Alteration of epigenetic methyl and acetyl marks by postnatal chromium(VI) exposure causes apoptotic changes in the ovary of the F1 offspring.

Hexavalent chromium, Cr(VI), is a heavy metal endocrine disruptor used widely in various industries worldwide and is considered a reproductive toxicant. Our previous studies demonstrated that lactational exposure to Cr(VI) caused follicular atresia, disrupted steroid hormone biosynthesis and signaling, and delayed puberty. However, the underlying mechanism was unknown. The current study investigated the effects of Cr(VI) exposure (25 ppm) during postnatal days 1-21 via dam's milk on epigenetic alterations in the ovary of F1 offspring. Data indicated that Cr(VI) disrupted follicle development and caused apoptosis by increasing DNMT3a /3b and histone methyl marks (H3K27me3 and H3K9me3) along with decreasing histone acetylation marks (H3K9ac and H3K27ac). Our study demonstrates that exposure to Cr(VI) causes changes in the epigenetic marks, partially contributing to the transcriptional repression of genes regulating ovarian development, cell proliferation (PCNA), cell survival (BCL-XL and BCL-2), and activation of genes regulating apoptosis (AIF and cleaved caspase-3), resulting in follicular atresia. The current study suggests a role for epigenetics in Cr(VI)-induced ovotoxicity and infertility.

Genomic insights into isolation of the threatened Florida crested caracara (Caracara plancus).

We conducted a population genomic study of the crested caracara (Caracara plancus) using samples (n = 290) collected from individuals in Florida, Texas, and Arizona, United States. Crested caracaras are non-migratory raptors ranging from the southern tip of South America to the southern United States, including a federally protected relict population in Florida long thought to have been isolated since the last ice age. Our objectives were to evaluate genetic diversity and population structure of Florida's apparently isolated population and to evaluate taxonomic relationships of crested caracaras at the northern edge of their range. Using DNA purified from blood samples, we conducted double-digest restriction site associated DNA sequencing and sequenced the mitochondrial ND2 gene. Analyses of population structure using over 9,000 SNPs suggest that two major clusters are best supported, one cluster including only Florida individuals and the other cluster including Arizona and Texas individuals. Both SNPs and mitochondrial haplotypes reveal the Florida population to be highly differentiated genetically from Arizona and Texas populations, whereas, Arizona and Texas populations are moderately differentiated from each other. The Florida population's mitochondrial haplotypes form a separate monophyletic group, while Arizona and Texas populations share mitochondrial haplotypes. Results of this study provide substantial genetic evidence that Florida's crested caracaras have experienced long-term isolation from caracaras in Arizona and Texas and thus, represent a distinct evolutionary lineage possibly warranting distinction as an Evolutionarily Significant Unit (ESU) or subspecies. This study will inform conservation strategies focused on long-term survival of Florida's distinct, panmictic population.

A systematic review and meta-analysis of left atrial strain in hypertrophic cardiomyopathy and its prognostic utility.

Despite advances in noninvasive imaging modalities to identify atrial fibrillation (AF) risk in Hypertrophic Cardiomyopathy (HCM), there is a paucity of evidence concerning the impact of low Left Atrial strain (LAS) on AF and major adverse cardiac events (MACE) incidence in these patients. This study investigated the diagnostic and prognostic significance of LAS in predicting AF and MACE in HCM. Findings revealed lower LA reservoir (MD: -11.79, 95% CI -14.83, -8.74; p<0.00001), booster (MD: -4.10, 95% CI -6.29, -1.91; p=0.0002), and conduit (MD: -7.52, 95% CI -9.39, -5.65; p<0.00001) strains in HCM patients versus healthy controls, and also indicated a significant association between low LA reservoir/conduit/booster strain and the development of new AF as well as MACE prevalence in HCM patients. The results from this study suggest the valuable role of LA strain in HCM and its utility in predicting the development of new AF and cardiac events in HCM patients.

Temporal trends and procedural safety of transcatheter mitral valve repair with mitraclip in patients with hypertrophic cardiomyopathy: Insights from the national inpatient sample.

