AXL is required for hypoxia-mediated hypoxia-inducible factor-1 alpha function in glioblastoma.

Glioblastoma (GBM) is the most aggressive type of central nervous system tumor. Molecular targeting may be important when developing efficient GBM treatment strategies. Sequencing of GBMs revealed that the receptor tyrosine kinase (RTK)/RAS/phosphatidylinositol-3-kinase pathway was altered in 88% of samples. Interestingly, AXL, a member of RTK, was proposed as a promising target in glioma therapy. However, the molecular mechanism of AXL modulation of GBM genesis and proliferation is still unclear. In this study, we investigated the expression and localization of hypoxia-inducible factor-1 alpha (HIF-1α) by AXL in GBM. Both AXL mRNA and protein are overexpressed in GBM. Short-interfering RNA knockdown of AXL in U251-MG cells reduced viability and migration. However, serum withdrawal reduced AXL expression, abolishing the effect on viability. AXL is also involved in hypoxia regulation. In hypoxic conditions, the reduction of AXL decreased the level and nuclear localization of HIF-1α. The co-expression of HIF-1α and AXL was found in human GBM samples but not normal tissue. This finding suggests a mechanism for GBM proliferation and indicates that targeting AXL may be a potential GBM therapeutic. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00195-z.

Impact assessment of a raw coal ban on maternal and child health outcomes in Ulaanbaatar: a protocol for an interrupted time series study.

INTRODUCTION: Despite a decade of policy actions, Ulaanbaatar's residents continue to be exposed to extreme levels of air pollution, a major public health concern, especially for vulnerable populations such as pregnant women and children. In May 2019, the Mongolian government implemented a raw coal ban (RCB), prohibiting distribution and use of raw coal in households and small businesses in Ulaanbaatar. Here, we present the protocol for an interrupted time series (ITS; a strong quasi-experimental study design for public health interventions) that aims to assess the effectiveness of this coal ban policy on environmental (air quality) and health (maternal and child) outcomes. METHODS AND ANALYSIS: Routinely collected data on pregnancy and child respiratory health outcomes between 2016 and 2022 in Ulaanbaatar will be collected retrospectively from the four main hospitals providing maternal and/or paediatric care as well as the National Statistics Office. Hospital admissions data for childhood diarrhoea, an unrelated outcome to air pollution exposure, will be collected to control for unknown or unmeasured coinciding events. Retrospective air pollution data will be collected from the district weather stations and the US Embassy. An ITS analysis will be conducted to determine the RCB intervention impact on these outcomes. Prior to the ITS, we have proposed an impact model based on a framework of five key factors, which were identified through literature search and qualitative research to potentially influence the intervention impact assessment. ETHICS AND DISSEMINATION: Ethical approval has been obtained via the Ministry of Health, Mongolia (No.445) and University of Birmingham (ERN_21-1403). To inform relevant stakeholders of our findings, key results will be disseminated on both (inter)national and population levels through publications, scientific conferences and community briefings. These findings are aimed to provide evidence for decision-making in coal pollution mitigation strategies in Mongolia and similar settings throughout the world.

Carbon monoxide levels in households using coal-briquette fuelled stoves exceed WHO air quality guidelines in Ulaanbaatar, Mongolia.

In 2019, a domestic raw coal ban (RCB) was introduced in Ulaanbaatar, Mongolia. Coal-briquettes have since been promoted in Ger district households, however implications for carbon monoxide (CO) exposure remains uncertain. We obtained 48-hour indoor CO concentrations in 23 Ger district households and compared these to 10 raw-coal households. Information on household characteristics, fuel use behaviour and stove venting practices was collected by survey. Mean 48-hour CO concentrations in coal-briquette households was 6.1 ppm (range 1.5-35.8 ppm) with no signfiicant differences by household, stove or venting factors. Peak time-weighted average CO concentrations exceeded WHO Indoor Air Quality guidelines in 9 (39%) households; with all surpassing the 8-hour guideline (>8.6 ppm); 3(13%) the 24-hour guideline (>6 ppm) and 2(9%) the 1-hour guideline (>30 ppm). Median CO levels were significantly lower in coal-briquette compared to raw coal households (p = 0.049). Indoor CO reduction was associated with RCB implementation although hazardous levels persist in this setting.

Heart rate variability and tension-type headache: A population-based cross-sectional study.

