Impaired Myocardial Work in Children with Hypertrophic Cardiomyopathy and Left Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging.

Echocardiography is pivotal for diagnosis and monitoring of hypertrophic cardiomyopathy (HCM) and can evaluate myocardial function using myocardial work (MW) calculations. Echocardiography is often supplemented by cardiovascular magnetic resonance (CMR) imaging, which can detect myocardial fibrosis using late gadolinium enhancement (LGE). We sought to study the relationship between baseline LGE and MW at baseline and during follow-up in pediatric HCM patients. During the study period (2008-2023), 75 patients were followed up for HCM. In 14 patients (age 14.2 ± 2.8 years, 50.0% male, 6.4 ± 2.9 years follow-up), both LGE-CMR and echocardiography were performed. Global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE) were measured, and myocardial fibrosis was estimated by qualitative assessment of LGE. Patients with LGE (n = 7) exhibited significantly impaired baseline MW, including GWI (mean difference, MD - 487.4 mmHg %, 95% CI [- 866.8 mmHg % to - 108.3 mmHg %], p = 0.027), GCW (MD - 536.8 mmHg %, 95% CI [- 929.8 mmHg % to - 144.4 mmHg %], p = 0.020), and GWE (MD - 4.4%, 95% CI [- 8.1% to - 0.7%], p = 0.039). Regional analysis revealed impaired MW indices in segments with LGE, notably basal and mid septal segments. GWI demonstrated high diagnostic performance for LGE presence (sensitivity 93%, specificity 88%, and area under receiver operating characteristic curve 0.85). Baseline LGE presence had no significant impact on MW deterioration during follow-up. MW is significantly impaired in HCM patients with myocardial fibrosis, highlighting potential utility of echocardiography-derived MW analysis as a valuable tool.

Genome-wide DNA methylation profiling confirms a case of low-level mosaic Kabuki syndrome 1.

Kabuki syndrome is a Mendelian disorder of the epigenetic machinery characterized by typical dysmorphic features, intellectual disability, and postnatal growth deficiency. Pathogenic variants in the genes encoding the chromatin modifiers KMT2D and KDM6A are responsible for Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), respectively. In addition, 11 cases of KS1 caused by mosaic variants in KMT2D have been reported in the literature. Some of these individuals display milder craniofacial and growth phenotypes, and most do not have congenital heart defects. We report the case of an infant with severe hypoplastic left heart syndrome with mitral atresia and aortic atresia (HLHS MA-AA), pulmonary vein stenosis, and atypical facies with a somatic mosaic de novo nonsense variant in KMT2D (c.8200C>T, p.R2734*) identified on trio exome sequencing of peripheral blood and present in 11.2% of sequencing reads. KS was confirmed with EpiSign, a diagnostic genome-wide DNA methylation platform used to identify epigenetic signatures. This case suggests that use of this newly available clinical test can guide the interpretation of low-level mosaic variants identified through sequencing and suggests a new lower limit of mosaicism in whole blood required for a diagnosis of KS.

Left ventricular myocardial work indices in pediatric hypertension: correlations with conventional echocardiographic assessment and subphenotyping.

