Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperoxia-Induced Cellular Senescence in Fetal Airway Smooth Muscle Cells.

Supplemental O2 (hyperoxia; 30-90% O2) is a necessary intervention for premature infants, but contributes to development of neonatal and pediatric asthma, necessitating better understanding of contributory mechanisms in hyperoxia-induced changes to airway structure and function. In adults, environmental stressors promote formation of senescent cells that secrete factors (senescence-associated secretory phenotype; SASP), which can be inflammatory and have paracrine effects that enhance chronic lung diseases. Hyperoxia-induced changes in airway structure and function are mediated in part by effects on airway smooth muscle (ASM). In the present study, using human fetal ASM cells as a model of prematurity, we ascertained the effects of clinically-relevant moderate hyperoxia (40% O2) on cellular senescence. Fetal ASM exposed to 40% O2 for 7 days exhibited elevated levels of senescence-associated markers including β-galactosidase (β-gal), cell cycle checkpoint proteins p16, p21 and p-p53, and the DNA damage marker p-γH2A. X. The combination of dasatinib and quercetin, compounds known to eliminate senescent cells (senolytics), reduced the number of hyperoxia exposed β-gal, p21, p16, and p-γH2A. X positive ASM cells. The SASP profile of hyperoxia-exposed cells included both pro-fibrotic and pro-inflammatory mediators. Naïve ASM exposed to media from hyperoxia-exposed senescent cells exhibited increased collagen and fibronectin and higher contractility. Our data show that induction of cellular senescence by hyperoxia leads to secretion of inflammatory factors and has a functional effect on naïve ASM. Cellular senescence in the airway may thus contribute to pediatric airway disease in the context of sequelae due to preterm birth.
Diffuse tibiofemoral cartilage change prior to the development of accelerated knee osteoarthritis: Data from the osteoarthritis initiative

We compared the spatial distribution of tibiofemoral cartilage change between individuals who will develop accelerated knee osteoarthritis (KOA) versus typical onset of KOA prior to the development of radiographic KOA. We conducted a longitudinal case–control analysis of 129 individuals from the Osteoarthritis Initiative. We assessed the percent change in tibiofemoral cartilage on magnetic resonance images at 36 informative locations from 2 to 1 year prior to the development of accelerated (n = 44) versus typical KOA (n = 40). We defined cartilage change in the accelerated and typical KOA groups at 36 informative locations based on thresholds of cartilage percent change in a no KOA group (n = 45). We described the spatial patterns of cartilage change in the accelerated KOA and typical KOA groups and performed a logistic regression to determine if diffuse cartilage change (predictor; at least half of the tibiofemoral regions demonstrating change in multiple informative locations) was associated with KOA group (outcome). There was a non‐significant trend that individuals with diffuse tibiofemoral cartilage change were 2.2 times more likely to develop accelerated knee OA when compared with individuals who develop typical knee OA (OR [95% CI] = 2.2 [0.90–5.14]. Adults with accelerated or typical KOA demonstrate heterogeneity in spatial distribution of cartilage thinning and thickening. These results provide preliminary evidence of a different spatial pattern of cartilage change between individuals who will develop accelerated versus typical KOA. These data suggest there may be different mechanisms driving the early structural disease progression between accelerated versus typical KOA. Clin. Anat. 32:369–378, 2019. © 2018 Wiley Periodicals, Inc.
Pulmonary Vascular Function and Aerobic Exercise Capacity at Moderate Altitude

