bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a new in vitro Sun Protection Factor method to include a wide range of sunscreen product emulsion types
Authors: Pissavini M. , Tricaud C. , Wiener G. , Lauer A. , Contier M. , Kolbe L. , Trullás Cabanas C. , Boyer F. , Meredith E. , de Lapuente J , Dietrich E. , Matts P.J.
Published: May 2020

In 2017, Cosmetics Europe performed a double‐blinded ring test of 24 emulsion‐type sunscreen products, across 3 in vivo test laboratories and 3 in vitro test laboratories, using a new candidate in vitro SPF test method. Based on the results of this work, an article was published showing how data derived from a new lead candidate method conform to new International Standards (ISO) acceptance criteria for alternative SPF test methods (Any alternative method should consider the matrix effect and if required, specify the matrix applicability of the method; Criterion 1a: Systematic differences between methods should be negligible: 95% of all individual results of an alternative method are within the range of ±2× reproducibility standard deviation of the in vivo method, that is overall bias must be below 0.5× reproducibility standard deviation of the in vivo method; Criterion 1b: Measurement uncertainty of an alternative method should be below the measurement uncertainty of the in vivo method. Candidate method predicted values must fall within the full ‘funnel’ (SPF 6‐50+) limits proposed by Cosmetics Europe (derived from the same minimum test design, that is using the ISO24444 Method to measure at least 24 products across at least 3 laboratories using at least 5 test subjects/laboratory, in a blinded fashion).). Of the 24 sunscreen products tested, the majority of emulsions were of the oil‐in‐water (O/W) type, whereas only one was water‐in‐oil (W/O) and there were no products with a mineral‐only sun filter system. In order to confirm the scope of this method, therefore, a new study was conducted that included 73 W/O (12 mineral + organic, 44 mineral only and 17 organic only) and 3 O/W mineral‐only, emulsion‐type sunscreen products (a total of 76 new sunscreen products). When combined with the previous 24 products (tested in 3 different laboratories), this yielded a new data set comprising a total of 100 emulsion‐type sunscreen products, with SPF values ranging from 6 to 50+ (with a total of 148 data points). These products were tested using the double‐plate in vitro SPF test method and compared with the ISO TC217/WG7 acceptance criteria for alternative SPF test methods. Over 95% of paired in vitro: in vivo SPF values lay within the upper and lower limits of the ISO acceptance criteria funnel, with no bias. This new in vitro SPF test method, therefore, meets the minimum requirements for an alternative SPF test method to ISO24444:2010, for emulsion‐type sunscreen products (which make up the majority of marketed sunscreen products).
HLA‐specific memory B‐cell detection in kidney transplantation: Insights and future challenges
Authors: Wehmeier Caroline , Karahan Gonca E. , Heidt Sebastiaan
Published: May 2020

Humoral alloimmunity mediated by anti‐human leucocyte antigen (HLA) antibodies is a major challenge in kidney transplantation and impairs the longevity of the transplanted organ. The immunological risk of an individual patient is currently mainly assessed by detection of HLA antibodies in the serum, which are produced by long‐lived bone marrow‐residing plasma cells. However, humoral alloimmunity is complex, and alloreactive memory B cells constitute an additional factor in the interplay of immune cells. These recirculating “silent” cells are responsible for the immunological recall response by differentiating into antibody‐producing cells upon antigen re‐encounter. Historically, due to the lack of appropriate and routinely applicable assays to determine the presence and HLA specificity of alloreactive memory B cells, their contribution to the humoral alloimmune response has clinically often been suspected but could not be determined. In this review, we give an overview of recent advances in techniques to detect alloreactive memory B cells and discuss their strengths and limitations. Furthermore, we summarize experiences with these techniques in alloimmunized individuals and transplant recipients, thereby emphasizing unmet needs to be addressed in future studies.
Effect of ICD implantation on cardiovascular outcomes in patients with cardiac amyloidosis: A systematic review and meta‐anaylsis
Authors: Halawa Ahmad , Woldu Henok G. , Kacey Kristina Gifft , Alpert Martin A.
Published: May 2020

Introduction

Cardiac amyloidosis is associated with a high rate of sudden cardiac death (SCD). Whether implantable cardioverter‐defibrillator (ICD) use in such patients prevents SCD is uncertain. This study assesses outcomes of ICD use in patients with cardiac amyloidosis.

Methods

A systematic review and meta‐analysis of data were performed after searching multiple databases and scientific sites pertaining to ICD use and cardiac amyloidosis. Of 8260 citations identified, six studies comprising 194 patients met inclusion criteria.

Results

Mean values and frequencies of patient characteristics were as follows: mean NT‐proBNP: 6867.9 pg/mL, mean left ventricular ejection fraction: 48.1%, heart failure: 67%, nonsustained ventricular tachycardia: 51%, syncope: 21%, and secondary prevention: 33%. During the mean follow‐up period of 18.21 months, 18% of patients received appropriate ICD treatment and 5% received inappropriate ICD treatment. The mortality rate was 31%. Two studies assessed the difference between patients with appropriate ICD treatment and patients with absence of appropriate ICD treatment. There was no difference between the two groups when stratified on multiple selected third variables except for two subgroups. Male gender was associated with a higher rate of appropriate ICD treatment, whereas New York Heart Association class III or IV heart failure patients was associated with a lower rate of appropriate ICD treatment.