Myocardial work (MW) is a novel parameter that incorporates non-invasive estimates of left ventricular (LV) systolic pressure into the interpretation of strain, thus overcoming the limitations of load dependency traditionally encountered with LV fractional shortening (LVFS), ejection fraction (LVEF), and global longitudinal strain (GLS). However, data on MW in the pediatric population with hypertension are lacking. Conventional markers of LV function and MW indices were obtained from 88 echocardiographic examinations in 76 children with hypertension (47 males, 15.5 ± 2.96 years). When compared with a previously published cohort of 52 healthy controls, global work index (GWI) and global constructive work (GCW) were both significantly elevated while LVEF and GLS were not impaired but rather mildly increased. On multivariable analysis, GWI was correlated with systolic blood pressure (slope = + 16, p < 0.001) and GLS (slope = -100, p < 0.001), while GCW was correlated with systolic blood pressure (slope = + 18, p < 0.001), GLS (slope = -101, p < 0.001), male sex (slope = -75, p = 0.016), and LV mass (slope = -0.93, p < 0.001). Global wasted work (GWW) was correlated with age at echo visit (slope = -4.5, p = 0.005) and GLS (slope = + 5.5, p < 0.001). The opposite occurred for global work efficiency (GWE; slope = + 0.20, p = 0.011, and slope = -0.48, p < 0.001, respectively). Principal component analysis and k-means clustering revealed 4 subphenotypes which differed in terms of etiology, afterload, and compensation stage of the disease.    Conclusion: Non-invasive MW shows a good correlation with conventional markers of LV function and may help refine the assessment of hypertensive heart disease in children. What is Known: • Myocardial work (MW) is a novel parameter that incorporates non-invasive estimates of left ventricular (LV) systolic pressure into the interpretation of strain, thereby accounting for both deformation and afterload. • Although the usefulness of MW in the assessment of myocardial function beyond conventional markers has been demonstrated in various clinical populations, data in the pediatric population with hypertension are currently lacking. What is New: • Compared to normal values in healthy children, global work index and global constructive work were increased in those with hypertension, while LV ejection fraction and global longitudinal strain were not impaired. • Machine learning identified 4 subphenotypes which differed in terms of etiology, afterload, and compensation stage of the disease.

Fetal Echocardiographic Predictors of Postnatal Surgical Strategies in Critical Pulmonary Stenosis or Atresia with Intact Ventricular Septum: A Meta-Analysis.

BACKGROUND: Critical pulmonary stenosis or atresia with intact ventricular septum (PSAIVS) may be managed either by biventricular repair or univentricular palliation. This systematic review and meta-analysis aimed to synthesize the evidence for the role of fetal echocardiography in predicting the postnatal treatment pathway. METHODS: PubMed/MEDLINE, CINHAL, Cochrane Library, Academic Search Complete, Web of Science, and Trip Pro were searched for observational studies published before July 2021. Random-effects meta-analysis was performed to identify factors associated with biventricular repair. RESULTS: Eleven individual studies published between 2006 and 2021, including a total of 285 participants (159 biventricular repair; 126 univentricular palliation), met our eligibility criteria. The pooled estimated prevalence of biventricular repair among patients with PSAIVS was 55.6% (95% confidence interval 48.5-62.5%). Those who underwent biventricular repair had greater right to left ventricle and tricuspid to mitral valve dimension ratios, greater TV z score, and longer TV inflow duration/cardiac cycle length by fetal echocardiography. They were also more likely to have significant tricuspid regurgitation and less likely to have ventriculo-coronary connections (VCCs). CONCLUSIONS: Commonly obtained fetal echocardiographic measurements have strong associations with treatment pathway choice for patients with PSAIVS. Greater RV growth appears to favor biventricular repair, whereas patients with VCC almost invariably undergo univentricular palliation. Future studies should aim to establish how these fetal echocardiographic parameters might predict outcomes for the two treatment pathways.

Secondary malignancies in long-term ovarian cancer survivors: results of the 'Carolin meets HANNA' study.

OBJECTIVE: To evaluate the rate of secondary malignancies in long-term survivors with ovarian cancer. METHODS: Long-term survivors with ovarian cancer (survival ≥8 years after initial diagnosis) with multiple malignancies were identified within the Tumorbank Ovarian Cancer and our study 'Carolin meets HANNA - Holistic Analyses of Long-term Survivors with Ovarian Cancer'. RESULTS: Of a total of 225 long-term survivors with ovarian cancer, 36 patients (16%) had at least one more cancer diagnosis before, concomitant with, or after, ovarian cancer. Median age was 52.5 years (range 37-79). A total of 60% were diagnosed with stage III/IV and most tumors were high-grade (88.6%), as well as of serous histology (63.9%). Median overall survival was 10 years (range 8-19). Secondary cancer after ovarian cancer was found in 17 long-term survivors (7.6%). Breast cancer was the most frequent secondary malignancy. Median duration between diagnosis of primary ovarian cancer and secondary cancer diagnosis was 78.5 months (range 12-220). BRCA was tested in 11 patients with seven patients being BRCA1 and one patient BRCA2 positive. Secondary cancers were detected by screening in 35.3% and self-detected in 29.4% of patients (breast self-examination). CONCLUSION: A secondary malignancy was diagnosed in 7.6% of long-term survivors. Routine follow-up and cancer screening should be performed in long-term ovarian cancer survivors.

