REVIEW: Evidence supporting the 'preparation for oxidative stress' (POS) strategy in animals in their natural environment.

Hypometabolism is a common strategy employed by resilient species to withstand environmental stressors that would be life-threatening for other organisms. Under conditions such as hypoxia/anoxia, temperature and salinity stress, or seasonal changes (e.g. hibernation, estivation), stress-tolerant species down-regulate pathways to decrease energy expenditures until the return of less challenging conditions. However, it is with the return of these more favorable conditions and the reactivation of basal metabolic rates that a strong increase of reactive oxygen and nitrogen species (RONS) occurs, leading to oxidative stress. Over the last few decades, cases of species capable of enhancing antioxidant defenses during hypometabolic states have been reported across taxa and in response to a variety of stressors. Interpreted as an adaptive mechanism to counteract RONS formation during tissue hypometabolism and reactivation, this strategy was coined "Preparation for Oxidative Stress" (POS). Laboratory experiments have confirmed that over 100 species, spanning 9 animal phyla, apply this strategy to endure harsh environments. However, the challenge remains to confirm its occurrence in the natural environment and its wide applicability as a key survival element, through controlled experimentation in field and in natural conditions. Under such conditions, numerous confounding factors may complicate data interpretation, but this remains the only approach to provide an integrative look at the evolutionary aspects of ecophysiological adaptations. In this review, we provide an overview of representative cases where the POS strategy has been demonstrated among diverse species in natural environmental conditions, discussing the strengths and weaknesses of these results and conclusions.

An Objective and Robust Bayes Factor for the Hypothesis Test One Sample and Two Population Means.

It has been over 100 years since the discovery of one of the most fundamental statistical tests: the Student's t test. However, reliable conventional and objective Bayesian procedures are still essential for routine practice. In this work, we proposed an objective and robust Bayesian approach for hypothesis testing for one-sample and two-sample mean comparisons when the assumption of equal variances holds. The newly proposed Bayes factors are based on the intrinsic and Berger robust prior. Additionally, we introduced a corrected version of the Bayesian Information Criterion (BIC), denoted BIC-TESS, which is based on the effective sample size (TESS), for comparing two population means. We studied our developed Bayes factors in several simulation experiments for hypothesis testing. Our methodologies consistently provided strong evidence in favor of the null hypothesis in the case of equal means and variances. Finally, we applied the methodology to the original Gosset sleep data, concluding strong evidence favoring the hypothesis that the average sleep hours differed between the two treatments. These methodologies exhibit finite sample consistency and demonstrate consistent qualitative behavior, proving reasonably close to each other in practice, particularly for moderate to large sample sizes.

The African Research Group for Oncology: A decade fostering colorectal cancer research in Nigeria.

The African Research Group for Oncology (ARGO) was formed in 2013 to undertake methodologically rigorous cancer research in Nigeria, and to strengthen cancer research capacity in the country through training and mentorship of physicians, scientists, and other healthcare workers. Here, we describe how ARGO's work in colorectal cancer (CRC) has evolved over the past decade. This includes the consortium's scientific contributions to the understanding of CRC in Nigeria and globally and its research capacity-building program.

State-Specific Prevalence of Depression Among Adults With and Without Diabetes - United States, 2011-2019.

