Tag: pubmed

Hypertension. 2022 Aug 23:101161HYPERTENSIONAHA12219183. doi: 10.1161/HYPERTENSIONAHA.122.19183. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension maintains rapid cell proliferation and vascular remodeling through metabolic reprogramming. Recent studies suggested that circRNAs play important role in pulmonary vascular remodeling and pulmonary arterial smooth muscle cells proliferation. However, the relationship between circRNA, cell proliferation, and metabolic reprogramming in pulmonary arterial hypertension has not been investigated.

METHODS: RNA-seq and qRT-PCR reveal the differential expression profile of circRNA in pulmonary arteries of pulmonary arterial hypertension rat models. Transfection was used to examine the effects of circSMOC1 on pulmonary artery smooth muscle cells, and the roles of circSMOC1 in vivo were investigated by adenoassociated virus. Mass spectrometry, RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assay were performed to investigate the signaling pathway of circSMOC1 regulating the metabolic reprogramming.

RESULTS: CircSMOC1 was significantly downregulated in pulmonary arteries of pulmonary arterial hypertension rats. CircSMOC1 knockdown promoted proliferation and migration and enhanced aerobic glycolysis of pulmonary artery smooth muscle cells. CircSMOC1 overexpression in vivo alleviates pulmonary vascular remodeling, right ventricular pressure, and right heart hypertrophy. In the nucleus, circSMOC1 directly binds to PTBP1 (polypyrimidine tract-binding protein), competitively inhibits the specific splicing of PKM (pyruvate kinase M) premRNA, resulting in the upregulation of PKM2 (pyruvate kinase M2), the key enzyme of aerobic glycolysis, to enhance glycolysis. In the cytoplasm, circSMOC1 acted as a miR-329-3p sponge, and its reduction in pulmonary arterial hypertension suppressed PDHB (pyruvate dehydrogenase E1 subunit beta) expression, leading to the impairment of mitochondrial oxidative phosphorylation.

CONCLUSIONS: circSMOC1 is crucially involved in the metabolic reprogramming of pulmonary artery smooth muscle cells through PTBP1 and miR-329-3p to regulate pulmonary vascular remodeling in pulmonary arterial hypertension.

PMID:35997022 | DOI:10.1161/HYPERTENSIONAHA.122.19183

Chem Commun (Camb). 2022 Aug 23. doi: 10.1039/d2cc03598g. Online ahead of print.

ABSTRACT

Advancements in computer science and software engineering have greatly facilitated mass spectrometry (MS)-based untargeted metabolomics. Nowadays, gigabytes of metabolomics data are routinely generated from MS platforms, containing condensed structural and quantitative information from thousands of metabolites. Manual data processing is almost impossible due to the large data size. Therefore, in the “omics” era, we are faced with new challenges, the big data challenges of how to accurately and efficiently process the raw data, extract the biological information, and visualize the results from the gigantic amount of collected data. Although important, proposing solutions to address these big data challenges requires broad interdisciplinary knowledge, which can be challenging for many metabolomics practitioners. Our laboratory in the Department of Chemistry at the University of British Columbia is committed to combining analytical chemistry, computer science, and statistics to develop bioinformatics tools that address these big data challenges. In this Feature Article, we elaborate on the major big data challenges in metabolomics, including data acquisition, feature extraction, quantitative measurements, statistical analysis, and metabolite annotation. We also introduce our recently developed bioinformatics solutions for these challenges. Notably, all of the bioinformatics tools and source codes are freely available on GitHub (https://www.github.com/HuanLab), along with revised and regularly updated content.

PMID:35997016 | DOI:10.1039/d2cc03598g

ESC Heart Fail. 2022 Aug 23. doi: 10.1002/ehf2.14112. Online ahead of print.

ABSTRACT

AIMS: Implantation of left ventricular-assist devices (LVAD) to treat end-stage heart failure is of increasing relevance due to donor shortage. Infections of the driveline are common adverse events. LVAD infections can lead to high urgency listings for transplantation. However, transplantation in patients with infection leads to worse post-transplantation outcomes. This study aims to evaluate specific risk factors for driveline infections at the time of implantation.