A Model for Estimating the Impact of Orthophosphate on Copper in Water.

The nature of copper phosphate minerals in drinking water distribution systems has remained largely unsolved despite being an important link to reducing cuprosolvency. Chemical equilibrium modeling has also largely failed to accurately predict soluble copper in the presence of orthophosphate. The objective of this work was to develop and validate an empirical copper solubility model that considered pH, dissolved inorganic carbon (DIC), and orthophosphate from a series of bench-scale copper precipitation experiments. An empirical model was constructed that allows for the determination of copper levels in a system given pH, DIC, and orthophosphate data. The predictive reliability of this model was assessed by evaluating a collection of cuprosolvency data from two decades of research and field observations and water treatment reports. The tests yielded a firm correlation between predicted and observed copper levels attested by a regression coefficient of 0.86 for a total of 851 observations.

[Cancer screening in Germany: availability and participation]. / Krebsfrüherkennungsuntersuchungen in Deutschland: Angebot und Inanspruchnahme.

In Germany, approximately 227,000 women and 249,000 men developed cancer in 2014, and nearly 223,000 patients died from the disease that year. Many cancers are curable or have a very good prognosis when they are diagnosed at an early stage. This is where the concept of early detection examinations comes into play.This article describes the current conditions of and participation in examinations for the early detection of cervical, breast, skin, prostate, and colon cancer as provided by Germany's statutory health services. Participation was derived from claims data from the statutory health insurance system as well as from Germany's mammography screening program (MSP). The survey "German Health Update" (GEDA 2014/2015-EHIS) served as an additional data source. According to the claims data and considering the intended intervals, participation quotas among insured persons who are entitled to participate lie between 16% (colonoscopy) and 48% (Pap test). In 2015, 51.5% of invited women participated in the MSP. The results according to self-reports of the GEDA survey lie in part substantially higher. The results according to the claims data, the MSP, as well as the self-reports suggest that a large part of the population utilizes the examinations. Colon and cervical cancer examinations will be expanded as organized and quality-assured early detection programs with regular invitations and information on benefits and risks. These efforts should contribute to reaching eligible people who have thus far not participated.

Survival in patients with acute myeloblastic leukemia in Germany and the United States: Major differences in survival in young adults.

Previous epidemiologic studies on AML have been limited by the rarity of the disease. Here, we present population level data on survival of patients with AML in Germany and the United States (US). Data were extracted from 11 population-based cancer registries in Germany and the Surveillance, Epidemiology, and End Results (SEER13) database in the US. Patients diagnosed with AML in 1997-2011 were included. Period analysis was used to estimate 5-year relative survival (RS) and trends in survival in the early 21st century. Overall 5-year age-adjusted RS for patients with AML in 2007-2011 was greater in Germany than in the US at 22.8% and 18.8%, respectively. Five-year RS was higher in Germany than in the US at all ages, with particularly large differences at ages 15-24 for whom 5-year RS was 64.3% in Germany and 55.0% in the US and 35-44, with 5-year RS estimates of 61.8% in Germany and 46.6% in the US. Most of the difference in 5-year RS was due to higher 1-year RS, with overall 1-year RS estimates of 47.0% in Germany and 38.5% in the US. A small increase in RS was observed between 2003-2005 and 2009-2011 in both countries, but no increase in survival was observed in either country for ages 75+. To our knowledge, this is the first detailed description of AML survival in Germany. Comparison to the US suggests that further analysis into risk factors for poor outcomes in AML in the US may be useful in improving survival.

Recent cancer survival in Germany: an analysis of common and less common cancers.

