bluuebunny/crossref_metadata_2025 huggingface dataset:
Informal employment and poor self-perceived health in Latin America and the Caribbean: a gender-based comparison between countries and welfare states in a pooled analysis of 176,786 workers
Authors: Utzet Mireia , Botías Ferran , Silva-Peñaherrera Michael , Tobías Aurelio , Benavides Fernando G.
Published: December 2021

Background

More than half of the working population in Latin American and Caribbean (LAC) countries is engaged in informal employment. The few previous studies indicate that this employment condition could have negative consequences for workers’ health. The aim of the present study was to estimate the association between self-perceived health and informality in LAC countries according to gender and welfare state type.

Methods

The cross-sectional study based on different working conditions and health national surveys was carried out in 13 LAC countries between 2012 and 2018. A sample of 176,786 workers was selected from these surveys. The association between health and informality was estimated using Poisson regression. Finally, a random effects meta-analysis was carried out by country. All results were stratified by sex and type of welfare state (statalist or familialist).

Results

Informal workers reported significantly worse health than formal workers, for both women (1.28 [95% CI 1.14-1.43]) and men (1.30 [1.12-1.50]). This difference was broader and more significant in countries with statalist welfare state regimes, among both women (1.40 [1.22-1.60]) and men (1.51 [1.30-1.74]), than in familialist regime countries (1.19 [1.03-1.38] and 1.24 [1.03-1.49], respectively).

Conclusions

This study provides strong evidence of the association between informal employment and worker health. Welfare states appear to have a modifying effect on this association. The transition from the informal to the formal labour market in LAC is essential to improving the health of the population.
Therapeutic effect of osimertinib plus cranial radiotherapy compared to osimertinib alone in NSCLC patients with EGFR-activating mutations and brain metastases: a retrospective study
Authors: Zhai Xiaoyang , Li Wanhu , Li Ji , Jia Wenxiao , Jing Wang , Tian Yaru , Xu Shuhui , Li Yuying , Zhu Hui , Yu Jinming
Published: December 2021

Background

The study aimed to compare the efficacy of osimertinib plus cranial radiotherapy (RT) with osimertinib alone in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations and brain metastases (BMs).

Methods

The clinical data of advanced NSCLC patients with BMs who received osimertinib were retrospectively collected. The patients were assigned to one of the two groups according to the therapeutic modality used: the osimertinib monotherapy group or the osimertinib plus RT group.

Results

This was a retrospective study and 61 patients were included from December 2015 to August 2020. Forty patients received osimertinib monotherapy, and twenty-one patients received osimertinib plus RT. Radiotherapy included whole-brain radiation therapy (WBRT, n = 14), WBRT with simultaneous integrated boost (WBRT-SIB, n = 5) and stereotactic radiosurgery (SRS, n = 2). The median number of prior systemic therapies in the two groups was one. Intracranial and systemic ORR and DCR were not significantly different between the two groups. No difference in iPFS was observed between the two groups (median iPFS: 16.67 vs. 13.50 months, P = 0.836). The median OS was 29.20 months in the osimertinib plus RT group compared with 26.13 months in the osimertinib group (HR = 0.895, P = 0.826). In the L858R mutational subgroup of 31 patients, the osimertinib plus RT group had a longer OS (P = 0.046). In the exon 19 deletion mutational subgroup of 30 patients, OS in the osimertinib alone group was longer than that in the osimertinib plus RT group (P = 0.011). The incidence of any-grade adverse events was not significantly different between the osimertinib plus RT group and the osimertinib alone group (47.6% vs. 32.5%, P = 0.762). However, six patients (28.5%) experienced leukoencephalopathy in the osimertinib plus RT group, and 50% (3/6) of the leukoencephalopathy was greater than or equal to grade 3.

Conclusion

The therapeutic effect of osimertinib with RT was similar to that of osimertinib alone in EGFR-positive NSCLC patients with BM. However, for patients with the L858R mutation, osimertinib plus RT could provide more benefit than osimertinib alone.
Optogenetically controlled human functional motor endplate for testing botulinum neurotoxins
Authors: de Lamotte Juliette Duchesne , Polentes Jérôme , Roussange Florine , Lesueur Léa , Feurgard Pauline , Perrier Anselme , Nicoleau Camille , Martinat Cécile
Published: December 2021

Background

The lack of physiologically relevant and predictive cell-based assays is one of the major obstacles for testing and developing botulinum neurotoxins (BoNTs) therapeutics. Human-induced pluripotent stem cells (hiPSCs)-derivatives now offer the opportunity to improve the relevance of cellular models and thus the translational value of preclinical data.

Methods

We investigated the potential of hiPSC-derived motor neurons (hMNs) optical stimulation combined with calcium imaging in cocultured muscle cells activity to investigate BoNT-sensitivity of an in vitro model of human muscle-nerve system.

Results

Functional muscle-nerve coculture system was developed using hMNs and human immortalized skeletal muscle cells. Our results demonstrated that hMNs can innervate myotubes and induce contractions and calcium transient in muscle cells, generating an in vitro human motor endplate showing dose-dependent sensitivity to BoNTs intoxication. The implementation of optogenetics combined with live calcium imaging allows to monitor the impact of BoNTs intoxication on synaptic transmission in human motor endplate model.