METHODS AND RESULTS: Four hundred forty-one patients receiving either Heartmate II or Heartware system from August 2009 to October 2013 were assessed. An expert committee sorted patients into four different groups concerning the likeliness of infection. Twenty-eight (6%) of discussed infection cases were judged as secured, 33 (7%) as likely, 18 (4%) as possible, and 20 (4%) as unlikely. The remaining 342 (78%) subjects showed either no signs of infection at all times (329 [75%]) or developed signs of infection in a second observation period within 1 year after ending of the first observation period (13 [3%]). For a better discriminatory power, cases of secured and likely infections were tested against the group with no infection at all times in a Cox proportional hazard model. Among all variables tested by univariate analysis (significance level P < 0.15), only age (P = 0.07), LVAD-type (P = 0.12), need for another thoracic operation (P = 0.02), and serum creatinine value (P = 0.02) reached statistical significance. These were subsequently subjected to multivariate analysis to calculate the cumulative risk of developing a drive infection. The multivariate analysis showed that of all the potential risk factors tested, only the necessity of re-thoracotomy or secondary thoracic closure had a significant, protective effect (hazard ratio [95% CI] = 0.45 [0.21-0.95]; P = 0.04).

CONCLUSION: This single-centre cohort study shows that driveline infections are common adverse events. The duration of support represents the major risk factor for LVAD driveline infections.

PMID:35997005 | DOI:10.1002/ehf2.14112

Elife. 2022 Aug 23;11:e76989. doi: 10.7554/eLife.76989. Online ahead of print.

ABSTRACT

Foraging mammals exhibit a familiar yet poorly characterized phenomenon, ‘alternation’, a pause to sniff in the air preceded by the animal rearing on its hind legs or raising its head. Rodents spontaneously alternate in the presence of airflow, suggesting that alternation serves an important role during plume-tracking. To test this hypothesis, we combine fully-resolved simulations of turbulent odor transport and Bellman optimization methods for decision-making under partial observability. We show that an agent trained to minimize search time in a realistic odor plume exhibits extensive alternation together with the characteristic cast-and-surge behavior observed in insects. Alternation is linked with casting and occurs more frequently far downwind of the source, where the likelihood of detecting airborne cues is higher relative to ground cues. Casting and alternation emerge as complementary tools for effective exploration with sparse cues. A model based on marginal value theory captures the interplay between casting, surging and alternation.

PMID:35996954 | DOI:10.7554/eLife.76989

Nepal J Ophthalmol. 2022 Jan;14(27):122-129. doi: 10.3126/nepjoph.v14i1.34285.

ABSTRACT

INTRODUCTION: Major cause of irreversible blindness is glaucoma which is increasing as a significant global health problem. Knowledge of glaucoma burden and its clinical characteristics in this region is essential.

MATERIALS AND METHODS: This was a cross-sectional hospital -based study conducted at Glaucoma unit in CHEERS Hospital, Bhaktapur from August 2015 to July 2019. Patients’ demographic profile, along with comprehensive eye examination findings were reviewed from the records. Data analysis was done with IBM SPSS version 24 and was presented in mean (±SD), frequency and proportions and a chi- square test was applied. P value < 0.05 was considered statistically significant.

RESULTS: Total of 310 glaucoma cases were included in this study. The mean age presentation was 61.89±14.4 years, and the majority of patients (52.9%) were in the age group 60-79 years. Most patients had primary open angle glaucoma (171, 55.2%) followed by primary angle closure glaucoma (92, 29.7%).

CONCLUSION: Primary open angle glaucoma is the most common form of glaucoma. The proportion of glaucoma increased with increasing age (> 40 years). Provision of screening programs targeting persons with risk factors and opportunistic eye examinations would be beneficial in detection of glaucoma.

PMID:35996911 | DOI:10.3126/nepjoph.v14i1.34285

Nepal J Ophthalmol. 2022 Jan;14(27):72-81. doi: 10.3126/nepjoph.v14i1.37965.

ABSTRACT

INTRODUCTION: This study aims to evaluate outcomes and complications of temporary suture tarsorrhaphy (TST) in cases of impending corneal ulcer perforation.