INTRODUCTION: In 2019 among US adults, 1 in 9 had diagnosed diabetes and 1 in 5 had diagnosed depression. Since these conditions frequently coexist, compounding their health and economic burden, we examined state-specific trends in depression prevalence among US adults with and without diagnosed diabetes. METHODS: We used data from the 2011 through 2019 Behavioral Risk Factor Surveillance System to evaluate self-reported diabetes and depression prevalence. Joinpoint regression estimated state-level trends in depression prevalence by diabetes status. RESULTS: In 2019, the overall prevalence of depression in US adults with and without diabetes was 29.2% (95% CI, 27.8%-30.6%) and 17.9% (95% CI, 17.6%-18.1%), respectively. From 2011 to 2019, the depression prevalence was relatively stable for adults with diabetes (28.6% versus 29.2%) but increased for those without diabetes from 15.5% to 17.9% (average annual percent change [APC] over the 9-year period = 1.6%, P = .015). The prevalence of depression was consistently more than 10 percentage points higher among adults with diabetes than those without diabetes. The APC showed a significant increase in some states (Illinois: 5.9%, Kansas: 3.5%) and a significant decrease in others (Arizona: -5.1%, Florida: -4.0%, Colorado: -3.4%, Washington: -0.9%). In 2019, although it varied by state, the depression prevalence among adults with diabetes was highest in states with a higher diabetes burden such as Kentucky (47.9%), West Virginia (47.0%), and Maine (41.5%). CONCLUSION: US adults with diabetes are more likely to report prevalent depression compared with adults without diabetes. These findings highlight the importance of screening and monitoring for depression as a potential complication among adults with diabetes.

Outcomes of chronic total occlusion percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the LATAM CTO registry.

OBJECTIVES: To evaluate the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in patients with and without prior coronary artery bypass graft (CABG) surgery. BACKGROUND: Data on the outcomes of CTO PCI in patients with versus without CABG remains limited and with scarce representation from developing regions like Latin America. METHODS: We evaluated patients undergoing CTO PCI in 42 centers participating in the LATAM CTO registry between 2008 and 2020. Statistical analyses were stratified according to CABG status. The outcomes of interest were technical and procedural success and in-hospital major adverse cardiac and cerebrovascular events (MACCE). RESULTS: A total of 1662 patients were included (n = 1411 [84.9%] no-CABG and n = 251 [15.1%] prior-CABG). Compared with no-CABG, those with prior-CABG were older (67 ± 11 vs. 64 ± 11 years; p < 0.001), had more comorbidities and lower left ventricular ejection fraction (52.8 ± 12.8% vs. 54.4 ± 11.7%; p = 0.042). Anatomic complexity was higher in the prior-CABG group (J-CTO score 2.46 ± 1.19 vs. 2.10 ± 1.22; p < 0.001; PROGRESS CTO score 1.28 ± 0.89 vs. 0.91 ± 0.85; p < 0.001). Absence of CABG was associated with lower risk of technical and procedural failure (OR: 0.60, 95% CI: 0.43-0.85 and OR: 0.58, 95% CI: 0.40-0.83, respectively). No significant differences in the incidence of in-hospital MACCE (3.8% no-CABG vs. 4.4% prior-CABG; p = 0.766) were observed between groups. CONCLUSION: In a contemporary multicenter CTO-PCI registry from Latin America, prior-CABG patients had more comorbidities, higher anatomical complexity, lower success, and similar in-hospital adverse event rates compared with no-CABG patients.

First morphological and molecular identification of the cercaria of Stomylotrema vicarium from the endemic apple snail Pomacea americanista.

The adult fluke Stomylotrema vicarium (Stomylotrematidae, Microphalloidea) was described for the first time in Theristicus caerulescens in 1901, but the complete life cycle has remained unknown to date. Here, we found a stomylotrematid trematode in the digestive gland of the endemic apple snail Pomacea americanista. The digestive gland's tubuloacini were compressed by the trematode larvae placed on connective tissues and haemocoel spaces. Non-virgulate, stylet-bearing cercariae showed three pairs of penetration glands with a body, oral sucker and stylet morphometrically similar to those of stylet-bearing, unencysted young metacercariae of S. vicarium found in the aquatic coleopteran Megadytes glaucus, and at a lesser extent with cercariae of S. gratiosus found in the apple snail Pomacea maculata. The larvae molecular phylogeny was inferred using the markers rRNA 28S and ITS1, being these sequences grouped with the sequences of S. vicarium obtained from adult flukes. Together, these findings indicate that the life cycle of S. vicarium begins in P. americanista, thus supporting the hypothesis that the ampullariid snails act as a first intermediate host.

