Bedside ultrasound of the internal jugular vein to assess fluid status and right ventricular function: The POCUS-JVD study.

BACKGROUND: Accurate estimation of fluid status is important in the management of heart failure patients, however, the current methods for bedside assessment can be unreliable or impractical for daily use. METHODS: Non-ventilated patients were enrolled immediately prior to scheduled right heart catheterization (RHC). Using M-mode, IJV maximum (Dmax) and minimum (Dmin) anteroposterior diameters were measured during normal breathing, while supine. Respiratory variation in diameter (RVD) was calculated as [(Dmax - Dmin)/Dmax] in percentage. Collapsibility with sniff maneuver (COS) was assessed. Lastly, inferior vena cava (IVC) was assessed. Pulmonary artery pulsatility index (PAPi) was calculated. Data was obtained by five investigators. RESULTS: Total 176 patients were enrolled. Mean BMI was 30.5 kg/m2, LVEF 14-69% (range), 38% with LVEF ≤35%. The POCUS of IJV could be performed in all patients in <5 min. Increasing RAP demonstrated progressive increase in IJV and IVC diameters. For high filling pressure (RAP ≥10 mmHg), an IJV Dmax ≥1.2 cm or IJV-RVD < 30% had specificity >70%. Combining the POCUS of IJV to physical examination improved the combined specificity to 97% for RAP ≥10 mmHg. Conversely, a finding of IJV-COS was 88% specific for normal RAP (<10 mmHg). An IJV-RVD <15% is suggested as a cutoff for RAP ≥15 mmHg. The performance of IJV POCUS was comparable to IVC. For RV function assessment, IJV-RVD < 30% had 76% sensitivity and 73% specificity for PAPi <3, while IJV-COS was 80% specific for PAPi ≥3. CONCLUSION: POCUS of IJV is an easy to perform, specific and reliable method for volume status estimation in daily practice. An IJV-RVD < 30% is suggested for estimation of RAP ≥10 mmHg and PAPi <3.

Two-Color Duplex Platform for Point-of-Care Differential Detection of Malaria and Typhoid Fever.

Malaria and typhoid fever are two febrile illnesses prevalent in the tropics that often present overlapping symptoms. In this work, we demonstrate an optical reader-based diagnostics platform for rapid codetection and quantification of two antigen targets: lipopolysaccharide (LPS) for typhoid fever and plasmodium lactate dehydrogenase (pLDH) for malaria infections. We report a limit of detection (LoD) of 5 ng/mL for LPS and 10 ng/mL for pLDH in a spiked serum test. We also validated the duplex test's performance of differentiating malaria infection, typhoid fever infection, and coinfection by testing clinical samples in human serum. Our platform provides the potential for further multiplexing by encoding different color codes to various detection targets. The rapid result (∼15 min), low cost (∼$2), and minimal volume requirement for human serum clinical samples (4 µL) of our diagnostic platform offer great potential for deployment in resource-limited settings to help distinguish common causes for acute febrile illnesses at the point-of-need.

Rapid Diagnostic Platform for Colorimetric Differential Detection of Dengue and Chikungunya Viral Infections.

In this work, we demonstrate a rapid diagnostic platform with potential to transform clinical diagnosis of acute febrile illnesses in resource-limited settings. Acute febrile illnesses such as dengue and chikungunya, which pose high burdens of disease in tropical regions, share many nonspecific symptoms and are difficult to diagnose based on clinical history alone in the absence of accessible laboratory diagnostics. Through a unique color-mixing encoding and readout strategy, our platform enabled consistent and accurate multiplexed detection of dengue and chikungunya IgM/IgG antibodies in human clinical samples within 30 min. Our multiplex assay offers several advantages over conventional rapid diagnostic tests deployed in resource-limited settings, including a low sample volume requirement and the ability to concurrently detect four analytes. Our platform is a step toward multiplexed diagnostics that will be transformative for disease management in resource-limited settings by enabling informed treatment decisions through accessible evidence-based diagnosis.

A two-colour multiplexed lateral flow immunoassay system to differentially detect human malaria species on a single test line.

