Alternative Sites Research Articles

Does initiating care in alternate care sites decrease time to disposition in the emergency department?

During the coronavirus disease 2019 (COVID-19) pandemic surge, alternate care sites (ACS) such as the waiting room or hospital lobby were created amongst hospitals nationwide to help alleviate emergency department (ED) overflow. Despite the end of the pandemic surge, many of these ACS remain functional given the burden of prolonged ED wait times, with providers now utilizing the waiting room or ACS to initiate care. Therefore, the objective of this study is to evaluate if initiating patient care in ACS helps to decrease time to disposition. Retrospective data were collected on 61,869 patient encounters presenting to an academic medical center ED. Patients with an emergency severity index (ESI) of 1 were excluded. The "pre-ACS" or control data consisted of 38,625 patient encounters from September 30, 2018 to October 1, 2019, prior to the development of ACS, in which the patient was seen by a physician after they were brought to an assigned ED room. The "post-ACS" study cohort consisted of 23,244 patient encounters from September 30, 2022 to October 1, 2023, after the initiation of ACS, during which patients were initially seen by a provider in an ACS. ACS at this institution included the three following areas: waiting room, ambulance waiting area, and a newly constructed ACS that was built next to the ED entrance on the first floor of the hospital. The newly constructed ACS consisted of 16 care spaces each containing an upright exam chair with dividers between each care space. Door-to-disposition time (DTD) was calculated by identifying the time when the patient entered the ED and the time when disposition was decided (admission requested or patient discharged). Using regression analysis, we compared the two data sets to determine significant differences among DTD time. The largest proportion of encounters were among ESI 3 patients, that is, 56.1%. There was a significant increase in median DTD for ESI 2 and 3 patients who were seen initially in an ACS compared to those who were not seen until they were in an assigned ER room. Specifically, there was a median increase of 40.9 min for ESI 2 patients and 18.8 min for ESI 3 patients who were seen initially in an ACS (p<0.001). There was a 29-min decrease in median DTD for ESI 5 patients who were seen in ACS (p=0.09). Initiating patient care earlier in ACS did not appear to decrease DTD time for patients in the ED. Overall, the benefits of early initiation of care likely lie elsewhere within patient care and the ED throughput process.

Myotendinous Junction Anesthesia: An Alternative Infiltration Site for Ultrasound-Guided Injections

The myotendinous junction is a highly specialized and complex structure between muscle and tendon. In recent years, various procedures have directly targeted the tendon, with corticosteroid, platelet-rich plasma, or biological therapy infiltrations being prominent. However, these interventions are painful, corticosteroids have demonstrated tendon damage, and anesthesia negatively impacts tenocyte proliferation and viability when used with platelet-rich plasma in the same injection site. There is a need to adapt the injection site to improve therapy effectiveness and pain tolerance. This article presents a proposal for an ultrasound-guided anesthetic block procedure in the myotendinous junction.

Alternate Care Sites: A Novel Concept in Nepal During Disaster and Public Health Emergencies.

Nepal has a health care system that is complicated by access, affordability, and availability. The geographical difficulty makes the health care reach to public more difficult. Nepal being a disasterprone country, it makes very important to strengthen the disaster preparedness up to the mark before the disaster strikes. During disaster and public health emergencies, the healthcare system quickly becomes overwhelmed or structural damage makes it non-functional, which necessitate the prior identification of Alternate Care Site by health service providers. Incorporating the identification of Alternate Care Sites into the Hospital Disaster Preparedness Plan represents a crucial transition from theoretical discussion to practical implementation for strengthening healthcare facilities. . This paper discusses the concept of Alternate Care site and its implementation in Nepal's health emergency preparedness for disaster and public health emergencies.