Conclusion

The frequency of appropriate ICD treatment in cardiac amyloidosis is low and is not predicted by nonsustained ventricular tachycardia. Male gender is associated with appropriate ICD treatment. New York Heart Association class III or IV heart failure is associated with lower rate of appropriate ICD treatment.
Hepatitis B virus‐induced hyperactivation of B cells in chronic hepatitis B patients via TLR4
Authors: Li Yang , Yin Shengxia , Chen Yuxin , Zhang Quan , Huang Rui , Jia Bei , Jie Wei , Yao Kefang , Wang Jian , Tong Xin , Liu Yong , Wu Chao
Published: May 2020

B cell hyperactivation and functional impairment were identified from patients with chronic hepatitis B virus (CHB) infection; however, the underlying mechanism remains unknown. Here, we aim to elucidate the mechanisms responsible for B cell hyperactivation during HBV infection. Peripheral CD19+ B cells isolated from 4 CHB patients and 4 healthy volunteers were analysed by RNA sequencing. A total of 1401 differentially expressed genes were identified from B cell transcriptome of CHB patients vs healthy volunteers. We found that B cells from CHB patients were functional impaired, with increased TLR4 expression, activated NF‐κB pathway and altered mitochondrial function. The expression of B cell activation‐related genes, including TLR4, was further validated using additional clinical samples. To further verify the role of TLR4 in B cell activation during CHB, B cell phenotypes were determined in wild‐type (WT) and TLR4−/− HBV‐carrier mice. Hyperactivated B cell and TLR4 signalling pathway were observed in WT HBV‐carrier mice, while TLR4 ablation failed to induce B cell hyperactivation, and downstream MyD88 and NF‐κB were also not altered. Taken together, TLR4 pathway plays a pivotal role in B cell hyperactivation during CHB, which might serve as a promising target for B cell function restoration.
Prostate‐specific membrane antigen expression in the vasculature of primary lung carcinomas associates with faster metastatic dissemination to the brain
Authors: Tanjore Ramanathan Jayendrakishore , Lehtipuro Suvi , Sihto Harri , Tóvári József , Reiniger Lilla , Téglási Vanda , Moldvay Judit , Nykter Matti , Haapasalo Hannu , Le Joncour Vadim , Laakkonen Pirjo
Published: May 2020

Glioblastomas and brain metastases (BM) of solid tumours are the most common central nervous system neoplasms associated with very unfavourable prognosis. In this study, we report the association of prostate‐specific membrane antigen (PSMA) with various clinical parameters in a large cohort of primary and secondary brain tumours. A tissue microarray containing 371 cases of ascending grades of gliomas pertaining to astrocytic origin and samples of 52 cases of primary lung carcinomas with matching BM with follow‐up time accounting to 10.4 years was evaluated for PSMA expression using immunohistochemistry. In addition, PSMA expression was studied in BM arising from melanomas and breast carcinomas. Neovascular expression of PSMA was evident alongside with high expression in the proliferating microvasculature of glioblastomas when compared to the tumour cell expression. This result correlated with the results obtained from the in silico (cancer genome databases) analyses. In gliomas, only the vascular expression of PSMA associated with poor overall survival but not the tumour cell expression. In the matched primary lung cancers and their BM (n = 52), vascular PSMA expression in primary tumours associated with significantly accelerated metastatic dissemination to the brain with a tendency towards poor overall survival. Taken together, we report that the vascular expression of PSMA in the primary and secondary brain tumours globally associates with the malignant progression and poor outcome of the patients.
ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARα/LDHB/ERK‐glycolysis signalling axis
Authors: Du Yan , Zhang Mei‐ju , Li Lan‐lan , Xu Xiao‐Lin , Chen Hao , Feng Yu‐bin , Li Yan , Peng Xiao‐qin , Chen Fei‐hu
Published: May 2020

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4‐Amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a novel all‐trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB‐targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK‐glycolysis signalling axis. Further studies should focus on the underlying leukaemia‐promoting mechanisms and investigate LDHB as a therapeutic target.
Tooth survival and clinical outcomes up to 26 years after guided tissue regeneration therapy in deep intra‐bony defects: Follow‐up investigation of three randomized clinical trials
Authors: Cieplik Fabian , Ihlenfeld Insa , Hiller Karl‐Anton , Pummer Andreas , Schmalz Gottfried , Buchalla Wolfgang , Christgau Michael
Published: May 2020

Aim

To investigate tooth survival and clinical long‐term outcomes up to 26 years following guided tissue regeneration (GTR) therapy in deep intra‐bony defects.

Methods

Patients from three prospective clinical split‐mouth studies, which investigated the outcomes of GTR therapy, were re‐evaluated 21–26 years after surgery independent of the membrane type used, and tooth survival was assessed according to several site‐specific and patient‐related factors.