Conclusions

Altogether, our findings demonstrate the promise of optogenetically hiPSC-derived controlled muscle-nerve system for pharmaceutical BoNTs testing and development.
Development of a simple and miniaturized sandwich-like fluorescence polarization assay for rapid screening of SARS-CoV-2 main protease inhibitors
Authors: Yan Gangan , Li Dongsheng , Lin Yuan , Fu Zhenghao , Qi Haiyan , Liu Xiaoping , Zhang Jing , Si Shuyi , Chen Yunyu
Published: December 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible and has caused a pandemic named coronavirus disease 2019 (COVID-19), which has quickly spread worldwide. Although several therapeutic agents have been evaluated or approved for the treatment of COVID-19 patients, efficacious antiviral agents are still lacking. An attractive therapeutic target for SARS-CoV-2 is the main protease (Mpro), as this highly conserved enzyme plays a key role in viral polyprotein processing and genomic RNA replication. Therefore, the identification of efficacious antiviral agents against SARS-CoV-2 Mpro using a rapid, miniaturized and economical high-throughput screening (HTS) assay is of the highest importance at the present.

Results

In this study, we first combined the fluorescence polarization (FP) technique with biotin-avidin system (BAS) to develop a novel and step-by-step sandwich-like FP screening assay to quickly identify SARS-CoV-2 Mpro inhibitors from a natural product library. Using this screening assay, dieckol, a natural phlorotannin component extracted from a Chinese traditional medicine Ecklonia cava, was identified as a novel competitive inhibitor against SARS-CoV-2 Mpro in vitro with an IC50 value of 4.5 ± 0.4 µM. Additionally, dieckol exhibited a high affinity with SARS-CoV-2 Mpro using surface plasmon resonance (SPR) analysis and could bind to the catalytic sites of Mpro through hydrogen-bond interactions in the predicted docking model.

Conclusions

This innovative sandwich-like FP screening assay enables the rapid discovery of antiviral agents targeting viral proteases, and dieckol will be an excellent lead compound for generating more potent and selective antiviral agents targeting SARS-CoV-2 Mpro.
A systemic comparative economic approach efficiency of fodder production
Authors: Lukyanova Milyausha , Kovshov Vitaliy , Zalilova Zariya , Lukyanov Vasily , Araslanbaev Irek
Published: December 2021

The purpose of the study is to determine the optimal volume of fodder and grain-fodder crops of appropriate quality to meet the needs of the livestock industry using a systemic comparative economic approach. For the economic assessment of crops for fodder purposes, a systemic comparative economic approach to their production efficiency has been developed. Accounting was carried out according to the three most important indicators in fodder units: quantitative indicators—productivity per hectare of sowing, qualitative—the content of vegetable protein and cost—the production cost. Oats were taken as the primary culture. Their comparison made it possible to determine economically interrelated partial indices, which are reduced to the index of the systemic comparative economic approach, which contributes to optimizing the structure of the cultivated areas of these crops. This technique allows to determine each forage crop’s location in each farm or region’s conditions, analyzing the real situation and assessing the prospects for the development of production. The optimal structure of sown areas for grain-fodder and fodder crops, focused on the cultivation of high-protein crops, for the enterprises of the Northern forest-steppe zone of the Republic of Bashkortostan is proposed. Due to a change in sown areas’ structure, the gross harvest increases by 8%, digestible protein by 2%, and reduced production costs by 48%.
Financial inclusion and development in the least developed countries in Asia and Africa
Authors: Cicchiello Antonella Francesca , Kazemikhasragh Amirreza , Monferrá Stefano , Girón Alicia
Published: December 2021

The purpose of this paper is to investigate the relationship between the financial inclusion index and development variables in the least developed countries in Asia and Africa by using annual data of 42 countries for the period 2000–2019. The pooled panel regression and panel data analysis technique are used to explore this relationship. The empirical finding indicates that economic growth leads to financial inclusion. Unemployment and literacy rates are among the factors contributing to financial inclusion, and it is observed that women are more vulnerable than men are to lack financial inclusion. In less developed countries, the economy relies heavily on agriculture, and people are less financially inclusive when they live in rural areas of these countries. Also, pay inequality reduces financial inclusion rates and has a negative impact on development. The low financial inclusion rate reduces the levels of development in these countries. The results of this study can lead to the development and empowerment of vulnerable groups in the studied countries. In order to improve the conditions for development, policymakers should consider policies that enhance literacy, eliminate gender inequality and increase pay equality.
The association of genetic polymorphisms in interleukin-1 receptors type 1 and type 2 with sudden sensorineural hearing loss in a Taiwanese population: A case control study
Authors: Chien Chen-Yu , Tai Shu-Yu , Li Kuan-Hui , Yang Hua-Ling , Chan Leong-Perng , Hsi Edward , Wang Ling-Feng , Ho Kuen-Yao , Chang Ning-Chia
Published: December 2021

Background

Sudden sensorineural hearing loss (SSNHL) is a disease with an unknown etiology; damage to the auditory nerve from inflammation due to viral infection or vascular incidents has been implicated. According to several studies, cytokines, including interleukins, are associated with SSNHL in terms of serum expression and genetic polymorphisms. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with SSNHL. This study analyzed the association of single nucleotide polymorphisms (SNPs) of IL-1 receptor (IL-1R) genes with SSNHL in Taiwan.