No evidence of adaptive tolerance of parasitism in a cavity-nesting brood parasite host

Abstract Acceptance of avian brood parasitism by hosts is one of the most enigmatic aspects of brood parasite–host coevolution. The most common explanation for acceptance of parasitism by hosts of the brown-headed cowbird (Molothrus ater) is evolutionary lag, which suggests that hosts have not had enough time to evolve defenses against parasitism. Alternatively, acceptance may be the optimal strategy when the costs of rejecting parasitism exceed the benefits. The lack of nest site hypothesis applies to secondary cavity-nesting birds that cannot excavate their own nests and predicts that hosts accept parasitism instead of deserting a parasitized nest when there are no vacant nest sites available in which to renest. I tested this hypothesis using the prothonotary warbler (Pronotaria citrea), a commonly parasitized, cavity-nesting cowbird host. I used a paired nest box design and predicted that if hosts accept parasitism because of a lack of alternative nest sites, they should desert parasitized nests and renest in the vacant nest box on their territory. I recorded 37 cases where a nest was parasitized and warblers only deserted 2 parasitized nest boxes for a vacant nest box. Both desertions were attributable to factors other than parasitism and the rate of desertion did not differ from controls that only had a single nest box. Moreover, 7 of the warblers initiated clutches in nest boxes that already contained cowbird egg despite having vacant nest boxes available on their territories. These results indicate that warblers do not accept parasitism because of tolerance, but likely due to evolutionary lag.

Characterizing a complex CT-rich haplotype in intron 4 of SNCA using large-scale targeted amplicon long-read sequencing

Parkinson’s disease (PD) is a common neurodegenerative disorder with a significant risk proportion driven by genetics. While much progress has been made, most of the heritability remains unknown. This is in-part because previous genetic studies have focused on the contribution of single nucleotide variants. More complex forms of variation, such as structural variants and tandem repeats, are already associated with several synucleinopathies. However, because more sophisticated sequencing methods are usually required to detect these regions, little is understood regarding their contribution to PD. One example is a polymorphic CT-rich region in intron 4 of the SNCA gene. This haplotype has been suggested to be associated with risk of Lewy Body (LB) pathology in Alzheimer’s Disease and SNCA gene expression, but is yet to be investigated in PD. Here, we attempt to resolve this CT-rich haplotype and investigate its role in PD. We performed targeted PacBio HiFi sequencing of the region in 1375 PD cases and 959 controls. We replicate the previously reported associations and a novel association between two PD risk SNVs (rs356182 and rs5019538) and haplotype 4, the largest haplotype. Through quantitative trait locus analyzes we identify a significant haplotype 4 association with alternative CAGE transcriptional start site usage, not leading to significant differential SNCA gene expression in post-mortem frontal cortex brain tissue. Therefore, disease association in this locus might not be biologically driven by this CT-rich repeat region. Our data demonstrates the complexity of this SNCA region and highlights that further follow up functional studies are warranted.

Alternative TSS use is widespread in Cryptococcus fungi in response to environmental cues and regulated genome-wide by the transcription factor Tur1.

Alternative transcription start site (TSS) usage regulation has been identified as a major means of gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. Here, we first re-analyzed TSS-seq data to define genuine TSS clusters in 2 species of pathogenic Cryptococcus. We identified 2 types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates alternative TSS (altTSS) usage genome-wide when cells switch from exponential phase to stationary phase. ChiP-Seq and DamID-Seq analyses suggest that at some loci, the role of Tur1 might be direct. Tur1 has been previously shown to be essential for virulence in C. neoformans. We demonstrated here that a tur1Δ mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the wild-type (WT) strain.

The interferon-regulated host factor hnRNPA0 modulates HIV-1 production by interference with LTR activity, mRNA trafficking, and programmed ribosomal frameshifting.

