Pediatric Type I Open Both Bone Forearm Fractures: Predicting Failure of Nonoperative Management.

BACKGROUND: In recent years, nonoperative treatment of pediatric type I open both bone forearm fractures (OBBFFs) with bedside irrigation, antibiotics, closed reduction, and casting has yielded low infection rates. However, risk factors for failure of type I OBBFF closed reduction have not been well described. Our purpose was to describe management of patients with type I OBBFFs at our institution and determine what factors are associated with failure of closed reduction in this population. METHODS: This was a review of patients between 5 and 15 years of age who received initial nonoperative management for type I OBBFFs at one institution between 2015 and 2021. Primary outcome was success or failure of nonoperative management (defined as progression to surgical management). Secondary outcomes included infections, compartment syndromes, and neuropraxias. Other variables of interest were demographic information, prereduction and postreduction translation and angulation of the radius and ulna, cast index, and antibiotic administration. RESULTS: Sixty-one patients (67.7% male) with 62 type I OBBFFs were included in this study. Following initial nonoperative management, 55 injuries (88.7%) were successfully treated in casts, while the remaining 7 (11.3%) required surgical intervention following loss of acceptable reduction in cast. Median cast index (0.84, IQR 0.8 to 0.9 vs. 0.75, IQR 0.7-0.8, P =0.020) and postreduction radius translation on anteroposterior films (32.0%, IQR 17.0% to 40.0% vs. 5.0%, IQR 0.0% to 26.0%, P =0.020) were higher among those who failed nonoperative management. Multivariable logistic regression models identified increased odds of failure for every SD (0.7) increase in cast index (OR 3.78, P =0.023, 95% CI: 1.4-14.3) and 25% increase in postreduction radius translation on anteroposterior films (OR 7.39, P =0.044, 95% CI 1.2-70.4). No infections or compartment syndromes and 2 transient ulnar neuropraxias occurred. CONCLUSIONS: Closed reduction of type I OBBFFs was successful in 88.7% of cases. There were no infections after nonoperative management. Increases in cast index of 0.7 and postreduction radius translation on anteroposterior radiographs of 25% were associated with increased likelihood of failure, thus requiring surgery; age was not. LEVEL OF EVIDENCE: Level IV-retrospective comparative study.

Immunomodulatory effect of probiotic exopolysaccharides in a porcine in vitro co-culture model mimicking the intestinal environment on ETEC infection.

The aim of this study was to evaluate the immunomodulatory effect of EPS-L26 isolated from the probiotic strain Lactobacillus (Limosilactobacillus) reuteri L26 Biocenol™, in a model of infection with an enterotoxigenic E. coli (ETEC) by establishing monocultures consisting of the IPEC-J2 cell line or monocyte-derived dendritic cells (moDCs) and creating a 3D model of cell co-cultures established with IPEC-J2 cells and moDCs. The immunomodulatory and immunoprotective potential of used EPS-L26 was confirmed in monocultures in an experimental group of pretreated cells, where our study showed that pretreatment of cells with EPS-L26 and subsequent exposure to infection resulted in significantly down-regulated mRNA levels of genes encoding inflammatory cytokines compared to ETEC challenge in single cell cultures (in IPEC-J2, decreased mRNA levels for TNF-α, IL-6, IL-1ß, IL-12p35; in moDCs, decreased mRNA levels for IL-1ß). Similar to monocultures, we also demonstrated the immunostimulatory potential of the ETEC strain in the co-culture model on directly treated IPEC-J2 cells cultivated on insert chambers (apical compartment) and also on indirectly treated moDCs cultivated in the lower chamber (basolateral compartment), however in the co-culture model the expression of inflammatory cytokines was attenuated at the mRNA level compared to monocultures. Pretreatment of the cells on the insert chambers pointed to the immunoprotective properties of EPS-L26, manifested by decreased mRNA levels in both cell lines compared to ETEC challenge (in IPEC-J2 decreased mRNA levels for IL-12p35; in moDCs decreased mRNA levels for IL-1ß, IL-6). Our results suggest intercellular communication via humoral signals derived from IPEC-J2 cells by influencing the gene expression of indirectly treated moDC cells located in the basolateral compartment.

Methamphetamine Intoxication and Perioperative Complications Following Orthopaedic Surgical Procedures.

