Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

CONTEXT: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). OBJECTIVE: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. METHODS: Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. RESULTS: Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. CONCLUSION: In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

Benchmarking performance of an automatic polysomnography scoring system in a population with suspected sleep disorders.

Aim: The current gold standard for measuring sleep disorders is polysomnography (PSG), which is manually scored by a sleep technologist. Scoring a PSG is time-consuming and tedious, with substantial inter-rater variability. A deep-learning-based sleep analysis software module can perform autoscoring of PSG. The primary objective of the study is to validate the accuracy and reliability of the autoscoring software. The secondary objective is to measure workflow improvements in terms of time and cost via a time motion study. Methodology: The performance of an automatic PSG scoring software was benchmarked against the performance of two independent sleep technologists on PSG data collected from patients with suspected sleep disorders. The technologists at the hospital clinic and a third-party scoring company scored the PSG records independently. The scores were then compared between the technologists and the automatic scoring system. An observational study was also performed where the time taken for sleep technologists at the hospital clinic to manually score PSGs was tracked, along with the time taken by the automatic scoring software to assess for potential time savings. Results: Pearson's correlation between the manually scored apnea-hypopnea index (AHI) and the automatically scored AHI was 0.962, demonstrating a near-perfect agreement. The autoscoring system demonstrated similar results in sleep staging. The agreement between automatic staging and manual scoring was higher in terms of accuracy and Cohen's kappa than the agreement between experts. The autoscoring system took an average of 42.7 s to score each record compared with 4,243 s for manual scoring. Following a manual review of the auto scores, an average time savings of 38.6 min per PSG was observed, amounting to 0.25 full-time equivalent (FTE) savings per year. Conclusion: The findings indicate a potential for a reduction in the burden of manual scoring of PSGs by sleep technologists and may be of operational significance for sleep laboratories in the healthcare setting.

Characteristics of In Vitro Culture and In Vivo Confocal Microscopy in Patients with Fungal Keratitis in a Tertiary Referral Hospital in Central China.

PURPOSE: To investigate the characteristics of in vitro culture and in vivo confocal microscopy (IVCM) in patients with fungal keratitis (FK) presented in a tertiary referral hospital in central China. METHODS: In this noncomparative retrospective study, patients with the diagnosis of FK between October 2021 and November 2022 were reviewed. An IVCM and fungal culture (corneal scraping specimens) were performed, and the characteristics were analyzed. RESULTS: During October 2021 and November 2022, 85 patients were diagnosed with FK. From 63 culture-positive cases, 8 species of fungus were identified. The proportions of isolated fungal species were Fusarium and Aspergillus equally accounting for 33.3% (21 of 63), Alternaria 9.5% (6 of 63), Curvularia 6.3% (4 of 63), Scedosporium apiospermum 6.3% (4 of 63), Paecilomyces lilacinus 3.2% (2 of 63), Exserohilum 3.2% (2 of 63), and Candida 4.8% (3 of 63), respectively. In positive culture cases, IVCM was found to be positive for hyphae or spores in 61 of 63 patients (96.8%). Different fungal species had a variety of cultural characteristics and IVCM manifestations. CONCLUSIONS: In a tertiary referral hospital in central China, Fusarium species, Aspergillus species, and Alternaria species were the 3 most common isolated fungal pathogens, and the proportion of Aspergillus species was significantly higher than that in other regions of China. Careful lesion depth examination by IVCM and OCT should be taken before lamellar keratoplasty to avoid postoperative recurrence. Identifying the IVCM image and culture characteristics will facilitate rapid diagnosis and proper treatment, but IVCM cannot yet replace fungal cultures to distinguish between different fungal species.

Sandwich (Amnion/Conjunctival-Limbal Autograft/Amnion) Transplantation for Recurrent Pterygium with Restrictive Strabismus.

(1) Background: This study aimed to evaluate the clinical outcome of Sandwich (Amnion/Conjunctival-Limbal Autograft/Amnion) transplantation for recurrent pterygium with restrictive strabismus. (2) Methods: This retrospective study included 11 eyes in 11 patients diagnosed with recurrent pterygium with restrictive strabismus who received sandwich transplantation. The outcomes were measured by pterygium recurrence, best-corrected visual acuity, esotropia (prism diopters), and treatment complications. (3) Results: Eleven patients (six males, five females) had a mean age of 60.5 (range 36-80) years. The previously received pterygium excision surgery number was 1.8 ± 1.02 (range 1-4). The mean follow-up period was 19.9 ± 8.41 (range 12-36) months. All patients had a restriction of abduction in the previously operated eye, causing esotropia in the primary position. Pre-operative esotropia was 17.2 (range 10-30) prims diopter (PD). Five eyes (45.5%) had symblepharon before surgery. All patients were orthotropic until the last follow-up. Symblepharon was released in all eyes. Free ocular motility was present in all eyes. No donor site scar formation, scleral melt, or corneal ulcer was noted. (4) Conclusions: Sandwich transplantation for recurrent pterygium with restrictive strabismus is safe and effective.