The interplay between host factors and viral components impacts viral replication efficiency profoundly. Members of the cellular heterogeneous nuclear ribonucleoprotein family (hnRNPs) have been extensively studied as HIV-1 host dependency factors, but whether they play a role in innate immunity is currently unknown. This study aimed to identify hnRNPA0 as a type I interferon (IFN)-repressed host factor in HIV-1-infected cells. Knockdown of hnRNPA0, a situation that mirrors conditions under IFN stimulation, increased LTR activity, export of unspliced HIV-1 mRNA, viral particle production, and thus, increased infectivity. Conversely, hnRNPA0 overexpression primarily reduced plasmid-driven and integrated HIV-1 long terminal repeat (LTR) activity, significantly decreasing total viral mRNA and protein levels. In addition, high levels of hnRNPA0 significantly reduced the HIV-1 programmed ribosomal frameshifting efficiency, resulting in a shift in the HIV-1 p55/p15 ratio. The HIV-1 alternative splice site usage remained largely unaffected by altered hnRNPA0 levels suggesting that the synergistic inhibition of the LTR activity and viral mRNA transcription, as well as impaired ribosomal frameshifting efficiency, are critical factors for efficient HIV-1 replication regulated by hnRNPA0. The pleiotropic dose-dependent effects under high or low hnRNPA0 levels were further confirmed in HIV-1-infected Jurkat cells. Finally, our study revealed that hnRNPA0 levels in PBMCs were lower in therapy-naive HIV-1-infected individuals compared to healthy controls. Our findings highlight a significant role for hnRNPA0 in HIV-1 replication and suggest that its IFN-I-regulated expression levels are critical for viral fitness allowing replication in an antiviral environment.IMPORTANCERNA-binding proteins, in particular, heterogeneous nuclear ribonucleoproteins (hnRNPs), have been extensively studied. Some act as host dependency factors for HIV-1 since they are involved in multiple cellular gene expression processes. Our study revealed hnRNPA0 as an IFN-regulated host factor, that is differently expressed after IFN-I treatment in HIV-1 target cells and lower expressed in therapy-naïve HIV-1-infected individuals. Our findings demonstrate the significant pleiotropic role of hnRNPA0 in viral replication: In high concentrations, hnRNPA0 limits viral replication by negatively regulating Tat-LTR transcription, retaining unspliced mRNA in the nucleus, and significantly impairing programmed ribosomal frameshifting. Low hnRNPA0 levels as observed in IFN-treated THP-1 cells, particularly facilitate HIV LTR activity and unspliced mRNA export, suggesting a role in innate immunity in favor of HIV replication. Understanding the mode of action between hnRNPA0 and HIV-1 gene expression might help to identify novel therapeutically strategies against HIV-1 and other viruses.

Swi/Snf chromatin remodeling regulates transcriptional interference and gene repression

Alternative transcription start sites can affect transcript isoform diversity and translation levels. In a recently described form of gene regulation, coordinated transcriptional and translational interference results in transcript isoform-dependent changes in protein expression. Specifically, a long undecoded transcript isoform (LUTI) is transcribed from a gene-distal promoter, interfering with expression of the gene-proximal promoter. Although transcriptional and chromatin features associated with LUTI expression have been described, the mechanism underlying LUTI-based transcriptional interference is not well understood. Using an unbiased genetic approach followed by functional genomics, we uncovered that the Swi/Snf chromatin remodeling complex is required for co-transcriptional nucleosome remodeling that leads to LUTI-based repression. We identified genes with tandem promoters that rely on Swi/Snf function for transcriptional interference during protein folding stress, including LUTI-regulated genes. This study provides clear evidence for Swi/Snf playing a direct role in gene repression via a cis transcriptional interference mechanism.

Insights into Allosteric Inhibition of the AcrB Efflux Pump: Role of Distinct Binding Pockets, Protomer Preferences, and Crosstalk Disruption.

AcrB, a key component in bacterial efflux processes, exhibits distinct binding pockets that influence inhibitor interactions. In addition to the well-known distal binding pocket within the periplasmic domain, a noteworthy pocket amidst the transmembrane (TM) helices serves as an alternate binding site for inhibitors. The bacterial efflux mechanism involves a pivotal functional rotation of the TM protein, inducing conformational changes in each protomer and propelling drugs toward the outer membrane domain. Surprisingly, inhibitors binding to the TM domain display a preference for L protomers over T protomers. Metadynamics simulations elucidate that Lys940 in the TM domain of AcrB can adopt two conformations in L protomers, whereas the energy barrier for such transitions is higher in T protomers. This phenomenon results in stable inhibitor binding in l protomers. Upon a detailed analysis of unbinding pathways using random accelerated molecular dynamics and umbrella sampling, we have identified three distinct routes for ligand exit from the allosteric site, specifically involving regions within the TM domains─TM4, TM5, and TM10. To explore allosteric crosstalk, we focused on the following key residues: Val452 from the TM domain and Ala831 from the porter domain. Surprisingly, our findings reveal that inhibitor binding disrupts this communication. The shortest path connecting Val452 and Ala831 increases upon inhibitor binding, suggesting sabotage of the natural interdomain communication dynamics. This result highlights the intricate interplay between inhibitor binding and allosteric signaling within our studied system.

EIF1 and eIF5 dynamically control translation start site fidelity.

