Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95?±?17.16 pg/ml, controls: 70.55?±?15.87 pg/ml, p?G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p?=?0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p?=?0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738–2.651) and 4.41 fold (95% CI 1.404–13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.     

Detection and enumeration of circulating tumor cells based on their invasive property

Circulating tumor cells (CTCs) are in limited numbers and heterogeneous, making their detection, isolation, and enumeration a major challenge. To overcome these difficulties, we developed a novel method to detect and enumerate CTCs with invasive property. Our assay consists of three simple steps: enrichment, Matrigel invasion assay, and immunostaining. We have validated this method using mouse xenograft tumor models and confirmed its utility in human cancer patients. Our method does not require special equipment and antigen expression for CTC selection, is less likely to be affected by the heterogeneity of the CTCs, and could be applicable to virtually all cancers. Most important, our method enumerates invasive CTCs, which may allow more accurate correlations with clinical outcome and treatment response compared with other CTC detection methods.     

Utilizing the Retrograde Flow of Internal Mammary Vessels as a Donor Pedicle

Introduction  The aim of this study is to assess the results of retrograde flow of internal mammary artery and vein (IMA/V) as a donor vessel for free flap microvascular anastomosis (MVA). This need arises with bipedicle deep inferior epigastric perforator (DIEP) flaps, when all four zones with extra fat need to be harvested for unilateral breast reconstruction coupled with poor midline crossover of circulation naturally or because of midline scar. Large anterolateral thigh flaps for chest wall cover, with multiple perforators from separate pedicles, also need supercharging. This needs an additional source of donor vessels, antegrade IMA/V being the first one. Materials and Methods  Retrospective study of microvascular breast reconstruction using retrograde internal mammary donor vessels. Results  Out of 35 cases, 20 cases had distal IMA/V, with retrograde flow, as donor vessel for second set of arterial and venous anastomosis. In two cases, retrograde IMA/V was used for the solitary set of MVA. In remaining 13 cases, either retrograde IMA or V was utilized either as a principal or accessory donor. No flap was lost. Venous and arterial insufficiency happened in one case each, both were salvaged. Two cases developed partial necrosis, needing debridement and suturing. One case developed marginal necrosis. Only one case developed fat necrosis with superadded infection on follow-up. Conclusion  Distal end of IMA and IMV on retrograde flow is safe for MVA as an additional or sole pedicle. It is convenient to use being in the same field. It enables preservation of other including thoracodorsal pedicle and latissimus dorsi flap for use in case of a complication or recurrence.     

Strong methane point sources contribute a disproportionate fraction of total emissions across multiple basins in the United States

Understanding, prioritizing, and mitigating methane (CH₄) emissions requires quantifying CH₄ budgets from facility scales to regional scales with the ability to differentiate between source sectors. We deployed a tiered observing system for multiple basins in the United States (San Joaquin Valley, Uinta, Denver-Julesburg, Permian, Marcellus). We quantify strong point source emissions (>10 kg CH₄ h⁻¹) using airborne imaging spectrometers, attribute them to sectors, and assess their intermittency with multiple revisits. We compare these point source emissions to total basin CH₄ fluxes derived from inversion of Sentinel-5p satellite CH₄ observations. Across basins, point sources make up on average 40% of the regional flux. We sampled some basins several times across multiple months and years and find a distinct bimodal structure to emission timescales: the total point source budget is split nearly in half by short-lasting and long-lasting emission events. With the increasing airborne and satellite observing capabilities planned for the near future, tiered observing systems will more fully quantify and attribute CH₄ emissions from facility to regional scales, which is needed to effectively and efficiently reduce methane emissions.