Background Methamphetamine use is increasing in prevalence. There is a theoretical increased risk of complication postoperative due to catecholamine depletion. When presented with an urgent surgical problem, there are little data to help counsel the patient on the risks of undergoing surgery in the setting of a positive methamphetamine test result. Aims and objectives The aim of this study was to examine the perioperative complication rate for patients who underwent emergent orthopaedic procedures in the setting of a positive methamphetamine drug screen. Additional data were collected in an attempt to further stratify risk factors for perioperative complications in this patient population. Design and methods A retrospective case series of 110 patients. Patients were identified by querying the medical record for patients with a positive methamphetamine result within 24 hours of the surgery start time. Data were collected on each patient, including the nature of the surgery, the type of injury sustained, disposition from the operating room, among other data points. The primary outcome was the presence of a perioperative cardiopulmonary complication, as determined by a new diagnosis made in the chart. The secondary outcome was whether the patient needed an increased level of care postoperatively. Results Of the 110 charts reviewed, three patients sustained complications during their hospitalization; an overall complication rate of 2.7%. One patient developed acute respiratory distress syndrome (ARDS), while two others developed surgical site infections. Of the 19 patients who went to the intensive care unit (ICU) postoperatively, none were because the patient required a higher level of care than the preoperative level. Conclusions Patients who underwent emergent surgical intervention in the setting of a positive methamphetamine drug test had a low complication rate. While the dogma is to delay surgery in the setting of methamphetamine use, the true risk of undergoing surgery in this setting is not fully understood. We advocate for continued research in this poorly studied group of patients. Larger studies will need to be done in order to fully understand the risks associated with operating in the setting of a positive methamphetamine drug screen.

Serum protein electrophoretic pattern in piglets during the early postnatal period.

The pattern of serum proteins, the typical features of the electrophoretogram in newborn piglets and during their postnatal development is not completely described. Therefore, the aim of this study was to characterize the changes in serum protein electrophoretic pattern and features of the electrophoretograms during the early postnatal period. Significant changes during the monitored period were found in all evaluated parameters (P < 0.001). The most marked changes were observed mainly in the period before weaning. The concentrations of total proteins, albumin and γ-globulins were before colostrum intake low, γ-globulins represented the smallest proportion of protein fractions. The proportion of α1-globulins was after birth a dominant protein fraction. Significant increase of total proteins, α2-, ß- and γ-globulins and decrease of α1-globulins was found 2 days after colostrum intake. The albumin and A/G values increased after birth gradually until weaning. After weaning a significant changes were found in absolute concentrations of total protein and albumin, and in relative values of ß-globulin fractions. Presented results showed marked developmental alterations in the serum protein pattern in piglets along with the age. The study also brings new knowledge in the field of description of typical features of electrophoretograms in the observed period of piglet's life.

Computational Design of gRNAs Targeting Genetic Variants Across HIV-1 Subtypes for CRISPR-Mediated Antiviral Therapy.

Clustered regularly interspaced short palindromic repeats (CRISPR)-based HIV-1 genome editing has shown promising outcomes in in vitro and in vivo viral infection models. However, existing HIV-1 sequence variants have been shown to reduce CRISPR-mediated efficiency and induce viral escape. Two metrics, global patient coverage and global subtype coverage, were used to identify guide RNA (gRNA) sequences that account for this viral diversity from the perspectives of cross-patient and cross-subtype gRNA design, respectively. Computational evaluation using these parameters and over 3.6 million possible 20-bp sequences resulted in nine lead gRNAs, two of which were previously published. This analysis revealed the benefit and necessity of considering all sequence variants for gRNA design. Of the other seven identified novel gRNAs, two were of note as they targeted interesting functional regions. One was a gRNA predicted to induce structural disruption in the nucleocapsid binding site (Ψ), which holds the potential to stop HIV-1 replication during the viral genome packaging process. The other was a reverse transcriptase (RT)-targeting gRNA that was predicted to cleave the subdomain responsible for dNTP incorporation. CRISPR-mediated sequence edits were predicted to occur on critical residues where HIV-1 has been shown to develop resistance against antiretroviral therapy (ART), which may provide additional evolutionary pressure at the DNA level. Given these observations, consideration of broad-spectrum gRNAs and cross-subtype diversity for gRNA design is not only required for the development of generalizable CRISPR-based HIV-1 therapy, but also helps identify optimal target sites.

Evaluating the economic impact of water scarcity in a changing world.

Water scarcity is dynamic and complex, emerging from the combined influences of climate change, basin-level water resources, and managed systems' adaptive capacities. Beyond geophysical stressors and responses, it is critical to also consider how multi-sector, multi-scale economic teleconnections mitigate or exacerbate water shortages. Here, we contribute a global-to-basin-scale exploratory analysis of potential water scarcity impacts by linking a global human-Earth system model, a global hydrologic model, and a metric for the loss of economic surplus due to resource shortages. We find that, dependent on scenario assumptions, major hydrologic basins can experience strongly positive or strongly negative economic impacts due to global trade dynamics and market adaptations to regional scarcity. In many cases, market adaptation profoundly magnifies economic uncertainty relative to hydrologic uncertainty. Our analysis finds that impactful scenarios are often combinations of standard scenarios, showcasing that planners cannot presume drivers of uncertainty in complex adaptive systems.