Translation initiation defines the identity of a synthesized protein through selection of a translation start site on a messenger RNA. This process is essential to well-controlled protein synthesis, modulated by stress responses, and dysregulated in many human diseases. The eukaryotic initiation factors eIF1 and eIF5 interact with the initiator methionyl-tRNAi Met on the 40S ribosomal subunit to coordinate start site selection. Here, using single-molecule analysis of in vitro reconstituted human initiation combined with translation assays in cells, we examine eIF1 and eIF5 function. During translation initiation on a panel of RNAs, we monitored both proteins directly and in real time using single-molecule fluorescence. As expected, eIF1 loaded onto mRNAs as a component of the 43S initiation complex. Rapid (~ 2 s) eIF1 departure required a translation start site and was delayed by alternative start sites and a longer 5' untranslated region (5'UTR). After its initial departure, eIF1 rapidly and transiently sampled initiation complexes, with more prolonged sampling events on alternative start sites. By contrast, eIF5 only transiently bound initiation complexes late in initiation immediately prior to association of eIF5B, which allowed joining of the 60S ribosomal subunit. eIF5 association required the presence of a translation start site and was inhibited and destabilized by alternative start sites. Using both knockdown and overexpression experiments in human cells, we validated that eIF1 and eIF5 have opposing roles during initiation. Collectively, our findings demonstrate how multiple eIF1 and eIF5 binding events control start-site selection fidelity throughout initiation, which is tuned in response to changes in the levels of both proteins.

The Effect of Alternative Splicing Sites on Mirtron Formation and Arm Selection of Precursor microRNAs.

Mirtrons represent a subclass of microRNAs (miRNAs) that rely on the splicing machinery for their maturation. However, the molecular details of this Drosha-independent processing are still not fully understood; as an example, the Microprocessor complex cannot process the mirtronic pre-miRNA from the transcript even if splice site mutations are present. To investigate the influence of alternative splicing sites on mirtron formation, we generated Enhanced Green Fluorescent Protein (EGFP) reporters containing artificial introns to compare the processing of canonical miRNAs and mirtrons. Although mutations of both splice sites generated a complex pattern of alternative transcripts, mirtron formation was always severely affected as opposed to the normal processing of the canonical hsa-mir-33b miRNA. However, we also detected that while its formation was also hindered, the mirtron-derived hsa-mir-877-3p miRNA was less affected by certain mutations than the hsa-mir-877-5p species. By knocking down Drosha, we showed that this phenomenon is not dependent on Microprocessor activity but rather points toward the potential stability difference between the miRNAs from the different arms. Our results indicate that when the major splice sites are mutated, mirtron formation cannot be rescued by nearby alternative splice sites, and stability differences between 5p and 3p species should also be considered for functional studies of mirtrons.

Perceptions of general surgery residents at military treatment facilities: Excellent training with crisis of confidence.

The declining operative volume at Military Treatment Facilities (MTFs) has resulted in Program Directors finding alternate civilian sites for resident rotations. The continued shift away from MTFs for surgical training is likely to have unintended negative consequences. An anonymous survey was generated and sent to the program directors of military general surgery training programs for distribution to their residents. A total of 42 residents responded (response rate 21%) with adequate representation from all PGY years. Ninety-five percent of residents believed that their programs provided the training needed to be a competent general surgeon. However, when asked about career choices, only 30.9% reported being likely/extremely likely to remain in the military beyond their initial service obligation, while 54.7% reported that it was unlikely/extremely unlikely and 19% reported uncertainty. Eighty-eight percent reported that decreasing MTF surgical volume directly influenced their decision to stay in the military, and half of respondents regretted joining the military. When asked to assess their confidence in the military to provide opportunities for skill sustainment as a staff surgeon, 90.4% were not confident or were neutral. Although military surgical residents have a generally positive perception of their surgical training, they also lack confidence in their future military surgical careers. Our findings suggest that declining MTF surgical volume will likely negatively impact long-term retention of military surgeons and may negatively impact force generation for Operational Commander. Prognostic and Epidemiological, Level IV.

Pan-cancer transcriptome analysis reveals widespread regulation through alternative tandem transcription initiation.