The monitoring of cancer survival by population-based cancer registries is a prerequisite to evaluate the current quality of cancer care. Our study provides 1-, 5- and 10-year relative survival as well as 5-year relative survival conditional on 1-year survival estimates and recent survival trends for Germany using data from 11 population-based cancer registries, covering around one-third of the German population. Period analysis was used to estimate relative survival for 24 common and 11 less common cancer sites for the period 2007-2010. The German and the United States survival estimates were compared using the Surveillance, Epidemiology and End Results 13 database. Trends in cancer survival in Germany between 2002-2004 and 2008-2010 were described. Five-year relative survival increased in Germany from 2002-2004 to 2008-2010 for most cancer sites. Among the 24 most common cancers, largest improvements were seen for multiple myeloma (8.0% units), non-Hodgkin lymphoma (6.2% units), prostate cancer (5.2% units) and colorectal cancer (4.6% units). In 2007-2010, the survival disadvantage in Germany compared to the United States was largest for cancers of the mouth/pharynx (-11.0% units), thyroid (-6.8% units) and prostate (-7.5% units). Although survival estimates were much lower for elderly patients in both countries, differences in age patterns were observed for some cancer sites. The reported improvements in cancer survival might reflect advances in the quality of cancer care on the population level as well as increased use of screening in Germany. The survival differences across countries and the survival disadvantage in the elderly require further investigation.

Incident cancers attributable to alcohol consumption in Germany, 2010.

PURPOSE: Germany lacks an up-to-date assessment of the cancer burden attributable to alcohol. Therefore, cancer incidence attributable to this exposure was estimated for colorectal, liver, breast, and upper aerodigestive tract (UADT) cancer. Additionally, the impact of alcohol on UADT cancer was analyzed by smoking status, to account for synergistic interactions between these two risk factors. METHODS: Alcohol consumption and smoking prevalence from a nationwide survey in Germany 2008-2011 were combined with relative risks of incident cancer from meta-analyses to obtain population attributable risks (PARs), indicating the proportion of cancers that could be avoided by eliminating a risk factor. Each PAR was multiplied with the respective cancer incidence for 2010 to calculate the absolute number of attributable cases. RESULTS: In Germany, for the year 2010, approximately 13,000 incident cancer cases could be attributed to alcohol consumption (3% of total cases). PAR was highest for esophageal cancer (men: 47.6% and women: 35.8%) and lowest for colorectal cancer in men (9.7%) and breast cancer in women (6.6%). Among women, moderate consumption levels account for the greatest PAR overall, whereas heavy drinking contributes considerably to overall PAR among men. Additionally, moderate-to-heavy drinking among smokers substantially contributes to the overall PAR of UADT cancers compared to drinking among non-smokers. CONCLUSION: In Germany, a substantial proportion of cases of common cancers can be attributed to alcohol consumption, even when consumed at moderate levels. Alcohol consumption with concurrent tobacco smoking is especially important for cancers of the UADT. These findings strengthen the rationale for prevention measures that address exposure at all levels.

Distinct muscle apoptotic pathways are activated in muscles with different fiber types in a rat model of critical illness myopathy.

Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe muscle atrophy (40-60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM. Caspase-3 and -8 activities, but not caspase-9 and -12, were elevated in TA and not in soleus muscle, while the caspase-independent proteins endonuclease G (EndoG) and apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle. Anti-apoptotic proteins HSP70, -27, and apoptosis repressor with a caspase recruitment domain (ARC) were elevated in soleus compared to TA muscle and ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types.

A prospective analysis of factors associated with decreased physical activity in patients with cirrhosis undergoing transplant evaluation.