Physical, chemical, and cell toxicity properties of mature/aged particulate matter (PM) trapped in a diesel particulate filter (DPF) along with the results from freshly produced PM of a diesel engine.

The lifetime and efficiency of diesel particulate filters (DPFs) strongly depend on the proper and periodic cleaning and servicing. Unfortunately, in some cases, inappropriate methods are applied to clean the DPFs, e.g., using air compressors without proper disposal procedures which can have negative impacts on human health, the environment, and DPF's efficiency. However, there is no information available about the properties of this kind of PM. This research is therefore presented to explore the physicochemical and toxicity properties of aged PM trapped in a DPF (using compressed air for PM sampling) employing STEM, SEM, EDS, Organic Carbon Analyzer, TGA/DSC, and Raman Spectrometer for investigating the physicochemical properties, and assays of cell viability, cellular reactive oxygen species (ROS), interleukin-6, and tumor necrosis factor-alpha (TNF-α) for investigating the toxicity properties. Also, analyses from fresh PM samples from the diesel vehicle at two engine speeds are presented. It is found that at a certain/fixed PM number/mass for all three samples tested, the PM from DPF compared with the fresh PM can have both positive (particularly having the lowest water-soluble total carbon ratio) and negative impacts on human health (particularly having the highest cell death rate of 13.4%, ROS, and TNF-α) and the environment.

Physicochemical and cell toxicity properties of particulate matter (PM) from a diesel vehicle fueled with diesel, spent coffee ground biodiesel, and ethanol.

The literature shows that information about the physical, chemical, and cell toxicity properties of particulate matter (PM) from diesel vehicles is not rich as the existence of a remarkable number of studies about the combustion, performance, and emissions of diesel vehicles using renewable liquid fuels, particularly biodiesels and alcohols. Also, the PM analyses from combustion of spent coffee ground biodiesel have not been comprehensively explored. Therefore, this research is presented. Pure diesel, 90% diesel + 10% biodiesel, and 90% diesel + 9% ethanol + 1% biodiesel, volume bases, were tested under a fast idle condition. STEM, SEM, EDS, Organic Carbon Analyzer, TGA/DSC, and Raman Spectrometer were employed for investigating the PM physical and chemical properties, and assays of cell viability, cellular reactive oxygen species, interleukin-6, and tumor necrosis factor-alpha were examined for investigating the PM cell toxicity properties. It is found that the application of both biodiesel and ethanol has the potential to change the PM properties, while the impact of ethanol is more than biodiesel on the changes. Regarding the important aspects, biodiesel can be effective for better human health (due to a decrease in cell death (-60.8%)) as well as good diesel particulate filter efficiency (due to lower activation energy (-7.6%) and frequency factor (-83.2%)). However, despite a higher impact of ethanol on the reductions in activation energy (-24.8%) and frequency factor (-99.0%), this fuel causes an increase in cell death (84.1%). Therefore, biodiesel can be an appropriate fuel to have a positive impact on human health, the environment, and emissions catalysts performance, simultaneously.

Why is the world not yet ready to use alternative fuel vehicles?

Despite the improvement in technologies for the production of alternative fuels (AFs), and the needs for using more AFs for motor vehicles for the reductions in air pollution and greenhouse gases, the number of alternative fuel vehicles (AFVs) in the global transportation sector has not been increasing significantly (there are even small drops for adapting some AFs through the projections) in recent years and even in the near future with projections to 2050. And gasoline and diesel fuels will remain as the main energy sources for motor vehicles. After reviewing the latest advantages and disadvantages of AFVs, including flexible-fuel, gas, electric, hybrid electric, and fuel cell electric vehicles, it is found that the higher price of AFVs, compared to that of gasoline and diesel vehicles, might be one of the main barriers for their wider adoption. But on the other hand, there is the "chicken and egg" problem. Because people mostly do not select AFVs due to their higher price and sometimes their less infrastructure availability compared to those of gasoline and diesel vehicles, however, governments and AFVs manufacturers claim that the insignificant demand volume and less interest by people to purchase them, is one of the main reasons for a higher price and less infrastructure availability of AFVs. So, what should we do for adopting AFVs? This review shows that there are two very important and fundamental points that might cause a rise in the demand and usage of AFVs, rather than waiting for the reduction in AFVs prices. Those points are car salespeople's and people's knowledge about AFVs and the environmental issues, and their encouragement to accept and use AFVs. Although the AFVs are available on the market for many years, many people around the world have no/less/old/wrong knowledge about the current AFVs. Thus, most of these people reject these vehicles for usage, even when their important parameters such as purchase price, operating cost, driving range, and fuel availability be the same (or close) as those of gasoline or diesel vehicles. Detailed information, examples, and recommendations to the increases in people's knowledge and encouragement are presented in this review.