Purpose There has been suggestion that a greater “pulmonary vascular reserve” defined by a low pulmonary vascular resistance (PVR) and a high lung diffusing capacity (DL) allow for a superior aerobic exercise capacity. How pulmonary vascular reserve might affect exercise capacity at moderate altitude is not known. Methods Thirty-eight healthy subjects underwent an exercise stress echocardiography of the pulmonary circulation, combined with measurements of DL for nitric oxide (NO) and carbon monoxide (CO) and a cardiopulmonary exercise test at sea level and at an altitude of 2250 m. Results At rest, moderate altitude decreased arterial oxygen content (CaO2) from 19.1 ± 1.6 to 18.4 ± 1.7 mL·dL−1, P < 0.001, and slightly increased PVR, DLNO, and DLCO. Exercise at moderate altitude was associated with decreases in maximum O2 uptake (V˙O2max), from 51 ± 9 to 43 ± 8 mL·kg−1⋅min−1, P < 0.001, and CaO2 to 16.5 ± 1.7 mL·dL−1, P < 0.001, but no different cardiac output, PVR, and pulmonary vascular distensibility. DLNO was inversely correlated to the ventilatory equivalent of CO2 (V˙E/V˙CO2) at sea level and at moderate altitude. Independent determinants of V˙O2max as determined by a multivariable analysis were the slope of mean pulmonary artery pressure–cardiac output relationship, resting stroke volume, and resting DLNO at sea level as well as at moderate altitude. The magnitude of the decrease in V˙O2max at moderate altitude was independently predicted by more pronounced exercise-induced decrease in CaO2 at moderate altitude. Conclusion Aerobic exercise capacity is similarly modulated by pulmonary vascular reserve at moderate altitude and at sea level. Decreased aerobic exercise capacity at moderate altitude is mainly explained by exercise-induced decrease in arterial oxygenation.
Inhibition of RAGE Attenuates Cigarette Smoke-Induced Lung Epithelial Cell Damage via RAGE-Mediated Nrf2/DAMP Signaling

The oxidative stress and cellular apoptosis by environmental factor including cigarette smoke induces alveolar airway remodeling leading to chronic obstructive pulmonary disease (COPD). Recently, the receptor for advanced glycan end products (RAGE) which is highly expressed in alveolar epithelium is emerging as a biomarker for COPD susceptibility or progression. However, it still remains unknown how RAGE plays a role in cigarette smoke extract (CSE)-exposed human alveolar type II epithelial cell line. Therefore, we determined the efficacy of RAGE-specific antagonist FPS-ZM1 in response to CSE-induced lung epithelial cells. CSE induced the elevated generation of RONS and release of pro-inflammatory cytokines, and impaired the cellular antioxidant defense system. Further, CSE induced the alteration of RAGE distribution via the activation of redox-sensitive DAMP (Damage-associated molecular patterns) signaling through Nrf2 in cells. Although pre-treatment with SB202190 (p38 inhibitor) or SP600125 (JNK inhibitor) failed to recover the alteration of RAGE distribution, treatment of FPS-ZM1 significantly exhibited anti-inflammatory and anti-oxidative/nitrosative effects, also inhibited the activation of redox-sensitive DAMP signaling through Nrf2 (nuclear factor erythroid 2-related factor 2) migration in the presence of CSE. Taken together, our data demonstrate that RAGE and Nrf2 play a pivotal role in maintenance of alveolar epithelial integrity.
An update on emerging drugs for the treatment of erectile dysfunction

ABSTRACT Introduction: Erectile dysfunction is an extremely frequent and extensively studied condition, currently affecting the lives of tens of millions of men around the globe. The extensive knowledge of its pathophysiology has led to the development of phosphodiesterase 5-inhibitors, which can facilitate sexual intercourse in a large number of patients. However, an ever-increasing number of patients is unresponsive to these drugs due to underlying comorbidities or previous surgery. Different molecular pathways need to be addressed to provide treatment for a larger patient population. Areas covered: In this paper, we will review the underlying molecular pathways, discuss already available treatment options and their limitations and provide an overview of the newest therapeutics in development. Centrally and peripherally acting agents will be discussed separately. Additionally, newest advances in regenerative medicine options will be discussed. Expert opinion: Even though novel drugs have not been tested in a phase III setting, several phase II clinical trial results are eagerly awaited. These newest therapeutics could be applied as monotherapy or combination therapy in the subset of patients unresponsive to traditional treatment options.
Pulse wave velocity reference values in 3,160 adults referred to a hypertension clinic for 24-hour ambulatory blood pressure monitoring