Methods

We conducted a case–control study involving 401 patients with SSNHL and 730 healthy controls. Four SNPs (IL-1R type 1 gene [ IL1R1] [rs3917225 and rs2234650] and IL-1R type 2 gene [ IL1R2] [rs4141134 and rs2071008]) were selected. The genotypes were determined using the TaqMan assay. The Hardy–Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated.

Results

The TT genotype of rs2234650 had an adjusted odds ratio (OR) of 2.988 (95% confidence interval [95% CI] 1.27–6.82) ( P = 0.012) compared with the CC genotype in patients with SSNHL. The SNP rs2234650 was associated with SSNHL in the recessive model (TT vs. CC + CT, P = 0.0206, OR = 2.681). The CT genotype of rs4141134 had an adjusted OR of 3.860 (95% CI 2.01–7.44; P < 0.0001) compared with the TT genotype, in patients with SSNHL. The SNP rs4141134 was associated with SSNHL under the dominant model (CC + CT vs. TT, P < 0.0001, OR = 4.087).

Conclusion

These findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan.
Does the wind stress always damp an oceanic eddy?
Authors: Teng Fangyuan , Dong Changming , Ji Jinlin , Bethel Brandon J. , Pan Aijun , Xu Chi
Published: December 2021

Up to now, the literature has shown that the relative wind stress does negative work on ocean mesoscale eddies. In other words, the relative wind stress inhibits the development of the eddies. However, based on a newly derived simplified theoretical model, the present study finds that under the action of a steady and uniform wind field, eddies can rapidly obtain kinetic energy from the wind field following several hours of adaption and adjustment, in which the wind stress transitions from doing negative to positive work. The finding is supported by the fact that the relative wind stress work on oceanic eddies over the northeastern tropical Pacific ocean is positive with the nearly constant gap wind. This implies that energy input from the wind is sensitive to eddy velocity structure, and hence, wind stress is not always a killer of eddies.
Sustainable functional finishing for cotton fabrics using screen-printing process and gallotannin
Authors: Hong Kyung Hwa
Published: December 2021

To seek a more environmentally friendly textile finishing technique, the screen-printing method was adopted to apply functional material to cotton fabrics. In addition, gallotannin was used as a functional material because it is naturally abundant in many plant-derived substances and shows various health-promoting features such as antimicrobial, antioxidant, and other attractive properties. Therefore, a gallotannin/thickener paste was applied to the surface of cotton fabrics through the screen-printing technique, and the gallotannin-printed cotton fabrics were thoroughly investigated using scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), and other methods. The gallotannin printed area was substantially brown in appearance, and gallotannin moiety appeared to combine with cotton cellulose through heat treatment. Furthermore, functional properties of the gallotannin-printed cotton fabrics were examined in terms of antibacterial activity, deodorizing property, and ultraviolet-blocking property, of which it demonstrated excellent abilities. However, the antibacterial ability toward Gram-negative bacteria (K. pneumoniae) decreased as the laundry cycle increased.
Dr. Vivian Pinn: a woman pioneer & leader
Authors: Bachmann Gloria , Woods Nancy
Published: December 2021

The Women’s Health Institute in collaboration with the Journal of Women’s Midlife Health hosted a national roundtable with Dr. Vivian Pinn via Zoom to honor her for her achievements in the areas of women’s health, wellness, and research. The panelists included Gloria A. Bachmann, MD, MMS, Sherri-Ann Burnett-Bowie, MD, MPH, and Sioban D. Harlow, PhD.
Detailed morphology of tentacular apparatus and central nervous system in Owenia borealis (Annelida, Oweniidae)
Authors: Temereva Elena , Rimskaya-Korsakova Nadezhda , Dyachuk Vyacheslav
Published: December 2021

The Oweniidae are marine annelids with many unusual features of organ system, development, morphology, and ultrastructure. Together with magelonids, oweniids have been placed within the Palaeoannelida, a sister group to all remaining annelids. The study of this group may increase our understanding of the early evolution of annelids (including their radiation and diversification). In the current research, the morphology and ulta-anatomy of the head region ofOwenia borealisis studied by scanning electron microscopy (SEM), 3D reconstructions, transmission electron microscopy (TEM), and whole-mount immunostaining with confocal laser scanning microscopy. According to SEM, the tentacle apparatus consists of 8–14 branched arms, which are covered by monociliary cells that form a ciliary groove extending along the oral side of the arm base. Each tentacle contains a coelomic cavity with a network of blood capillaries. Monociliary myoepithelial cells of the tentacle coelomic cavity form both the longitudinal and the transverse muscles. The structure of this myoepithelium is intermediate between a simple and pseudo-stratified myoepithelium. Overall, tentacles lack prominent zonality, i.e., co-localization of ciliary zones, neurite bundles, and muscles. This organization, which indicates a non-specialized tentacle crown inO. borealisand other oweniids with tentacles, may be ancestral for annelids. TEM, light, and confocal laser scanning microscopy revealed that the head region contains the anterior nerve center comprising of outer and inner (=circumoral) nerve rings. Both nerve rings are organized as concentrated nerve plexus, which contains perikarya and neurites extending between basal projections of epithelial cells (radial glia). The outer nerve ring gives rise to several thick neurite bundles, which branch and extend along aboral side of each tentacle. Accordingly to their immunoreactivity, both rings of the anterior nerve center could be homologized with the dorsal roots of circumesophageal connectives of the typical annelids. Accordingly to its ultrastructure, the outer nerve ring ofO. borealisand so-called brain of other oweniids can not be regarded as a typical brain, i.e. the most anterior ganglion, because it lacks ganglionic structure.
Early neurovascular retinal changes detected by swept-source OCT in type 2 diabetes and association with diabetic kidney disease
Authors: da Silva Monica Oliveira , do Carmo Chaves Anne Elise Cruz , Gobbato Glauber Corrêa , dos Reis Mateus Augusto , Lavinsky Fabio , Schaan Beatriz D’Agord , Lavinsky Daniel
Published: December 2021