An 86-Year-Old Woman Presenting With 2 Weeks of Worsening Dyspnea and Cough.

CASE PRESENTATION: An 86-year-old Singaporean Malay woman with no known respiratory condition presented with 2 weeks of progressively worsening dyspnea, cough, and pleuritic chest pain. There was a positive sick contact and recent long-distance travel to Norway. However, further history revealed her symptoms presented even prior to her overseas trip. Red flag symptoms of hemoptysis, loss of appetite/weight, and risk factors such as smoking/occupational exposure, and personal and familial history of cancer were absent.

Active meta polarizer for terahertz frequencies.

Active meta polarizers based on phase-change materials have recently led to emerging developments in terahertz devices and systems for imaging, security, and high-speed communications. Existing technologies of adaptive control of meta polarizers are limited to the complexity of external stimuli. Here, we introduce an active terahertz polarizer consisting of a single layer of large array patterns of vanadium dioxide material integrated with metallic patch matrix to dynamically reconfigure the polarization of the terahertz waves. The proposed active polarizer is simple in structure and can independently manipulate the polarization of the incident THz waves in two orthogonal directions. In addition, the device can also be performing as a highly efficient reflector at the same frequencies. We demonstrate that efficient and fast polarization changes of THz waves can be achieved over a wide operating bandwidth. Compared with other active polarizers using mechanical, optical and thermal controls, it can be conveniently manipulated with DC bias without any external actuators, intense laser source or heater. Therefore, with the advantages of high efficiency, compact size, low loss, low cost and fast response, the proposed polarizer can be highly integrative and practical to operate within adaptive terahertz circuits and systems.

Positional Therapy for Positional Obstructive Sleep Apnea.

Positional therapy appears to be an attractive strategy for many patients with positional obstructive sleep apnea (OSA). However, under the American Academy of Sleep Medicine OSA guidelines, positional therapy is considered as only an alternative therapy, because previous research has demonstrated poor treatment tolerance and adherence. Recent technological advances have renewed interest in positional therapy, with the invention of new sophisticated vibratory positional therapy devices. These devices have shown great promise with efficacy, markedly improved patient tolerance, and long-term adherence. We review the literature on positional therapy and explore the most current evidence on the new positional therapy devices.

Comparing treatment effects of a convenient vibratory positional device to CPAP in positional OSA: a crossover randomised controlled trial.

OBJECTIVES: Up to 77% of patients with obstructive sleep apnoea (OSA) have positional OSA (POSA) but traditional positional therapy (PT) methods have failed as they were poorly tolerated. New convenient vibratory PT devices have been invented but while recent studies suggest high treatment efficacy and adherence, there are no published data comparing these devices directly with continuous positive airway pressure (CPAP). Our objective is to evaluate if a convenient vibratory PT device is non-inferior to CPAP in POSA treatment. METHODS: In this crossover randomised controlled trial, we enrolled patients with POSA with significant daytime sleepiness (Epworth Sleepiness Scale (ESS)≥10). POSA diagnosis was based on: (1) total Apnoea/Hypopnoea Index (AHI)>10/hour and non-supine AHI<10/hour (2) supine AHI≥2 × non-supine AHI. Patients used their initial allocated devices (PT or CPAP) for 8 weeks before crossing to the alternative intervention after a 1 week washout. The primary aim is to measure changes in ESS between the two treatments. Secondary outcomes include sleep study parameters and patient treatment preference (ClinicalTrials.gov: NCT03125512). RESULTS: 40 patients completed the trial between April 2017 and December 2018. Difference in ESS after 8 weeks of device use (PT minus CPAP) was 2.0 (95% CI 0.68 to 3.32), exceeding our predetermined non-inferiority margin of 1.5. AHI on CPAP was lower than with PT (4.0±3.2 vs 13.0±13.8 events/hour, respectively, p=0.001), although both were lower than at baseline. Time spent supine was significantly lower with PT than CPAP (p<0.001). 60% of patients preferred CPAP, 20% preferred PT, while 20% preferred neither device. CONCLUSIONS: The non-inferiority ESS endpoint for PT compared with CPAP was not met and the results were inconclusive. Future trials with larger sample sizes or in less symptomatic patients are warranted to provide further insight into the role of these new vibratory PT devices.