Preventable Emergency Department Visits After Colorectal Surgery.

BACKGROUND: The emergency department plays a common and critical role in the treatment of postoperative patients. However, many quality improvement databases fail to record these interactions. As such, our understanding of the prevalence and etiology of postoperative emergency department visits in contemporary colorectal surgery is limited. Visits with potentially preventable etiologies represent a significant target for quality improvement, particularly in the current era of rapidly evolving postoperative and ambulatory care patterns. OBJECTIVE: We aimed to characterize postoperative emergency department visits and identify factors associated with these visits for potential intervention. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at an academic medical center. PATIENTS: Consecutive patients undergoing colectomy or proctectomy within the division of colorectal surgery at an academic medical center between 2014 and 2018 were included. MAIN OUTCOME MEASURES: Frequency and indication for emergency department visits, as well as clinical and sociodemographic factors associated with emergency department visits in the postoperative period, were included measures. RESULTS: From the 1763 individual operations, there were 207 emergency department visits from 199 patients (11%) within 30 days of discharge. Two thirds of emergency department visits led to readmission. Median (interquartile range) time to presentation was 8 days (4-16 d). Median time in the emergency department was 7.8 hours (6.0-10.1 h). One third of visits were identified as potentially preventable, most commonly for pain (17%) and stoma complications (excluding dehydration; 13%). A primary language other than English was associated with any postoperative emergency department visit risk ratio of 2.7 (95% CI, 1.3-5.3), as well as a preventable visit risk ratio of 3.6 (95% CI, 1.7-8.0). LIMITATIONS: This was a single-center study and a retrospective review. CONCLUSIONS: One third of emergency department visits after colorectal surgery are potentially preventable. Special attention should be directed toward those patients who do not speak English as a primary language. See Video Abstract at http://links.lww.com/DCR/B648. SE PUEDEN EVITAR LAS VISITAS AL SERVICIO DE URGENCIA DESPUS DE UNA CIRUGA COLORECTAL: ANTECEDENTES:Las unidades de emergencia tienen un rol fundamental en el periodo posterior a una cirugía. Sin embargo muchos de los registros en las bases de datos de estas secciones no son de buena calidad. Por esto analizar la prevalencia y etiología de las visitas postoperatorias en cirugía colorectal resulta ser bastante limitada. Para lograr una mejoría en la calidad es fundamental analizar las causas potencialmente evitables, especialmente al considerer la rapida evolucion de los parametros de medición actuales.OBJETIVO:Nuestro objetivo es caracterizar las visitas postoperatorias al servicio de urgencias e identificar los factores asociados potencialmente evitables.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Centro médico académico, 2014-2018.PACIENTES:Pacientes consecutivos sometidos a colectomía o proctectomía dentro de la división de cirugía colorrectal en un centro médico académico entre 2014 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:Frecuencia e indicación de las visitas al servicio de urgencias en el period postoperatorio: factores clínicos y sociodemográficos.RESULTADOS:De 1763 operaciones individuales, hubo 207 visitas al departamento de emergencias de 199 pacientes (11%) en los 30 días posteriores al alta. Dos tercios de las visitas al servicio de urgencias dieron lugar a readmisiones. La mediana [rango intercuartílico] de tiempo hasta la presentación fue de 8 [4-16] días. La mediana de tiempo en el servicio de urgencias fue de 7,8 [6-10,1] horas. Un tercio de las visitas se identificaron como potencialmente evitables, más comúnmente dolor (17%) y complicaciones del estoma (excluida la deshidratación) (13%). En los pacientes con poco manejo del inglés se asoció con una mayor frecuencia razón de visitas al departamento de emergencias posoperatorias [IC del 95%] 2,7 [1,3-5,3], así como opetancialmente evitables con un RR de 3,6 [1,7-8,0].LIMITACIONES:Estudio de un solo centro y revisión retrospectiva.CONCLUSIÓN:Al menos un tercio de las visitas al servicio de urgencias después de una cirugía colorrectal son potencialmente evitables. Se debe prestar especial atención a los pacientes que no hablan inglés como idioma materno. Consulte Video Resumen en http://links.lww.com/DCR/B648.

