Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging technology to augment proximal blood pressure during the resuscitation of patients with noncompressible torso ...hemorrhage. Currently, placement choice, supraceliac (Zone 1) versus infrarenal (Zone 3) aorta, depends on injury patterns, but remains a highly debated topic. We sought to compare the proximal hemodynamic support provided by Zone 1 versus Zone 3 REBOA placement and the degree of hemodynamic instability upon reperfusion following intervention.
Eighteen anesthetized swine underwent controlled hemorrhage of 25% total blood volume, followed by 45 minutes of Zone 1 REBOA, Zone 3 REBOA, or no intervention (control). They were then resuscitated with shed blood, aortic balloons were deflated, and 5 hours of critical care ensued prior to euthanasia. Physiologic parameters were recorded continuously, and blood was drawn for analysis at specified intervals. Significance was defined as p < 0.05.
There were no significant differences between groups at baseline or during the initial 30 minutes of hemorrhage. During the intervention period, average proximal MAP was significantly greater in Zone 1 animals when compared with Zone 3 animals (127.9 ± 1.3 vs. 53.4 ± 1.1 mm Hg) and greater in Zone 3 animals when compared with control animals (42.9 ± 0.9 mm Hg). Lactate concentrations were significantly higher in Zone 1 animals (9.6 ± 0.4 mmol/L) when compared with Zone 3 animals (5.1 ± 0.3 mmol/L) and control animals (4.2 ± 0.8 mmol/L).
In our swine model of hemorrhagic shock, Zone 3 REBOA provided minimal proximal hemodynamic support when compared with Zone 1 REBOA, albeit with less ischemic burden and instability upon reperfusion. In cases of impending hemodynamic collapse, Zone 1 REBOA placement may be more efficacious regardless of injury pattern, whereas Zone 3 should be reserved only for relatively stable patients with ongoing distal hemorrhage.
Packaged drinking water (PW) sold in bottles and plastic bags/sachets is widely consumed in low- and middle-income countries (LMICs), and many urban users in sub-Saharan Africa (SSA) rely on packaged ...sachet water (PSW) as their primary source of water for consumption. However, few rigorous studies have investigated PSW quality in SSA, and none have compared PSW to stored household water for consumption (HWC). A clearer understanding of PSW quality in the context of alternative sources is needed to inform policy and regulation. As elsewhere in SSA, PSW is widely consumed in Sierra Leone, but government oversight is nearly nonexistent. This study examined the microbiological and chemical quality of a representative sample of PSW products in Freetown, Sierra Leone at packaged water manufacturing facilities (PWMFs) and at points of sale (POSs). Samples of HWC were also analyzed for comparison. The study did not find evidence of serious chemical contamination among the parameters studied. However, 19% of 45 PSW products sampled at the PWMF contained detectable Escherichia coli (EC), although only two samples exceeded 10 CFU/100 mL. Concentrations of total coliforms (TC) in PSW (but not EC) increased along the supply chain. Samples of HWC from 60 households in Freetown were significantly more likely to contain EC and TC than PSW at the point of production (p<0.01), and had significantly higher concentrations of both bacterial indicators (p<0.01). These results highlight the need for additional PSW regulation and surveillance, while demonstrating the need to prioritize the safety of HWC. At present, PSW may be the least unsafe option for many households.
Packaged water products provide an increasingly important source of water for consumption. However, recent studies raise concerns over their safety.
To assess the microbial safety of packaged water, ...examine differences between regions, country incomes, packaged water types, and compare packaged water with other water sources.
We performed a systematic review and meta-analysis. Articles published in English, French, Portuguese, Spanish and Turkish, with no date restrictions were identified from online databases and two previous reviews. Studies published before April 2014 that assessed packaged water for the presence of Escherichia coli, thermotolerant or total coliforms were included provided they tested at least ten samples or brands.
A total of 170 studies were included in the review. The majority of studies did not detect fecal indicator bacteria in packaged water (78/141). Compared to packaged water from upper-middle and high-income countries, packaged water from low and lower-middle-income countries was 4.6 (95% CI: 2.6-8.1) and 13.6 (95% CI: 6.9-26.7) times more likely to contain fecal indicator bacteria and total coliforms, respectively. Compared to all other packaged water types, water from small bottles was less likely to be contaminated with fecal indicator bacteria (OR = 0.32, 95%CI: 0.17-0.58) and total coliforms (OR = 0.10, 95%CI: 0.05, 0.22). Packaged water was less likely to contain fecal indicator bacteria (OR = 0.35, 95%CI: 0.20, 0.62) compared to other water sources used for consumption.
Policymakers and regulators should recognize the potential benefits of packaged water in providing safer water for consumption at and away from home, especially for those who are otherwise unlikely to gain access to a reliable, safe water supply in the near future. To improve the quality of packaged water products they should be integrated into regulatory and monitoring frameworks.
Policy Matters Young, David C; White, Robert E; Williams, Monica A
2023
eBook
Never have policy initiatives been so important than in today's society. Neoliberal manifestations, climate change, civil rights movements, and governmental reactions to these issues have created a ...backdrop where greater education in policy analysis and development is vital.