Joint emulation of Earth System Model temperature-precipitation realizations with internal variability and space-time and cross-variable correlation: fldgen v2.0 software description.

Earth System Models (ESMs) are excellent tools for quantifying many aspects of future climate dynamics but are too computationally expensive to produce large collections of scenarios for downstream users of ESM data. In particular, many researchers focused on the impacts of climate change require large collections of ESM runs to rigorously study the impacts to both human and natural systems of low-frequency high-importance events, such as multi-year droughts. Climate model emulators provide an effective mechanism for filling this gap, reproducing many aspects of ESMs rapidly but with lower precision. The fldgen v1.0 R package quickly generates thousands of realizations of gridded temperature fields by randomizing the residuals of pattern scaling temperature output from any single ESM, retaining the spatial and temporal variance and covariance structures of the input data at a low computational cost. The fldgen v2.0 R package described here extends this capability to produce joint realizations of multiple variables, with a focus on temperature and precipitation in an open source software package available for community use (https://github.com/jgcri/fldgen). This substantially improves the fldgen package by removing the requirement that the ESM variables be normally distributed, and will enable researchers to quickly generate covarying temperature and precipitation data that are synthetic but faithful to the characteristics of the original ESM.

Investigating the distribution of HIV-1 Tat lengths present in the Drexel Medicine CARES cohort.

Human immunodeficiency virus type 1 (HIV-1) encodes for Tat, a multi-functional regulatory protein involved in transcriptional enhancement and in causing neurotoxicity/central nervous system (CNS) dysfunction. This study examines Sanger sequencing of HIV-1 subtype B Tat from 2006 to 2014 within the Drexel University College of Medicine CNS AIDS Research and Eradication Study (CARES) Cohort to investigate Tat length in patients. The Los Alamos National Laboratory (LANL) database was used as a comparator. Miscoded stop codons were present in the CARES Cohort and LANL and protein variability was highly similar. Tat proteins in CARES and LANL were predominantly 101 residues. There was no observed correlation between Tat length and clinical parameters within the CARES Cohort. Unique Tat lengths found in the CARES Cohort and not in LANL were 31, 36, and 39 residues. When CARES patients were longitudinally examined, sequence lengths of 101 had a low probability of reducing to below 48, and sequences had a high probability of increasing to above 86 residues during their next visit, when below 48 residues in length. This suggests that Tat length is conserved to retain the majority of the proteins function highlighting its importance in viral replication.

The Paris pledges and the energy-water-land nexus in Latin America: Exploring implications of greenhouse gas emission reductions.

In the 2015 Paris Agreement, nations worldwide pledged emissions reductions (Nationally Determined Contributions-NDCs) to avert the threat of climate change, and agreed to periodically review these pledges to strengthen their level of ambition. Previous studies have analyzed NDCs largely in terms of their implied contribution to limit global warming, their implications on the energy sector or on mitigation costs. Nevertheless, a gap in the literature exists regarding the understanding of implications of the NDCs on countries' Energy-Water-Land nexus resource systems. The present paper explores this angle within the regional context of Latin America by employing the Global Change Assessment Model, a state-of-the-art integrated assessment model capable of representing key system-wide interactions among nexus sectors and mitigation policies. By focusing on Brazil, Mexico, Argentina and Colombia, we stress potential implications on national-level water demands depending on countries' strategies to enforce energy-related emissions reductions and their interplays with the land sector. Despite the differential implications of the Paris pledges on each country, increased water demands for crop and biomass irrigation and for electricity generation stand out as potential trade-offs that may emerge under the NDC policy. Hence, this study underscores the need of considering a nexus resource planning framework (known as "Nexus Approach") in the forthcoming NDCs updating cycles as a mean to contribute toward sustainable development.

[Barriers of the initiation of insulin treatment in type 2 diabetic patients - conquering the "psychological insulin resistance"]. / Az inzulinkezelés elkezdésének gyakorlati akadályai 2-es típusú cukorbetegekben ­ a "pszichológiai inzulinrezisztencia" leküzdése.

Type 2 diabetes is a progressive disease and its consequence is the gradual decrease of endogenous insulin secretion to a very low level. Beyond this point, without insulin it is not possible to achieve proper metabolic compensation. The authors are trying to explain why the insulin therapy is often delayed in type 2 diabetic patients despite existing guidelines about its initiation and continuation. The causes of delay can be divided into two groups. One is the fear and disagreement of the patients (psychological insulin resistance - PIR) arising from different cognitive, emotional and other reasons. The second is the "clinical inertia", when the physicians are not able to explain in an effective and persuasive way the rationale and necessity of insulin treatment to their patients. The common background of both causes is the lack of sufficient knowledge about the pathogenesis of type 2 diabetes and the rationale of insulin treatment together with an insufficient level of communication between doctor and patient. The authors see the solution in the improvement of pre- and postgradual education of doctors and other health care providers (nurses, educators, psychologists), in their mutual cooperation and the translation of their knowledge towards a system of successful patient education. Orv Hetil. 2019; 160(3): 93-97.