Purpose

To evaluate retinal thickness and capillary density in patients with type 2 diabetes (T2D) and their association with diabetic kidney disease (DKD) using swept-source optical coherence tomography (SS-OCT).

Methods

A cross-sectional study was conducted with T2D patients with mild or no diabetic retinopathy (DR) and nondiabetic controls. Inner retinal layer thickness was measured with SS-OCT. Retinal capillary density and the foveal avascular zone (FAZ) were measured with SS-OCT angiography (OCTA). SS-OCT parameters were compared in patients with and without diabetic kidney disease (DKD) and nondiabetic controls.

Results

131 DKD eyes showed decreased ganglion cell layer plus (GCL+) (p = 0.005 TI; p = 0.022 I), retinal nerve fiber layer (RNFL) (p = 0.003), and central retinal thickness (CRT) (p = 0.032), as well as foveal avascular zone (FAZ) enlargement (p = 0.003) and lower capillary density in the superficial vascular plexus (p = 0.016, central quadrant), compared to controls. No statistically significant changes were found between diabetic patients without significant DKD and controls.

Conclusion

Our findings suggest early neurovascular damage in patients with T2D; these changes were more significant in patients with DKD. Larger longitudinal studies are warranted to determine the role of early neurovascular damage in the pathophysiology of severe DR.
A case report of isolated abducens nerve palsy: idiopathic or ophthalmoplegic neuropathy?
Authors: Husain Zainab Irshad , AlSayegh Rawaa , Humaidan Hani
Published: December 2021

Background

Abducens nerve is the most common nerve affected among other cranial nerves in terms of isolated ocular palsy. Despite its prevalence and progression made in neuroimaging, incidence of idiopathic cases continues to rise.

Case presentation

We report a young adult male with no previous illnesses, who presented with sudden onset of binocular diplopia and headache and was later diagnosed with an isolated ipsilateral abducens nerve palsy secondary to an unknown cause and treated with steroids. The palsy and diplopia had resolved in 2-month time but the patient still continued to suffer from a migraine, such as headache.

Conclusion

Although, we labelled the patient as idiopathic initially, another plausible cause for this kind of presentation could be recurrent painful ophthalmoplegic neuropathy (RPON) owing to the nature of the presentation. Cases labelled as idiopathic could be attributed to a defined pathogenesis with detailed history and follow-up. Follow-up is vital for all patients, especially those labelled as idiopathic as recurrence of the illness have the chance of changing the diagnosis if supported by the detailed history and physical examination findings.
Quality of life after ischaemic stroke—accent on patients with thrombolytic therapy
Authors: Tsalta-Mladenov Mihael Emilov , Andonova Silva Peteva
Published: December 2021

Background

Intravenous thrombolysis is a widely approved treatment method for acute ischemic stroke (AIS). Nevertheless, there is a growing interest in its impact on functional outcomes and Health-related Quality of life (HR-QoL). We aimed to evaluate and compare the HR-QoL in patients receiving intravenous thrombolysis (IVT) and in those without thrombolytic therapy during the first 3-month post-stroke in a defined Bulgarian population.

Results

Patients treated with IVT have simillar functional outcomes and HR-QoL on the third month as the group with conservative treatment, besides their higher NIHSS on admission. Patients with IVT had better self-assessed recovery after the AIS. The higher NIHSS and mRS scores and the lower HR-QoL on discharge are reliable predictors for a poor functional outcome on the third month. A door-to-needle of 60 min or less, and the absence of pathological neuroimaging findings 24-h post IVT predict more beneficial HR-QoL outcome.

Conclusion

There were no significant differences in HR-QoL and functional outcomes between the groups. Nevertheless, IVT is a treatment option with great importance for improving the clinical outcomes after ischemic stroke, which should be performed in well selected patients.
Helicobacter pylori antibodies and multiple sclerosis: a single-center study and a short review of the literature
Authors: Cantero-Fortiz Yahveth , Murrieta-Álvarez Iván , León-Peña Andrés Aurelio , López-Trujillo Miguel Antonio , Córdova-Ramírez Alejandra Carmina , Rivera-Álvarez Montserrat , Elias-de-la-Cruz Gilberto David , Olivares-Gazca Juan Carlos , Ruiz-Delgado Guillermo J. , Ruiz-Argüelles Guillermo J.
Published: December 2021

Background

Multiple sclerosis is an immune-mediated disease which has been associated to a great variety of mechanisms that could influence its pathogenesis. Numerous reports in the medical literature suggest that Helicobacter pylori may be a mediator of the disease. However, it is unknown if there is any clear association between MS and HP.