Neuromyelitis optica (NMO) is a rare autoimmune disease that affects the optic nerve and spinal cord. Most NMO patients ( > 70%) are seropositive for circulating autoantibodies against aquaporin 4 ...(NMO-IgG+). Here, we meta-analyze whole-genome sequences from 86 NMO cases and 460 controls with genome-wide SNP array from 129 NMO cases and 784 controls to test for association with SNPs and copy number variation (total N = 215 NMO cases, 1244 controls). We identify two independent signals in the major histocompatibility complex (MHC) region associated with NMO-IgG+, one of which may be explained by structural variation in the complement component 4 genes. Mendelian Randomization analysis reveals a significant causal effect of known systemic lupus erythematosus (SLE), but not multiple sclerosis (MS), risk variants in NMO-IgG+. Our results suggest that genetic variants in the MHC region contribute to the etiology of NMO-IgG+ and that NMO-IgG+ is genetically more similar to SLE than MS.
In this trial, patients with atrial fibrillation undergoing mitral-valve surgery were assigned to surgical ablation of AF or no ablation. At 6 and 12 months, more patients in the ablation group were ...free from AF, but more patients in that group required permanent pacemakers.
Atrial fibrillation, which is associated with reduced survival and increased risk of stroke, is present in 30 to 50% of patients presenting for mitral-valve surgery.
1
,
2
The development of open surgical procedures for the ablation of atrial fibrillation has led to their widespread application during cardiac operations, but their effectiveness and safety have not been rigorously established. It is hypothesized that long-term outcomes can be improved by successful ablation in patients with preexisting persistent or long-standing persistent atrial fibrillation who are undergoing mitral-valve surgery.
The Cox maze III operation (sometimes called the “cut-and-sew” maze operation) is a complex surgical procedure . . .
Inhibitors that target the receptor tyrosine kinase (RTK)/Ras/mitogen-activated protein kinase (MAPK) pathway have led to clinical responses in lung and other cancers, but some patients fail to ...respond and in those that do resistance inevitably occurs (Balak et al., 2006; Kosaka et al., 2006; Rudin et al., 2013; Wagle et al., 2011). To understand intrinsic and acquired resistance to inhibition of MAPK signaling, we performed CRISPR-Cas9 gene deletion screens in the setting of BRAF, MEK, EGFR, and ALK inhibition. Loss of
, a negative regulator of NFE2L2/NRF2, modulated the response to BRAF, MEK, EGFR, and ALK inhibition in BRAF-, NRAS-, KRAS-, EGFR-, and ALK-mutant lung cancer cells. Treatment with inhibitors targeting the RTK/MAPK pathway increased reactive oxygen species (ROS) in cells with intact KEAP1, and loss of KEAP1 abrogated this increase. In addition, loss of KEAP1 altered cell metabolism to allow cells to proliferate in the absence of MAPK signaling. These observations suggest that alterations in the KEAP1/NRF2 pathway may promote survival in the presence of multiple inhibitors targeting the RTK/Ras/MAPK pathway.
A stable sol of cerium oxide nanoparticles forms spontaneously when cerium(iv) ammonium nitrate (CAN) is dissolved in room-temperature water at mM concentrations. Electron microscopy experiments ...reveal the formation of highly crystalline cerium oxide particles several nm in diameter and suggest that they are formed from amorphous particles that are similar in size. Under the low pH conditions of the experiments, the nanoparticles form a stable dispersion and show no evidence of aggregation, even many months after synthesis. The absence of particles large enough to scatter light significantly makes it possible to observe the crystallization kinetics through dramatic changes in the UV-visible absorption spectra that occur during solution aging. Measurements show that the cerium oxide nanocrystals are formed roughly an order of magnitude more slowly in D
O than in H
O solution. This large solvent kinetic isotope effect (k
/k
∼ 10), which is reported here for the first time for the crystallization of a solid metal oxide phase, indicates a rate-determining proton transfer reaction, which is assigned to the conversion of hydroxy to oxo bridges. In D
O solution, the absorption per mole of cerium ions increases by over 400% at 290 nm as the weakly absorbing precursor phase is transformed into nanocrystalline cerium oxide. An isosbestic point is detected at 368 nm, and the absorption spectra can be modeled throughout aging by the sum of spectra of just two interconverting species. Preliminary ultrafast transient absorption experiments confirm that the optical properties of the amorphous precursors differ greatly from those of the final, nanocrystalline phase. Crystallization of CeO
from CAN in water has much in common with the crystallization of iron oxides from iron(iii) salts, including the importance of non-classical nucleation and growth pathways. It is an outstanding system for studying the poorly understood events that cause molecularly solvated ions to self-assemble into nanocrystals, following hydrolysis. At the same time, the strong susceptibility of CAN to spontaneously form CeO
nanocrystals under the mildest of reaction conditions indicates that caution is needed when working with this common sacrificial oxidant.
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