Abnormal transcription initiation from alternative first exon has been reported to promote tumorigenesis. However, the prevalence and impact of gene expression regulation mediated by alternative tandem transcription initiation were mostly unknown in cancer. Here, we developed a robust computational method to analyze alternative tandem transcription start site (TSS) usage from standard RNA sequencing data. Applying this method to pan-cancer RNA sequencing datasets, we observed widespread dysregulation of tandem TSS usage in tumors, many of which were independent of changes in overall expression level or alternative first exon usage. We showed that the dynamics of tandem TSS usage was associated with epigenomic modulation. We found that significant 5' untranslated region shortening of gene TIMM13 contributed to increased protein production, and up-regulation of TIMM13 by CRISPR-mediated transcriptional activation promoted proliferation and migration of lung cancer cells. Our findings suggest that dysregulated tandem TSS usage represents an addtional layer of cancer-associated transcriptome alterations.

Arabidopsis and maize terminator strength is determined by GC content, polyadenylation motifs and cleavage probability

The 3’ end of a gene, often called a terminator, modulates mRNA stability, localization, translation, and polyadenylation. Here, we adapted Plant STARR-seq, a massively parallel reporter assay, to measure the activity of over 50,000 terminators from the plants Arabidopsis thaliana and Zea mays. We characterize thousands of plant terminators, including many that outperform bacterial terminators commonly used in plants. Terminator activity is species-specific, differing in tobacco leaf and maize protoplast assays. While recapitulating known biology, our results reveal the relative contributions of polyadenylation motifs to terminator strength. We built a computational model to predict terminator strength and used it to conduct in silico evolution that generated optimized synthetic terminators. Additionally, we discover alternative polyadenylation sites across tens of thousands of terminators; however, the strongest terminators tend to have a dominant cleavage site. Our results establish features of plant terminator function and identify strong naturally occurring and synthetic terminators.

Deciphering the cis-regulatory landscape of natural yeast Transcript Leaders.

Protein synthesis is a vital process that is highly regulated at the initiation step of translation. Eukaryotic 5' transcript leaders (TLs) contain a variety of cis-regulatory features that influence translation and mRNA stability. However, the relative influences of these features in natural TLs are poorly characterized. To address this, we used massively parallel reporter assays (MPRAs) to quantify RNA levels, ribosome loading, and protein levels from 11,027 natural yeast TLs in vivo and systematically compared the relative impacts of their sequence features on gene expression. We found that yeast TLs influence gene expression over two orders of magnitude. While a leaky scanning model using Kozak contexts and uAUGs explained half of the variance in expression across transcript leaders, the addition of other features explained ~70% of gene expression variation. Our analyses detected key cis-acting sequence features, quantified their effects in vivo, and compared their roles to motifs reported from an in vitro study of ribosome recruitment. In addition, our work quantitated the effects of alternative transcription start site usage on gene expression in yeast. Thus, our study provides new quantitative insights into the roles of TL cis-acting sequences in regulating gene expression.

Osmia3DNest—Novel designed 3D printed artificial nest for solitary cavity‐nesting bees

Abstract The availability and appropriateness of nesting sites significantly influence the reproductive success and overall welfare of wild bees. Human‐induced factors contribute to the destruction of natural nesting habitats. To address these limitations, innovative solutions such as the development of artificial nests, offer alternative nest sites to support wild bee populations. We designed the Osmia3DNest, a 3D printed standardized nest tube for solitary cavity‐nesting bees, aiming to provide a safe for the environment, long‐life, time‐saving and biodegradable product that anyone can print. We proudly present the two Osmia3DNest models for mason bees—closed and open—using polylactic acid filament. We demonstrate the effectiveness of Osmia3DNest on mason bee reproduction parameters compared with traditional reed nests. Osmia3DNest can be an alternative to the other artificial nests, which people can customize for their necessity depending on their place of living (rural or urban area), and they can also be washed and reused several times and then decomposed. Osmia3DNest holds potential for wildlife biologists, management of pollinators, and educational outreach, offering adaptability for different bee species and experimental needs.