Results

We studied 144 persons with multiple sclerosis prospectively enrolled in our hematopoietic stem cell transplantation program. In 144 persons, 14% patients were positive for IgG-HP whereas 86% were negative, 8.3% pwMS were IgM-HP positive while 91.6% pwMS were negative, 18% patients were positive and 82% negative for IgA-HP. Significantly lower concentrations of anti-HP IgG were found in RRMS in comparison with SPMS (− 28.5, 95% CI 4.3–52.7). While concentrations of anti-HP IgA were significantly lower in SPMS in comparison with RRMS (0.54, 95% CI 0.1–0.9). In a multivariate analysis, positivity rate of anti-HP IgG was found to be higher in SPMS patients (OR 4.7, 95% CI 1.1–19.6).

Conclusions

There was a negative correlation between the presence of anti-HP antibodies and MS. Further larger studies with specific laboratory testing methods are needed to discard or confirm the potential role of anti-HP antibodies as protective for MS.
Cholesterol modified DP7 and pantothenic acid induce dendritic cell homing to enhance the efficacy of dendritic cell vaccines
Authors: Zhang Rui , Tang Lin , Li Qing , Tian Yaomei , Zhao Binyan , Zhou Bailing , Yang Li
Published: December 2021

Dendritic cell (DC)-based cancer vaccines have so far achieved good therapeutic effects in animal experiments and early clinical trials for certain malignant tumors. However, the overall objective response rate in clinical trials rarely exceeds 15%. The poor efficiency of DC migration to lymph nodes (LNs) (< 5%) is one of the main factors limiting the effectiveness of DC vaccines. Therefore, increasing the efficiency of DC migration is expected to further enhance the efficacy of DC vaccines. Here, we used DP7-C (cholesterol modified VQWRIRVAVIRK), which can promote DC migration, as a medium. Through multiomics sequencing and biological experiments, we found that it is the metabolite pantothenic acid (PA) that improves the migration and effectiveness of DC vaccines. We clarified that both DP7-C and PA regulate DC migration by regulating the chemokine receptor CXCR2 and inhibiting miR-142a-3p to affect the NF-κB signaling pathway. This study will lay the foundation for the subsequent use of DP7-C as a universal substance to promote DC migration, further enhance the antitumor effect of DC vaccines, and solve the bottleneck problem of the low migration efficiency and unsatisfactory clinical response rate of DC vaccines.
New Horizons. A New Paradigm for Treating to Target with Second-Generation Obesity Medications
Authors: Garvey W Timothy
Published: December 2021

In treating obesity as a chronic disease, the essential goal of weight loss therapy is not the quantity of weight loss as an end unto itself but rather the prevention and treatment of complications to enhance health and mitigate morbidity and mortality. This perspective on obesity care is consistent with the complications-centric American Association of Clinical Endocrinology (AACE) obesity guidelines and the diagnostic term of adiposity-based chronic disease (ABCD). Many complications require 10% to 20% weight loss to achieve therapeutic goals; however, existing obesity medications fail to produce ≥10% weight loss in the majority of patients. In June, 2021, semaglutide 2.4 mg/week was approved for chronic weight management. Phase 3 clinical trials demonstrated that this medication produced > 10% placebo-subtracted weight loss, more than half of patents lost ≥15%, and over one third lost ≥20% of baseline weight. This essentially doubles effectiveness over existing obesity medications, provides sufficient weight loss to ameliorate a broad range of complications, and qualifies as the first member of a second-generation class of obesity medications. The advent of second-generation medications fully enables a treat-to-target approach for management of ABCD as a chronic disease. Specifically, with this degree of efficacy, second-generation medications permit active management of body weight as a biomarker to targets associated with effective treatment and prevention of specific complications. ABCD can now be managed similar to other chronic diseases such as type 2 diabetes, hypertension, and atherosclerosis, which are treated to biomarker targets that can be modified based on the clinical status of individual patients [ie, hemoglobin A1c (HbA1c), blood pressure, and low-density lipoprotein cholesterol (LDL-c)] to prevent the respective complications of these diseases.
Low Progesterone and Low Estradiol Levels Associate With Abdominal Aortic Aneurysms in Men
Authors: Ohlsson Claes , Langenskiöld Marcus , Smidfelt Kristian , Poutanen Matti , Ryberg Henrik , Norlén Anna-Karin , Nordanstig Joakim , Bergström Göran , Tivesten Åsa
Published: December 2021

Context

Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.

Objective

We aimed to describe the associations between serum sex steroids and early, screening-detected AAA in men.

Methods

We validated a high-sensitivity liquid chromatography–tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥ 30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men.

Outcomes included

associations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence.

Results

Dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI, 1.18-2.22]) and estradiol (1.40 [95% CI, 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI, 2.25-7.31]).

Conclusion

Measured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independent of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.
Oral Contraceptive and Menopausal Hormone Therapy Use and Risk of Pituitary Adenoma: Cohort and Case-Control Analyses
Authors: Cote David J , Kilgallon John L , Nawabi Noah L A , Dawood Hassan Y , Smith Timothy R , Kaiser Ursula B , Laws Edward R , Manson JoAnn E , Stampfer Meir J
Published: December 2021

Context

No prospective epidemiologic studies have examined associations between use of oral contraceptives (OCs) or menopausal hormone therapy (MHT) and risk of pituitary adenoma in women.

