Exhaled breath condensate contains extracellular vesicles (EVs) that carry miRNA cargos of lung tissue origin that can be selectively purified and analyzed.

Lung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC). A few studies have suggested that EBC contains extracellular vesicles (EVs) whose microRNA (miRNA) cargos may be useful for evaluating different lung conditions, but the cellular origin of these EVs remains unknown. In this study, we used nanoparticle tracking, transmission electron microscopy, Western blot analyses and super resolution nanoimaging (ONi) to detect and validate the identity of exhaled EVs (exh-EVs). Using our customizable antibody-purification assay, EV-CATCHER, we initially determined that exh-EVs can be selectively enriched from EBC using antibodies against three tetraspanins (CD9, CD63 and CD81). Using ONi we also revealed that some exh-EVs harbour lung-specific proteins expressed in bronchiolar Clara cells (Clara Cell Secretory Protein [CCSP]) and Alveolar Type II cells (Surfactant protein C [SFTPC]). When conducting miRNA next generation sequencing (NGS) of airway samples collected at five different anatomic levels (i.e., mouth rinse, mouth wash, bronchial brush, bronchoalveolar lavage [BAL] and EBC) from 18 subjects, we determined that miRNA profiles of exh-EVs clustered closely to those of BAL EVs but not to those of other airway samples. When comparing the miRNA profiles of EVs purified from matched BAL and EBC samples with our three tetraspanins EV-CATCHER assay, we captured significant miRNA expression differences associated with smoking, asthma and lung tumor status of our subjects, which were also reproducibly detected in EVs selectively purified with our anti-CCSP/SFTPC EV-CATCHER assay from the same samples, but that confirmed their lung tissue origin. Our findings underscore that enriching exh-EV subpopulations from EBC allows non-invasive sampling of EVs produced by lung tissues.

Non-Pharmacological Approach to Diet and Exercise in Metabolic-Associated Fatty Liver Disease: Bridging the Gap between Research and Clinical Practice.

This review provides a practical and comprehensive overview of non-pharmacological interventions for metabolic-associated fatty liver disease (MASLD), focusing on dietary and exercise strategies. It highlights the effectiveness of coffee consumption, intermittent fasting, and Mediterranean and ketogenic diets in improving metabolic and liver health. The review emphasizes the importance of combining aerobic and resistance training as a critical approach to reducing liver fat and increasing insulin sensitivity. Additionally, it discusses the synergy between diet and exercise in enhancing liver parameters and the role of gut microbiota in MASLD. The paper underscores the need for a holistic, individualized approach, integrating diet, exercise, gut health, and patient motivation. It also highlights the long-term benefits and minimal risks of lifestyle interventions compared to the side effects of pharmacological and surgical options. The review calls for personalized treatment strategies, continuous patient education, and further research to optimize therapeutic outcomes in MASLD management.

Initial development and testing of an exhaled microRNA detection strategy for lung cancer case-control discrimination.

For detecting field carcinogenesis non-invasively, early technical development and case-control testing of exhaled breath condensate microRNAs was performed. In design, human lung tissue microRNA-seq discovery was reconciled with TCGA and published tumor-discriminant microRNAs, yielding a panel of 24 upregulated microRNAs. The airway origin of exhaled microRNAs was topographically "fingerprinted", using paired EBC, upper and lower airway donor sample sets. A clinic-based case-control study (166 NSCLC cases, 185 controls) was interrogated with the microRNA panel by qualitative RT-PCR. Data were analyzed by logistic regression (LR), and by random-forest (RF) models. Feasibility testing of exhaled microRNA detection, including optimized whole EBC extraction, and RT and qualitative PCR method evaluation, was performed. For sensitivity in this low template setting, intercalating dye-based URT-PCR was superior to fluorescent probe-based PCR (TaqMan). In application, adjusted logistic regression models identified exhaled miR-21, 33b, 212 as overall case-control discriminant. RF analysis of combined clinical + microRNA models showed modest added discrimination capacity (1.1-2.5%) beyond clinical models alone: all subjects 1.1% (p = 8.7e-04)); former smokers 2.5% (p = 3.6e-05); early stage 1.2% (p = 9.0e-03), yielding combined ROC AUC ranging from 0.74 to 0.83. We conclude that exhaled microRNAs are qualitatively measureable, reflect in part lower airway signatures; and when further refined/quantitated, can potentially help to improve lung cancer risk assessment.

The Cost Effectiveness of Coronary CT Angiography and the Effective Utilization of CT-Fractional Flow Reserve in the Diagnosis of Coronary Artery Disease.