Background: The relationship between tension-type headache (TTH) and autonomic functions is poorly understood, although TTH is one of the most prevalent disorders in the general population. The aim of this study was to investigate the direct and indirect effects of TTH on the autonomic functions measured by heart rate variability (HRV). Methods: This population-based cross-sectional study was carried out in the general population of Ulaanbaatar between July and September in 2020. After physical examination, trained researchers applied structured interviews to examine the remote history of TTH and mental distress, followed by a recording of HRV to detect autonomic activity. Psychological factors and the quality of life were measured using Hospital Anxiety Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), and the World Health Organization Quality of Life-Brief (WHOQOL-BREF). Binary logistic regression and GLM mediation model analysis were used to examine the effects of risk factors on the associations between TTH and autonomic functions. Results: Among participants (n = 217, mean age=41.8 ±â€¯11.5 years), a total of 117 (53.9%) participants had a remote history of TTH. The age and sex-adjusted prevalence was 43%. Groups did not differ statistically in the HRV indices. LF/HF (ratio of low-frequency to high frequency), the index of sympathovagal balance, was correlated with the HADS anxiety. TTH was associated with mental distress. Binary logistic regression analysis confirms the relationship suggesting that TTH was associated with increased likelihood of mental distress, and decreasing RMSSD (root mean square of the sum of the squares of differences between adjacent NN intervals) and pNN50 (NN50 divided by the total number of NN intervals) were the independent predictors of TTH. GLM mediation model indicated that the relationship between TTH and RMSSD was mediated by mental distress. Conclusions: The present study suggests that mental distress is a critical factor in the association between TTH and autonomic dysfunction. Additionally, our findings demonstrate the influence of age and gender on TTH. These results highlight the need to understand the mechanisms underlying pathophysiology to facilitate targeted and efficacious prevention and management approaches for TTH.

Obstructive Sleep Apnea in a Clinical Population: Prevalence, Predictive Factors, and Clinical Characteristics of Patients Referred to a Sleep Center in Mongolia.

Obstructive sleep apnea (OSA) disrupts sleep. This study examined factors related to OSA severity. A cross-sectional, prospective, hospital-based study was conducted with 205 patients who underwent polysomnography (PSG). Demographic, anthropometric, clinical, PSG, and sleep quality assessment data were analyzed. Participants (N = 205) were classified into four groups based on apnea-hypopnea index (AHI); no OSA (AHI < 5/h; N = 14), mild (mOSA, 5 < AHI < 15/h; N = 50), moderate (modOSA, 15 < AHI < 30/h; N = 41), severe (sOSA, 30 < AHI < 60/h; N = 50), and very severe (vsOSA, AHI ≥ 60; N = 50). Men had more severe OSA than women (p < 0.001). Anthropometric characteristics differed with OSA severity (p < 0.001). OSA patients had decreased sleep quality and increased excessive daytime sleepiness (EDS). Body mass index (BMI), neck/waist circumference, and blood pressure (BP) differed between groups (p < 0.001). Patients with vsOSA had the highest Mallampati grades (p < 0.001). Multiple linear regression indicated that OSA severity was related to gender and sleep quality. PSG parameters (oxygen saturation, systolic BP, and arousal/respiratory arousal) were strongly related to OSA severity. In conclusion, about half of study-referred patients had severe/very severe OSA; these groups were predominantly obese men with high BP. OSA severity associated with high BP, BMI, waist circumference, and neck circumference.

SARS-CoV-2 seroprevalence in Mongolia: Results from a national population survey.