A study of the temperature distribution in the OTEC cold water pipe using a heat and mass transfer approach

Abstract The difference between sea water temperature at a depth of around 1000 m and sea water temperature at sea level is generally used as a parameter in the design of Ocean Thermal Energy Conversion (OTEC). In practice, electricity generation is determined by the difference between the temperature of the cold seawater coming out of the Cold Water Pipe (CWP) and the temperature of the seawater at the surface. The temperature of cold sea water increases due to heat transfer experienced by cold sea water flowing through the CWP, which comes into contact with surrounding sea water which has a higher temperature. This in turn provides a lower actual temperature difference, and therefore reduces the design power capacity. However, many previous studies did not consider these lower temperature differences. This may be acceptable for cases with practically small heat transfer such as CWP with low thermal conductivity combined with good insulation used in 1000 m CWP vertical floating systems. Unfortunately, this may not be the case for many of OTEC’s proposed alternative sites, which are located on land systems that require CWP lengths of five km or more. This raises the need for careful investigation to determine the temperature of the sea water coming out of the CWP, where it is necessary to calculate the temperature distribution of the cold sea water flowing through the CWP. This paper aims to estimate the temperature distribution of cold sea water flowing through the CWP and the increase in temperature of cold sea water leaving the CWP. Analysis based on the principles of mass and heat transfer was carried out in this research, where modelling was carried out numerically using a finite volume approach. For the case considered, the change in sea water temperature at CWP from depth to the surface occurs 1-3°C, which is the accumulation of each change in sea water depth. The results of this research illustrate that designing an OTEC system with a long CWP must consider the temperature distribution of cold sea water flowing through the CWP to produce a more realistic design.

Shifts in Religious and Cultural Diversity Support Across ObGyn Residencies with a Focus on Abortion Training: A Two-Year Follow-Up

Introduction: The Accreditation Council for Graduate Medical Education (ACGME) has recognized cultural competency as part of three out of six core competencies residency programs provide training in. Religion and culture are interwoven, and efforts to increase inclusivity by incorporating religious and culturally competent medical education has become a vital aspect of residency training. Inclusivity in healthcare has enhanced the recruitment of a racially, religiously, and culturally diverse workforce overall, thus enhancing the patient-provider experience through representation. Similarly, diversity among residency candidates has also improved. While current literature highlights the steps taken to ensure various forms of equity, there is little focus on religious or cultural support provided to OB/GYN residents. More recently, access to abortion training may impact which residency programs a candidate chooses to apply to, as ACGME requires such training opportunities to be provided without implications unless precluded by religious restrictions. However, minimal data exists on the training provided, institutional or alternative (outsourced services), and the methodology for abstention from abortion education. As program websites are often the primary source of information for residency applicants, this study aimed to identify shifts in cultural and religious support depicted on OB/GYN residency websites in the past two years while assessing the publicly-listed abortion training variations among such programs. Methods: During April 2022 and April 2023, websites of ACGME-accredited OB/GYN residency programs in the United States were evaluated using a novel 20-attribute collector tool that objectively benchmarks programs from religious/cultural diversity and incorporation of corresponding competency training into resident education. A religiously representative diverse focus group developed our tool. Items assessed included holistic reviews of applications, explicit interest in the recruitment of residents from diverse religious/cultural backgrounds, presence of religious/ethnic indicators depicted on the website, reported support for those with religious obligations, and if cultural/religious or diversity, equity, and inclusion (DEI) competency were cited. Additionally, the 2023 data collection focused on abortion references with guided support per ACGME-required training while providing an overview of protections and restrictions using the Guttmacher Institute website. Results: A total of 576 websites were analyzed, with 285 websites accessible for review in 2022 and 291 in 2023. Due to the program count discrepancy across both years, percentages were used to compare the data (as a result of an increase in accredited programs and website accessibility). An increase of 2% was noted in referencing holistic reviews and ethnic/religious support. Additionally, a 12% increase in spiritual and cultural-focused research was noted on websites with an additional 8% verbalizing such support. A 9% reduction in overall inclusivity advocacy was listed on websites, while an additional 10% reduction was explicitly noted in cultural competency. A 1% reduction in referencing religious diversity and a 2% reduction in websites referencing time allocations for religious holidays were identified. Furthermore, 12% had fewer stated opt-out options for religious obligations. There was a 7% increase in the discussion of religious or ethnic support, with a 5% increase in the focus on race. However, there was a 5% decline in referencing either concept. Although ACGME specifically suggested having Opt-Out options for programs, 1% had the Opt-In option, 12% stated the Opt-Out, 19% vaguely referenced either, and 68% did not mention abortion abstinence options or support on their website. Only 2% of websites suggested alternative sites for residents’ training due to legislation, whereas 27% referenced fellowship and supplementary post-residency training opportunities. Regarding the concept of abortion, 14% stated support for abortion, 14% mentioned abortion but provided limited details, and 72% did not reference it on the website. Concerning current state-specific legislature, 41% are distinctly protective of abortion rights, 46% are restrictive, with the remaining having both protections and restrictions. Conclusion: Our study suggests that the overall focus on religious and cultural diversity across OB/GYN residencies websites has become slightly accentuated over the past two years. The investment or deference of abortion training has not been adequately referenced to permit making informed decisions by prospective trainees. Having cultural and religious congruency of residents with program offerings may potentiate resident success while training.