Metagenomics-guided analysis of microbial chemolithoautotrophic phosphite oxidation yields evidence of a seventh natural CO2 fixation pathway.

Dissimilatory phosphite oxidation (DPO), a microbial metabolism by which phosphite (HPO32-) is oxidized to phosphate (PO43-), is the most energetically favorable chemotrophic electron-donating process known. Only one DPO organism has been described to date, and little is known about the environmental relevance of this metabolism. In this study, we used 16S rRNA gene community analysis and genome-resolved metagenomics to characterize anaerobic wastewater treatment sludge enrichments performing DPO coupled to CO2 reduction. We identified an uncultivated DPO bacterium, Candidatus Phosphitivorax (Ca. P.) anaerolimi strain Phox-21, that belongs to candidate order GW-28 within the Deltaproteobacteria, which has no known cultured isolates. Genes for phosphite oxidation and for CO2 reduction to formate were found in the genome of Ca. P. anaerolimi, but it appears to lack any of the known natural carbon fixation pathways. These observations led us to propose a metabolic model for autotrophic growth by Ca. P. anaerolimi whereby DPO drives CO2 reduction to formate, which is then assimilated into biomass via the reductive glycine pathway.

Introduction of hospital quality measures may lead to a temporary decrease in patient outcomes.

OBJECTIVES: To analyse the impact of hospital quality indicators on hip fracture mortality in Israel. STUDY DESIGN: A retrospective observational study. METHODS: Data were collected on all patients aged ≥65 years with an isolated hip fracture in the years 2010-2016 from the Israel's National Trauma Registry. These data were then cross checked with information on co-morbidities and medication intake from the Clalit medical fund. All successfully matched patients constituted the study population. The main outcome measures were in-hospital and 1-year mortality. Trend analysis of surgery on hip fractures within 48 h of hospitalisation (referred to as early hip fracture surgeries) and mortality was performed. The introduction of the proportion of early hip fracture surgeries as an official quality parameter in 2013 was considered an intervention. RESULTS: The proportion of early hip fracture surgeries continuously increased during the study period and, after the introduction of the quality measure, a significant increase in the uniformity of practice among hospitals was observed. The mortality trend was not related to the early surgeries trend, with a sharp upward spike detected in 2014, followed by a gradual return to previous levels in the subsequent years. The analysis has shown that when adjusting for demographic factors and co-morbidity, both in 2010-2013 and in 2015-2016, a clear benefit in survival existed for patients who were operated on within the first 48 h. In 2014, which was the first year of open publication of achieved quality measures reported in the media, no such benefit was found. CONCLUSIONS: Even when an improvement in a promoted practice is achieved, its positive impact on clinical outcomes may be delayed, possibly indicating the need for a learning period.

Signatures of Divergence, Invasiveness, and Terrestrialization Revealed by Four Apple Snail Genomes.

The family Ampullariidae includes both aquatic and amphibious apple snails. They are an emerging model for evolutionary studies due to the high diversity, ancient history, and wide geographical distribution. Insight into drivers of ampullariid evolution is hampered, however, by the lack of genomic resources. Here, we report the genomes of four ampullariids spanning the Old World (Lanistes nyassanus) and New World (Pomacea canaliculata, P. maculata, and Marisa cornuarietis) clades. The ampullariid genomes have conserved ancient bilaterial karyotype features and a novel Hox gene cluster rearrangement, making them valuable in comparative genomic studies. They have expanded gene families related to environmental sensing and cellulose digestion, which may have facilitated some ampullarids to become notorious invasive pests. In the amphibious Pomacea, novel acquisition of an egg neurotoxin and a protein for making the calcareous eggshell may have been key adaptations enabling their transition from underwater to terrestrial egg deposition.