Data on utilization and safety of mitral Transcatheter Edge-to-Edge Repair (TEER) among hypertrophic cardiomyopathy (HCM) patients is limited. Our study aimed to assess the national utilization, safety, and clinical outcomes of TEER procedures among HCM patients using a nationwide real-world cohort. HCM patients undergoing TEER hospitalizations between 2015-2020 were identified using ICD-10 (International Classification of Diseases, (ICD-10-CM/PCS). HCM-TEER and HCM No-TEER formed the two comparison groups. Demographic characteristics, baseline comorbidities, procedural complications, inpatient mortality, length of stay (LOS), and cost of hospitalization were compared between the propensity-matched cohorts. Numeric values of 10 or less were not reported per NIS data use agreements. A total of 39,625 weighted cases of TEER were identified from 2015-2020. Of the included patients, 335 patients had the HCM diagnosis. The median age of the HCM-TEER group was 74 (70-79) vs. 79 (72-85) for the no-TEER cohort. The TEER procedure was more frequently performed among Caucasians (86.57%) and females (53.73%). The TEER procedure among HCM patients had similar in-hospital mortality (Adjusted odds ratio: aOR 1.50, 95% CI [0.68-3.29]; p = 0.30) and net adverse cardiac events (NACE) (aOR 1.16, 95% CI [0.73-1.85]; p = 0.51). TEER among HCM was associated with higher odds of gastrointestinal/hematological (aOR 2.33, 95% CI [1.29-4.19]; p = 0.003) complications. However, the odds of cardiac complications (aOR 0.57, 95% CI [0.33-0.96]; p = 0.03) were not higher. The median length of stay was similar in both the groups (median: 2 vs. 2, p = 0.74), although TEER among HCM was associated with higher costs of hospitalization ($44729.36 vs. $40513.82, p < 0.01). TEER is a minimally invasive procedure and could be a safe option for symptomatic HCM patients with significant MR who are poor surgical candidates. Mitral TEER among HCM has been increasingly utilized in recent years in the United States more commonly in obstructive HCM and is associated with no difference in mortality and net adverse cardiac events but higher odds for gastrointestinal/hematological complications than non-HCM patients.

Effects of hunting on mating, relatedness, and genetic diversity in a puma population.

Hunting mortality can affect population abundance, demography, patterns of dispersal and philopatry, breeding, and genetic diversity. We investigated the effects of hunting on the reproduction and genetic diversity in a puma population in western Colorado, USA. We genotyped over 11,000 single nucleotide polymorphisms (SNPs), using double-digest, restriction site-associated DNA sequencing (ddRADseq) in 291 tissue samples collected as part of a study on the effects of hunting on puma population abundance and demography in Colorado from 2004 to 2014. The study was designed with a reference period (years 1-5), during which hunting was suspended, followed by a treatment period (years 6-10), in which hunting was reinstated. Our objectives were to examine the effects of hunting on: (1) paternity and male reproductive success; (2) the relatedness between pumas within the population, and (3) genetic diversity. We found that hunting reduced the average age of male breeders. The number of unique fathers siring litters increased each year without hunting and decreased each year during the hunting period. Mated pairs were generally unrelated during both time periods, and females were more closely related than males. Hunting was also associated with increased relatedness among males and decreased relatedness among females in the population. Finally, genetic diversity increased during the period without hunting and decreased each year when hunting was present. This study demonstrates the utility of merging demographic data with large-scale genomic datasets in order to better understand the consequences of management actions. Specifically, we believe that this study highlights the need for long-term experimental research in which hunting mortality is manipulated, including at least one non-harvested control population, as part of a broader adaptive, zone management scheme.

Overcoming Fear, Uncertainty, and Doubt: Artificial Intelligence (AI) and the Value of Trust.

This is an editorial based on personal experience dealing with the fear, uncertainty, and doubt regarding artificial intelligence (AI) and radiology (my field of specialization). In the end, the most important tools to engage with these are education, research, and policy or regulation with the ultimate goal of forging trust, not just in the AI but also in the people that help make this technology possible.

Point-of-Care Ultrasound Overview and Curriculum Implementation in Internal Medicine Residency Training Programs in the United States.

Point-of-care ultrasonography (POCUS) augments physical examination and expedites diagnostic care and clinical decision-making. The use of POCUS in internal medicine (IM) appears inconsistent despite its commendable benefits. It is not fully incorporated into the IM residency core competency skills or academic curriculum. This narrative literature review explores the benefits of POCUS and evaluates the need for an IM-focused POCUS curriculum. The obstacles and a proposed curriculum are also described.

Mortality in Patients Hospitalized With Acute Myocardial Infarction Without Standard Modifiable Risk Factors: The ARIC Study Community Surveillance.