Prediction of Human Immunodeficiency Virus Type 1 Subtype-Specific Off-Target Effects Arising from CRISPR-Cas9 Gene Editing Therapy.

Chronic human immunodeficiency virus type 1 (HIV-1) disease is characterized by the retention of provirus within latently infected cells. Anti-HIV-1 CRISPR-Cas9 gene editing is an attractive strategy to excise or inactivate the HIV-1 genome. Recent strategies have focused on designing gRNAs that target the long terminal repeat (LTR) because 5' and 3' LTR symmetry can facilitate proviral excision. However, the promiscuity of CRISPR-Cas9 gene editing system necessitates the investigation of potential off-target effects. Here, potential gRNAs designed from HIV-1 phylogenetic subtypes using the CRISPRseek tool were investigated. Across the LTR, it was found that certain regions show higher human homology than others. When using recommended cutoffs, 96.40% of gRNAs were predicted to have no high probability off-target effects. Given this observation, while high-probability off-target effects are a potential danger, they can be avoided with proper gRNA design.

Impact of Spatial Scales on the Intercomparison of Climate Scenarios.

Scenario analysis has been widely applied in climate science to understand the impact of climate change on the future human environment, but intercomparison and similarity analysis of different climate scenarios based on multiple simulation runs remain challenging. Although spatial heterogeneity plays a key role in modeling climate and human systems, little research has been performed to understand the impact of spatial variations and scales on similarity analysis of climate scenarios. To address this issue, the authors developed a geovisual analytics framework that lets users perform similarity analysis of climate scenarios from the Global Change Assessment Model (GCAM) using a hierarchical clustering approach.

Role of the Freight Sector in Future Climate Change Mitigation Scenarios.

The freight sector's role is examined using the Global Change Assessment Model (GCAM) for a range of climate change mitigation scenarios and future freight demand assumptions. Energy usage and CO2 emissions from freight have historically grown with a correlation to GDP, and there is limited evidence of near-term global decoupling of freight demand from GDP. Over the 21st century, greenhouse gas (GHG) emissions from freight are projected to grow faster than passenger transportation or other major end-use sectors, with the magnitude of growth dependent on the assumed extent of long-term decoupling. In climate change mitigation scenarios that apply a price to GHG emissions, mitigation of freight emissions (including the effects of demand elasticity, mode and technology shifting, and fuel substitution) is more limited than for other demand sectors. In such scenarios, shifting to less-emitting transportation modes and technologies is projected to play a relatively small role in reducing freight emissions in GCAM. By contrast, changes in the supply chain of liquid fuels that reduce the fuel carbon intensity, especially deriving from large-scale use of biofuels coupled to carbon capture and storage technologies, are responsible for the majority of freight emissions mitigation, followed by price-induced reduction in freight demand services.

Soil carbon change and net energy associated with biofuel production on marginal lands: a regional modeling perspective.

The use of marginal lands for biofuel production has been proposed as a promising solution for meeting biofuel demands while avoiding food-feed-fuel conflicts. However, uncertainty surrounds whether marginal lands can be reliably located, as well as their inherent biofuel potential and the possible environmental impacts. We developed a quantitative approach that integrates high-resolution land cover and land productivity to classify productive croplands and nonarable marginal lands in a nine-county region in southern Michigan. The classified lands were then examined with the spatially explicit modeling framework using the Environmental Policy Integrated Climate (EPIC) model to estimate net energy (NE) and soil organic carbon (SOC) changes associated with the cultivation of different annual and perennial production systems. Simulation results suggest that biofuel production systems underperform on marginal lands when compared to productive croplands. However, we found perennial grasses could perform better than annual crops. Hence, when growing perennial bioenergy crops on marginal lands instead of productive croplands, less additional land (about 0.09 ha per each hectare planted) would be needed to achieve the same NE than if growing annual bioenergy crops (additional 0.17 ha per hectare planted). Miscanthus ( × ) and switchgrass ( L.) can produce 112.43 and 74.61 GJ ha yr NE, respectively, and have the potential to sequester, on average, 0.59 and 0.23 Mg C ha yr SOC, respectively. Notably, simulation results indicate substantial variability of the NE and SOC storage potential across the study region. Thus, although perennial energy crops are promising options for biofuel production on marginal lands, given the large spatial variability, regional- and site-specific management strategies are required for sustainable biofuel production.