BACKGROUND: Malaria continues to impose a tremendous burden in terms of global morbidity and mortality, yet even today, a large number of diagnoses are presumptive resulting in lack of or inappropriate treatment. METHODS: In this work, a two-colour lateral flow immunoassay (LFA) system was developed to identify infections by Plasmodium spp. and differentiate Plasmodium falciparum infection from the other three human malaria species (Plasmodium vivax, Plasmodium ovale, Plasmodium malariae). To achieve this goal, red and blue colours were encoded to two markers on a single test line of strips, for simultaneous detection of PfHRP2 (red), a marker specific for P. falciparum infection, and pLDH (blue), a pan-specific marker for infections by all species of Plasmodium. The assay performance was first optimized and evaluated with recombinant malarial proteins spiked in washing buffer at various concentrations from 0 to 1000 ng mL-1. The colour profiles developed on the single test line were discriminated and quantified: colour types corresponded to malaria protein species; colour intensities represented protein concentration levels. RESULTS: The limit of detection (the lowest concentrations of malaria antigens that can be distinguished from blank samples) and the limit of colour discrimination (the limit to differentiate pLDH from PfHRP2) were defined for the two-colour assay from the spiked buffer test, and the two limits were 31.2 ng mL-1 and 7.8 ng mL-1, respectively. To further validate the efficacy of the assay, 25 human whole blood frozen samples were tested and successfully validated against ELISA and microscopy results: 15 samples showed malaria negative; 5 samples showed P. falciparum positive; 5 samples showed P. falciparum negative, but contained other malaria species. CONCLUSIONS: The assay provides a simple method to quickly identify and differentiate infection by different malarial parasites at the point-of-need and overcome the physical limitations of traditional LFAs, improving the multiplexing potential for simultaneous detection of various biomarkers.

Structures of exocyclic R,R- and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine adducts induced by 1,2,3,4-diepoxybutane.

1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N(6) position of adenine in DNA. Two enantiomers of bis-N(6)-dA adducts of DEB have been identified: R,R-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (R,R-DHB-dA), and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (S,S-DHB-dA) [ Seneviratne , U. , Antsypovich , S. , Dorr , D. Q. , Dissanayake , T. , Kotapati , S. , and Tretyakova , N. ( 2010 ) Chem. Res. Toxicol. 23 , 1556 -1567 ]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5'-d(C(1)G(2)G(3)A(4)C(5)X(6)A(7)G(8)A(9)A(10)G(11))-3':5'-d(C(12)T(13)T(14)C(15)T(16)T(17)G(18)T(19)C(20)C(21)G(22))-3' duplex [X(6) = R,R-DHB-dA (R(6)) or S,S-DHB-dA (S(6))]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N(6) bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N(6) bond, allows the complementary thymine, T(17), to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T(17) N3H imino proton. The loss of the second Watson-Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as compared to the corresponding unmodified duplex. The reduced base stacking at the adduct sites may also contribute to the thermal instability.

Accessible interview practices for disabled scientists and engineers.

Increasing representation of people with disabilities in science and engineering will require systemic changes to the culture around support and accommodations. Equitable interview practices can help foster such changes. We, an interdisciplinary group of disabled and nondisabled early-career scientists who care deeply about making science more accessible to all, present a framework of suggestions based on Universal Design principles for improving the accessibility and equitability of interviews for people with disabilities and other underrepresented groups. We discuss potential challenges that may arise when implementing these suggestions and provide questions to guide discussions about addressing them.

Navigating mental health challenges in graduate school.

Many graduate students experience mental health struggles that lead them to question their place in academia. Two scientists who experienced extreme lows in graduate school reflect on what helped them during their low points, and suggest strategies for everyone to contribute to mentally healthier workplaces in academia.

A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum.