Objective

Our aim was to determine the association between use of OC and MHT and risk of pituitary adenoma in two separate datasets.

Methods

We evaluated the association of OC/MHT with risk of pituitary adenoma in the Nurses’ Health Study and Nurses’ Health Study II by computing multivariable-adjusted hazard ratios (MVHR) of pituitary adenoma by OC/MHT use using Cox proportional hazards models. Simultaneously, we carried out a matched case-control study using an institutional data repository to compute multivariable-adjusted odds ratios (MVOR) of pituitary adenoma by OC/MHT use.

Results

In the cohort analysis, during 6 668 019 person-years, 331 participants reported a diagnosis of pituitary adenoma. Compared to never-users, neither past (MVHR = 1.05; 95% CI, 0.80-1.36) nor current OC use (MVHR = 0.72; 95% CI, 0.40-1.32) was associated with risk. For MHT, compared to never-users, both past (MVHR = 2.00; 95% CI, 1.50-2.68) and current use (MVHR = 1.80; 95% CI, 1.27-2.55) were associated with pituitary adenoma risk, as was longer duration (MVHR = 2.06; 95% CI, 1.42-2.99 comparing more than 5 years of use to never, P trend = .002). Results were similar in lagged analyses, when stratified by body mass index, and among those with recent health care use. In the case-control analysis, we included 5469 cases. Risk of pituitary adenoma was increased with ever use of MHT (MVOR = 1.57; 95% CI, 1.35-1.83) and OC (MVOR = 1.27; 95% CI, 1.14-1.42) compared to never.

Conclusion

Compared to never use, current and past MHT use and longer duration of MHT use were positively associated with higher risk of pituitary adenoma in 2 independent data sets. OC use was not associated with risk in the prospective cohort analysis and was associated with only mildly increased risk in the case-control analysis.
Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1
Authors: Mozar Fitya , Sharma Vikas , Gorityala Shashank , Albert Jeffrey M , Xu Yan , Montano Monica M
Published: December 2021

We have previously reported that hexamethylene bis-acetamide inducible protein 1 (HEXIM1) inhibits the activity of ligand-bound estrogen receptor α (ERα) and the androgen receptor (AR) by disrupting the interaction between these receptors and positive transcriptional elongation factor b (P-TEFb) and attenuating RNA polymerase II (RNAPII) phosphorylation at serine 2. Functional consequences of the inhibition of transcriptional activity of ERα and AR by HEXIM1 include the inhibition of ERα- and AR-dependent gene expression, respectively, and the resulting attenuation of breast cancer (BCa) and prostate cancer (PCa) cell proliferation and growth. In our present study, we determined that HEXIM1 inhibited AKR1C3 expression in BCa and PCa cells. AKR1C3, also known as 17β-hydroxysteroid dehydrogenase (17β-HSD) type 5, is a key enzyme involved in the synthesis of 17β-estradiol (E2) and 5-dihydrotestosterone (DHT). Downregulation of AKR1C3 by HEXIM1 influenced E2 and DHT production, estrogen- and androgen-dependent gene expression, and cell proliferation. Our studies indicate that HEXIM1 has the unique ability to inhibit both the transcriptional activity of the ER and AR and the synthesis of the endogenous ligands of these receptors.
Glucocorticoid Production in Lymphoid Organs: Acute Effects of Lipopolysaccharide in Neonatal and Adult Mice
Authors: Salehzadeh Melody , Hamden Jordan E , Li Michael X , Bajaj Hitasha , Wu Ruolan S , Soma Kiran K
Published: December 2021

Glucocorticoids (GCs) are critical modulators of the immune system. The hypothalamic-pituitary-adrenal (HPA) axis regulates circulating GC levels and is stimulated by endotoxins. Lymphoid organs also produce GCs; however, it is not known how lymphoid GC levels are regulated in response to endotoxins. We assessed whether an acute challenge of lipopolysaccharide (LPS) increases lymphoid levels of progesterone and GCs, and expression of steroidogenic enzymes and key HPA axis components (eg, corticotropin-releasing hormone [CRH], adrenocorticotropic hormone [ACTH]). We administered LPS (50 µg/kg intraperitoneally) or vehicle control to male and female C57BL/6J neonatal (postnatal day [PND] 5) and adult (PND90) mice and collected blood, bone marrow, thymus, and spleen 4 hours later. We measured progesterone, 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone via liquid chromatography–tandem mass spectrometry. We measured gene expression of key steroidogenic enzymes (Cyp11b1, Hsd11b1, and Hsd11b2) and HPA axis components (Crh, Crhr1, Pomc, and Mc2r) via quantitative polymerase chain reaction. At PND5, LPS induced greater increases in steroid levels in lymphoid organs than in blood. In contrast, at PND90, LPS induced greater increases in steroid levels in blood than in lymphoid organs. Steroidogenic enzyme transcripts were present in all lymphoid organs, and LPS altered steroidogenic enzyme expression predominantly in the spleen. Lastly, we detected transcripts of key HPA axis components in all lymphoid organs, and there was an effect of LPS in the spleen. Taken together, these data suggest that LPS regulates GC production by lymphoid organs, similar to its effects on the adrenal glands, and the effects of LPS might be mediated by local expression of CRH and ACTH.
Deletion of Gαq/11 or Gαs Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice
Authors: Stamatiades George A , Toufaily Chirine , Kim Han Kyeol , Zhou Xiang , Thompson Iain R , Carroll Rona S , Chen Min , Weinstein Lee S , Offermanns Stefan , Boehm Ulrich , Bernard Daniel J , Kaiser Ursula B
Published: December 2021