Results

About 50 patients contributing 102 defects were available for this long‐term follow‐up. After up to 26 years (median 23.3 years), 52.9% of the teeth were still in situ. The median survival of the extracted teeth was 13.8 years. Patients with diabetes mellitus and/or smoking history lost significantly more teeth in the long term. Compared to the 1‐year situation, there was no new median CAL loss after up to 26 years in the teeth which were still in situ.

Conclusions

Within the limitations of this study, our data show that more than 50% of the initially seriously diseased teeth were still in situ up to 26 years following GTR therapy despite an overall limited adherence to SPT. In the majority of these teeth, the CAL gain 1 year after GTR could be maintained over this long period.
Efficacy of an anhydrous stannous fluoride toothpaste for relief of dentine hypersensitivity: A randomized clinical study
Authors: Tao Danying , Ling Martin R. , Feng Xi‐ping , Gallob John , Souverain Audrey , Yang Wenjie , Alavi Anousheh
Published: May 2020

Aim

To compare efficacy of an anhydrous 0.454% w/w stannous fluoride/sodium fluoride toothpaste (Test) versus a sodium monofluorophosphate toothpaste (Negative control) and a stannous chloride/sodium fluoride toothpaste (Positive control) for dentine hypersensitivity relief after 8 weeks’ twice‐daily use.

Materials and Methods

In this randomized, examiner‐blind, stratified, parallel study, primary and secondary efficacy variables were mean changes in Schiff score (evaporative [air] sensitivity) and tactile threshold (Yeaple probe), respectively, from baseline to Week 8 between Test (n = 62) and Negative control (n = 62). Test and Positive control (n = 61) comparisons were exploratory objectives.

Results

All groups significantly improved from baseline on both dentine hypersensitivity measures (p < .0001). Difference between adjusted mean changes from baseline in Schiff sensitivity scores at Week 8 for Test versus Negative control groups was 0.19 (95% CI 0.002, 0.374), in favour of the Negative control (p = .0476; 12.57% difference). Difference in tactile threshold was −7.20 g (95% CI −16.376, 1.975), and this was not statistically significant (p = .3715; −21.83% difference). Test group showed no significant difference versus Positive control for either measure. Toothpastes were generally well tolerated.

Conclusion

While twice‐daily use of Test toothpaste significantly reduced dentine hypersensitivity from baseline, there was no significant advantage over negative or positive controls. Study registration: Clinicaltrials.gov; NCT03310268.
Reply to Wachholz and Jacinto
Authors: D'Adamo Heather , Yoshikawa Thomas , Ouslander Joseph G.
Published: May 2020

This letter comments on the letter by Patrick Wachholz
Israel Ad Hoc COVID‐19 Committee: Guidelines for Care of Older Persons During a Pandemic
Authors: Clarfield A. Mark , Dwolatzky Tzvi , Brill Shai , Press Yan , Glick Shimon , Shvartzman Pesach , Doron Israel (Issi)
Published: May 2020

Early on, geriatricians in Israel viewed with increasing alarm the spread of coronavirus disease 2019 (COVID‐19). It was clear that this viral disease exhibited a clear predilection for and danger to older persons. Informal contacts began with senior officials from the country's Ministry of Health, the Israel Medical Association, and the country's largest health fund; this was done to plan an approach to the possible coming storm. A group was formed, comprising three senior geriatricians, a former dean, a palliative care specialist, and a lawyer/ethicist. The members made every effort to ensure that their recommendations would be practical while at the same time taking into account the tenets of medical ethics. The committee's main task was to think through a workable approach because intensive care unit/ventilator resources may be far outstripped by those requiring such care. Recommendations included the approach to older persons both in the community and in long‐term care institutions, a triage instrument, and palliative care. Patient autonomy was emphasized, with a strong recommendation for people of all ages to update their advance directives or, if they did not have any, to quickly draw them up. Considering the value of distributive justice, with respect to triage, a “soft utilitarian” approach was advocated with the main criteria being function and comorbidity. Although chronological age was rejected as a sole criterion, in the case of an overwhelming crisis, “biological age” would enter into the triage considerations, but only in the case of distinguishing between people with equal non–age‐related deficits. The guideline emphasized that no matter what, in the spirit of beneficence, anyone who fell ill must receive active palliative care throughout the course of a COVD‐19 infection but especially at the end of life. Furthermore, in the spirit of nonmaleficence, the frail, very old, and severely demented would be actively protected from dying on ventilation. J Am Geriatr Soc 68:1370‐1375, 2020.
Effect of pelvic floor muscle training program in reducing postpartum levator hiatus area in Japanese women: A prospective cohort study using three‐dimensional ultrasonography
Authors: Takaoka Satoko , Kobayashi Yasue , Taniguchi Tamami
Published: May 2020

Aim

To assess the effect of a pelvic floor muscle training (PFMT) program on postpartum levator hiatus area.