ABSTRACT Background: Carotid-femoral pulse wave velocity (PWV) is a direct measure of aortic stiffness used in the stratification of cardiovascular risk. Its clinical application in Latin America has been limited by the absence of reference values. The objective of this study was to establish PWV reference values among adults referred to a specialized cardiology center for 24-hour ambulatory blood pressure monitoring (ABPM) in Medellín, Colombia. Methods: A descriptive study of 3,160 records of adult (older than 18 years) patients without pharmacological treatment assessed for PWV using a Mobil-O-Graph® 24-hour PWA device (IEM, Stolberg, Germany) and 24-hour ABPM with hemodynamic parameters based on suspected hypertension or hypotension was conducted. Patient records were categorized by decade of age and sub-divided based on the following 24-hour ABPM categories: normal (< 130/80 mmHg), grade I hypertension (between 130–150/80–90 mmHg), and grade II hypertension (> 150/90 mmHg). Results: PWV increased with age (r = 0,894; p < 0,001) and blood pressure category (ρ = 0,081; p < 0,001); the age-related increase was more pronounced among the patients in the higher blood pressure categories. Measures of central tendency and dispersion regarding PWV are presented, and reference values are proposed from the 90th percentile based on the age and 24-hour ABPM categories. Conclusions: PWV is directly related to age and blood pressure and can be predicted using a simple equation that includes these two variables. To stratify the cardiovascular risk of patients and make clinical decisions, the 90th percentile based on the age and 24-hour ABPM categories is recommended as a cut-off.
Burnout and Quality of Work Life Among Nurse Practitioners in Ventricular Assist Device Programs in the United States

Background: A mixed-method study of role stress and work intensity among nurse practitioners (NPs) in mechanical circulatory support (MCS) programs in the United States reported a qualitative data related to burnout. We empirically investigated this phenomenon by pursuing the following specific aims: (1) describe levels of personal burnout (PB), work-related (WB) burnout, and client-related burnout (CB) and quality of work life (QOWL) among MCS-NPs; (2) determine the relationship between burnout and QOWL variables; and (3) identify which type of burnout is a predictor of QOWL. Methods: We employed an exploratory correlational research design. Demographics, work characteristics, and psychometrically robust measures of burnout and QOWL were completed by 47 MCS-NPs from various regions of the United States. Data were analyzed with descriptive and inferential statistics. Results: Higher levels of burnout (PB, WB, and CB) were associated with lower levels of QOWL (r = −.52 to −.64, P < .001). Of the 3 types of burnout, WB burnout showed a significant predictor of QOWL (R2 = .44, P < .01). Multiple regression models showed that a 1 point increase in mean score of WB would decrease a mean QOWL score by 0.64 after controlling the effect of PB and CB. Some dimensions of QOWL were associated with work/hospital characteristics (r > −.30, P values <.05). Conclusion: Work-related burnout is negatively associated with low QOWL among NPs. Hospital/work environment was contributing factors to high burnout and low QOWL. Further research is needed to confirm the findings including the effect of burnout and QOWL on patient and ventricular assist device program outcomes.
Lack of Sphenoid Pneumatization Does Not Affect Endoscopic Endonasal Pediatric Skull Base Surgery Outcomes

Currently, due to the rarity of pathology, there are limited data surrounding outcomes of pediatric skull base surgery. Traditionally, surgeons have proceeded with caution when electing endonasal endoscopic transsellar/transplanum approaches to the skull base in pediatric patients due to poor sphenoid pneumatization. In this study, we review outcomes of endoscopic pediatric skull base surgery based on sphenoid pneumatization patterns.
Meanings of feeling well among women with Parkinson's disease

We conducted a qualitative inquiry to describe the meanings of feeling well as experienced by women with Parkinson's disease. Nine women were interviewed and we analysed the interviews using a reflective lifeworld approach based on phenomenological epistemology. We present the analysis as five constituents: the body as unnoticed; being able to move on; feeling joy by being connected; finding peace and harmony; and being the director of one's own life. Our findings can be used to understand and promote well-being among women with Parkinson's disease. In care meetings, knowledge about the lived and experienced health processes supports the women's striving to not let illness dominate their experience of daily life.
Phosphatidylcholine-specific phospholipase C inhibition reduces HER2-overexpression, cell proliferation and in vivo tumor growth in a highly tumorigenic ovarian cancer model