Both quiescent and proliferating cells circulate in the blood of the invasive apple snail Pomacea canaliculata.

Gastropod hematopoiesis occurs at specialized tissues in some species, but the evidence also suggests that hemocyte generation is maybe widespread in the connective tissues or the blood system in others. In Ampullariidae (Caenogastropoda), both the kidney and the lung contain putative hematopoietic cells, which react to immune challenges. In the current study, we wanted to explore if hematopoiesis occurs in the blood of Pomacea canaliculata. Thus, we obtained circulating hemocytes from donor animals and tested their ability to proliferate in the blood of conspecific recipients. We tracked cell proliferation by labeling the donors' hemocytes with the fluorescent cell proliferation marker carboxyfluorescein diacetate succinimidyl ester (CFSE). Transferred CFSE-labeled hemocytes survived and proliferated into the recipients' circulation for at least 17 days. We also determined the cell cycle status of circulating hemocytes by using the propidium iodide (PI) and acridine orange (AO) staining methods. Flow cytometry analyses showed that most PI-stained hemocytes were in the G1 phase (~96%), while a lower proportion of cells were through the G2/S-M transition (~4%). When we instead used AO-staining, we further distinguished a subpopulation of cells (~5%) of low size, complexity-granularity, and RNA content. We regarded this subpopulation as quiescent cells. In separate experimental sets, we complemented these findings by assessing in circulating hemocytes two evolutionary conserved features of quiescent, undifferentiated cells. First, we used JC-1 staining to determine the mitochondrial membrane potential (Ψm) of circulating hemocytes, which is expected to be low in quiescent cells. Most hemocytes (~87%) showed high aggregation of JC-1, which indicates a high Ψm. Besides that, a small hemocyte subpopulation (~11%) showed low aggregation of the dye, thus indicating a low Ψm. It is known that the transition from a quiescent to a proliferating state associates with an increase of the Ψm. The specificity of these changes was here controlled by membrane depolarization with the Ψm disruptor CCCP. Second, we stained hemocytes with Hoechst33342 dye to determine the efflux activity of ABC transporters, which participate in the multixenobiotic resistance system characteristic of undifferentiated cells. Most hemocytes (>99%) showed a low dye-efflux activity, but a small proportion of cells (0.06-0.12%) showed a high dye-efflux activity, which was significantly inhibited by 100 and 500 µM verapamil, and thus is indicative of an undifferentiated subpopulation of circulating hemocytes. Taken together, our results suggest that, among circulating hemocytes, there are cells with the ability to proliferate or to stay in a quiescent state and behave as progenitor cells later, either in the circulation or the hematopoietic tissues/organs.

Integrative Proteomic Analysis of Digestive Tract Glycosidases from the Invasive Golden Apple Snail, Pomacea canaliculata.

The freshwater snail Pomacea canaliculata, an invasive species of global significance, possesses a well-developed digestive system and diverse feeding mechanisms enabling the intake of a wide variety of food. The identification of glycosidases in adult snails would increase the understanding of their digestive physiology and potentially generate new opportunities to eradicate and/or control this invasive species. In this study, liquid chromatography coupled to tandem mass spectrometry was applied to define the occurrence, diversity, and origin of glycoside hydrolases along the digestive tract of P. canaliculata. A range of cellulases, hemicellulases, amylases, maltases, fucosidases, and galactosidases were identified across the digestive tract. The digestive gland and the contents of the crop and style sac yield a higher diversity of glycosidase-derived peptides. Subsequently, peptides derived from 81 glycosidases (46 proteins from the public database and 35 uniquely from the transcriptome database) that were distributed among 13 glycoside hydrolase families were selected and quantified using multiple reaction monitoring mass spectrometry. This study showed a high glycosidase abundance and diversity in the gut contents of P. canaliculata which participate in extracellular digestion of complex dietary carbohydrates. Salivary and digestive glands were the main tissues involved in their synthesis and secretion.