Methods

A prospective cohort study was conducted at a clinic in Japan. Training and control groups were recruited from outpatient pregnant women at two separate time periods. Only the training group underwent the PFMT program, including education for home PFMT, home PFMT, and follow‐up instructions. Education for home PFMT was held by 1 month postpartum to acquire the correct contraction of the pelvic floor muscle. Home PFMT was prescribed between 1 and 5 months postpartum; during this period, follow‐up instructions were provided to keep the women motivated. Before and after home PFMT, the levator hiatus area was measured using ultrasonography.

Results

In total, 44 women in the training group and 45 in the control group were analyzed. There were 36 women who reached a high adherence to three daily sets of home PFMT. The reduction in the levator hiatus area at rest was not statistically higher in the training group than that in the control group. For the subgroup with high adherence, the reduction in the area at rest was significantly higher by 4.43% in the training group than that in the control group (19.90% vs. 15.49%).

Conclusions

Although the PFMT program did not significantly reduce the postpartum levator hiatus area at rest, performing at least three sets of home PFMT each day significantly reduced the levator hiatus area by 4.43%.

Clinical trial registration

UMIN Clinical Trials Registry (ID; UMIN 000026188, Date; 17 February 2017).
Hydration Choices, Sugary Beverages, and Kidney Injury in Agricultural Workers in California
Authors: Moyce Sally , Mitchell Diane , Vega Alondra , Schenker Marc
Published: May 2020

Purpose

Agricultural workers working in high ambient temperatures are at risk for acute kidney injury. Despite recommendations to maintain hydration, workers likely do not drink enough to protect their renal function. Additionally, new research suggests that rehydration with sugary beverages adds additional risk to kidneys already stressed by high heat and workload. We assessed hydration choices during a work shift and tested associations of rehydration using sugary beverages with acute kidney injury.

Methods

We recruited a convenience sample of workers on farms over two summers. We estimated acute kidney injury via pre‐ and post‐shift serum creatinine readings from capillary blood samples. We used self‐reported measures of the volume and type of fluids workers consumed during their shifts. We also measured changes in core body temperature, ambient temperature, and workload. We used logistic regression to estimate associations of sugary drinks with acute kidney injury, while controlling for physiologic and occupational variables.

Findings

In our sample of 445 participants, we found that men drink more than women do overall, including more than a liter of water than women (2.9 L compared to 1.9 L, respectively). The total volume workers drank was associated with increased odds of acute kidney injury (adjusted odds ratio 1.47, 95% confidence interval 1.09–1.99). We found no association of sugary drinks with acute kidney injury.

Conclusions

These findings provide important information about what men and women use to hydrate during the work day and suggest that they do not drink enough to maintain adequate hydration. Increased fluid intake during the work day may be a result of vigorous workload, which could explain the increased risk for acute kidney injury. Nurses play an important role in educating agricultural workers about the importance of maintaining hydration at work.

Clinical Relevance

This study advances current knowledge of occupational risk factors for acute kidney injury in agricultural workers. Nurses may be the only point of care for this vulnerable population and are therefore in a unique position to educate on the importance of proper hydration during work.
Predicting labor induction success by cervical funneling in uncomplicated pregnancies
Authors: Kim Yoo‐Na , Kwon Ja Young , Kim Eui Hyeok
Published: May 2020

Aim

Predictive accuracy of cervical funneling for successful vaginal delivery prior to labor induction was compared to that of conventional methods such as Bishop score and cervical length.

Methods

Prospective observational study was conducted on nulliparous women at 38 gestational weeks or more with intact membranes who delivered vaginally following labor induction. Transvaginal ultrasound was performed prior to labor induction to evaluate the cervix, to determine the cervical length and to check for the presence of funneling. Following pelvic examinations, the Bishop score was calculated. Predictive accuracy of the three different methods, namely cervical funneling, cervical length and Bishop, were compared.

Results

A total of 235 nulliparous women with intact membranes were recruited. Of these, 194 women (82.6%) had successful vaginal deliveries following induction. Cervical funneling was observed in 105 women (44.7%). The rate of successful vaginal delivery was significantly higher in women with cervical funneling than in those without funneling (90.5% vs 76.2%, P < 0.004). Multivariable analysis showed that cervical funneling, similar to traditional measures such as the Bishop score and cervical length, was an independent predictor of successful vaginal delivery following labor induction (odds ratio = 2.95; 95% confidence interval: 1.38–6.47; P = 0.007).

Conclusions

Similar to the conventional methods of cervical evaluation, such as the Bishop score and cervical length, cervical funneling may serve as a useful and valid predictor of successful vaginal deliveries prior to labor induction.
Sex‐Specific Differences in Life Span Brain Volumes in Multiple Sclerosis
Authors: Jakimovski Dejan , Zivadinov Robert , Bergsland Niels , Ramasamy Deepa P. , Hagemeier Jesper , Weinstock‐Guttman Bianca , Kolb Channa , Hojnacki David , Dwyer Michael G.
Published: May 2020

BACKGROUND AND PURPOSE

Numerous sex‐specific differences in multiple sclerosis (MS) susceptibility, disease manifestation, disability progression, inflammation, and neurodegeneration have been previously reported. Previous magnetic resonance imaging (MRI) studies have shown structural differences between female and male MS brain volumes. To determine sex‐specific global and tissue‐specific brain volume throughout the MS life span in a real‐world large MRI database.