BACKGROUND: Early and accurate determination of bacterial infections as a potential cause for a patient's systemic inflammatory response is required for timely administration of appropriate treatment and antibiotic stewardship. Procalcitonin (PCT) and C-reactive protein (CRP) have both been used as biomarkers to infer bacterial infections, particularly in the context of sepsis. There is an urgent need to develop a platform for simultaneous quantification of PCT and CRP, to enable the potential use of these biomarkers at the point-of-care. METHODS: A multiplexed lateral flow assay (LFA) and a fluorescence optical reader were developed. Assay performance was validated by testing spiked antigens in the buffer, followed by a validation study comparing results with conventional assays (Roche Cobas e411 Elecsys PCT and Siemens ADVIA XPT CRP) in 25 archived remnant human serum samples. FINDINGS: A linear regression correlation of 0·97 (P < 0·01) was observed for PCT, and a correlation of 0·95 (P < 0·01) was observed for CRP using direct patient samples. We also validated our platform's ability to accurately quantify high-dose CRP in the hook effect range where excess unlabeled analytes occupy binding sites at test lines. INTERPRETATION: A fluorescence reader-based duplex LFA for simultaneous quantification of PCT and CRP was developed and successfully validated with clinical samples. The rapid, portable, and low-cost nature of the platform offers potential for differentiation of bacterial and viral infections in emergency and low-resource settings at the point-of-care. FUNDING: NIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University.

Why we need scientists to make sustainable policies.

The COVID-19 pandemic taught us the importance of having scientists in public health policymaking. As with the pandemic, humanity faces another crisis at a greater scale: global climate change. Here, two carbontech researchers and Forbes 30 Under 30 honorees reflect on their unique paths toward influencing sustainable policies in government and international organizations. They reason that science advice is often ignored by governments and that we need more STEM scientists in sustainability policymaking. They also offer their advice to other young scientists who are looking to make an impact beyond academia.

Feasibility of Mobile Technology to Identify and Address Patients' Unmet Social Needs in a Primary Care Clinic.

Mobile health tools may overcome barriers to social needs screening; however, there are limited data on the feasibility of using these tools in clinical settings. The objective was to determine the feasibility of using a mobile health system to screen for patients' social needs. In one large primary care clinic, the authors tested a tablet-based system that screens patients for social needs, transmits results to the electronic health record, and alerts providers. All adult patients presenting for a nonurgent visit were eligible. The authors evaluated the feasibility of the system and conducted follow-up surveys to determine acceptability and if patients accessed resources through the process. All providers were surveyed. Of the 252 patients approached, 219 (86.9%) completed the screen. Forty-three (19.6%) required assistance with the tablet, and 150 (68.5%) screened positive for at least 1 unmet need (food, housing, or transportation). Of the 150, 103 (68.7%) completed a follow-up survey. The majority agreed that people would learn to use the tablet quickly. Forty-eight patients (46.6%) reported contacting at least 1 community organization through the process. Of the 27 providers, 23 (85.2%) completed a survey and >70% agreed the system would result in patients having better access to resources. It was feasible to use a tablet-based system to screen for social needs. Clinics considering using mobile tools will need to determine how to screen patients who may need assistance with the tool and how to connect patients to resources through the system based on the burden of unmet needs.

HI-Light: A Glass-Waveguide-Based "Shell-and-Tube" Photothermal Reactor Platform for Converting CO2 to Fuels.

In this work, we introduce HI-Light, a surface-engineered glass-waveguide-based "shell-and-tube" type photothermal reactor which is both scalable in diameter and length. We examine the effect of temperature, light irradiation, and residence time on its photo-thermocatalytic performance for CO2 hydrogenation to form CO, with a cubic phase defect-laden indium oxide, In2O3-x(OH)y, catalyst. We demonstrate the light enhancement effect under a variety of reaction conditions. Notably, the light-on performance for the cubic nanocrystal photocatalyst exhibits a CO evolution rate at 15.40 mmol gcat -1 hr-1 at 300°C and atmospheric pressure. This is 20 times higher conversion rate per unit catalyst mass per unit time beyond previously reported In2O3-x(OH)y catalyst in the cubic form under comparable operation conditions and more than 5 times higher than that of its rhombohedral polymorph. This result underscores that improvement in photo-thermocatalytic reactor design enables uniform light distribution and better reactant/catalyst mixing, thus significantly improving catalyst utilization.