Morphological characterization and molecular phylogeny of zoonotic trematodes in the freshwater snail Asolene platae.

In the context of a broader program dealing with the symbiotic associations of apple snails, we sampled three species that coexist in Lake Regatas (Palermo, Buenos Aires, Argentina). The population of Asolene platae, (but not those of Pomacea canaliculata and Pomacea scalaris) showed trematode larvae (echinocercariae and xiphidiocercariae) in haemocoelic spaces and connective tissue of the digestive gland. The echinocercariae resembled those of the genus Echinochasmus, but lacked sensory hairs on their body and tail; whereas xiphidiocercariae were similar to the xiphidiocercariae armatae belonging to the Opisthoglyphe type. The phylogenetical positions of these trematodes were inferred by the 28S rRNA, ITS1 and mtCOXI gene sequences. The 28S rRNA gene linked the echinocercarial sequences with the polyphyletic genus Echinochasmus (Echinochasmidae), while the xiphidiocercarial sequences were linked with the genus Phaneropsolus (Phaneropsolidae). The molecular markers used were able to distinguish two cryptic molecular entities of the single echinocercarial morphotype. Although ITS1 and mtCOXI did not allow resolving phylogeny beyond the family level because of the scarce number of sequences in the molecular databases, both cercariae (echinocercariae and xiphidiocercariae) could be distinguished by the Internal Transcribed Spacer 1 amplicon size. This is the first correlative morphological and molecular study of zoonotic trematodes in Neotropical ampullariids.

Twenty years of the 'Preparation for Oxidative Stress' (POS) theory: Ecophysiological advantages and molecular strategies.

Freezing, dehydration, salinity variations, hypoxia or anoxia are some of the environmental constraints that many organisms must frequently endure. Organisms adapted to these stressors often reduce their metabolic rates to maximize their chances of survival. However, upon recovery of environmental conditions and basal metabolic rates, cells are affected by an oxidative burst that, if uncontrolled, leads to (oxidative) cell damage and eventually death. Thus, a number of adapted organisms are able to increase their antioxidant defenses during an environmental/functional hypoxic transgression; a strategy that was interpreted in the 1990s as a "preparation for oxidative stress" (POS). Since that time, POS mechanisms have been identified in at least 83 animal species representing different phyla including Cnidaria, Nematoda, Annelida, Tardigrada, Echinodermata, Arthropoda, Mollusca and Chordata. Coinciding with the 20th anniversary of the postulation of the POS hypothesis, we compiled this review where we analyze a selection of examples of species showing POS-mechanisms and review the most recent advances in understanding the underlying molecular mechanisms behind those strategies that allow animals to survive in harsh environments.

Deep Green Diagnostics: Urban Green Space Analysis Using Deep Learning and Drone Images.

Nowadays, more than half of the world's population lives in urban areas, and this number continues increasing. Consequently, there are more and more scientific publications that analyze health problems of people associated with living in these highly urbanized locations. In particular, some of the recent work has focused on relating people's health to the quality and quantity of urban green areas. In this context, and considering the huge amount of land area in large cities that must be supervised, our work seeks to develop a deep learning-based solution capable of determining the level of health of the land and to assess whether it is contaminated. The main purpose is to provide health institutions with software capable of creating updated maps that indicate where these phenomena are presented, as this information could be very useful to guide public health goals in large cities. Our software is released as open source code, and the data used for the experiments presented in this paper are also freely available.

Surgical Management of Type II Odontoid Fractures in a Resource-Limited Setting: A Case Series.