Pacemaker-induced atrial fibrillation reconsidered-associations with different pacing sites and prevention approaches.

The incidence of atrial fibrillation (AF) is significantly higher in patients with pacemakers than in the general population, which could be due to patient characteristics and the diagnostic tool of the pacemaker in detecting atrial high-rate episodes and subclinical AF, but also to the pacemaker itself providing AF-promoting conditions. It is well known that high ventricular pacemaker burden increases the likelihood of AF occurrence. However, the sites of atrial and ventricular pacing may also influence the risk for AF. The conventional sites for atrial and ventricular pacing are in the right atrial appendage and in the right ventricular apex. However, growing evidence suggests that alternative pacing sites may be superior for the prevention of AF. Bachmann bundle pacing, for example, promotes interatrial excitation conduction, resulting in atrial synchronicity and a shorter total atrial activation time, which may be preventive for the occurrence of AF. Moreover, in recent years, new ventricular pacing sites have come into focus with His bundle and left bundle branch pacing. In addition to the hemodynamic and electrophysiological cardiac benefits, these new options may also offer benefits in the prevention of AF. This review provides an overview of pacing-induced AF mechanisms and the association with different pacing sites, as well as approaches for prevention of pacing-induced AF, highlighting different sites and modes of atrial pacing and the newer sites of ventricular pacing.

Identification of antennal alternative splicing by combining genome and full-length transcriptome analysis in Bactrocera dorsalis.

Alternative splicing is an essential post-transcriptional regulatory mechanism that diversifies gene function by generating multiple protein isoforms from a single gene and act as a crucial role in insect environmental adaptation. Olfaction, a key sense for insect adaptation, relies heavily on the antennae, which are the primary olfactory organs expressing most of the olfactory genes. Despite the extensive annotation of olfactory genes within insect antennal tissues facilitated by high-throughput sequencing technology advancements, systematic analyses of alternative splicing are still relatively less. In this study, we focused on the oriental fruit fly (Bactrocera dorsalis), a significant pest of fruit crops. We performed a detailed analysis of alternative splicing in its antennae by utilizing the full-length transcriptome of its antennal tissue and the insect's genome. The results revealed 8600 non-redundant full-length transcripts identified in the oriental fruit fly antennal full-length transcriptome, spanning 4,145 gene loci. Over 40% of these loci exhibited multiple isoforms. Among these, 161 genes showed sex-biased isoform switching, involving seven different types of alternative splicing. Notably, events involving alternative transcription start sites (ATSS) and alternative transcription termination sites (ATTS) were the most common. Of all the genes undergoing ATSS and ATTS alternative splicing between male and female, 32 genes were alternatively spliced in protein coding regions, potentially affecting protein function. These genes were categorized based on the length of the sex-biased isoforms, with the highest difference in isoform fraction (dIF) associated with the ATSS type, including genes such as BdorABCA13, BdorCAT2, and BdorTSN3. Additionally, transcription factor binding sites for doublesex were identified upstream of both BdorABCA13 and BdorCAT2. Besides being expressed in the antennal tissues, BdorABCA13 and BdorCAT2 are also expressed in the mouthparts, legs, and genitalia of both female and male adults, suggesting their functional diversity. This study reveals alternative splicing events in the antennae of Bactrophora dorsalis from two aspects: odorant receptor genes and other types of genes expressed in the antennae. This study not only provides a research foundation for understanding the regulation of gene function by alternative splicing in the oriental fruit fly but also offers new insights for utilizing olfaction-based behavioral manipulation techniques to manage this pest.