MATERIALS AND METHODS: Case records of patients who underwent temporary suture tarsorrhaphy at Mechi Eye Hospital during a period of 18 months were retrospectively evaluated. All the smear positive fungal keratitis with more than 5mm infiltration involving central and/or paracentral cornea with impending corneal perforation were included. Demographic and clinical profile including – visual acuity, indication for temporary suture tarsorrhaphy, duration of signs and symptoms were noted. The outcomes were evaluated after 1 month and 3 months post tarsorrhaphy, in relation with time to epithelial healing, anatomical success rate, best corrected visual acuity, complications associated with non-healing corneal ulcer, number of temporary suture tarsorrhaphy needed and complications of TST.

RESULTS: The study included 119 cases of smear positive fungal keratitis with mean age of 51.34 + 15.56 years. In this study, 56.30% of the patients developed epithelial healing at 2 – 4 weeks with mean duration of 23.24 + 12.09 days of temporary suture tarsorrhaphy. Out of 119 patients, the corneal ulcer healed in 84 patients (70.6%), whereas 35 (29.4%) did not heal. Among those with non-healing ulcers, 15 patients (12.6%) had to undergo evisceration. The anatomical success rate was 87.39% which was statistically significant (P = 0.001). Regarding visual outcome, in 62 patients (52.10%) BCVA improved by 2 or more lines, which was statistically significant (P<0.05) resulting in a functional success of 26.89%.

CONCLUSION: This study concludes that temporary suture tarsorrhaphy could be a useful option for management of corneal ulcers with impending perforation in eye centers with limited resources settings and high disease burden with good anatomical and functional outcome.

PMID:35996906 | DOI:10.3126/nepjoph.v14i1.37965

Nepal J Ophthalmol. 2022 Jan;14(27):49-58. doi: 10.3126/nepjoph.v14i1.35401.

ABSTRACT

INTRODUCTION: Hypertensive retinopathy is a common complication in patients with hypertension. This study aims to assess the prevalence, associated factors and awareness of hypertensive retinopathy among an elderly population with hypertension in Bhaktapur, Nepal.

MATERIALS AND METHODS: This is a population-based, cross-sectional study conducted from 2013 to 2015 in Bhaktapur district, Nepal. The sample size was 2100 subjects aged 60 years and above. From this sample, all diagnosed patients with hypertension were analyzed. A detailed history was obtained, and an ocular examination was performed.

RESULTS: Information was complete for 1860 (88.57%) subjects. The age of the study population ranged from 60 to 95 years with the mean age of 69.64±7.31 years. Hypertension was found in 643 subjects (34.61%), of which 224 (12.04%) were newly diagnosed cases. Among the subjects with hypertension, hypertensive retinopathy was found in 81 cases (12.6%). Hypertensive retinopathy was more frequent in the age group 70-79 years (15.23%), males (13.25%), illiterates (13.56%), diabetics (16.49%), and body mass index (BMI) ≥25 kg/m2 (14%). None of the factors was found to be statistically significant. Among the study participants, awareness regarding the effect of hypertension on eye, retina and vision was found to be 13.84%, 8.4%, and 11.98% respectively.

CONCLUSION: Prevalence of hypertension and hypertensive retinopathy among an elderly population of 60 years and above in Bhaktapur district, Nepal were similar to other countries. Hypertensive retinopathy was higher among males, illiterates, diabetes and BMI> 25kg/m2. Awareness of hypertensive retinopathy was 8.4% among hypertensive subjects. Emphasis should be directed toward improving awareness campaigns.

PMID:35996903 | DOI:10.3126/nepjoph.v14i1.35401

Diabet Med. 2022 Aug 23:e14941. doi: 10.1111/dme.14941. Online ahead of print.

ABSTRACT

AIMS: The objectives of this scoping review were to: 1) identify the target audience and contexts in which strategies to improve type 2 diabetes mellitus (T2DM) medication adherence have been used, 2) provide an overview of behaviour change techniques (BCTs) used, 3) describe the determinants of behaviour targeted by strategies, and 4) to identify current gaps in strategies.

METHODS: A systemic search for articles related to T2DM, medication adherence, and strategies was conducted in EMBASE, Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily using the OvidSP platform on March 11, 2021. All publications involving strategies to overcome medication non-adherence among adults with T2DM were included. Strategies were categorized according to the BCT taxonomy and the determinants of behaviour targeted by each strategy was classified by using the Theoretical Domains Framework (TDF).