Antagonizing the oncogenic effects of human epidermal growth factor receptor 2 (HER2) with current anti-HER2 agents has not yet yielded major progress in the treatment of advanced HER2-positive epithelial ovarian cancer (EOC). Using preclinical models to explore alternative molecular mechanisms affecting HER2 overexpression and oncogenicity may lead to new strategies for EOC patient treatment. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) exerts a pivotal role in regulating HER2 overexpression in breast cancer cells. The present study, conducted on two human HER2-overexpressing EOC cell lines - SKOV3 and its in vivo-passaged SKOV3.ip cell variant characterized by enhanced in vivo tumorigenicity - and on SKOV3.ip xenografts implanted in SCID mice, showed: a) about 2-fold higher PC-PLC and HER2 protein expression levels in SKOV3.ip compared to SKOV3 cells; b) physical association of PC-PLC with HER2 in non-raft domains; c) HER2 internalization and ca. 50% reduction of HER2 mRNA and protein expression levels in SKOV3.ip cells exposed to the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609); d) differential effects of D609 and trastuzumab on HER2 protein expression and cell proliferation; e) decreased in vivo tumor growth in SKOV3.ip xenografts during in vivo treatment with D609; f) potential use of in vivo magnetic resonance spectroscopy (MRS) and imaging (MRI) parameters as biomarkers of EOC response to PC-PLC inhibition. Overall, these findings support the view that PC-PLC inhibition may represent an effective means to target the tumorigenic effects of HER2 overexpression in EOC and that in vivo MR approaches can efficiently monitor its effects.
Maternal history of miscarriages and measures of fertility in relation to childhood asthma

The miracle of life is that conception and birth is turning out to be vitally important for airway diseases. Parental factors and events during pregnancy influence neonatal outcomes and infant bronchiolitis,1 2 and increase the risk of childhood asthma and adult COPD.3 4 Crucially, data are now emerging from randomised controlled trials that interventions during pregnancy can modify the incidence of childhood asthma.5–7 Because asthma is so common, and is manageable, this raises the possibility that asthma in pregnancy is an important and potentially modifiable risk factor for the associated adverse maternal and fetal outcomes, and for childhood asthma outcomes. This knowledge is now driving intense interest in the developmental origins of adult lung disease, and the role of interventions to prevent adult lung disease.8 What’s been missing from this conversation is sex, or more specifically conception. Is there something going on here that is also relevant to the development of childhood asthma? In this issue of Thorax , the article by Maria Magnus and colleagues says the answer is yes, and then goes on to tease out some of the relevant factors (Magnus M et al ). 9 It’s a little known fact that women with asthma have more trouble conceiving than non-asthmatic women. Time to pregnancy is increased in asthma, and this is particularly obvious after the age of 35.10 11 This leads to …
Critical Reflexivity in Indigenous and Cross‐cultural Psychology: A Decolonial Approach to Curriculum?

Critical reflexivity is a mechanism for working toward decoloniality in higher education, with the potential to prompt students' to critique the contexts in which they are embedded, and facilitate transformative learning. We present a critical examination of the tensions surrounding decoloniality and critical reflexivity in an undergraduate unit on Indigenous and cross-cultural psychology at a large Australian university. We invited students in the unit to participate in a written reflexive exercise at the beginning (N = 44) and end of semester (N = 23) and analyzed these reflections qualitatively for level (four-category scheme for coding) and content (causal layered analysis) of reflection. Findings suggest that, while students' primarily demonstrate reflective engagement at levels preordinate to critical reflexivity, they are also engaged in active and nuanced processes of negotiating discomfort and uncertainty in this space. We pose critical commentary on the notion of safety in teaching practice, and consider the role of the academic institution in parametrizing the decolonial stance. This research holds application and transferability to higher education settings, and for the enduring project of engaging a decolonial approach to the curriculum within psychology.
Listeriolysin O: A phagosome‐specific cytolysin revisited