METHODS

A total of 2,199 MS patients (female/male ratio of 1,651/548) underwent structural MRI imaging on either a 1.5‐T or 3‐T scanner. Global and tissue‐specific volumes of whole brain (WBV), white matter, and gray matter (GMV) were determined by utilizing Structural Image Evaluation using Normalisation of Atrophy Cross‐sectional (SIENAX). Lateral ventricular volume (LVV) was determined with the Neurological Software Tool for REliable Atrophy Measurement (NeuroSTREAM). General linear models investigated sex and age interactions, and post hoc comparative sex analyses were performed.

RESULTS

Despite being age‐matched with female MS patents, a greater proportion of male MS patients were diagnosed with progressive MS and had lower normalized WBV (P < .001), GMV (P < .001), and greater LVV (P < .001). In addition to significant stand‐alone main effects, an interaction between sex and age had an additional effect on the LVV (F‐statistics = 4.53, P = .033) and GMV (F‐statistics = 4.59, P = .032). The sex and age interaction was retained in both models of LVV (F‐statistics = 3.31, P = .069) and GMV (F‐statistics = 6.1, P = .003) when disease subtype and disease‐modifying treatment (DMT) were also included. Although male MS patients presented with significantly greater LVV and lower GMV during the early and midlife period when compared to their female counterparts (P < .001 for LVV and P < .019 for GMV), these differences were nullified in 60+ years old patients. Similar findings were seen within a subanalysis of MS patients that were not on any DMT at the time of enrollment.

CONCLUSION

There are sex‐specific differences in the LVV and GMV over the MS life span.
Age, tissue, genotype and virus infection regulate Wolbachia levels in Drosophila
Authors: Kaur Rupinder , Martinez Julien , Rota‐Stabelli Omar , Jiggins Francis M. , Miller Wolfgang J.
Published: May 2020

The bacterial symbiont Wolbachia can protect insects against viral pathogens, and the varying levels of antiviral protection are correlated with the endosymbiont load within the insects. To understand why Wolbachia strains differ in their antiviral effects, we investigated the factors controlling Wolbachia density in five closely related strains in their natural Drosophila hosts. We found that Wolbachia density varied greatly across different tissues and between flies of different ages, and these effects depended on the host–symbiont association. Some endosymbionts maintained largely stable densities as flies aged while others increased, and these effects in turn depended on the tissue being examined. Measuring Wolbachia rRNA levels in response to viral infection, we found that viral infection itself also altered Wolbachia levels, with Flock House virus causing substantial reductions in symbiont loads late in the infection. This effect, however, was virus‐specific as Drosophila C virus had little impact on Wolbachia in all of the five host systems. Because viruses have strong tissue tropisms and antiviral protection is thought to be cell‐autonomous, these effects are likely to affect the virus‐blocking phenomenon. However, we were unable to find any evidence of a correlation between Wolbachia and viral titres within the same tissues. We conclude that Wolbachia levels within flies are regulated in a complex host–symbiont–virus‐dependent manner and this trinity is likely to influence the antiviral effects of Wolbachia.
Gray whales hear and respond to signals from a 21–25 kHz active sonar
Authors: Frankel Adam S. , Stein Peter J.
Published: May 2020

Shore‐based theodolite tracking of eastern gray whale (Eschrichtius robustus) movements was conducted to test for potential whale responses to a high‐frequency sonar system. Southbound migrating whales were observed from two California shore observation stations as the whales swam past the source vessel that was moored in their migration path. The sonar transducer was deployed from the vessel during all observations, broadcasting 21–25 kHz sweeps for half of each day, the other half remaining silent. The order of control and experimental periods was randomized. No readily apparent response to sonar transmissions was observed in the field or in the visual data. Statistical analysis of tracking data indicates that, compared to control data, gray whales deflected inshore at ranges of 1–2 km from the vessel during sonar transmissions at a received sound pressure level of approximately 148 dB re 1 μPa2 (134 dB re 1 μPa2s). These data suggest that the functional hearing sensitivity of gray whales extends to at least 21 kHz.
Intravenous itraconazole compared with liposomal amphotericin B as empirical antifungal therapy in patients with neutropaenia and persistent fever
Authors: Yoshida Isao , Saito Akiko M. , Tanaka Shiro , Choi Ilseung , Hidaka Michihiro , Miyata Yasuhiko , Inoue Yoshiko , Yamasaki Satoshi , Kagoo Toshiya , Iida Hiroatsu , Niimi Hiromasa , Komeno Takuya , Yoshida Chikamasa , Tajima Fumihito , Yamamoto Hideyuki , Takase Ken , Ueno Hironori , Shimomura Takeshi , Sakai Tatsunori , Nakashima Yasuhiro , Yoshida Chikashi , Kubonishi Shiro , Sunami Kazutaka , Yoshida Shinichiro , Sakurai Aki , Kaneko Yukihiro , Miyazaki Yoshitsugu , Nagai Hirokazu
Published: May 2020

Background

Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required.