BACKGROUND: Physical activity (PA) has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes. AIM: To evaluate predictors of PA and grip strength in patients with cirrhosis undergoing liver transplant evaluation. METHODS: Single-center, prospective analysis. RESULTS: One hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic steatohepatitis (27%), hepatitis C (22%) and alcoholic liver disease (21%). Mean model of end-stage liver disease (MELD) score was 13.5. Forty-one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire (IPAQ). The median total PA score was 33 metabolic equivalent (MET)-min/wk. The mean total grip strength was 62.1 ± 22 lb. Total grip strength was found to be an independent predictor of low-moderate PA (OR 4.7, 95% CI 1.4-16.2, p = 0.038), and smoking was the only significant factor associated with reduced grip strength (OR 3.4, 95% CI 1.4-8, p = 0.005). CONCLUSIONS: Patients with end-stage liver disease undergoing liver transplant evaluation have reduced total PA by IPAQ. Total grip strength was found to be a significant predictor of low-moderate PA in patients with cirrhosis. Smoking is a risk factor for reduced grip strength, an important indicator of muscle wasting in cirrhotics.

Minimally invasive surgery for intracerebral haemorrhage.

PURPOSE OF REVIEW: Spontaneous intracerebral haemorrhage (ICH) imposes a significant health and economic burden on society. Despite this, ICH remains the only stroke subtype without a definitive treatment. Without a clearly identified and effective treatment for spontaneous ICH, clinical practice varies greatly from aggressive surgery to supportive care alone. This review will discuss the current modalities of treatments for ICH including preliminary experience and investigative efforts to advance the care of these patients. RECENT FINDINGS: Open surgery (craniotomy), prothrombotic agents and other therapeutic interventions have failed to significantly improve the outcome of these stroke victims. Recently, the Surgical Trial in Intracerebral Haemorrhage (STICH) II assessed the surgical management of patients with superficial intraparenchymal haematomas with negative results. MISTIE II and other trials of minimally invasive surgery (MIS) have shown promise for improving patient outcomes and a phase III trial started in late 2013. SUMMARY: ICH lacks a definitive primary treatment as well as a therapy targeting surrounding perihematomal oedema and associated secondary damage. An ongoing phase III trial using MIS techniques shows promise for providing treatment for these patients.

Time course of hypertension and myocardial dysfunction following anthracycline chemotherapy in pediatric patients.

Background: Anthracyclines are associated with cardiac dysfunction. Little is known about the interplay of pre-existing hypertension and treatment response. We aimed to investigate the relationship between hypertension and the development of cancer therapy-related cardiac dysfunction (CTRCD) in pediatric patients treated with anthracycline chemotherapy. Methods: Pediatric patients with cancer who received anthracycline chemotherapy from 2013 to 2021 were retrospectively included. Serial cardiac assessments were conducted during and after chemotherapy. The primary outcome was the development of CTRCD, classified as mild, moderate, or severe according to contemporary definitions. Results: Among 190 patients undergoing anthracycline chemotherapy, 34 patients (17.9 %) had hypertension (24 patients Stage 1, and 10 patients Stage 2) at baseline evaluation. Patients underwent chemotherapy for a median of 234.4 days (interquartile range 127.8-690.3 days) and were subsequently followed up. Hypertension was frequent during follow-up 31.3 % (0-3 months), 15.8 % (3-6 months), 21.9 % (0.5-1 years), 24.7 % (1-2 years), 31.1 % (2-4 years) and 35.8 % (beyond 4 years) (P for trend < 0.001). Freedom from mild CTRCD at 5 years was 45.0 %, freedom from moderate CTRCD was 87.8 % at 5 years. Baseline hypertension did not increase the risk of mild (HR 0.77, 95 % CI: 0.41-1.42, P = 0.385) or moderate CTRCD (HR 0.62, 95 % CI: 0.14-2.72, P = 0.504). Patients with baseline hypertension showed different global longitudinal strain (P < 0.001) and LVEF (P < 0.001) patterns during follow-up. Conclusions: Pediatric patients often develop CTRCD post-anthracycline chemotherapy. Those with pre-existing hypertension show a unique treatment response, despite no increased CTRCD risk, warranting further investigation.

ALSUntangled #73: Lion's Mane.