Listeriolysin O (LLO) is an essential determinant of Listeria monocytogenes pathogenesis that mediates the escape of L. monocytogenes from host cell vacuoles, thereby allowing replication in the cytosol without causing appreciable cell death. As a member of the cholesterol‐dependent cytolysin (CDC) family of pore‐forming toxins, LLO is unique in that it is secreted by a facultative intracellular pathogen, whereas all other CDCs are produced by pathogens that are largely extracellular. Replacement of LLO with other CDCs results in strains that are extremely cytotoxic and 10,000‐fold less virulent in mice. LLO has structural and regulatory features that allow it to function intracellularly without causing cell death, most of which map to a unique N‐terminal region of LLO referred to as the proline, glutamic acid, serine, threonine (PEST)‐like sequence. Yet, while LLO has unique properties required for its intracellular site of action, extracellular LLO, like other CDCs, affects cells in a myriad of ways. Because all CDCs form pores in cholesterol‐containing membranes that lead to rapid Ca2+ influx and K+ efflux, they consequently trigger a wide range of host cell responses, including mitogen‐activated protein kinase activation, histone modification, and caspase‐1 activation. There is no debate that extracellular LLO, like all other CDCs, can stimulate multiple cellular activities, but the primary question we wish to address in this perspective is whether these activities contribute to L. monocytogenes pathogenesis.
Two New Sulfonoglycolipids from the Green Alga Codium dwarkense

Two new sulfonoglycosides named Codioside E (1) and Codioside F (2) have been isolated from the MeOH extract of the marine green alga Codium dwarkense collected from the coastal areas of the Gulf of Oman. The structures of these secondary metabolites were elucidated by combined analysis of 1D (1H- and 13C-) and 2D (H–C correlations; HSQC and HMBC) NMR spectroscopic and MS data.
Histopathologic Patterns of Urological Malignancies in Calabar, South-Southern Nigeria: A Ten-Year Review

Background: Malignant diseases have become more prominent in Nigeria over the past years with urological malignancies contributing significantly to cancer related morbidity and mortality. Cancers of the prostate, bladder, kidney, testis and penis are documented as the most common group of non-cutaneous cancers. This study was carried out to document the pattern and distribution of urological malignancies seen in a tertiary hospital in Calabar, South-southern Nigeria over a 10-year period. Materials and Methods: This was a retrospective study carried out in the Department of Urology, University of Calabar Teaching Hospital, Nigeria. Cases of all pathologically proven urological malignancies managed between January 2006 and December 2015 were included. Data were retrieved from patients' case notes, operation registers and histopathology records. The histological slides of all cases were retrieved and reviewed. Patients' demographic data, tumour Original Research Article Isiwele et al.; JCTI, 8(1): 1-10, 2018; Article no.JCTI. 43949 2 site, histologic diagnoses as well as pathologic grades of malignancies were extracted and analysed. Results: A total of 617 cases of urological malignancies were included in the study over the 10 years under review, comprising of 598 (96.9%) males and 19 (3.1%) females giving a male: female ratio of 31.5:1. There were 600 adults (97.2%) and 17 children (2.8%). The median age was 43 years with range of 1-100 years. The frequency of urological cancers showed prostate cancer to be the most common urologic cancer as follows: Prostate cancer constituted 564 (91.4%), Kidneys 27 (4.4%), Urinary bladder 9 (1.5%), Testis 8 (1.3%), Scrotum 5 (0.8%), Penis 2 (0.3%) and Urethra 2 (0.3%). The most common histologic type of prostate cancer was adenocarcinoma with Gleason Grade III being the commonest grade. Out of the 17 childhood urological malignancies recorded, 13(76.47%) were kidney malignancies, 3 (17.65%) were testicular malignancies and 1 (5.88%) was bladder malignancy. Conclusion: Prostate cancer is by far the commonest urological malignancy, with renal cancer being a distant second in Calabar, ahead of bladder cancers. Childhood urological malignancies in Calabar are predominantly nephroblastomas. The need for increased effort in creating awareness about prostate cancer and for routine screening is reiterated.