Gonadotropin-releasing hormone (GnRH) regulates gonadal function via its stimulatory effects on gonadotropin production by pituitary gonadotrope cells. GnRH is released from the hypothalamus in pulses and GnRH pulse frequency differentially regulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis and secretion. The GnRH receptor (GnRHR) is a G protein–coupled receptor that canonically activates Gα q/11-dependent signaling on ligand binding. However, the receptor can also couple to Gα s and in vitro data suggest that toggling between different G proteins may contribute to GnRH pulse frequency decoding. For example, as we show here, knockdown of Gα s impairs GnRH-stimulated FSH synthesis at low- but not high-pulse frequency in a model gonadotrope-derived cell line. We next used a Cre-lox conditional knockout approach to interrogate the relative roles of Gα q/11 and Gα s proteins in gonadotrope function in mice. Gonadotrope-specific Gα q/11 knockouts exhibit hypogonadotropic hypogonadism and infertility, akin to the phenotypes seen in GnRH- or GnRHR-deficient mice. In contrast, under standard conditions, gonadotrope-specific Gα s knockouts produce gonadotropins at normal levels and are fertile. However, the LH surge amplitude is blunted in Gα s knockout females and postgonadectomy increases in FSH and LH are reduced both in males and females. These data suggest that GnRH may signal principally via Gα q/11 to stimulate gonadotropin production, but that Gα s plays important roles in gonadotrope function in vivo when GnRH secretion is enhanced.
New and Consolidated Therapeutic Options for Pubertal Induction in Hypogonadism: In-depth Review of the Literature
Authors: Federici Silvia , Goggi Giovanni , Quinton Richard , Giovanelli Luca , Persani Luca , Cangiano Biagio , Bonomi Marco
Published: December 2021

Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at “the child with delayed puberty of uncertain etiology” risk being misapplied to older adolescents likely to have permanent hypogonadism.
The Effect of Curative Treatment on Hyperglycemia in Patients With Cushing Syndrome
Authors: Herndon Justine , Kaur Ravinder Jeet , Romportl Mark , Smith Emily , Koenigs Amy , Partlow Brenda , Arteaga Leonardo , Bancos Irina
Published: December 2021

Context

Hyperglycemia is a common complication of Cushing syndrome (CS).

Objective

We aimed to determine the impact of curative procedure on hyperglycemia and its management in patients with CS.

Methods

This retrospective longitudinal cohort study took place 2000 to 2019 in a referral center among adults with endogenous CS and hyperglycemia. Main outcome measures included glycated hemoglobin A1c (HbA1c), intensity of hyperglycemia therapy, and improvement of hyperglycemia.

Results

In 174 patients with CS (pituitary in 106, ectopic in 25, adrenal in 43), baseline median HbA1c was 6.9% (range, 4.9-13.1), with 41 (24%) patients not on any therapy for hyperglycemia, 93 (52%) on oral medications, and 64 (37%) on insulin (median daily units of 58; range, 10-360). Following CS remission, at the end of follow-up (median 10.5 months), 37 (21%) patients demonstrated resolution of hyperglycemia, 82 (47%) demonstrated improvement, and 55 (32%) had no change or worsening in hyperglycemia. At the end of follow-up, HbA1c decreased by 0.84% (P < .001) and daily insulin dose decreased by a mean of 30 units (P < .001). Biochemical hypercortisolism severity score (severe vs moderate/mild: odds ratio [OR] of 2.4 [95% CI, 1.1-4.9]), and CS subtype (nonadrenal vs adrenal: OR of 2.9 [95% CI, 1.3-6.4]), but not type of hyperglycemia (diabetes vs prediabetes: OR of 2.1 [0.9-4.9]) were associated with hyperglycemia improvement at the end of follow-up.

Conclusion

Two-thirds of patients with CS and hyperglycemia demonstrate resolution or improvement of hyperglycemia after a curative procedure. Close monitoring during CS recovery is needed to ensure appropriate therapy modification.
Plasma FGF-21 and Sclerostin Levels, Glycemia, Adiposity, and Insulin Sensitivity in Normoglycemic Black and White Adults
Authors: Umekwe Nkiru , Owei Ibiye , Stentz Frankie , Dagogo-Jack Sam
Published: December 2021