Given the high global disease burden of coronary artery disease (CAD), a major problem facing healthcare economic policy is identifying the most cost-effective diagnostic strategy for patients with suspected CAD. The aim of this review is to assess the long-term cost-effectiveness of coronary computed tomography angiography (CCTA) when compared with other diagnostic modalities and to define the cost and effective diagnostic utilization of computed tomography-fractional flow reserve (CT-FFR). A search was conducted through the MEDLINE database using PubMed with 16 of 119 manuscripts fitting the inclusion and exclusion criteria for review. An analysis of the data included in this review suggests that CCTA is a cost-effective strategy for both low risk acute chest pain patients presenting to the emergency department (ED) and low-to-intermediate risk stable chest pain outpatients. For patients with intermediate-to-high risk, CT-FFR is superior to CCTA in identifying clinically significant stenosis. In low-to-intermediate risk patients, CCTA provides a cost-effective diagnostic strategy with the potential to reduce economic burden and improve long-term health outcomes. CT-FFR should be utilized in intermediate-to-high risk patients with stenosis of uncertain clinical significance. Long-term analysis of cost-effectiveness and diagnostic utility is needed to determine the optimal balance between the cost-effectiveness and diagnostic utility of CT-FFR.

Overlapping Presentations of HELLP Syndrome and COVID-19.

Introduction: Haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome is a leading cause of maternal mortality. The emergence of coronavirus disease 2019 (COVID-19) has led to challenges in diagnosing HELLP syndrome due to overlapping clinical and laboratory presentations. We report a case of HELLP syndrome complicated by COVID-19 infection. Case Description: An otherwise healthy pregnant 31-year-old woman presented with fever, myalgia and headache. She was found to be COVID-positive with laboratory signs of HELLP syndrome. Symptoms and laboratory findings trended toward normal after delivery confirming the diagnosis of HELLP syndrome. Discussion: A prompt diagnosis of HELLP syndrome is essential to avoid maternal and fetal complications. Clinicians should be aware of the similarities in presentation between HELLP syndrome and COVID-19 for timely diagnosis and treatment. LEARNING POINTS: SARS-CoV-2 preferentially binds to ACE2 which is expressed in extrapulmonary tissue including placental tissue.COVID-19, HELLP syndrome and preeclampsia may have similar characteristics including elevated blood pressures, liver dysfunction, cardiopulmonary complaints and hypercoagulability.The temporal relationship of symptomatic improvement with delivery and after delivery may better differentiate HELLP syndrome from COVID-19.

The Merits, Limitations, and Future Directions of Cost-Effectiveness Analysis in Cardiac MRI with a Focus on Coronary Artery Disease: A Literature Review.

Cardiac magnetic resonance (CMR) imaging has a wide range of clinical applications with a high degree of accuracy for many myocardial pathologies. Recent literature has shown great utility of CMR in diagnosing many diseases, often changing the course of treatment. Despite this, it is often underutilized possibly due to perceived costs, limiting patient factors and comfort, and longer examination periods compared to other imaging modalities. In this regard, we conducted a literature review using keywords "Cost-Effectiveness" and "Cardiac MRI" and selected articles from the PubMed MEDLINE database that met our inclusion and exclusion criteria to examine the cost-effectiveness of CMR. Our search result yielded 17 articles included in our review. We found that CMR can be cost-effective in quality-adjusted life years (QALYs) in select patient populations with various cardiac pathologies. Specifically, the use of CMR in coronary artery disease (CAD) patients with a pretest probability below a certain threshold may be more cost-effective compared to patients with a higher pretest probability, although its use can be limited based on geographic location, professional society guidelines, and differing reimbursement patterns. In addition, a stepwise combination of different imaging modalities, with conjunction of AHA/ACC guidelines can further enhance the cost-effectiveness of CMR.

Evaluation of The Sealing Ability of Gutta Percha with Bioroot RCS, MTA Fillapex and Sealapex - An SEM Study.

Aim of the Study: The objective of this in-vitro study was to assess the screening capabilities of three endodontic sealers, namely the BioRoot RCS, the MTA Fillapex, and Sealapex (a calcium hydroxide-based sealer), and the gutta-percha cone by using a scanning electron microscopy to the dentine walls. The results from the research are presented here. Results: ZOE exhibited more gaps in the sealing materials evaluated with the least dental sealing performance, followed by the cervical third by the MTA Fillapex, the Sealapex, and the BioRoot RCS. The ZOE, followed by Sealapex, MTA Fillapex, and BioRoot RCS, exhibited inadequate dental wall sealing capacity in the middle of the third. The third apical ZOE exhibited more deficiencies in the formation of dental walls, followed by Sealapex, MTA Fillapex, and BioRoot RCS. Conclusion: Under the constraints of the investigation, it can be stated that for the bioceramic sealer, a minimal gap was seen, with RCS of BioRoot superior to Fillapex of MTA. In the middle third, Sealapex was better adapted to the calcium hydroxide-based sealant than the MTA Fillapex sealer. MTA Filllapex had lower gap development than Sealapex in cervical or apical thirds.

Understanding Patient Perceptions Towards Direct Primary Care: A Focus Group Study.