Due to its short atmospheric lifetime and strong contribution to global radiative forcing, methane (CH₄) has been a focus for near-term climate mitigation efforts (1). Robust, unbiased accounting systems are requisite to prioritizing and validating CH₄ mitigation, ideally from multiple independent data streams. Atmospheric observations of CH₄ can be key for mitigation, as observed CH₄ concentrations are used to quantify emission rates and attribute emissions to sources. Findings from many independent research efforts have shown that CH₄ emissions across multiple sectors follow heavy-tailed distributions (2–5), meaning that a small fraction of emission sources emits at disproportionately higher rates than the full population of emitters. CH₄ sources can be intermittent or persistent in duration, which may be associated with short-lasting process-driven releases or long-lasting emissions due to abnormal or otherwise avoidable operating conditions such as malfunctions or leaks (5). Isolating populations of large emitters at varying levels of intermittency while quantifying their contribution to regional budgets creates a clear direction for mitigation focus. This tiered observing system strategy can be deployed in data-rich regions where multiple independent layers of observations are jointly leveraged to quantify and isolate emissions, and then drive action.Advances in CH₄ remote sensing have enabled quantification of emissions from global to facility scales. Generally, these observing systems operate by measuring solar backscattered radiance in shortwave infrared regions where CH₄ is a known absorber. Global mapping satellite missions have been used to identify CH₄ hotspots and infer global- to regional-scale CH₄ emission fluxes (6–8). In particular, the TROPOspheric Monitoring Instrument [TROPOMI (9)] onboard the Sentinel-5p satellite has proven capable of quantifying fluxes at basin scales (10, 11). Due to the kilometer-scale resolution of measurements from these global mapping missions, further attribution to particular facilities or even emission sectors is often not feasible. Less precise, target-mode satellites [e.g., PRISMA (12), GHGSat (13)] have proven capable of quantifying very large emissions at an ∼30-m scale, allowing for direct emission attribution to facilities or even subfacility-level infrastructure. However, the current generation of CH₄ plume imaging satellites lack the spatial and temporal coverage to provide quantification completeness across multiple basins. For global mapping, high–spatial resolution multispectral satellites such as Sentinel-2 and Landsat are capable of CH₄ detection (14, 15), but only for large emission sources (e.g., 2+ t h⁻¹) over very bright surfaces.Airborne imaging spectrometers with shortwave infrared sensitivities and sufficient instrument signal-to-noise ratios can also quantify column CH₄ concentrations. These remote sensing platforms are capable of resolving CH₄ concentrations at high spatial resolution (∼3 to 5 m) depending on flight altitude, and can quantify point source emissions as low as 5 to 10 kg h⁻¹ (16, 17). These instruments are sensitive to concentrated point-source emissions, and less sensitive to diffuse emissions spread over large areas (e.g., wetlands). Given the heavy-tailed nature of anthropogenic emissions, point-source detections above an imaging spectrometer’s detection limit may constitute a sizable fraction of the total regional CH₄ flux, but independent measurements are needed to provide that context. Therefore, in this study, we flew a combination of the Global Airborne Observatory (GAO) and next-generation Airborne Visible/Infrared Imaging Spectrometer (AVIRIS-NG) over multiple CH₄ emitting regions between 2019 and 2021, including the southern San Joaquin Valley (SJV), the Permian, the Denver-Julesburg (DJ), the Unita, and the southwestern Pennsylvania portion of the Marcellus. We generally mapped each basin at least three times during each campaign to quantify persistence of emission sources. For the Permian, DJ, and SJV, we surveyed each region again after several months to assess trends and identify long-lasting emission sources. We also performed simultaneous regional CH₄ flux inversions based on TROPOMI CH₄ retrievals to quantify the total CH₄ flux for each survey and compared against the quantified airborne point source budgets. With this tiered approach, we are able to quantify the contribution of unique point sources by sector on the regional budget, therefore highlighting specific points of action for mitigation.     

Vaccination Decreases the Infectious Viral Load of Delta Variant SARS-CoV-2 in Asymptomatic Patients

The Delta variant of SARS-CoV-2 has caused many breakthrough infections in fully vaccinated individuals. While vaccine status did not generally impact the number of viral RNA genome copies in nasopharyngeal swabs of breakthrough patients, as measured by Ct values, it has been previously found to decrease the infectious viral load in symptomatic patients. We quantified the viral RNA, infectious virus, and anti-spike IgA in nasopharyngeal swabs collected from individuals asymptomatically infected with the Delta variant of SARS-CoV-2. Vaccination decreased the infectious viral load, but not the amount of viral RNA. Furthermore, vaccinees with asymptomatic infections had significantly higher levels of anti-spike IgA in their nasal secretions compared to unvaccinated individuals with asymptomatic infections. Thus, vaccination may decrease the transmission risk of Delta, and perhaps other variants, despite not affecting the amount of viral RNA measured in nasopharyngeal swabs.