Lion's Mane (Hericium erinaceus) has historically been used as traditional medicine in Asia and Europe for its potential benefits in fighting infection and cancer. It has gained interest in the neurodegenerative disease field because of its mechanisms of action; these include anti-inflammation, neuroprotection, and promoting neurite growth demonstrated in various cell and animal models. A very small, double-blind, placebo-controlled trial in patients with mild cognitive impairment showed a temporary improvement in cognitive function; this finding has yet to be replicated. However, there have been no studies in ALS cell or animal models or in humans with ALS. Lion's Mane appears safe and inexpensive when consumed in powder or capsule, but one anaphylactic case was reported after a patient consumed fresh Lion's Mane mushroom. Currently, we do not have enough information to support the use of Lion's Mane for treating ALS. We support further research in ALS disease models and clinical trials to study its efficacy.

Detection of missed deaths in cancer registry data to reduce bias in long-term survival estimation.

Background: Population-based cancer survival estimates can provide insight into the real-world impacts of healthcare interventions and preventive services. However, estimation of survival rates obtained from population-based cancer registries can be biased due to missed incidence or incomplete vital status data. Long-term survival estimates in particular are prone to overestimation, since the proportion of deaths that are missed, for example through unregistered emigration, increases with follow-up time. This also applies to registry-based long-term prevalence estimates. The aim of this report is to introduce a method to detect missed deaths within cancer registry data such that long-term survival of cancer patients does not exceed survival in the general population. Methods: We analyzed data from 15 German epidemiologic cancer registries covering the years 1970-2016 and from Surveillance, Epidemiology, and End Results (SEER)-18 registries covering 1975-2015. The method is based on comparing survival times until exit (death or follow-up end) and ages at exit between deceased patients and surviving patients, stratified by diagnosis group, sex, age group and stage. Deceased patients with both follow-up time and age at exit in the highest percentile were regarded as outliers and used to fit a logistic regression. The regression was then used to classify each surviving patient as a survivor or a missed death. The procedure was repeated for lower percentile thresholds regarding deceased persons until long-term survival rates no longer exceeded the survival rates in the general population. Results: For the German cancer registry data, 0.9% of total deaths were classified as having been missed. Excluding these missed deaths reduced 20-year relative survival estimates for all cancers combined from 140% to 51%. For the whites in SEER data, classified missed deaths amounted to 0.02% of total deaths, resulting in 0.4 percent points lower 20-year relative survival rate for all cancers combined. Conclusion: The method described here classified a relatively small proportion of missed deaths yet reduced long-term survival estimates to more plausible levels. The effects of missed deaths should be considered when calculating long-term survival or prevalence estimates.

Post hypoxic myoclonus: A tale of two minds.

Post hypoxic myoclonus (PHM) is considered a poor prognostic sign and may influence decisions regarding withdrawal of treatment. PHM is generally categorized in literature as either acute or chronic (also commonly referred to as Lance-Adams Syndrome) based on the onset of myoclonus. However, it may be more accurate to differentiate between the various presentations of PHM based on the clinical characteristics and electroencephalogram (EEG) findings for prognostication. Here, we describe a case of a 33-year-old female who presented after a cardiopulmonary arrest. MRI of the brain and cervical spine on admission were unremarkable. Twelve hours later, she developed generalized, stimulus-sensitive myoclonus suggestive of acute PHM. Various medications were trialed, and her symptoms eventually improved on clonazepam. On day 14, she started having resting and intention myoclonus, and dysarthria, consistent with LAS. Several adjustments were again made to her regimen, and she was eventually switched from clonazepam to baclofen which improved her resting myoclonus. This case highlights that PHM can present differently and have a markedly different outcome. It is important to develop a better understanding of the various types of PHM so as to avoid premature withdrawal of care.

Direct Writing of Aligned Carbon Nanotubes across a Trench.

Aligned and suspended carbon nanotubes can outperform randomly oriented networks in electronic biosensing and thin-film electronics. However, carbon nanotubes tend to bundle and form random networks. Here, we show that carbon nanotubes spontaneously align in an ammonium deoxycholate surfactant gel even under low shear forces, allowing direct writing and printing of nanotubes into electrically conducting wires and aligned thin layers across trenches. To demonstrate its application potential, we directly printed arrays of disposable electrical biosensors, which show femtomolar sensitivity in the detection of DNA and SARS-CoV-2 RNA.