Author Correction: Drug screening of cancer cell lines and human primary tumors using droplet microfluidics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Asthma phenotypes in a multi-ethnic Asian cohort.

BACKGROUND: Identification of asthma phenotypes facilitates our understanding of asthma pathobiologies. Phenotypes observed in homogenous Asian cohorts have distinct differences from those described in Caucasian cohorts, suggesting that ethnicity may influence phenotypic expression. Phenotypic clusters in a multi-ethnic Southeast Asian cohort have not been described before, and direct comparisons of these clusters within a single study may reveal how ethnicity affects phenotypic expression. METHODS: Six hundred and thirty adult asthma patients from two healthcare institutions in Singapore were randomly assigned in a 2:1 fashion to a test and validation cohort. Latent class analysis was performed on both cohorts using age of asthma onset, sex, ethnicity, smoking status, body mass index, lung function, blood eosinophil count, asthma control test score, and exacerbation frequency as input variables. Phenotypic clusters between the test and validation cohorts were compared RESULTS: Three clusters were identified in both the test and validation cohorts, with corresponding clusters of each cohort sharing similar characteristics. Ethnic representation and asthma control were significantly different between clusters. Cluster one comprised Chinese females with late-onset asthma and the best asthma control. Cluster two comprised non-Chinese females with obesity and the worst asthma control. Cluster three was multi-ethnic with the greatest proportion of atopic patients. CONCLUSION: We identified three phenotypic clusters in our multi-ethnic Southeast Asian population, with distinct differences in ethnicity which may be attributable to inherent differences in baseline characteristics among ethnic groups.

Persistence of DNA in the Singapore context.

The relevance and not merely the presence of one's DNA at a crime scene has become the emerging issue in courtrooms all over the world today. By studying the length of time DNA is likely to persist in an environment until detection, a more holistic assessment of DNA evidence in the context of a case can be made. The current study looks at the persistence of DNA from blood, keratinocytes, and several types of mock exhibits under various conditions, in the tropical rainforest climate of Singapore. While DNA on articles left outdoors showed highly variable persistence subject to the presence of rainfall, DNA from items placed indoors at ambient temperature and under controlled temperature and humidity is comparatively stable. The information gathered from this study, while not exhaustive, serves to provide investigators and the courts with a better understanding of the relevance of DNA recovered from crime scenes of different environmental conditions.

Positional Therapy for Positional Obstructive Sleep Apnea.

Positional therapy appears to be an attractive strategy for many patients with positional obstructive sleep apnea (OSA). However, under the American Academy of Sleep Medicine OSA guidelines, positional therapy is considered as only an alternative therapy, because previous research has demonstrated poor treatment tolerance and adherence. Recent technological advances have renewed interest in positional therapy, with the invention of new sophisticated vibratory positional therapy devices. These devices have shown great promise with efficacy, markedly improved patient tolerance, and long-term adherence. We review the literature on positional therapy and explore the most current evidence on the new positional therapy devices.

Predictors of future exacerbations in a multi-ethnic Asian population with asthma.

OBJECTIVE: Exacerbations are important outcomes in asthma. Risk factors for exacerbations may differ in different populations. Although various demographic and clinical variables were examined in previous studies on exacerbation risks in asthma, important variables such as ethnicity, adherence, and medication titration were not included. This study examined independent predictors of future exacerbations in a multi-ethnic asthma population in Asia, while including the variables of ethnicity, medication adherence, and medication change in our analysis. METHODS: We recruited patients with physician-diagnosed asthma in a tertiary hospital in Singapore over a one-year period. Exacerbations requiring ≥3 days of systemic corticosteroids one year prior to study enrolment (previous exacerbations) and the year following enrolment (future exacerbations) were recorded from electronic medical records. Medication adherence was based on pharmacy refill. An increase or a decrease in the Global Initiative for Asthma treatment steps were considered to be medication up- and down-titration, respectively. A multivariate logistic regression model was constructed to determine independent predictors of future exacerbations. RESULTS: The study cohort of 340 patients comprised mainly of Chinese (53.2%), Malay (32.9%), and Indian (9.7%) ethnicities. After multivariate analysis, only Indian ethnicity (OR 3.75, 95% CI 1.077-13.051, p = 0.038), Asthma Control Test score (OR 0.913, 95% CI 0.839-0.995, p = 0.037), and the number of previous exacerbations (OR 1.84, 95% CI 1.416-2.391, p < 0.001) were independent predictors of future exacerbations. CONCLUSIONS: There are ethnic differences in exacerbation risk in Asian populations. Each incremental worsening of the asthma symptom control score and each additional exacerbation also increases the risk of future exacerbations.