Direct primary care (DPC) is a growing model of care that is suggested as an alternative to traditional fee-for-service healthcare. Patient-reported experiences of DPC can provide unique insight into the impact of joining the model and inform quality improvement. The purpose of this study was to investigate patient perceptions of DPC. Thirty-one participants were initially recruited for the study and completed a survey assessing patient demographics. Of the 31 participants, 10 went on to complete the focus group interviews. Qualitative analysis of focus group transcripts identified common themes and subthemes. Focus group findings were stratified into 4 themes including quality of care, access to care, affordability, physician qualities, and reasons for choosing DPC. The top positive subthemes were good communication, joining DPC due to poor past healthcare experiences, and physician personability. The most common negative subthemes were difficulty referring to specialists outside the practice, poor communication, and poor access to medications. All findings were presented and discussed with the investigated clinic to facilitate improvements in healthcare delivery.

Single-cell analysis of somatic mutations in human bronchial epithelial cells in relation to aging and smoking.

Although lung cancer risk among smokers is dependent on smoking dose, it remains unknown if this increased risk reflects an increased rate of somatic mutation accumulation in normal lung cells. Here, we applied single-cell whole-genome sequencing of proximal bronchial basal cells from 33 participants aged between 11 and 86 years with smoking histories varying from never-smoking to 116 pack-years. We found an increase in the frequency of single-nucleotide variants and small insertions and deletions with chronological age in never-smokers, with mutation frequencies significantly elevated among smokers. When plotted against smoking pack-years, mutations followed the linear increase in cancer risk until about 23 pack-years, after which no further increase in mutation frequency was observed, pointing toward individual selection for mutation avoidance. Known lung cancer-defined mutation signatures tracked with both age and smoking. No significant enrichment for somatic mutations in lung cancer driver genes was observed.

Right Unilateral Versus Bilateral Electroconvulsive Therapy in Patients With Clinical Depression.

Introduction Electroconvulsive therapy (ECT) is a functional treatment for a significant mental illness that involves a momentary application of electrical stimulation to induce generalized seizures. The use of right unilateral (RUL) and bilateral (BL) ECT has been controversial. Thus, the study aimed at comparing the effectiveness of RUL ECT and BL ECT in treating depression. Methodology A longitudinal study was conducted between September 2016 and January 2021 at a tertiary care hospital in Sindh, Pakistan. All patients over the age of 18 with clinically diagnosed depression in the last month were included in the study. Baseline depression scores and post-treatment scores were determined using Hamilton Depression Rating Scale (HDRS). All patients were assigned to each treatment group. Group A was administered right unilateral electroconvulsive therapy, while group B was administered bilateral electroconvulsive therapy. Adverse effects were documented right after treatment, at four hours, and then one day after therapy. Depression severity was determined after each ECT session using the HDRS scale. Electroconvulsive therapy was discontinued when an HDRS score of 10 was achieved.  Results  The mean HDRS score at baseline in the bilateral ECT group was 24.99 ± 3.938, which lowered to 17.56 ± 2.65 by the 3rd session, 12.45 ± 3.76 by the 6th session, and to 11.86 ± 2.3 by the end of treatment (p<0.0001). Similarly, the right unilateral ECT was equally effective in improving the depressive symptoms (p<0.0001). There was no significant difference between the efficacy of bilateral and unilateral placements of electrodes in electroconvulsive therapy (p=0.116).

Oral Health Related Awareness and Practices among Pregnant Women in Bagalkot District, Karnataka, India.

BACKGROUND: Cumulative evidence in the dental literature strongly supports the fact that poor oral hygiene practices and inadequate attention toward oral health during pregnancy have an impact on developing the fetus and significant adverse postnatal effects. Available literature suggests that the research is deficit in assessing knowledge and practices related to exposure to radiation, use of medication and safe period for dental treatment during pregnancy. Assessing the knowledge and practices among pregnant women could be a valuable tool for policy makers to improve the oral health. To assess knowledge and practices of pregnant woman regarding oral health. MATERIALS AND METHODS: This study was a cross sectional survey. A total of 332 samples were selected by convenience sampling technique. A questionnaire containing 14 close-ended questions related to knowledge and practices pertaining to oral health during pregnancy along with sociodemographic data were used for collecting baseline information. RESULTS: The overall level of knowledge and practice was 27.17% and 55%, respectively. Majority of respondents (89.10%) were not aware that gum diseases are common during pregnancy. Most of them (73.07%) were not aware of safe period for undergoing dental treatment during pregnancy. Only 19.87% were aware that exposure to high dose of radiation was hazardous to their babies. Around 18.6% did not brush when they experienced bleeding, 35.25% cleaned their teeth using finger. CONCLUSION: The overall results suggest that knowledge and practices of pregnant women need to be greatly improved. All necessary measures should be taken for maintenance of oral hygiene and to avoid complications with the use of drugs and exposure to radiation.