty‐five of 29 patients (86.2%) had normal serum alanine aminotransferase levels after 45 days (range: 10‐138 days) and total bilirubin of 46 days (range: 0‐551 days). One patient was rechallenged with He Shou Wu and two developed autoimmune features. One patient died of liver failure and three had chronic persistent liver injury.

Conclusions

The main clinicopathological injury pattern of He Shou Wu‐induced liver injury is moderate to severe hepatitis with or without cholestasis. Most patients recover completely; however, chronic disease and death do occur.
Does pollution influence small mammal diet in the field? A metabarcoding approach in a generalist consumer
Authors: Ozaki Shinji , Fritsch Clémentine , Valot Benoit , Mora Frédéric , Cornier Thierry , Scheifler Renaud , Raoul Francis
Published: August 2018

Mammals are mainly exposed to trace metals (TMs) via consuming contaminated food. Several studies have demonstrated relationships between metal concentrations in food and in animal tissues. However, potential effects of TMs on feeding behaviour of wildlife have been poorly documented under field conditions, despite experimental evidence showing that food selection is impacted by resource contamination. Here, we test the hypothesis that the diet of a generalist rodent, the wood mouse (Apodemus sylvaticus), is altered by soil TM contamination in the field. Wood mice were sampled in spring and in autumn along a gradient of soil contamination in the surroundings of a former smelter located in northern France. Available resources in the field were inventoried, and the diet of the animals was analysed using DNA “metabarcoding.” We demonstrated that (a) relationship between the resource richness in the diet and their richness in the field was altered by soil metal contamination. Wood mice specialized their diet along the gradient of soil metal contamination for both plant and invertebrate resources in spring. We also showed that (b) preference for Salicaceae, a plant family accumulating metals, decreased when soil contamination increased. These results suggest that environmental TM pollution could act as a force modulating trophic interactions in terrestrial food webs, thereby affecting wildlife exposure to contaminants by trophic route.
Novel parotid sialo‐cone‐beam computerized tomography features in patients with suspected Sjogren’s syndrome
Authors: Keshet Naama , Aricha Adi , Friedlander‐Barenboim Silvina , Aframian Doron J. , Nadler Chen
Published: August 2018

Objective

Sjogren’s syndrome (SjS) causes salivary gland impairment leading to oral dryness. Parotid sialo‐cone‐beam computerized tomography (sialo‐CBCT) demonstrates ductal architecture and to a lesser extent gland activity. This study characterizes radiographic features of patients suspected for SjS and looks for a possible correlation with the diagnosis of SjS.

Methods

The clinical and radiographic data of suspected SjS/dry mouth patients referred for sialo‐CBCT in 2011–2014 were reviewed retrospectively. Two observers studied the scans for various radiographic features including duct morphology, level of branching, ductopenia and sialectasia. These features were analysed taking the specific clinical data and two sets of SjS criteria: The 2002 American‐European Consensus Group (AECG) and the 2012 American College of Rheumatology (ACR) Group.

Results

Sialo‐CBCT scans of 67‐referred patients suffering from dry mouth (115 parotid glands) were included. Intraradiographic association was found between ductopenia and all other radiographic parameters. Minimal, yet important, radiographic differences were found between left and right parotid glands. AECG‐confirmed‐SjS patients showed strong correlation with radiographic features, whereas ACR 2012‐confirmed‐SjS patients did not.

Conclusion

Sialo‐CBCT demonstrates novel radiographic features which may clarify the diagnosis of SjS. Further studies are needed to determine the role of sialo‐CBCT in diagnosis of SjS.