Adherence to Continuous Positive Airway Pressure therapy in Singaporean patients with Obstructive Sleep Apnea.

PURPOSE: To investigate the rates of Continuous Positive Airway Pressure (CPAP) uptake and adherence amongst Singaporean patients diagnosed with Obstructive Sleep Apnea (OSA), and to evaluate factors correlated with CPAP uptake and adherence. STUDY DESIGN: Retrospective review of medical records. METHODS: Medical records were reviewed for baseline demographics, daytime sleepiness, presence of nasal symptoms and OSA severity, initial treatment choice, the rate of CPAP treatment uptake and CPAP adherence at 1 and 12 months. RESULTS: 2160 patients were diagnosed with OSA within the 5-year period (2011-2015). 463 (21.4%) had mild OSA, 583 (27.0%) had moderate OSA and 1114 (51.6%) had severe OSA. For initial therapy, 751 (34.8%) patients opted for a 1-month CPAP trial, 288 (13.3%) patients chose surgery upfront, 291 (13.5%) patients chose adjunctive treatments (weight loss, positional therapy, dental appliance, intranasal steroid spray for allergic rhinitis) and 830 (38.4%) patients rejected all forms of treatment. 337 out of 751 patients (44.9%) were adherent to CPAP therapy during the 1 month trial. 381 out of 751 (50.7%) patients took up CPAP therapy following the trial period, of which 299 out of 381 (78.5%) patients were adherent to CPAP therapy at 1 year. CPAP adherence during the 1-month trial was a predictor for eventual CPAP treatment uptake and CPAP adherence at 1 year (p < 0.001). Age (p < 0.001), BMI (p < 0.001) and normal ESS (p = 0.01) were predictors of treatment rejection. 24 patients underwent upper airway surgery during their first year of using CPAP. 21 out of the 24 patients (87.5%) were adherent to CPAP at 1 year after undergoing surgery. These patients had a higher rate of CPAP adherence compared to the overall cohort (87.5% versus 78.5%), but this was not statistically significant (p > 0.05). CONCLUSION: Singaporean patients who accept CPAP therapy after an initial 1-month CPAP trial will generally be adherent to CPAP therapy. Initial patterns of CPAP usage are predictive of long term CPAP adherence. However, there is a high rate of CPAP treatment rejection both at the time of diagnosis and after the CPAP trial. Upper airway surgery in selected patients may improve CPAP adherence.

Simple and Rapid Tissue Clearing Method for Three-Dimensional Histology of the Pancreas.

Previously, high-resolution three-dimensional imaging of a whole and intact pancreas was not possible, since light is scattered when it passes through cell compartments with different refractive indices. CLARITY is one of the tissue clearing techniques that has yielded success with the central nervous system. To preserve tissue integrity after delipidation, conventional protocols embed tissue in an acrylamide-based hydrogel, which involves the use of specialized equipment. Recently, we determined that the hydrogel-embedding step could be simplified and replaced by passive tissue fixation in 4% paraformaldehyde (PFA). The whole procedure is less time-consuming and less error-prone, and can be completed within a week, compared to conventional CLARITY protocols that may take weeks to complete. Here, the detailed stepwise procedures involved in the simplified CLARITY workflow are applied to the pancreas of wild-type and gene-knockout 6-week old mice expressing green fluorescent protein (GFP) under the mouse insulin 1 promoter (MIP-GFP). This technique could facilitate high-resolution, three-dimensional imaging of pancreatic islets and comparison between different mouse genotypes under different disease and treatment conditions. © 2017 by John Wiley & Sons, Inc.

The relationship between pulmonary hypertension and obstructive sleep apnea.

PURPOSE OF REVIEW: Although obstructive sleep apnea (OSA)-associated pulmonary hypertension is not uncommon and carries a worse prognosis if left untreated, it is less well recognized by clinicians. This review provides information on prevalence, pathophysiology, clinical presentation, treatment, and prognosis of pulmonary hypertension in OSA. RECENT FINDINGS: The prevalence of pulmonary hypertension in OSA ranges from 17 to 53%. The underlying pathophysiology is complex and yet to be fully understood. Continuous positive airway pressure has been proven to be efficacious in the treatment of OSA-associated pulmonary hypertension. SUMMARY: There is still lack of research in this field. We look forward to more well designed studies to help us understand this disease entity better.