Objective

We conducted a multicentre, open‐label, randomised, non‐inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever.

Methods

Patients with haematological malignancies who developed fever refractory to broad‐spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d).

Results

Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model‐based estimate of a 4% difference (90% CI, −12% to 20%), did not fulfil the statistical non‐inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3‐4 hypokalaemia‐related events than LAmB group patients (P < .01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P = .07).

Conclusion

ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non‐inferiority.
The role of ambulatory 24‐hour esophageal manometry in clinical practice
Authors: Kamal Afrin N. , Clarke John O. , Oors Jac M. , Bredenoord Albert J.
Published: May 2020

High‐resolution manometry revolutionized the assessment of esophageal motility disorders and upgraded the classification through the Chicago Classification. A known disadvantage of standard HRM, however, is the inability to record esophageal motility function for an extended time interval; therefore, it represents only a more snapshot view of esophageal motor function. In contrast, ambulatory esophageal manometry measures esophageal motility over a prolonged period and detects motor activity during the entire circadian cycle. Furthermore, ambulatory manometry has the ability to measure temporal correlations between symptoms and motor events. This article aimed to review the clinical implications of ambulatory esophageal manometry for various symptoms, covering literature on the manometry catheter, interpretation of findings, and relevance in clinical practice specific to the evaluation of non‐cardiac chest pain, chronic cough, and rumination syndrome.
Short‐term outcome after singular hydraulic EsoFLIP dilation in patients with achalasia: A feasibility study
Authors: Schnurre Larissa , Murray Fritz Ruprecht , Schindler Valeria , Runggaldier Daniel , Fischbach Lara , Bordier Valentine , Pohl Daniel
Published: May 2020

Background

Achalasia is a chronic esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter, determined by an elevated integrated relaxation pressure (IRP > 15 mm Hg) and absent peristalsis. Goal of treatment is facilitation of flow across the EGJ but minimizing postinterventional reflux. A new advanced hydraulic dilation technology, the esophageal functional luminal imaging probe (EsoFLIP), allows dynamic monitoring of hollow organ dimensions while performing hydraulic dilation. The aim of our study was to evaluate the treatment response after single EsoFLIP dilation in achalasia patients.

Methods

Dilation was performed under endoscopic control with the EsoFLIP device using a self‐developed dilation algorithm. Symptom scores were assessed by the Eckardt score (ES) before and 1‐4 weeks after intervention. Esophageal emptying before and after intervention was recorded with timed barium esophagogram.

Key Results

We studied 28 consecutive untreated achalasia patients (8 female) with a median age of 43 years (range 19‐82 years) undergoing their first dilation performed with the EsoFLIP, aiming at a maximum dilation diameter of 25 mm. Total ES was significantly reduced from 7 at baseline to 2 postintervention (P < .001). The median height of the barium column after 5 minutes was significantly reduced from 4.5 cm at baseline to 1.7 cm (P = .0087). No major complications occurred.

Conclusions & Inferences

We found good efficacy in both subjective and objective short‐term treatment outcome after singular EsoFLIP dilation in treatment‐naive achalasia patients. Our findings suggest that EsoFLIP is a promising dilation technology that should be further studied in a larger, controlled setting with longer follow‐up.
Comparative expression profiling in the intestine of patients with Giardia‐induced postinfectious functional gastrointestinal disorders
Authors: Martínez Cristina , Lasitschka Felix , Thöni Cornelia , Wohlfarth Carolin , Braun Alexander , Granzow Martin , Röth Ralph , Dizdar Vernesa , Rappold Gudrun A. , Hausken Trygve , Langeland Nina , Hanevik Kurt , Niesler Beate
Published: May 2020

Background

A Giardia outbreak in Bergen, Norway, caused postinfectious functional gastrointestinal disorders (PI‐FGIDs). Despite the devastating effects of this outbreak, it presented a unique chance to investigate the implication on the dysregulation of genetic pathways in PI‐FGID.

Methods

We performed the first comparative expression profiling of miRNAs and their potential target genes in microdissected rectal biopsies from 20 Giardia‐induced PI‐FGID patients vs 18 healthy controls by nCounter analysis. Subsequently, candidates were validated on protein level by immunostaining.

Key Results

miRNA profiling on rectal biopsy samples from 5 diarrhea‐predominant PI‐IBS cases compared to 10 healthy controls revealed differential expression in the epithelial layer. The top five regulated miRNAs were implicated in GI disease, inflammatory response, and immunological disease. Subsequently, these miRNAs and 100 potential mRNA targets were examined in 20 PI‐FGID cases and 18 healthy controls in both the mucosal epithelium and the lamina propria. Although deregulation of the selected miRNAs could not be verified in the larger sample set, mRNAs involved in barrier function were downregulated in the epithelium. Pro‐inflammatory genes and genes implicated in epigenetic modifications were upregulated in the lamina propria. Immunostaining for selected candidates on 17 PI‐FGID cases and 16 healthy controls revealed increased tryptase levels as well as a decreased and aberrant subcellular expression of occludin.