Background Prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; diabetes, hypertension, smoking, hypercholesterolemia) are critical to improving cardiovascular disease outcomes. However, acute myocardial infarction (AMI) among individuals who lack 1 or more SMuRFs is not uncommon. Moreover, the clinical characteristics and prognosis of SMuRFless individuals are not well characterized. Methods and Results We analyzed AMI hospitalizations from 2000 to 2014 captured by the ARIC (Atherosclerosis Risk in Community) study community surveillance. AMI was classified by physician review using a validated algorithm. Clinical data, medications, and procedures were abstracted from the medical record. Main study outcomes included short- and long-term mortality within 28 days and 1 year of AMI hospitalization. Between 2000 and 2014, a total of 742 (3.6%) of 20 569 patients with AMI were identified with no documented SMuRFs. Patients without SMuRFs were less likely to receive aspirin, nonaspirin antiplatelet therapy, or beta blockers and less often underwent angiography and revascularization. Compared with those with one or more SMuRFs, patients without SMuRFs had significantly higher 28-day (odds ratio, 3.23 [95% CI, 1.78-5.88]) and 1-year (hazard ratio, 2.09 [95% CI, 1.29-3.37]) adjusted mortality. When examined across 5-year intervals from 2000 to 2014, the incidence of 28-day mortality significantly increased for patients without SMuRFs (7% to 15% to 27%), whereas it declined for those with 1 or more SMuRFs (7% to 5% to 5%). Conclusions Individuals without SMuRFs presenting with AMI have an increased risk of all-cause mortality with an overall lower prescription rate for guideline-directed medical therapy. These findings highlight the need for evidence-based pharmacotherapy during hospitalization and the need to discover new markers and mechanisms for early risk identification in this population.

Continuous Remote Patient Monitoring in Patients With Heart Failure (Cascade Study): Protocol for a Mixed Methods Feasibility Study.

BACKGROUND: Heart failure (HF) is a prevalent chronic disease and is associated with increases in mortality and morbidity. HF is a leading cause of hospitalizations and readmissions in the United States. A potentially promising area for preventing HF readmissions is continuous remote patient monitoring (CRPM). OBJECTIVE: The primary aim of this study is to determine the feasibility and preliminary efficacy of a CRPM solution in patients with HF at NorthShore University HealthSystem. METHODS: This study is a feasibility study and uses a wearable biosensor to continuously remotely monitor patients with HF for 30 days after discharge. Eligible patients admitted with an HF exacerbation at NorthShore University HealthSystem are being recruited, and the wearable biosensor is placed before discharge. The biosensor collects physiological ambulatory data, which are analyzed for signs of patient deterioration. Participants are also completing a daily survey through a dedicated study smartphone. If prespecified criteria from the physiological data and survey results are met, a notification is triggered, and a predetermined electronic health record-based pathway of telephonic management is completed. In phase 1, which has already been completed, 5 patients were enrolled and monitored for 30 days after discharge. The results of phase 1 were analyzed, and modifications to the program were made to optimize it. After analysis of the phase 1 results, 15 patients are being enrolled for phase 2, which is a calibration and testing period to enable further adjustments to be made. After phase 2, we will enroll 45 patients for phase 3. The combined results of phases 1, 2, and 3 will be analyzed to determine the feasibility of a CRPM program in patients with HF. Semistructured interviews are being conducted with key stakeholders, including patients, and these results will be analyzed using the affective adaptation of the technology acceptance model. RESULTS: During phase 1, of the 5 patients, 2 (40%) were readmitted during the study period. The study completion rate for phase 1 was 80% (4/5), and the study attrition rate was 20% (1/5). There were 57 protocol deviations out of 150 patient days in phase 1 of the study. The results of phase 1 were analyzed, and the study protocol was adjusted to optimize it for phases 2 and 3. Phase 2 and phase 3 results will be available by the end of 2022. CONCLUSIONS: A CRPM program may offer a low-risk solution to improve care of patients with HF after hospital discharge and may help to decrease readmission of patients with HF to the hospital. This protocol may also lay the groundwork for the use of CRPM solutions in other groups of patients considered to be at high risk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36741.