RESULTS: The search identified 58 articles and 61 strategies. The BCT categories Antecedents and Natural consequences and BCTs Feedback on outcome(s) of behaviour, Adding objects to the environment, and Information about health consequences were identified most frequently as components of strategies resulting in statistically significant improvement in medication adherence. Strategies targeting the TDF domains Reinforcement and Beliefs about Consequences most often resulted in statistically significant improvements in adherence measures.

CONCLUSIONS: The findings from this review identify BCTs and targeted behaviours with demonstrated success. Further exploration of the myriad of BCTs and the corresponding determinants of behaviour which were not accessed may be warranted for the development of future strategies to improve medication adherence in type 2 diabetes.

PMID:35996880 | DOI:10.1111/dme.14941

Clin Nurs Res. 2022 Aug 23:10547738221113385. doi: 10.1177/10547738221113385. Online ahead of print.

ABSTRACT

This cross-sectional study examined colorectal cancer (CRC) survivors’ symptom and symptom cluster characteristics (occurrence, frequency, and severity), positive psychology (benefit-finding and post-traumatic growth), and quality of life (QoL), and determined whether positive psychology moderates symptoms and QoL relationship during acute cancer survivorship, time from diagnosis to treatment completion. A total of 117 CRC survivors completed demographics, symptoms, QoL, and positive psychology questionnaires. Descriptive statistics, multiple linear regression, and moderation analyses were performed. Participants reported high QoL (94%, M = 5.15) and moderate-high positive psychology (75%, M = 3.21). Nineteen symptoms and five symptom clusters were inversely related to QoL (p < .05). Positive psychology (M = ~≥3.24) moderated the relationship of QoL (p < .05) with symptoms occurrence (n = 10), symptom severity (n = 1), and with the generalized symptom cluster (weakness, fatigue, dizziness, drowsy, sleep disturbances, and pain). Positive psychology aids in symptom management and improves QoL. Nurses are poised to identify, prevent, promote, and advocate self-management skills to improve health-related outcomes.

PMID:35996878 | DOI:10.1177/10547738221113385

Cancer. 2022 Aug 23. doi: 10.1002/cncr.34420. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by KIT D816V and other mutations. Data were collected from the patient perspective on disease burden and included an SM-specific symptom assessment tool.

METHODS: US adults aged 18 years and older with a self-reported SM diagnosis completed an online TouchStone SM Patient Survey of 100 items, including the 12-item Short-Form Health Survey, the Indolent Systemic Mastocytosis Symptom Assessment Form, and the Work Productivity and Activity Impairment Questionnaire, as well as questions about SM diagnosis, the impact of SM on daily activities, work impairment, and health care use. The results were analyzed using descriptive statistics.

RESULTS: Fifty-six individuals completed the survey (89% women; median age, 48 years; mean time since diagnosis, 6.7 years), reporting indolent SM (66%), aggressive SM (9%), smoldering SM (5%), and unknown SM subtype (18%). Over a 1-year recall, respondents reported seeking emergency care for anaphylaxis (30%) and taking three or more prescription medications (52%) for SM. Over one half of patients (54%) reduced their work hours because of SM, and 64% avoided leaving home because of symptoms. A majority of respondents (93%) had experienced ≥10 SM-related symptoms, noting that the most bothersome were anaphylactic episodes (18%), abdominal/stomach pain (16%), diarrhea/loose stools (13%), and fatigue (11%). Whereas an Indolent Systemic Mastocytosis Symptom Assessment Form-derived total symptom score of 28 is used to indicate moderate-to-severe symptoms, the mean total symptom score was 52.7. Mental and physical component summary scores from the 12-item Short-Form Health Survey were below population norms.

CONCLUSIONS: Patients who were surveyed reported substantial symptom burden and unmet needs because of SM, as evidenced by seeking emergency care and reporting bothersome symptoms, poor quality of life, and reduced work hours and productivity.

LAY SUMMARY: The objective of this research was to understand the burden and unmet needs in the rare disease of systemic mastocytosis (SM) to guide future care. Fifty-six patients completed an online survey containing questions about their diagnosis, medications, health care use, quality of life, and SM symptoms. The results demonstrated that SM is associated with severe and burdensome symptoms, anaphylactic events, emergency department visits, use of multiple medications, reduced ability to work, and poor physical and psychological quality of life. These findings suggest the need for future advances to address unmet needs in patients affected by SM.

PMID:35996873 | DOI:10.1002/cncr.34420