Conclusions and Inferences

Genes relevant to immune and barrier function as well as stress response and epigenetic modulation are differentially expressed in PI‐FGIDs and may contribute to disease manifestation.
Acute stress induces visceral hypersensitivity via glucocorticoid receptor–mediated membrane insertion of TRPM8: Involvement of a non‐receptor tyrosine kinase Pyk2
Authors: Luo Qing‐Qing , Wang Bo , Chen Xin , Qiu Hong‐Yi , Li Wen‐Ting , Yan Xiu‐Juan , Chen Sheng‐Liang
Published: May 2020

Background

Psychological stress is an important factor for the development and recurrence of irritable bowel syndrome (IBS). The mechanisms underlying stress‐induced visceral hypersensitivity (VH), a key pathophysiological component in IBS, are still incompletely understood. We aimed to test whether transient receptor potential melastatin 8 (TRPM8) participates in acute stress–induced VH.

Methods

Rats were subjected to 1‐hour water avoidance stress (WAS). Visceral sensitivity was measured with visceromotor response to colorectal distension. Western blot and immunofluorescence were applied to evaluate the expression of GR and TRPM8 and activation of PKA, Akt, and PKC pathways.

Results

WAS‐caused VH depended on glucocorticoid receptors (GRs) and TRPM8 channels. In a dorsal root ganglion (DRG)–derived cell line, corticosterone rapidly (within 30 minutes) induced membrane expression of TRPM8. This effect was inhibited by GR antagonism and was mimicked by membrane‐impermeable corticosterone. PKA, PI3K/Akt, and PKC pathways, which lied downstream of GR and acted in parallel to promote membrane expression of TRPM8, contributed to WAS‐induced VH. The non‐receptor tyrosine kinase Pyk2, which may serve as a convergence point for PKA, PI3K/Akt, and PKC pathways, facilitated membrane insertion of TRPM8 via tyrosine‐phosphorylating TRPM8 in L6‐S2 DRGs and participated in WAS‐induced VH.

Conclusions

Collectively, acute stress–induced VH could involve membrane‐bound GR‐dependent enhancement of TRPM8 function in nociceptive DRG neurons. Mechanistically, Pyk2 could act as a key mediator that coordinates multiple protein kinase signaling and triggers phosphorylation and membrane insertion of TRPM8.
Wound‐ and mechanostimulated electrical signals control hormone responses
Authors: Farmer Edward E. , Gao Yong‐Qiang , Lenzoni Gioia , Wolfender Jean‐Luc , Wu Qian
Published: May 2020

Plants in nature are constantly exposed to organisms that touch them and wound them. A highly conserved response to these stimuli is a rapid collapse of membrane potential (i.e. a decrease of electrical field strength across membranes). This can be coupled to the production and/or action of jasmonate or ethylene. Here, the various types of electrical signals in plants are discussed in the context of hormone responses. Genetic approaches are revealing genes involved in wound‐induced electrical signalling. These include clade 3 GLUTAMATE RECEPTOR‐LIKE (GLR) genes, Arabidopsis H+‐ATPases (AHAs), RESPIRATORY BURST OXIDASE HOMOLOGUEs (RBOHs), and genes that determine cell wall properties. We briefly review touch‐ and wound‐induced increases in cytosolic Ca2+ concentrations and their temporal relationship to electrical activities. We then look at the questions that need addressing to link mechanostimulation and wound‐induced electrical activity to hormone responses. Utilizing recently published results, we also present a hypothesis for wound‐response leaf‐to‐leaf electrical signalling. This model is based on rapid electro‐osmotic coupling between the phloem and xylem. The model suggests that the depolarization of membranes within the vascular matrix triggered by physical stimuli and/or chemical elicitors is linked to changes in phloem turgor and that this plays vital roles in leaf‐to‐leaf electrical signal propagation.
NLRP3 sparks the Greek fire in the war against lipid‐related diseases
Authors: Jiang Shuai , Xiao Haoxiang , Wu Zhen , Yang Zhi , Ding Baoping , Jin Zhenxiao , Yang Yang
Published: May 2020

In recent years, the obesity rate worldwide has reached epidemic proportions and contributed to the growing prevalence of lipid‐related diseases. A strong link between inflammation and metabolism is becoming increasingly evident. Compelling evidence has indicated the activation of the nucleotide‐binding and oligomerization domain‐like receptor, leucine‐rich repeat and pyrin domain‐containing 3 (NLRP3) inflammasome, a cytoplasmic complex containing multiple proteins, in a variety of lipid‐related diseases including obesity, atherosclerosis, liver diseases, and type 2 diabetes. Recent studies have further clarified the regulatory mechanisms and the optional therapeutic agents that target NLRP3 inflammasomes. In this study, we review the recent progress in the research on NLRP3 inflammasomes and discuss their implications for a better understanding of inflammation in lipid‐related disease and the prospects of targeting the NLRP3 inflammasome for therapeutic intervention.
Palatal changes in crossbite patients treated with rapid maxillary expansion vs untreated ones: A geometric morphometric study
Authors: Oliva Giorgio , Huanca Ghislanzoni Luis , Dalessandri Domenico , Silvestrini‐Biavati Armando , Ugolini Alessandro
Published: May 2020

Objective

The present study aimed to analyse palatal changes due to rapid maxillary expansion (RME) by using modern geometric morphometric analysis (GMA) on 3D models.