An atypical case of a 14-year-old Filipino female with non-classical congenital adrenal hyperplasia presenting with alopecia universalis

Introduction@#Non-classical congenital adrenal hyperplasia (CAH) represents a group of inherited, autosomal recessive disor- ders that typically presents with androgenetic alopecia, but may present with alopecia universalis on rare occasions.@*Case report@#We report a case of a 14-year-old Filipino female with non-classical congenital adrenal hyperplasia presenting with alopecia universalis, treated with a combination of Tretinoin and Minoxidil solution, low dose prednisone and an oral supplement containing zinc gluconate, nicotinamide, superoxide dismutase, vitamin E and selenium, with noted gradual hair regrowth and improvement in Dermatology Life Quality Index (DLQI).@*Conclusion@#Alopecia universalis in a patient diagnosed with non-classical congenital adrenal hyperplasia is a rare and atypical manifestation, with no case reports available to describe its occurrence. Due to its rarity, there is no standard treatment for pa- tients with this condition. However, the combination of tretinoin and minoxidil solution, low dose prednisone and an oral supple- ment containing zinc gluconate, nicotinamide, superoxide dismutase, vitamin E and selenium shows promising results.

Continuous Remote Patient Monitoring: Evaluation of the Heart Failure Cascade Soft Launch.

OBJECTIVE: We report on our experience of deploying a continuous remote patient monitoring (CRPM) study soft launch with structured cascading and escalation pathways on heart failure (HF) patients post-discharge. The lessons learned from the soft launch are used to modify and fine-tune the workflow process and study protocol. METHODS: This soft launch was conducted at NorthShore University HealthSystem's Evanston Hospital from December 2020 to March 2021. Patients were provided with non-invasive wearable biosensors that continuously collect ambulatory physiological data, and a study phone that collects patient-reported outcomes. The physiological data are analyzed by machine learning algorithms, potentially identifying physiological perturbation in HF patients. Alerts from this algorithm may be cascaded with other patient status data to inform home health nurses' (HHNs') management via a structured protocol. HHNs review the monitoring platform daily. If the patient's status meets specific criteria, HHNs perform assessments and escalate patient cases to the HF team for further guidance on early intervention. RESULTS: We enrolled five patients into the soft launch. Four participants adhered to study activities. Two out of five patients were readmitted, one due to HF, one due to infection. Observed miscommunication and protocol gaps were noted for protocol amendment. The study team adopted an organizational development method from change management theory to reconfigure the study protocol. CONCLUSION: We sought to automate the monitoring aspects of post-discharge care by aligning a new technology that generates streaming data from a wearable device with a complex, multi-provider workflow into a novel protocol using iterative design, implementation, and evaluation methods to monitor post-discharge HF patients. CRPM with structured escalation and telemonitoring protocol shows potential to maintain patients in their home environment and reduce HF-related readmissions. Our results suggest that further education to engage and empower frontline workers using advanced technology is essential to scale up the approach.

Iatrogenic Atrial Septal Defect Closure Following Mitral Transcatheter Edge-to-Edge Repair: When Do You Close?

Transcatheter edge-to-edge repair has revolutionized the management of mitral regurgitation in the high surgical-risk population. Iatrogenic atrial septal defects (iASDs) are an obligatory consequence of the procedure. The long-term sequelae of persistent iASDs are unknown but are believed to be dependent on their size, directionality of flow, and underlying hemodynamics. We discuss an uncommon scenario of a post-transcatheter edge-to-edge repair iASD that required immediate closure. (Level of Difficulty: Intermediate.).

An approach for high-resolution genetic mapping of distant wild relatives of bread wheat: example of fine mapping of Lr57 and Yr40 genes.

KEY MESSAGE: The article reports a powerful but simple approach for high-resolution mapping and eventual map-based cloning of agronomically important genes from distant relatives of wheat, using the already existing germplasm resources. Wild relatives of wheat are a rich reservoir of genetic diversity for its improvement. The effective utilization of distant wild relatives in isolation of agronomically important genes is hindered by the lack of recombination between the homoeologous chromosomes. In this study, we propose a simple yet powerful approach that can be applied for high-resolution mapping of a targeted gene from wheat's distant gene pool members. A wheat-Aegilops geniculata translocation line TA5602 with a small terminal segment from chromosome 5 Mg of Ae. geniculata translocated to 5D of wheat contains genes Lr57 and Yr40 for leaf rust and stripe rust resistance, respectively. To map these genes, TA5602 was crossed with a susceptible Ae. geniculata 5 Mg addition line. Chromosome pairing between the 5 Mg chromosomes of susceptible and resistant parents resulted in the development of a high-resolution mapping panel for the targeted genes. Next-generation-sequencing data from flow-sorted 5 Mg chromosome of Ae. geniculata allowed us to generate 5 Mg-specific markers. These markers were used to delineate Lr57 and Yr40 genes each to distinct ~ 1.5 Mb physical intervals flanked by gene markers on 5 Mg. The method presented here will allow researchers worldwide to utilize existing germplasm resources in genebanks and seed repositories toward routinely performing map-based cloning of important genes from tertiary gene pools of wheat.