Increased circulating fibroblast growth factor (FGF)-21 and sclerostin levels have been reported in patients with type 2 diabetes (T2D). We assessed the association of FGF-21 and sclerostin with adiposity, glycemia, and glucoregulatory measures in healthy subjects. We studied 20 normoglycemic Black and White offspring of parents with T2D. Assessments included oral glucose tolerance test, insulin sensitivity (Si-clamp), insulin secretion (homeostasis model assessment index of b-cell function [HOMA-B]), and body fat (dual-energy X-ray absorptiometry). Fasting plasma FGF-21 and sclerostin levels were measured with enzyme-linked immunosorbent assays. The participants’ mean (+SD) age was 50.4 ± 5.97 years; body mass index (BMI) 32.5 ± 5.86 kg/m2; fasting plasma glucose (FPG) 96.1 ± 5.21 mg/dL, and 2-hour postload glucose 116 ± 5.45 mg/dL. FGF-21 levels were similar in Black people vs White people (0.36 ± 0.15 ng/mL vs 0.39 ± 0.25 ng/mL), men vs women (0.45 ± 0.14 vs 0.44 ± 0.07 ng/mL), correlated positively with BMI (r = 0.23, P = .05) and waist circumference (r = 0.27, P = .04), and inversely with FPG (r = –0.26, P = .05). Sclerostin levels also were similar in Black people (33.5 ± 17.1 pmol/L) vs White people (34.2 ± 6.41 pmol/L), men vs women (35.3 ± 9.01 pmol/L vs 32.3 ± 15.8 pmol/L), and correlated inversely with FPG (r = –0.11 to –0.44) but not adiposity measures. The correlation coefficient between Si-clamp values and FGF-21 levels was –0.31 (P = .09) compared with 0.04 (P = .89) for sclerostin levels. FGF-21 and sclerostin levels were not correlated with each other or HOMA-B. Among healthy Black and White subjects, plasma FGF-21 and sclerostin showed differential associations with adiposity but concordant association with FPG levels.
The mathematical description of the bulk fluid flow and that of the content impurity dispersion, obtained by replacing integer order temporal derivatives with general temporal Caputo or general temporal Riemann-Liouville fractional order derivatives, are objective
Authors: BALINT Agneta M. , BALINT Stefan
Published: December 2021

In the field of fractional calculus applications, there is a tendency to admit that “integer-order derivatives cannot simply be replaced by fractional-order derivatives to develop fractional-order theories”. There are different arguments for that: initialization problem, inconsistency, use of nonsingular or singular kernels, loss of objectivity. In this paper it is shown that the mathematical description of the bulk fluid flow and that of the content impurity spread replacing integer order temporal derivatives with general temporal Caputo or general temporal Riemann-Liouville fractional order derivatives, are objective. More precisely, it is proven that, the mathematical description of the bulk fluid 2D flow and that of the content impurity spread, in a horizontal unconfined aquifer, obtained replacing integer order temporal derivatives with general temporal Caputo or general temporal Riemann-Liouville fractional order derivatives, are objective. It is also proven that, the mathematical description of a Newtonian, incompressible, viscous bulk fluid 3D flow and that of the contained impurity dispersion, obtained replacing integer order temporal derivatives with general temporal Caputo or general temporal Riemann-Liouville fractional order derivatives, are objective. The obtained results show the compatibility of the general temporal Caputo and general temporal Riemann-Liouville fractional order derivatives with the understanding of the “measured time” evolution. In the same time these results reveal that, the objectivity violation, when integer order temporal derivatives are replaced by classic temporal Caputo or classic temporal Riemann-Liouville fractional order derivatives, is originated in the incompatibility of the classic fractional order derivatives, with the understanding of the “measured time” evolution.
Morphing Winglet Design for Aerodynamic Performance Optimization of the CRJ-700 Aircraft. Part 1 – Structural Design
Authors: MEYRAN Paul , PAIN Hugo , BOTEZ Ruxandra Mihaela , LALIBERTÉ Jeremy
Published: December 2021

This study aims to design a morphing winglet structure for the CRJ-700 regional transport aircraft. The morphing technology is applied on winglets to demonstrate a significant increase of the aerodynamic performance of aircraft. From the aerodynamic data of the LARCASE Virtual Research Simulator VRESIM, the aerodynamic benefits in the cruising phase were obtained through a study on the ParaView software. The morphing winglet design was drawn using CATIA V5; this new concept included several structural components, as well as a simple and light mechanism allowing to orientate the winglet angles between 90° and -90° of inclination. The structural model was exported to HyperMesh structural analysis software. Maximum stresses were obtained, and the model demonstrated its resistance to maximum aerodynamic loads as well as load factors of -2G to 7G.
Structural Design and Control of a Morphing Winglet to optimize the Aerodynamic Performance of the CRJ-700 Aircraft. Part 2 – Control
Authors: MEYRAN Paul , PAIN Hugo , BOTEZ Ruxandra Mihaela , LALIBERTÉ Jeremy
Published: December 2021

In this study, the morphing technology was applied on winglets for the CRJ-700 transport regional aircraft with the aim to improve its aerodynamic performance. The LARCASE Virtual Research Simulator VRESIM is equipped with highest Level D certified flight data for the CRJ-700. The flight and geometrical data of the CRJ-700 were used to quantify the aerodynamic benefits of the CRJ-700 equipped with a morphing winglet versus its reference winglet. The structural design and the mechanism allowing its rotation were used to allow the orientation of the winglet with angles between 90° and -90°. The control of the orientation of the morphing winglet with its mechanism was finally carried out using the Matlab/ Simulink interface. Therefore, a new concept of morphing winglet was obtained in this research.