Settings and sample population

Forty children with posterior crossbite and maxillary deficiency were selected for this study. Twenty children were treated with RME (mean age 7.4 ± 0.8 years), whereas 20 children were not treated (mean age 7.2 ± 1.1 years).

Materials and Methods

In the treated group, RME screw was activated until overcorrection was achieved and the RME appliance remained in place for 11 months. Digital dental casts were recorded before treatment and 1 year after the end of active treatment. GMA was performed to compare shape and dimensional variations among groups (between‐group principal component analysis).

Results

All children in the treated group achieved crossbite correction. None of the control group children achieved crossbite self‐correction. No significant shape and dimensional changes were noted in the control group after 1 year. On the other hand, significant shape and dimensional changes were noted in the treated group after 1 year (P < .05). Most of the shape changes in the treated group were similar but more pronounced compared to those observed in the control group. All major changes in palatal morphology occurred on the lateral sides of the palatal vault (widening) and at the height (shortening). Some shape changes were observed in the treated group alone.

Conclusions

Application of GMA to evaluate the effects of RME in crossbite patients revealed significant changes in palatal morphology compared with the absence of changes in the control group.
Incremental or maximal mandibular advancement in the treatment of class II malocclusion through functional appliances: A systematic review with meta‐analysis
Authors: Santana Lucas Garcia , Avelar Kimberlly , Flores‐Mir Carlos , Marques Leandro Silva
Published: May 2020

To systematically review the effects of functional appliances (FA) using incremental vs maximal mandibular advancement regarding cephalometric measurements in class II malocclusion individuals and to assess patient‐centred‐outcomes. Six electronic databases were searched without restrictions up to April 2020. We included randomized and non‐randomized controlled trials using identical FA. Trials involving participants who used adjunct appliances, inter‐maxillary elastics, who received surgical treatment or that recruited individuals with cleft lip/palate or craniofacial deformity/syndrome were excluded. Risks of bias assessments were performed using the Cochrane risk of bias tool‐2 and ROBINS‐I tools. Mean differences (MD) with their 95% confidence intervals were calculated from random‐effects meta‐analyses. The GRADE tool was used to assess the certainty of the evidence. Six studies were included. Low to very low certainty of evidence indicated that incremental mandibular advancement resulted in greater gains in mandibular length (MD = 0.89 [0.38, 1.34], P = .0005), anterior mandibular displacement (MD = 0.73 [0.40, 1.06], P < .0001) and SNB angle (MD = 0.44 [0.02, 0.85], P = .04). No significant differences were found for maxillary, dento‐alveolar and upper airway outcomes between construction bite protocols (P > .05). Study design and appliance‐related factors influenced the results of the subgroup analyses. Existing evidence is inadequate to assess patient‐related response and long‐term outcome could not be assessed. Currently, there are a heterogeneous number of studies with low quality and methodological issues can lead to biases that strongly limit an evidence‐based conclusion. Weak evidence suggests gains in mandibular skeletal parameters in the short term using FA with incremental mandibular advancement. Randomized trials evaluating key topics such as patient‐centred outcomes need to be conducted to guide clinical management. PROSPERO (CRD42019147436).
Effects of environmental factors and heavy metals on the vertical distribution of bryophytes in a sinkhole environment
Authors: Li C. , Zhang Z. , Wang Z. , Wu Q.
Published: May 2020

A sinkhole ecosystem, as a refuge for plant diversity, has been subjected to intensive exploitation, leading to ecosystem destruction of sinkholes in China. Understanding the responses of bryophyte distribution to destruction of the sinkhole environment are crucial to implementing protection measures for bryophyte diversity.

Haolong sinkhole in Guangxi Zhuang Autonomous Region of China, the third largest sinkhole in the world, was selected as the study area. The Wilson Shmida index was used to analyse bryophyte species diversity; a Generalized Linear Model (GLM) was used to reveal species vertical distribution of bryophytes, the Single and Multiple Species Distribution Models (SSDM, MSDM) were used for analysis of the relationship between bryophyte species distribution, environmental factors and heavy metals.

A total of 183 species from 74 genera in 36 families of bryophytes were collected from Haolong sinkhole, of which 26 species are endemic to China. Bryophyte species diversity was ranked in the order: agricultural section < forest section < grassland. In the vertical direction, bryophyte distribution was divided into point, disjunctive and continuous distributions using the GLM. The SSMA and MSDM indicated that bryophyte species of each of these three distributions can be divided into a temperature–slope zone, light–depth–pH–humidity zone, Pb (B)–Hg (B) zone and mixed heavy metals zone according to the effect of environmental factors and heavy metals such as As.

Environmental factors or heavy metals, such as As, in Haolong sinkhole effectively cooperate in bryophyte distribution. An effective way to protect bryophyte diversity, in particular species endemic to China in the sinkhole environment, is through education and involvement of the local villagers to minimize further damage to the sinkhole environment.