Childhood severe asthma: relationship among asthma control scores, FeNO, spirometry and impulse oscillometry.

INTRODUCTION: The evaluation of the asthmatic patient is usually based on clinical and functional parameters that do not necessarily evidence the degree of airway inflammation. The aim of this study was to analyze whether clinical scores (CS) correlate with spirometry (S), impulse oscillometry (IO) and FeNO, in severe asthmatic children. MATERIAL AND METHODS: A multicentric, prospective, cross-sectional study was conducted over a 12-month period. All SA patients (6-18 years old) followed-up in the Pulmonology Department were recruited. CS, FeNO measurements, IO and S were consecutively performed on the same day. Asthma control was ascertained using ACT and GINAq. A cut-off value of ≥ 25 parts per billion (ppb) was used to define airway inflammation. RESULTS: Eighty-one patients were included. ACT: 75% (n 61) were controlled; GINAq: 44.5% (n 36) were controlled; 39.5% (n 32) were partly controlled, and 16% (n 13) were uncontrolled. FeNO had a median value of 24 ppb (IQR 14-41); FeNO ≥ 25 ppb was observed in 49% of patients (n 39). ROC AUC for FeNO vs. ACT was 0.71 (95%CI 0.57-0.86), PPV 0.47, NPV 0.87, SE 0.61, SP 0.80; FeNO vs. GINAq was ROC AUC 0.69 (95%CI 0.54-0.85), PPV 0.34, NPV 0.91, SE 0.62, SP 0.77; Youden cut-off FeNO > 39 ppb for both CS. CONCLUSION: In severe asthmatic children, current symptoms control as evidenced by ACT and GINA correlates with low FeNO values. Clinical scores showed good correlation with airway inflammation.

Seguimiento de niños con diagnóstico de asma grave antes y durante la pandemia por COVID-19 / Follow-up of children diagnosed with severe asthma before and during the COVID-19 pandemic

En la pandemia por COVID-19 se exploraron estrategias de atención para garantizar el seguimiento de niños con asma grave. Estudio prospectivo, observacional, comparativo. Se incluyeron pacientes del programa de asma grave de un hospital pediátrico de tercer nivel (n 74). Se evaluó el grado de control, exacerbaciones y hospitalizaciones durante un período presencial (PP), marzo 2019-2020, y uno virtual (PV), abril 2020-2021. En el PP, se incluyeron 74 pacientes vs. 68 (92 %) del PV. En el PP, el 68 % (46) de los pacientes presentaron exacerbaciones vs. el 46 % (31) de los pacientes en el PV (p 0,003). En el PP, se registraron 135 exacerbaciones totales vs. 79 en el PV (p 0,001); hubo una reducción del 41 %. En el PP, el 47 % (32) de los pacientes tuvieron exacerbaciones graves vs. el 32 % (22) de los pacientes en el PV (p 0,048). Hubo 91 exacerbaciones graves en el PP vs. 49 en el PV (p 0,029), reducción del 46 %. No hubo diferencias en las hospitalizaciones (PP 10, PV 6; p 0,9). La telemedicina fue efectiva para el seguimiento de pacientes con asma grave

During the COVID-19 pandemic, health care strategies were explored to ensure the follow-up of children with severe asthma. This was a prospective, observational, and comparative study. Patients in the severe asthma program of a tertiary care children's hospital were included (n: 74). The extent of control, exacerbations, and hospitalizations during an in-person period (IPP) (March 2019­2020) and an online period (OP) (April 2020­2021) was assessed. A total of 74 patients were enrolled in the IPP compared to 68 (92%) in the OP. During the IPP, 68% (46) of patients had exacerbations versus 46% (31) during the OP (p = 0.003). During the IPP, 135 total exacerbations were recorded compared to 79 during the OP (p = 0.001); this accounted for a 41% reduction. During the IPP, 47% (32) of patients had severe exacerbations versus 32% (22) during the OP (p = 0.048). A total of 91 severe exacerbations were recorded during the IPP compared to 49 during the OP (p = 0.029); the reduction was 46%. No differences were observed in terms of hospitalization (IPP: 10, OP: 6; p = 0,9). Telemedicine was effective for the follow-up of patients with severe asthma.

Assessing the implementation of a multi-component hypertension program in a Guatemalan under-resourced dynamic context: an application of the RE-AIM/PRISM extension for sustainability and health equity.

BACKGROUND: The COVID-19 pandemic necessitated rapid changes in healthcare delivery in Guatemala's public primary care settings. A new hypertension program, implemented as part of a type 2 hybrid trial since 2019, exemplifies an implementation effort amidst a changing context in an under-resourced setting. We assessed the implementation of an evidence-based intervention (EBI; protocol-based hypertension treatment) and one of its main implementation strategies (team-based collaborative care), raising implications for health equity and sustainability. We present innovative application of systems thinking visuals. METHODS: Conducting a convergent mixed methods analysis, we assessed implementation in response to contextual changes across five Ministry of Health (MoH) districts at the pandemic's onset. Utilizing quantitative programmatic data and qualitative interviews with stakeholders (n=18; health providers, administrators, study staff), we evaluated dimensions of "Reach, Effectiveness, Adoption, Implementation and Maintenance," RE-AIM (Reach, Implementation delivery + adaptations), and "Practical Robust Implementation and Sustainability Model," PRISM (Organizational perspective on the EBI, Fit, Implementation and sustainability infrastructure) frameworks. We assessed representativeness by comparing participants to census data. To assess implementation delivery, we built behavior-over-time (BOT) graphs with quantitative programmatic data (July 2019-July 2021). To assess adaptations and contextual changes, we performed matrix-based thematic qualitative analysis. We converged quantitative implementation delivery data + qualitative adaptations data in joint displays. Finally, we analyzed qualitative and quantitative results across RE-AIM/PRISM and health districts to identify equity and sustainability considerations. RESULTS: Contextual factors that facilitated program delivery included the perception that the EBI was beneficial, program champions, and staff communication. Key barriers to implementation delivery included competition with other primary care activities and limited implementation infrastructure (e.g., equipment, medications). Contextual changes related to COVID-19 hindered implementation delivery, threatened sustainability, and may have exacerbated inequities. However, adaptations that were planned enhanced implementation delivery and may have supported improved equity and sustainability. CONCLUSIONS: Recognition of an EBI's benefits and program champions are important for supporting initial uptake. The ability to plan adaptations amid rapid contextual changes has potential advantages for sustainability and equitable delivery. Systems thinking tools and mixed methods approaches may shed light on the relations between context, adaptations, and equitable and sustainable implementation. TRIAL REGISTRATION: NCT03504124.

Predictive Factors for the Application of Pelvic Binders in the Prehospital Setting.

OBJECTIVES: Early pelvic binder placement in the field stabilizes pelvic fractures and tamponades potential hemorrhage within the pelvis. Despite known risk factors for pelvic fracture, it remains challenging to quickly triage and correctly apply a pelvic binder. We aim to develop a prediction model that exclusively uses prehospital criteria to inform the decision to place a pelvic binder. METHODS: The trauma registry was used to identify all trauma patients admitted to an urban Level I trauma center between January 2013 and December 2017. Variables collected included patient demographics, mechanism of injury, prehospital vital signs, and the presence of a pelvic fracture. Participants were randomly assigned to a training group (70%) or a validation group (30%). Univariate analyses were used to identify significant predictors for use in multivariate predictive models. RESULTS: A total of 8,480 (65% male; median age 49; median ISS 9) and 3,676 (65% male; median age 48; median ISS 9) trauma patients were randomly assigned to the training and validation groups, respectively. Univariate analysis showed significant likelihood of pelvic fracture associated with female sex, hemodynamic instability (initial systolic blood pressure < 90 mmHg), blunt injury type, specific mechanisms of injury (motor vehicle collision, motorcycle collision, pedestrian struck by motor vehicle, crushing injury, and riding an animal), impact location, and position in vehicle. Multivariate models adjusting for blunt type injury, hemodynamic instability, impact location, and position in vehicle showed that presence of two or more of these risk factors is significantly associated with presence of pelvic fracture. CONCLUSION: Establishing select prehospital criteria for the empiric application of pelvic binders for patients in the field with blunt injuries, hemodynamic instability, frontal or side motor vehicle collision impact, and non-front seat passenger may improve outcomes among patients with pelvic fractures.

Follow-up of children diagnosed with severe asthma before and during the COVID-19 pandemic. / Seguimiento de niños con diagnóstico de asma grave antes y durante la pandemia por COVID-19.

During the COVID-19 pandemic, health care strategies were explored to ensure the follow-up of children with severe asthma. This was a prospective, observational, and comparative study. Patients in the severe asthma program of a tertiary care children's hospital were included (n: 74). The extent of control, exacerbations, and hospitalizations during an in-person period (IPP) (March 2019-2020) and an online period (OP) (April 2020-2021) was assessed. A total of 74 patients were enrolled in the IPP compared to 68 (92%) in the OP. During the IPP, 68% (46) of patients had exacerbations versus 46% (31) during the OP (p = 0.003). During the IPP, 135 total exacerbations were recorded compared to 79 during the OP (p = 0.001); this accounted for a 41% reduction. During the IPP, 47% (32) of patients had severe exacerbations versus 32% (22) during the OP (p = 0.048). A total of 91 severe exacerbations were recorded during the IPP compared to 49 during the OP (p = 0.029); the reduction was 46%. No differences were observed in terms of hospitalization (IPP: 10, OP: 6; p = 0,9). Telemedicine was effective for the follow-up of patients with severe asthma.

En la pandemia por COVID-19 se exploraron estrategias de atención para garantizar el seguimiento de niños con asma grave. Estudio prospectivo, observacional, comparativo. Se incluyeron pacientes del programa de asma grave de un hospital pediátrico de tercer nivel (n 74). Se evaluó el grado de control, exacerbaciones y hospitalizaciones durante un período presencial (PP), marzo 2019-2020, y uno virtual (PV), abril 2020-2021. En el PP, se incluyeron 74 pacientes vs. 68 (92 %) del PV. En el PP, el 68 % (46) de los pacientes presentaron exacerbaciones vs. el 46 % (31) de los pacientes en el PV (p 0,003). En el PP, se registraron 135 exacerbaciones totales vs. 79 en el PV (p 0,001); hubo una reducción del 41 %. En el PP, el 47 % (32) de los pacientes tuvieron exacerbaciones graves vs. el 32 % (22) de los pacientes en el PV (p 0,048). Hubo 91 exacerbaciones graves en el PP vs. 49 en el PV (p 0,029), reducción del 46 %. No hubo diferencias en las hospitalizaciones (PP 10, PV 6; p 0,9). La telemedicina fue efectiva para el seguimiento de pacientes con asma grave.

Quantification of Salmonella Infantis transfer from transport drawer flooring to broiler chickens during holding.

Transportation is a potential point of cross-contamination before broiler chickens arrive at the processing plant for slaughter. Previous studies have associated the use of uncleaned transport containers with the introduction of pathogenic bacteria onto uncontaminated broilers. The objective of this study was to quantify the transfer of Salmonella from transport drawer perforated flooring to broiler chickens during different holding times. For traceability, the flooring of each drawer was inoculated with fecal content slurry containing a marker strain of Salmonella Infantis. Three drawers per treatment were used, and each drawer was subjected to one of the following treatments: pressure wash, disinfectant, and pressure wash (A), pressurized steam followed by forced hot air (B), or no cleaning (C). Drawers were classified as top, middle, or bottom based on their relative position with each other. After treatment, broilers were introduced to each drawer and held for 2, 4, or 6 h. At each timepoint, broilers were removed from drawers, euthanized, and carcasses rinsed to obtain Salmonella counts. Samples under the limit of direct plating detection were enriched, plated, and later confirmed positive or negative. Differences were observed per treatment, holding time, and drawer relative position (P < 0.0001). Broilers placed in transport containers that underwent a cleaning procedure (A or B) had lower levels of Salmonella when compared to broilers placed in noncleaned containers (C). However, most of the samples below the limit of detection were positive after enrichment, indicating that both procedures evaluated need improvement for efficient pathogen inactivation. A decrease in Salmonella transfer was observed after 6 h in rinsates obtained from broilers placed in noncleaned containers (C). Rinsates obtained from top drawers had less Salmonella than the middle or bottom drawers when broilers were placed in transport containers that underwent a cleaning procedure (A and B). The application of pressurized steam and forced hot air was comparable to the use of water washes and disinfectant indicating a potential role in cleaning poultry transport containers.

Application of pressurized steam and forced hot air for cleaning broiler transport container flooring.

In the United States, cleaning poultry transport containers prior to arrival at the broiler grow-out farm is not currently a widely adopted practice in the industry. However, previous studies have shown that transport containers have an important role in cross-contamination before the broilers arrive at the processing plant. The objective of this study was to evaluate the efficacy of pressurized steam followed by forced hot air to clean transport container flooring and compare it to conventional cleaning procedures. Fiberglass and plastic flooring were cut into even pieces and inoculated with chicken intestinal contents containing Salmonella Infantis or Campylobacter jejuni. The cleaning treatments were pressurized steam, forced hot air, pressurized steam followed by forced hot air, water pressure washing, water pressure washing before and after disinfectant, and no cleaning. Counts for Salmonella, Campylobacter, Escherichia coli, coliforms, and aerobic bacteria were assessed. All reductions were made in comparison to noncleaned samples. Forced hot air applied by itself was not efficient in reducing Campylobacter, coliforms, and E. coli; and limited reductions (less than 1 log10 CFU/cm2) were observed for Salmonella and aerobic bacteria. Then, for all bacteria types evaluated, pressurized steam by itself showed reductions of 2.4 to 3.5 log10 CFU/cm2. Samples that were cleaned with a single-pressure water wash showed reductions of 4.0 to 4.6 log10 CFU/cm2 for all bacteria types. For Salmonella, Campylobacter, and E. coli, the greatest reductions were observed when samples were cleaned with pressurized steam followed by forced hot air (4.3-6.1 log10 CFU/cm2) or water washed before and after disinfectant (4.5-6.2 log10 CFU/cm2), and these treatments did not differ from each other. Pressurized steam followed by forced hot air was shown to be an efficient cleaning procedure to reduce poultry-associated pathogens on transport cage flooring, with the benefit of using less water than conventional water cleaning. Processors may be able to adapt this process to reduce potential cross-contamination and lessen the level of pathogens entering the processing plant.

Statelessness of Children born to Venezuelan Parents in Colombia: Lawmaking without Convincing Policies

This article examines the Colombian legislation against statelessness issued due to the humanitarian emergency in Venezuela in recent years. There have been three waves of Venezuelan migration: the first, in 2005; the second, in 2017; and the last wave, from 2017 to the present day. For this analysis, it was used a qualitative socio-legal method adopting a descriptive approach. The paper affirms that, despite the efforts of Colombian entities to regulate the statelessness of minors born to Venezuelan parents, these regulations contain legal vacua due to a lack of communication between the different State bodies. Such void causes legal contradictions and legal uncertainty in the national system, and, subsequently, violates in a direct manner the fundamental rights of children born to Venezuelan migrants in Colombia.

En el presente artículo se analiza la legislación colombiana contra la apatridia expedida a raíz de la migración ocasionada por la emergencia humanitaria en Venezuela durante los últimos años. La migración venezolana se puede dividir en tres oleadas, la primera en el año de 2005, la segunda en el año de 2010 y la última desde el año de 2017 hasta la actualidad. Para la realización del presente artículo, se utilizó el método cualitativo de carácter sociojurídico con un enfoque descriptivo. Finalmente, se concluye que, a pesar del esfuerzo de las entidades colombianas por regular la apatridia de los menores hijos de padres venezolanos, dicha legislación presenta vacíos normativos por la falta de comunicación de los diferentes órganos del Estado. Dichos vacíos crean contradicciones, generan inseguridad jurídica en el ordenamiento nacional y, ulteriormente, violentan de manera directa los derechos fundamentales de los menores hijos de migrantes venezolanos nacidos en Colombia.

Este artigo analisa a legislação colombiana contra a apatridia emitida como resultado da migração causada pela emergência humanitária na Venezuela nos últimos anos. A migração venezuelana pode ser dividida em três ondas, a primeira em 2005, a segunda em 2010 e a última de 2017 até o presente. Para este artigo, usamos um método sociojurídico qualitativo com uma abordagem descritiva. Por fim, conclui-se que, apesar dos esforços das entidades colombianas para regulamentar a apatridia de menores nascidos de pais venezuelanos, essa legislação apresenta lacunas regulatórias devido à falta de comunicação entre os diferentes órgãos do Estado. Essas lacunas criam contradições, geram insegurança jurídica no sistema jurídico nacional e, consequentemente, violam diretamente os direitos fundamentais das crianças nascidas na Colômbia de migrantes venezuelanos.

The enzymes of the oxidative phase of the pentose phosphate pathway as targets of reactive species: consequences for NADPH production.

The pentose phosphate pathway (PPP) is a key metabolic pathway. The oxidative phase of this process involves three reactions catalyzed by glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL) and 6-phosphogluconate dehydrogenase (6PGDH) enzymes. The first and third steps (catalyzed by G6PDH and 6PGDH, respectively) are responsible for generating reduced nicotinamide adenine dinucleotide phosphate (NAPDH), a key cofactor for maintaining the reducing power of cells and detoxification of both endogenous and exogenous oxidants and electrophiles. Despite the importance of these enzymes, little attention has been paid to the fact that these proteins are targets of oxidants. In response to oxidative stimuli metabolic pathways are modulated, with the PPP often up-regulated in order to enhance or maintain the reductive capacity of cells. Under such circumstances, oxidation and inactivation of the PPP enzymes could be detrimental. Damage to the PPP enzymes may result in a downward spiral, as depending on the extent and sites of modification, these alterations may result in a loss of enzymatic activity and therefore increased oxidative damage due to NADPH depletion. In recent years, it has become evident that the three enzymes of the oxidative phase of the PPP have different susceptibilities to inactivation on exposure to different oxidants. In this review, we discuss existing knowledge on the role that these enzymes play in the metabolism of cells, and their susceptibility to oxidation and inactivation with special emphasis on NADPH production. Perspectives on achieving a better understanding of the molecular basis of the oxidation these enzymes within cellular environments are given.

In vitro Effect of Photoactive Compounds Curcumin and Chlorophyllin Against Single Strains of Salmonella and Campylobacter.

Salmonella and Campylobacter are two of the most common foodborne pathogens associated with poultry meat. Regulatory restrictions and consumer concerns have increased the interest for plant-derived antimicrobials and emerging novel technologies. The objective of this study was to determine the antimicrobial activity of photoactive compounds curcumin (CUR) and chlorophyllin (CH) followed by activating light exposure for the reduction of Salmonella and Campylobacter. Peroxyacetic acid (PAA) was also evaluated as a poultry industry standard antimicrobial processing aid. CUR and CH were evaluated in 96-well plates at concentrations of 100, 500, and 1,000 ppm, along with PAA at 100, 200, and 300 ppm, or distilled water (DW). Each well was inoculated with 105 CFU/mL of Salmonella Typhimurium or Campylobacter jejuni, and plates were exposed to activating light (430 nm) for 0 or 5 min. No detectable reductions were observed for Salmonella or Campylobacter when treated with CUR, CH, or 100 ppm PAA. However, when Salmonella was treated with 200 ppm PAA, counts were reduced from 4.57 to 2.52 log10 CFU/mL. When Salmonella was treated with 300 ppm PAA, counts were reduced to below detectable levels (5 CFU/mL). Campylobacter was reduced from 4.67 to 2.82 log10 CFU/mL when treated with 200 ppm PAA. However, no further reductions were observed when Campylobacter was treated with 300 ppm PAA (2.50 log10 CFU/mL). These results indicate that CUR and CH were not effective as antimicrobials under the evaluated conditions, particularly in comparison to the commonly used antimicrobial, PAA.

Early career acute care surgeons' priorities and perspectives: A mixed-methods analysis to better understand full-time employment.

BACKGROUND: Understanding the expectations of early career acute care surgeons will help clarify the practice and employment models that will attract and retain high-quality surgeons, thereby sustaining our workforce. This study aimed to outline the clinical and academic preferences and priorities of early career acute care surgeons and to better define full-time employment. METHODS: A survey on clinical responsibilities, employment preferences, work priorities, and compensation was distributed to early career acute care surgeons in the first 5 years of practice. A subset of agreeable respondents underwent virtual semistructured interviews. Both quantitative and thematic analysis were used to describe current responsibilities, expectations, and perspectives. RESULTS: Of 471 surgeons, 167 responded (35%), the majority of whom were assistant professors within the first 3 years of practice (80%). The median desired clinical volume was 24 clinical weeks and 48 call shifts per year, 4 weeks less than their median current clinical volume. Most respondents (61%) preferred a service-based model. The top priorities cited in choosing a job were geography, work schedule, and compensation. Qualitative interviews identified themes related to defining full-time employment, first job expectations and realities, and the often-misaligned system and surgeon. CONCLUSION: Understanding the perspectives of early career surgeons entering the workforce is important particularly in the field of acute care surgery where no standard workload or practice model exists. The wide variety of expectations, practice models, and schedule preferences may lead to a mismatch between surgeon desires and employment expectation. Consistent employment standards across our specialty would provide a framework for sustainability. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

The efficacy of various Enoxaparin dosing regimens in general surgery patients: A systematic review.

BACKGROUND: Patients undergoing surgical procedures are at an increased risk of venous thromboembolism events. A fixed Enoxaparin dosing regimen is the standard of care for chemoprophylaxis in most institutions; however, breakthrough venous thromboembolism events are still reported. We aimed to systematically review the literature to determine the ability of various Enoxaparin dosing regimens to achieve adequate prophylactic anti-Xa levels for venous thromboembolism prevention in hospitalized general surgery patients. Additionally, we aimed to assess the correlation between subprophylactic anti-Xa levels and the development of clinically significant venous thromboembolism events. METHODS: A systematic review was conducted using major databases from January 1, 1993, to February 17, 2023. Two independent researchers screened titles and abstracts, followed by a full-text review. Articles were included if Enoxaparin dosing regimens were evaluated by anti-Xa levels. Exclusion criteria included systematic reviews, pediatric population, nongeneral surgery (defined as trauma, orthopedics, plastics, and neurosurgery), and non-Enoxaparin chemoprophylaxis. The primary outcome was peak Anti-Xa level measured at steady state concentration. The risk of bias was assessed using the Risk of Bias in Nonrandomized studies-of Intervention tool. RESULTS: A total of 6,760 articles were extracted, of which 19 were included in the scoping review. Nine studies included bariatric patients, whereas 5 studies explored abdominal surgical oncology patients. Three studies assessed thoracic surgery patients, and 2 studies included patients undergoing "general surgery" procedures. A total of 1,502 patients were included. The mean age was 47 years, and 38% were males. The percentages of patients reaching adequate prophylactic anti-Xa levels were 39%, 61%, 15%, 50%, and 78% across the 40 mg daily, 40 mg twice daily, 30 mg twice daily, and weight-tiered, and body mass index-based groups, respectively. The overall risk of bias was low to moderate. CONCLUSION: Fixed Enoxaparin dosing regimens are not correlated with adequate anti-Xa levels in general surgery patients. Additional research is warranted to assess the efficacy of dosing regimens based on novel physiologic parameters (such as estimated blood volume).

Nanoporous Amorphous Carbon with Exceptional Ultra-High Strength.

Nanoporous materials show a promising combination of mechanical properties in terms of their relative density; while there are numerous studies based on metallic nanoporous materials, here we focus on amorphous carbon with a bicontinuous nanoporous structure as an alternative to control the mechanical properties for the function of filament composition.Using atomistic simulations, we study the mechanical response of nanoporous amorphous carbon with 50% porosity, with sp3 content ranging from 10% to 50%. Our results show an unusually high strength between 10 and 20 GPa as a function of the %sp3 content. We present an analytical analysis derived from the Gibson-Ashby model for porous solids, and from the He and Thorpe theory for covalent solids to describe Young's modulus and yield strength scaling laws extremely well, revealing also that the high strength is mainly due to the presence of sp3 bonding. Alternatively, we also find two distinct fracture modes: for low %sp3 samples, we observe a ductile-type behavior, while high %sp3 leads to brittle-type behavior due to high high shear strain clusters driving the carbon bond breaking that finally promotes the filament fracture. All in all, nanoporous amorphous carbon with bicontinuous structure is presented as a lightweight material with a tunable elasto-plastic response in terms of porosity and sp3 bonding, resulting in a material with a broad range of possible combinations of mechanical properties.

Anti-Factor Xa Monitoring of Enoxaparin Thromboembolism Prophylaxis in Emergency General Surgery Patients.

BACKGROUND: Rates of venous thromboembolism (VTE) remain high in emergency general surgery (EGS) patients despite chemical VTE prophylaxis. Emerging literature supports anti-factor Xa (AFXa) monitoring for patients on enoxaparin (LMWH), although a significant knowledge gap remains regarding the optimal dosing and monitoring in EGS patients. We hypothesize that standard dose VTE prophylaxis regimens provide inadequate VTE prophylaxis in EGS patients. STUDY DESIGN: A prospective cohort study of all adult EGS patients at a single institution between August 2021 and February 2022 receiving standard dose LMWH for VTE prophylaxis was performed. AFXa levels were obtained 4 hours after the third dose of enoxaparin with a target range of 0.3 to 0.5 IU/mL. Adjustment to dosing and repeat AFXa measurement after the adjusted third dose was obtained. RESULTS: A total of 81 patients underwent AFXa monitoring, the majority (75%) of whom were started on 40 mg LMWH daily. Initial peak AFXa measurement was low in 87.7% of patients (mean 0.16 IU/mL). Of patients who had an initial low AFXa, remained admitted, and underwent dosing adjustment and AFXa reassessment (27%), the majority were adjusted to either 30 or 40 mg of LMWH twice daily (23.7% and 55%, respectively), with 82% of patients remaining low. There were no significant differences in demographics or BMI between those with low vs adequate AFXa levels at either initial or subsequent measurement. CONCLUSIONS: Standard LMWH dosing provides inadequate AFXa inhibition for adequate VTE prophylaxis. These findings highlight the importance of ongoing AFXa monitoring and the need to establish clinical protocols to improve VTE prophylaxis in EGS patients.

Antioxidant Capacity of Free and Peptide Tryptophan Residues Determined by the ORAC (Oxygen Radical Absorbance Capacity) Assay Is Modulated by Radical-Radical Reactions and Oxidation Products.

The ORAC (Oxygen Radical Absorbance Capacity) assay is commonly employed for determining the antioxidant capacity of bioactive peptides. To gain insights into the meaning of this index for peptides containing a single Trp, we studied the consumption of this residue and fluorescein (FLH, the probe of ORAC method), induced by radicals generated by AAPH (2,2'-Azo-bis(2-amidinopropane) dihydrochloride) thermolysis. ORAC values were rationalized from kinetics and computational calculations of bond dissociation energies (BDE) of the N-H bond (indole ring of Trp). Free Trp, di- and tri- peptides, and three larger peptides were studied. Solutions containing 70 nM FLH, 1-5 µM free Trp or peptides, and 10 mM AAPH were incubated at 37 °C in phosphate buffer. Kinetic studies showed that FLH minimally affected Trp consumption. However, a clear protection of FLH, characterized by pseudo-lag times, was evidenced, reflecting radical-radical reactions and FLH repairing. Peptides showed similar ORAC values (~1.9-2.8 Trolox equivalents), while BDE varied between 91.9 and 103.5 kcal. These results, added to the protection of FLH observed after total consumption of Trp, indicate a lack of discrimination of the assay for the chemical structure of peptides and the contribution of oxidation products to the index.

Implications of differential peroxyl radical-induced inactivation of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase for the pentose phosphate pathway.

Escherichia coli glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) are key enzymes of the pentose phosphate pathway, responsible for the NADPH production in cells. We investigated modification of both enzymes mediated by peroxyl radicals (ROO·) to determine their respective susceptibilities to and mechanisms of oxidation. G6PDH and 6PGDH were incubated with AAPH (2,2'-azobis(2-methylpropionamidine)dihydrochloride), which was employed as ROO· source. The enzymatic activities of both enzymes were determined by NADPH release, with oxidative modifications examined by electrophoresis and liquid chromatography (LC) with fluorescence and mass (MS) detection. The activity of G6PDH decreased up to 62.0 ± 15.0% after 180 min incubation with 100 mM AAPH, whilst almost total inactivation of 6PGDH was determined under the same conditions. Although both proteins contain abundant Tyr (particularly 6PGDH), these residues were minimally affected by ROO·, with Trp and Met being major targets. LC-MS and in silico analysis showed that the modification sites of G6PDH are distant to the active site, consistent with a dispersed distribution of modifications, and inactivation resulting from oxidation of multiple Trp and Met residues. In contrast, the sites of oxidation detected on 6PGDH are located close to its catalytic site indicating a more localized oxidation, and a consequent high susceptibility to ROO·-mediated inactivation.

Explanatory models of hypertension in Guatemala: recognizing the perspectives of patients, family members, health care providers and administrators, and national-level health system stakeholders.

BACKGROUND: Uncontrolled hypertension is a major public health burden and the most common preventable risk factor for cardiovascular diseases in Guatemala and other low- and middle-income countries. Prior to an initial trial that evaluated a hypertension intervention in rural Guatemala, we collected qualitative information on the needs and knowledge gaps of hypertension care within Guatemala's public healthcare system. This analysis applied Kleinman's Explanatory Models of Illness to capture how patients, family members, community-, district-, and provincial-level health care providers and administrators, and national-level health system stakeholders understand hypertension.  METHODS: We conducted in-depth interviews with three types of participants: 1) national-level health system stakeholders (n = 17), 2) local health providers and administrators from district, and health post levels (25), and 3) patients and family members (19) in the departments of Sololá and Zacapa in Guatemala. All interviews were conducted in Spanish except for 6 Maya-Kaqchikel interviews. We also conducted focus group discussions with auxiliary nurses (3) and patients (3), one in Maya-Tz'utujil and the rest in Spanish. Through framework and matrix analysis, we compared understandings of hypertension by participant type using the Explanatory Model of Illness domains -etiology, symptoms, pathophysiology, course of illness, and treatment. RESULTS: Health providers and administrators, and patients described hypertension as an illness that spurs from emotional states like sadness, anger, and worry; is inherited and related to advanced age; and produces symptoms that include a weakened body, nerves, pain, and headaches. Patients expressed concerns about hypertension treatment's long-term consequences, despite trying to comply with treatment. Patients stated that they combine biomedical treatment (when available) with natural remedies (teas and plants). Health providers and administrators and family members stated that once patients feel better, they often disengage from treatment. National-level health system stakeholders referred to lifestyle factors as important causes, considered patients to typically be non-compliant, and identified budget limitations as a key barrier to hypertension care. The three groups of participants identified structural barriers to limited hypertension care (e.g., limited access to healthy food and unaffordability of medications). CONCLUSION: As understandings of hypertension vary between types of participants, it is important to describe their similarities and differences considering the role each has in the health system. Considering different perceptions of hypertension will enable better informed program planning and implementation efforts.

Tratamiento mínimamente invasivo/percutáneo de fracturas de pilón tibial con asistencia artroscópica en Hospital Regional de Talca / Minimally invasive/percutaneous treatment of tibial pilon fractures with arthroscopic assistance at the Regional Hospital

Tibial pilon fractures are a complex injury to treat due to the great involvement of soft and bone tissues. The classic surgical treatment is based on open reduction with internal fixation (ORIF), adding morbidity to the soft tissues, increasing the risk of complications. This has motivated the development of minimally invasive and/or percutaneous techniques to reduce complications, and with the advent of arthroscopy, achieve anatomical reductions. METHODS: A retrospective observational study of twelve patients with tibial pilon fractures who were treated in our center with minimally invasive and/ or percutaneous osteosynthesis with arthroscopic support was carried out between January 2019 and June 2021. Fractures were characterized using the AO/OTA classification for tibial pilon. Age, sex, fracture mechanism, exposure and initial management in the emergency department (cast immobilization or external fixation), definitive treatment, complications and clinical and functional evaluation twelve months after definitive osteosynthesis. For this last point, plantar flexion, dorsiflexion and the AOFAS and FAOS Score were measured. RESULTS: The operated patients were 12, 8 were men (67%) and 4 were women (33%). The average age was 49 (17-68) years. The definitive treatment was carried out after an average of 8 days (5-12 days). Surgical treatment schemes were as follows: percutaneous osteosynthesis with medial anatomical plate and arthroscopic support (OPAA), minimally invasive osteosynthesis with cannulated screws and arthroscopic support (OMIAA) and osteosynthesis with external circular guide and arthroscopic support (OTCAA). In the AOFAS Score, three patients had excellent results (≥ 90 points), 6 patients had good results (≥ 80 points) and 3 patients had acceptable results (≥ 70 points). In the FAOS Score, eight patients had over 80% (good results) and 4 patients had over 60% (accep - table results). DISCUSSION: Historically, tibial pilon fractures have been considered non-reconstructable and with poor long-term results. Initially this paradigm changed with the principles of Rüedi for the reconstruction of the tibial pilon and improve the results. ORIF has been widely used until today, it allows achieving an anatomical joint reduction, it allows to give stability and length to the fibula, graft contribution and sta - bilization with the medial plate. Today this concept is changing again, since the emphasis is on the care of the soft tissues to allow a better recovery of the patient and reduce the complications of the classic approach, it is in this context that the appearance of minimally invasive and/or percutaneous techniques with arthroscopic assistance has allowed us to have excellent functional and clinical results with less da - mage to the soft tissues. CONCLUSION: The proper management and care of the soft tissues in a high-energy fracture of the tibial pilon is essential to obtain favorable clinical results and thus achieve restoration of ankle function. Percutaneous and minimally invasive management has optimized management of the tibial pilon, redu - cing the rates of complications, amputation, and pri - mary arthrodesis.

Mechanical Ventilation Does Not Predict Pneumothorax Observation Failure in the Severely Injured.

BACKGROUND: Observative management of small traumatic pneumothoraces (PTX) has been shown to decrease chest tube utilization in non-mechanically ventilated patients without compromising outcomes. This approach could be used in mechanically ventilated (MV) patients, though many feel these patients are at increased risk of observation failure. METHODS: A single center retrospective study of all adults undergoing observation of a computed tomography (CT) diagnosed PTX from 2015-2019. Patients with chest tube placement within 4-hours of arrival, concurrent hemothorax, or death within 24-hours were excluded. Observation failure was defined as chest tube placement. RESULTS: Of 340 patients, 64 were on MV. The groups were of similar age, BMI, underlying pulmonary comorbidities, and PTX size (10.1 mm vs 8.8 mm, P = .20). The MV group was more severely injured (ISS [25+] [60.9% vs 11.2%, P < .001]). There was no difference in observation failure rates by MV status overall (6.3% vs 5.1%, P = .75) or by PTX size (<15 mm [5% vs 2.2%, P = .37], <20 mm [4.8% vs 3.1%, P = .45], <25 mm [4.8% vs 4.1%, P = .73], <30 mm [4.8% vs 4.1%, P = .73], <35 mm [4.8% vs 4.7%, P = 1.00]). MV was not an independent predictor of observation failure on multivariable analysis (OR .64, 95% CI .18-2.20), though PTX size was (OR 1.11, 95% CI 1.05-1.17). When comparing those who failed vs those who did not, the only difference was PTX size (9.34 mm vs 19.41 mm, P < .001). CONCLUSION: MV is not an independent predictor of PTX observation failure. While PTX size appears to play a role, further studies are needed to outline safe parameters for observation in those undergoing MV.

Role of amino acid oxidation and protein unfolding in peroxyl radical and peroxynitrite-induced inactivation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides.

The mechanisms underlying the inactivation of Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase (G6PDH) induced by peroxyl radicals (ROO●) and peroxynitrite (ONOO-), were explored. G6PDH was incubated with AAPH (2,2' -azobis(2-methylpropionamidine)dihydrochloride), used as ROO● source, and ONOO-. Enzymatic activity was assessed by NADPH generation, while oxidative modifications were analyzed by gel electrophoresis and liquid chromatography (LC) with fluorescence and mass detection. Changes in protein conformation were studied by circular dichroism (CD) and binding of the fluorescent dye ANS (1-anilinonaphthalene-8-sulfonic acid). Incubation of G6PDH (54.4 µM) with 60 mM AAPH showed an initial phase without significant changes in enzymatic activity, followed by a secondary time-dependent continuous decrease in activity to ∼59% of the initial level after 90 min. ONOO- induced a significant and concentration-dependent loss of G6PDH activity with ∼46% of the initial activity lost on treatment with 1.5 mM ONOO-. CD and ANS fluorescence indicated changes in G6PDH secondary structure with exposure of hydrophobic sites on exposure to ROO●, but not ONOO-. LC-MS analysis provided evidence for ONOO--mediated oxidation of Tyr, Met and Trp residues, with damage to critical Met and Tyr residues underlying enzyme inactivation, but without effects on the native (dimeric) state of the protein. In contrast, studies using chloramine T, a specific oxidant of Met, provided evidence that oxidation of specific Met and Trp residues and concomitant protein unfolding, loss of dimer structure and protein aggregation are involved in G6PDH inactivation by ROO●. These two oxidant systems therefore have markedly different effects on G6PDH structure and activity.