Type II odontoid fracture, classified by Anderson and D'Alonzo, is the most common traumatic injury to the odontoid process. Surgical management of this lesion is particularly challenging in underresourced countries. This study aims to report the preliminary experience of the Kinshasa University Teaching Hospital in Kinshasa, Democratic Republic of the Congo, particularly using adaptive techniques. Three patients, aged 22, 30, and 32 years, respectively, were admitted to the neurosurgery department with Anderson and D'Alonzo type II odontoid fractures as confirmed by CT scan imaging. The first two patients underwent anterior odontoid fixation using a non-cannulated orthopaedic screw with an image intensifier. In the third case, partial resection of the C1 posterior arch was performed, followed by immobilisation using a rigid Philadelphia neck brace. Postoperative follow-up in all three cases was uneventful, and neurological outcomes were satisfactory. Odontoid surgery remains challenging for developing countries. The use of a non-cannulated orthopaedic screw for anterior fixation and posterior spinal cord decompression via partial resection of the C1 posterior arch, followed by external cervical immobilisation with a rigid neck brace for neglected fractures, could be effective alternatives to conventional surgical techniques. However, randomised multicentre studies are required to confirm the efficacy and safety of these techniques.

Trends and Inequalities in Diabetes-Related Complications Among U.S. Adults, 2000-2020.

OBJECTIVE: We examined national trends in diabetes-related complications (heart failure [HF], myocardial infarction [MI], stroke, end-stage renal disease [ESRD], nontraumatic lower-extremity amputation [NLEA], and hyperglycemic crisis) among U.S. adults with diagnosed diabetes during 2000-2020 by age-group, race and ethnicity, and sex. We also assessed trends in inequalities among those subgroups. RESEARCH DESIGN AND METHODS: Hospitalization rates for diabetes-related complications among adults (≥18 years) were estimated using the 2000-2020 National (Nationwide) Inpatient Sample. The incidence of diabetes-related ESRD was estimated using the United States Renal Data System. The number of U.S. adults with diagnosed diabetes was estimated from the National Health Interview Survey. Annual percent change (APC) was estimated for assessment of trends. RESULTS: After declines in the early 2000s, hospitalization rates increased for HF (2012-2020 APC 3.9%, P < 0.001), stroke (2009-2020 APC 2.8%, P < 0.001), and NLEA (2009-2020 APC 5.9%, P < 0.001), while ESRD incidence increased (2010-2020 APC 1.0%, P = 0.044). Hyperglycemic crisis increased from 2000 to 2020 (APC 2.2%, P < 0.001). MI hospitalizations declined during 2000-2008 (APC -6.0%, P < 0.001) and were flat thereafter. On average, age inequalities declined for hospitalizations for HF, MI, stroke, and ESRD incidence but increased for hyperglycemic crisis. Sex inequalities increased on average for hospitalizations for stroke and NLEA and for ESRD incidence. Racial and ethnic inequalities declined during 2012-2020 for ESRD incidence but increased for HF, stroke, and hyperglycemic crisis. CONCLUSIONS: There was a continued increase of several complications in the past decade. Age, sex, and racial and ethnic inequalities have worsened for some complications.

Electroporation-mediated gene transfer directly to the swine heart.

In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease. In the current study, we investigated the use of in vivo electroporation for gene transfer using three different penetrating electrodes and one non-penetrating electrode. The hearts of adult male swine were exposed through a sternotomy. Eight electric pulses synchronized to the rising phase of the R wave of the electrocardiogram were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein. Four sites on the anterior wall of the left ventricle were treated. Animals were killed 48 h after injection and electroporation and gene expression was determined. Results were compared with sites in the heart that received plasmid injection but no electric pulses or were not treated. Gene expression was higher in all electroporated sites when compared with injection only sites demonstrating the robustness of this approach. Our results provide evidence that in vivo electroporation can be a safe and effective non-viral method for delivering genes to the heart, in vivo.