Use of Web-Based Patient Portals in Patients With Atrial Fibrillation Is Associated With Higher Readmissions.

Background: The impact of web-based patient portals on patient outcomes-specifically hospital readmissions in patients with atrial fibrillation (AF)-remains understudied. Methods: This single-center retrospective cohort study investigated the use of an online portal system (MyChart) by patients hospitalized from January 1, 2014 to June 30, 2017 for AF. During the study period, 11,334 unique AF admissions were identified; 50.3% were MyChart users and 49.7% were non-MyChart users. Patients who experienced inpatient mortality were excluded. The study groups were analyzed for demographic variables, comorbidities, readmission rates, and the frequency of MyChart use during the 3.5-year time frame. Results: MyChart users were younger (median age, 74 years, interquartile range [IQR] 66-82 vs 77 years, IQR 68-85; P<0.0001) and more likely to be white (91.9% vs 84.6%; P<0.0001), but the sex distribution was similar between groups, with 51.8% males in the MyChart group vs 53.2% in the non-MyChart group. MyChart users had a significantly higher rate of readmission compared to non-MyChart users at 1 year (43.0% vs 32.0%, respectively; P<0.0001). MyChart users who were readmitted had a higher median number of logins to MyChart (121 [IQR 32-270.5]) than MyChart users who were not readmitted (91 [IQR 26-205]; P<0.0001). Multivariable regression analysis demonstrated that MyChart use was associated with readmission (odds ratio 1.57, 95% CI 1.49-1.70; P<0.0001). Conclusion: Among patients with AF, MyChart use was associated with higher readmissions in this single-center cohort. Use and benefit of bespoke portals require further study.

ABA and BAP improve the accumulation of carbohydrates and alter carbon allocation in potato plants at elevated CO2.

Elevated CO2 interactions with other factors affects the plant performance. Regarding the differences between cultivars in response to CO2 concentrations, identifying the cultivars that better respond to such conditions would maximize their potential benefits. Increasing the ability of plants to benefit more from elevated CO2 levels alleviates the adverse effects of photoassimilate accumulation on photosynthesis and increases the productivity of plants. Despite its agronomic importance, there is no information about the interactive effects of elevated CO2 concentration and plant growth regulators (PGRs) on potato (Solanum tuberosum L.) plants. Hence, the physiological response and source-sink relationship of potato plants (cvs. Agria and Fontane) to combined application of CO2 levels (400 vs. 800 µmol mol-1) and plant growth regulators (PGR) [6-benzylaminopurine (BAP) + Abscisic acid (ABA)] were evaluated under a controlled environment. The results revealed a variation between the potato cultivars in response to a combination of PGRs and CO2 levels. Cultivars were different in leaf chlorophyll content; Agria had higher chlorophyll a, b, and total chlorophyll content by 23, 43, and 23%, respectively, compared with Fontane. The net photosynthetic rate was doubled at the elevated compared with the ambient CO2. In Agria, the ratio of leaf intercellular to ambient air CO2 concentrations [Ci:Ca] was declined in elevated-CO2-grown plants, which indicated the stomata would become more conservative at higher CO2 levels. On the other hand, the increased Ci:Ca in Fontane showed a stomatal acclimation to higher CO2 concentration. The higher leaf dark respiration of the elevated CO2-grown and BAP + ABA-treated plants was associated with a higher leaf soluble carbohydrates and starch content. Elevated CO2 and BAP + ABA shifted the dry matter partitioning to the belowground more than the above-media organs. The lower leaf soluble carbohydrate content and greater tuber yield in Fontane might indicate a more efficient photoassimilate translocation than Agria. The results highlighted positive synergic effects of the combined BAP + ABA and elevated CO2 on tuber yield and productivity of the potato plants.