BACKGROUND: With the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in early 2020, Mongolia implemented rapid emergency measures and did not report local transmission until November 2020. We conducted a national seroprevalence survey to monitor the burden of SARS-CoV-2 in Mongolia in the months surrounding the first local transmission. METHODS: During October-December 2020, participants were randomly selected using age stratification and invited for interviews and blood samples at local primary health centres. We screened for total SARS-CoV-2 antibodies, followed by two-step quantitative SARS-CoV-2 IgG serology tests for positive samples. Weighted and test-adjusted seroprevalences were estimated. We used chi-square, Fisher's exact and other tests to identify variables associated with seropositivity. FINDINGS: A total of 5000 subjects were enrolled. We detected SARS-CoV-2 IgG antibodies in 72 samples. Crude seroprevalence of SARS-CoV-2 antibodies was 1·44% (95%CI,1·21-1·67). Population weighted and test-adjusted seroprevalences were 1·36% (95%CI,1·11-1·63) and 1·45% (95%CI,1·11-1·63), respectively. Age, sex, geographical, and occupational factors were not associated with seropositivity (p>0·05). Symptoms and signs within past 3 months and seropositivity were not associated at the time of the survey (p>0·05). INTERPRETATION: SARS-CoV-2 seroprevalence in Mongolia was low in the first year of the pandemic potentially due to strong public health measures, including border restrictions, educational facilities closure, earlier adoption of mask-wearing and others. Our findings suggest large-scale community transmission could not have occurred up to November 2020 in Mongolia. Additional serosurveys are needed to monitor the local pandemic dynamic and estimate how far from herd immunity Mongolia will be following-up with vaccination programme in 2021 and 2022. FUNDING: World Health Organisation, WHO UNITY Studies initiative, with funding by the COVID-19 Solidarity Response Fund and the German Federal Ministry of Health (BMG) COVID-19 Research and development. TRANSLATION: Cyrillic and Traditional Mongolian translation of abstract is available on appendix section.

Pancreas-Brain Crosstalk.

The neural regulation of glucose homeostasis in normal and challenged conditions involves the modulation of pancreatic islet-cell function. Compromising the pancreas innervation causes islet autoimmunity in type 1 diabetes and islet cell dysfunction in type 2 diabetes. However, despite the richly innervated nature of the pancreas, islet innervation remains ill-defined. Here, we review the neuroanatomical and humoral basis of the cross-talk between the endocrine pancreas and autonomic and sensory neurons. Identifying the neurocircuitry and neurochemistry of the neuro-insular network would provide clues to neuromodulation-based approaches for the prevention and treatment of diabetes and obesity.

Prevalence of restless leg syndrome in Mongolian adults: Mon-TimeLine study.

We conducted an epidemiologic study based on survey neuroscience screening for restless leg syndrome in the Mongolian to determine the prevalence of restless leg syndrome. We used baseline data from the Mon-TimeLine study, a multidisciplinary, prospective, population-based cohort study. The total number of participants (n = 1572) ranged from 18 to 65 years of age. We found the prevalence of restless leg syndrome to be 6.6% (n = 103), among which 4.1% (n = 16) were males and 7.3% (n = 87) were females. The peak prevalence age for both genders was 45-55, and we found a positive correlation with body mass index (P < 0.05). Most cases were mild (44.7%) or moderate (35.9%), but 18.4% and 1% of the cases were severe or very severe, respectively. The severe groups showed a positive association with chronic kidney disease, as well as with gastritis. In conclusion, the prevalence of restless leg syndrome in Mongolia approximates that in other countries.

Beneficial effects of Diplectria barbata (Wall. Ex C. B. Clarke) Franken et Roos extract on aging and antioxidants in vitro and in vivo.

The purpose of this study is to explore the effects of Diplectria barbata (Wall. Ex C.B. Clarke) Franken & Roons (DFR) on wound healing, antioxidant and aging in Normal Human Dermal Fibroblast cell (NHDF) cells and mouse skin models. We investigated the effects of the aging process in vitro and in vivo. DFRtreated NHDF cells showed a concentration-dependent increase in the expression of extracellular matrix (ECM) proteins (Collagen-2.5-fold increase at 50 µg/ml, Elastin-1.5-fold increase at 1µg/ml) as well as an increase in proteins related to cell survival, differentiation, and development, while expression of aging proteins such as matrix metalloproteinase 3 (MMP-3) was decreased (5-fold decrease at 50 µg/ml). DFR treatment also led to enhanced expression of antioxidant proteins such as nuclear factor erythroid 2-related factor 2 (10-fold increase at 50 µg/ml) and heme oxygenase 1 (1.5-fold increase at 25 µg/ml). To further investigate the antioxidative effects of DFR extracts, the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities were also evaluated. DFR extracts improved wound healing and resulted in increased expression of ECM proteins, while enzymes involved in collagen degradation, including MMP-3, were decreased in NHDF cells as well as in a mouse model. This study demonstrates the anti-aging, antioxidant, and wound healing properties of DFR extracts. Therefore, DFR extracts present may facilitate skin protection and care.

Clinical practice guidelines for the management of adult diffuse gliomas.

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries.