Repair of Parastomal Hernias.

Parastomal hernias are an inevitable consequence of ostomy formation and their repairs remain a challenge to many surgeons. With multiple systems of classification and a multitude of techniques for hernia repair ranging from suture to mesh repair, the literature remains sparse with regards to the optimal method of repair. The authors describe the most commonly adopted techniques, discuss preventative measures, and review the current literature in the context of perioperative outcomes and hernia recurrence.

Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques (Macaca mulatta).

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype-a gene-by-environment interaction that leaves a lasting developmental signature.

From traditional to transactional: exploration of khat use in Ethiopia through an interpretative phenomenological analysis.

Khat, a naturally growing stimulant, has seen a significant increase in both consumption and cultivation in eastern Ethiopia. This reliance on khat in the region comes despite its known physiological complications, with users unable to restrict khat use due to its pervasive impact on their livelihood. This qualitative study sought to understand the meaning that those in eastern Ethiopia attribute to khat and explore their firsthand experiences with the substance. In June and July of 2023, six unstructured interviews were conducted among residents of the Haramaya District in Ethiopia. To promote a holistic comprehension of the participants' lived experiences, an interpretative phenomenological analysis approach was employed when collecting and analyzing the data. Participant responses were coded independently from one another by two different researchers identifying superordinate and corresponding subordinate themes. Among the participants, six superordinate themes were captured: economic backbone of the region, market disruption & fluctuation, pesticide use, societal relationships around khat, applications of khat, and access to healthcare. The participants' responses indicated that the normalization of khat use, coupled with the downplaying of its addictive potential, has established a framework where khat consumption is not only allowed but, in some cases, even encouraged. The unique interplay between communal practice and individual preservation creates a cyclical effect of using khat to supplement energy to farm khat and then sell or stimulate further work on their farm. This study illuminates the transitionfrom what was once the traditional or spiritual use of khat, to a more practical use for ensuring economic livelihood.

A Novel Taxonomy of Intraoperative Cholangiograms in Suspected Choledocholithiasis: A Tool for Advancing Laparoscopic Common Bile Duct Exploration Outcomes Research.

BACKGROUND: Cholangiography for visualization of the biliary tree during laparoscopic cholecystectomy is an important diagnostic roadmap in the context of suspected choledocholithiasis (CDL). The renewed interest in transcystic laparoscopic common bile duct exploration (LCBDE) necessitates a general description of the range of CDL presentations. Our aim was to establish a novel classification system of intraoperative cholangiograms (IOCs) to advance research efforts in this field. METHODS: A novel cholangiogram classification system, featuring 8 distinct presentations of choledocholithiasis, was applied to a data set of 80 preintervention IOCs for suspected choledocholithiasis. The classification system is as follows: A (no common bile duct stones, duodenal filling present, and concern for air bubbles), B (no common bile duct stones, no duodenal filling, and concern for sludge), C1 (stone(s) < 2x size of cystic duct with duodenal filling), C2 (stone(s) < 2x size of cystic duct without duodenal filling), D1 (stone(s) ≥ 2x size of cystic duct with duodenal filling), D2 (stone(s) ≥ 2x size of cystic duct without duodenal filling), E1 (congenital anatomical variant and/or common duct stricture), and E2 (surgically altered biliary anatomy). RESULTS: Cholangiogram review yielded preintervention classifications for 6 of 8 variants (A-E): A (7.5%), B (3.75%), C1 (23.75%), C2 (42.5%), D1 (15%), and D2 (7.5%). Analysis of cystic duct diameter yielded no significant differences among classification groups, indicating no predominant pattern of cystic duct anatomy within a given classification. DISCUSSION: An IOC classification system for suspected choledocholithiasis is foundational to answering key clinical questions for transcystic laparoscopic common bile duct exploration.

Total aortic arch debranching with antegrade Thoracic Endovascular Aortic Repair (TEVAR) in acute non-A non-B aortic dissection.

BACKGROUND: The surgical evaluation and management of non-A non-B aortic dissections, in the absence of ascending aortic involvement, remains a grey area. It is in these scenarios when thorough evaluation of patient/family history, clinical presentation, but also overall lifestyle, is of immense importance when determining an optimal intervention. CASE PRESENTATION: We present a 38-year-old patient with a physically demanding lifestyle as a professional wrestler, uncontrolled hypertension due to history of medical non-adherence, and family history of aortic dissection who presented with acute non-A non-B aortic dissection. He was spared a total arch replacement by undergoing a hybrid approach of complete aortic debranching with antegrade Thoracic Endovascular Aortic Repair (TEVAR). The patient was able to benefit from reduced cardiopulmonary bypass (CPB) time, avoidance of aortic cross clamp, circulatory arrest, and hypothermic circulation. CONCLUSIONS: This patient's unique composition of a physically demanding lifestyle, personal history of medical non-adherence, family history of aortic dissection, and clinical presentation required a holistic approach to understanding an ideal intervention that would be best suited long-term. Due to this contextualization, the patient was able to be spared a total arch replacement, or suboptimal medical management, by instead undergoing a hybrid-approach with total aortic arch debranching with antegrade TEVAR.

Khat use and related determinants among pregnant women within Haramaya, Ethiopia: a mixed methods study.

Introduction: Khat, a green leafy plant grown in East Africa and throughout the Arabian Peninsula, is chewed for its psychoactive and amphetamine-like effects, serving as a significant aspect of culture, economic livelihood, and global trade. Khat consumption during pregnancy has been associated with adverse effects, including anemia, premature rupture of membranes, and low birth weight, among others. Methods: This cross-sectional, explanatory sequential mixed methods study was conducted in the Haramaya District of eastern Ethiopia using a questionnaire and focus group discussions. Questionnaires assessed socio-demographic information, pregnancy history, and diet, including khat use. Data were analyzed using SPSS v28 to include descriptive statistics, proportions, odds ratios, binary logistic regression, and chi-square analysis. FGDs expanded on the knowledge, attitudes, and practices of khat in the region, including pregnant or lactating women from two different kebeles. Two independent reviewers conducted a qualitative content analysis to examine the qualitative findings from the FGDs. Transcripts from the focus groups were entered into NVivo 14 to aid in capturing salient themes. Results: A total of 444 pregnant women with a median age of 25 years completed the questionnaire. Two-thirds of the women, 66.9%, reported currently consuming khat while pregnant, and 72.7% of them reported daily consumption. The FGD analysis resulted in the discovery of five themes: Economic Livelihood, Maternal Significance, Medicinal Implications of Khat, Pesticide Use, and Social and Cultural Applications. Discussion: This study revealed an alarming high prevalence of khat consumption among pregnant women in the Haramaya District, highlighting the pressing need for long-term studies to assess the health consequences. The role of khat as both an economic staple and an energy source for daily activities underscores the challenges in curbing its use. The documented health risks associated with the chemicals used in khat cultivation, including cancer, call for interventions to enhance safe agricultural practices in households involved in khat farming.

A Comparative Analysis of "Surgery First" vs. "Endoscopy First" for Pediatric Choledocholithiasis Presenting at the End of the Week.

BACKGROUND: Choledocholithiasis in children is commonly managed with an "endoscopy first" (EF) strategy (endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) under a separate anesthetic). Endoscopic Retrograde Cholangiopancreatography is limited at the end of the week (EoW). We hypothesize that a "surgery first" (SF) approach with LC, intraoperative cholangiogram (IOC), and possible laparoscopic common bile duct exploration (LCBDE) can decrease length of stay (LOS) and time to definitive intervention (TTDI). METHODS: This is a retrospective single-center cohort study conducted between 2018 and 2023 in pediatric patients with suspected choledocholithiasis. Work week (WW) presentation included admission between Monday and Thursday. Time to definitive intervention was defined as time to LC. RESULTS: 88 pediatric patients were identified, 61 managed with SF (33 WW and 28 EoW) and 27 managed with EF (18 WW and 9 EoW). Both SF groups had shorter mean LOS for WW and EoW presentation (64.5 h, 92.4 h, 112.9 h, and 113.0 h; P < .05). There was a downtreading TTDI in the SF groups (SF: WW 24.7 h and EoW 21.7 h; EF: WW 31.7 h and EoW 35.9 h; P = .11). 44 patients underwent LCBDE with similar success rates (91.6% WW and 85% EoW; P = 1.0). All EF patients received 2 procedures; 69% of SF patients were definitively managed with one. CONCLUSION: Children with choledocholithiasis at the EoW have a longer LOS and TTDI. These findings are amplified when children enter an EF treatment pathway. An SF approach results in shorter LOS with fewer procedures, regardless of the time of presentation.

Management of recurrent benign paroxysmal positional vertigo.

BACKGROUND: Benign paroxysmal positional vertigo is the most common episodic vestibular disorder, although it is often quiescent by the time patients visit a specialist clinic, making the diagnosis difficult to confirm. Patients fear the consequences of a relapse and it is not clear what follow up should be provided. OBJECTIVE: This evaluation reviewed the results of an open access pathway that offered priority appointments to patients with a history of positional vertigo. RESULTS AND CONCLUSION: In total, 664 patients were included in the analysis, 52 per cent of whom had unconfirmed benign paroxysmal positional vertigo. Open follow up improved diagnostic rates by approximately 40 per cent. The rate of benign paroxysmal positional vertigo recurrence was 34 per cent in patients with follow up of at least one year, 41 per cent with follow up of one to two years, and 53 per cent with follow up of two years or more. One in five recurrences occurred in a different semi-circular canal. These results suggest that specialist follow up is required for management of recurrent benign paroxysmal positional vertigo.

Controlling genome topology with sequences that trigger post-replication gap formation during replisome passage: the E. coli RRS elements.

We report that the Escherichia coli chromosome includes novel GC-rich genomic structural elements that trigger formation of post-replication gaps upon replisome passage. The two nearly perfect 222 bp repeats, designated Replication Risk Sequences or RRS, are each 650 kb from the terminus sequence dif and flank the Ter macrodomain. RRS sequence and positioning is highly conserved in enterobacteria. At least one RRS appears to be essential unless a 200 kb region encompassing one of them is amplified. The RRS contain a G-quadruplex on the lagging strand which impedes DNA polymerase extension producing lagging strand ssDNA gaps, $ \le$2000 bp long, upon replisome passage. Deletion of both RRS elements has substantial effects on global genome structure and topology. We hypothesize that RRS elements serve as topological relief valves during chromosome replication and segregation. There have been no screens for genomic sequences that trigger transient gap formation. Functional analogs of RRS could be widespread, possibly including some enigmatic G-quadruplexes in eukaryotes.

Pediatric and Young Adult Trauma Recidivism.

INTRODUCTION: Unintentional injury is the leading cause of death among children. Much can be gleaned from the adult literature in understanding the characteristics that lead to recidivism in efforts to establish interventions for prevention. Our study aims to evaluate the rates, demographics, and features of pediatric trauma recidivism. METHODS: This was a retrospective single-institution review at a level-1 pediatric trauma center of children and young adults (ages 0-28) with traumatic injuries from January 2008 to April 2023. Patients with 1 or more prior visits to our institution's trauma center (recidivists) were identified and compared with those with single admissions. Chi-square tests were used to statistically analyze the two groups. RESULTS: Pediatric/young adult trauma recidivists were 4.4% of the total trauma population captured (n = 14,613). Of the total trauma group, 55% were under 18 years old. Recidivists had higher percentages of patients who were male (82% vs 69%, P < .01), African American (36% vs 24%, P < .01), involved in penetrating trauma (33% vs 17%, P < .01), self-pay/uninsured (17% vs 12%, P < .01), and have abuse reported (5% vs 4%, P = .04). The primary county for recidivism patients was Forsyth with most patients from a specific zip code in an urban area of the county. The average time between visits for recidivists was 1,066 days. CONCLUSIONS: Pediatric/young adult trauma recidivism is associated with specific characteristics including male, African American race, penetrating trauma, and uninsured status. Recidivists are primarily presenting from a zip code with low socioeconomic status. It is critical to develop targeted interventions to help this population in trauma prevention.

Gender systems in the Putin autocracy.

Over the last 23 years, Russian President Vladimir Putin's autocracy has revealed a set of interlocking gender systems that have come to the fore particularly vividly since the full-scale invasion of Ukraine on February 24, 2022. How, this article asks, have the masculinist cultural and political practices of the Putin regime undermined democratic practices and engagement broadly speaking? How have they organized Russian state and society in ways that have led to today's war in Ukraine with its massive destruction, violence, and brutality? And have there been earlier signals that should have warned observers that this regime might undertake such a war of aggression? Drawing on public, mass media data, this article analyzes the gendered structures of power in Russia that have contributed to the degeneration of democracy in three main areas: (1) male-on-male domination in discourse and practice that supports Putin's personal rule and emasculates his enemies; (2) the elevation of male power clans, including the President's personal praetorian guard and the Russian private military companies; and (3) the overall taming and emasculation of the Russian Parliament combined with the elevation of tough women deputies, whom I call the Baba Commissars. These female MPs support the President's domination by creating an appearance of a threatening outside world that needs to be kept at bay. At the same time, they support a neo-traditional gender order with women managing the house under the direction of the patriarchal male leader.

Lingering Effects of Early Institutional Rearing and Cytomegalovirus Infection on the Natural Killer Cell Repertoire of Adopted Adolescents.

Adversity during infancy can affect neurobehavioral development and perturb the maturation of physiological systems. Dysregulated immune and inflammatory responses contribute to many of the later effects on health. Whether normalization can occur following a transition to more nurturing, benevolent conditions is unclear. To assess the potential for recovery, blood samples were obtained from 45 adolescents adopted by supportive families after impoverished infancies in institutional settings (post-institutionalized, PI). Their immune profiles were compared to 39 age-matched controls raised by their biological parents (non-adopted, NA). Leukocytes were immunophenotyped, and this analysis focuses on natural killer (NK) cell populations in circulation. Cytomegalovirus (CMV) seropositivity was evaluated to determine if early infection contributed to the impact of an atypical rearing. Associations with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), two cytokines released by activated NK cells, were examined. Compared to the NA controls, PI adolescents had a lower percent of CD56bright NK cells in circulation, higher TNF-α levels, and were more likely to be infected with CMV. PI adolescents who were latent carriers of CMV expressed NKG2C and CD57 surface markers on more NK cells, including CD56dim lineages. The NK cell repertoire revealed lingering immune effects of early rearing while still maintaining an overall integrity and resilience.

Functional quality of life among newly diagnosed young adult colorectal cancer survivors compared to older adults: results from the ColoCare Study.

PURPOSE: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. METHODS: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. RESULTS: Participants (N = 1590) were n = 81 YAs, n = 196 aged 40-49, n = 627 aged 50-64, and n = 686 aged 65 + . Average physical function was better among YAs than participants aged 50-64 (p = 0.010) and 65 + (p < 0.001), and average social function was worse among YAs than aged 65 + (p = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40-49 OR = 0.13, 95%CI = 0.06-0.29; aged 50-64 OR = 0.10, 95%CI = 0.05-0.21; aged 65 + OR = 0.07, 95%CI = 0.04-0.15) and role dysfunction (aged 40-49 OR = 0.36, 95%CI = 0.18-0.75; aged 50-64 OR = 0.41, 95%CI = 0.22-0.78; aged 65 + OR = 0.32, 95%CI = 0.17-0.61). Participants aged 40-49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19-0.93). CONCLUSION: YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. TRIAL REGISTRATION: NCT02328677, registered December 2014.

MAN VERSUS MACHINE: PROVIDER DIRECTED VERSUS PRECISION AUTOMATED CRITICAL CARE MANAGEMENT IN A PORCINE MODEL OF DISTRIBUTIVE SHOCK.

ABSTRACT: Background: Critical care management of shock is a labor-intensive process. Precision Automated Critical Care Management (PACC-MAN) is an automated closed-loop system incorporating physiologic and hemodynamic inputs to deliver interventions while avoiding excessive fluid or vasopressor administration. To understand PACC-MAN efficacy, we compared PACC-MAN to provider-directed management (PDM). We hypothesized that PACC-MAN would achieve equivalent resuscitation outcomes to PDM while maintaining normotension with lower fluid and vasopressor requirements. Methods : Twelve swine underwent 30% controlled hemorrhage over 30 min, followed by 45 min of aortic occlusion to generate a vasoplegic shock state, transfusion to euvolemia, and randomization to PACC-MAN or PDM for 4.25 h. Primary outcomes were total crystalloid volume, vasopressor administration, total time spent at hypotension (mean arterial blood pressure <60 mm Hg), and total number of interventions. Results : Weight-based fluid volumes were similar between PACC-MAN and PDM; median and IQR are reported (73.1 mL/kg [59.0-78.7] vs. 87.1 mL/kg [79.4-91.8], P = 0.07). There was no statistical difference in cumulative norepinephrine (PACC-MAN: 33.4 µg/kg [27.1-44.6] vs. PDM: 7.5 [3.3-24.2] µg/kg, P = 0.09). The median percentage of time spent at hypotension was equivalent (PACC-MAN: 6.2% [3.6-7.4] and PDM: 3.1% [1.3-6.6], P = 0.23). Urine outputs were similar between PACC-MAN and PDM (14.0 mL/kg vs. 21.5 mL/kg, P = 0.13). Conclusion : Automated resuscitation achieves equivalent resuscitation outcomes to direct human intervention in this shock model. This study provides the first translational experience with the PACC-MAN system versus PDM.

The intrinsically disordered linker in the single-stranded DNA-binding protein influences DNA replication restart and recombination pathways in Escherichia coli K-12.

Tetrameric single-stranded (ss) DNA-binding proteins (SSBs) stabilize ssDNA intermediates formed during genome maintenance reactions in Bacteria. SSBs also recruit proteins important for these processes through direct SSB-protein interactions, including proteins involved in DNA replication restart and recombination processes. SSBs are composed of an N-terminal oligomerization and ssDNA-binding domain, a C-terminal acidic tip that mediates SSB-protein interactions, and an internal intrinsically disordered linker (IDL). Deletions and insertions into the IDL are well tolerated with few phenotypes, although the largest deletions and insertions exhibit some sensitivity to DNA-damaging agents. To define specific DNA metabolism processes dependent on IDL length, ssb mutants that lack 16, 26, 37, or 47 residues of the 57-residue IDL were tested for synthetic phenotypes with mutations in DNA replication restart or recombination genes. We also tested the impact of integrating a fluorescent domain within the SSB IDL using an ssb::mTur2 insertion mutation. Only the largest deletion tested or the insertion mutation causes sensitivity in any of the pathways. Mutations in two replication restart pathways (PriA-B1 and PriA-C) showed synthetic lethalities or small colony phenotypes with the largest deletion or insertion mutations. Recombination gene mutations del(recBCD) and del(ruvABC) show synthetic phenotypes only when combined with the largest ssb deletion. These results suggest that a minimum IDL length is important in some genome maintenance reactions in Escherichia coli. These include pathways involving PriA-PriB1, PriA-PriC, RecFOR, and RecG. The mTur2 insertion in the IDL may also affect SSB interactions in some processes, particularly the PriA-PriB1 and PriA-PriC replication restart pathways.IMPORTANCEssb is essential in Escherichia coli due to its roles in protecting ssDNA and coordinating genome maintenance events. While the DNA-binding core and acidic tip have well-characterized functions, the purpose of the intrinsically disordered linker (IDL) is poorly understood. In vitro studies have revealed that the IDL is important for cooperative ssDNA binding and phase separation. However, single-stranded (ss) DNA-binding protein (SSB) variants with large deletions and insertions in the IDL support normal cell growth. We find that the PriA-PriB1 and PriA-C replication restart, as well as the RecFOR- and RecG-dependent recombination, pathways are sensitive to IDL length. This suggests that cooperativity, phase separation, or a longer spacer between the core and acidic tip of SSB may be important for specific cellular functions.

Formation of memory assemblies through the DNA-sensing TLR9 pathway.

As hippocampal neurons respond to diverse types of information1, a subset assembles into microcircuits representing a memory2. Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage3-5. Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early events, some neurons acquired an inflammatory phenotype involving activation of TLR9 signalling and accumulation of centrosomal DNA damage repair complexes6. Neuron-specific knockdown of Tlr9 impaired memory while blunting contextual fear conditioning-induced changes of gene expression in specific clusters of excitatory CA1 neurons. Notably, TLR9 had an essential role in centrosome function, including DNA damage repair, ciliogenesis and build-up of perineuronal nets. We demonstrate a novel cascade of learning-induced molecular events in discrete neuronal clusters undergoing dsDNA damage and TLR9-mediated repair, resulting in their recruitment to memory circuits. With compromised TLR9 function, this fundamental memory mechanism becomes a gateway to genomic instability and cognitive impairments implicated in accelerated senescence, psychiatric disorders and neurodegenerative disorders. Maintaining the integrity of TLR9 inflammatory signalling thus emerges as a promising preventive strategy for neurocognitive deficits.

The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.

BACKGROUND: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. The ENGaging and Activating cancer survivors in Genetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing. METHODS: The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services. DISCUSSION: With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.

Behavioral inhibition in a translational nonhuman primate model: A pilot study of Kagan's behavioral inhibition paradigm modified for use in infant rhesus macaques (Macaca mulatta).

Behavioral inhibition (BI), a temperamental trait first described by Jerome Kagan, is characterized by wariness to unfamiliar persons and novel situations. BI is a moderately stable trait, with biological and genetic underpinnings. Kagan's methodology for assessing BI is widely used in humans. Although this paradigm could be readily translated for use in nonhuman primates, thereby increasing generalizability from nonhuman primates to humans and fortifying evidence that BI is evolutionarily conserved, researchers have not done so. To address this, this study utilized a modified version of Kagan's paradigm to assess behaviors and biological markers of BI in nonhuman primates. Over the first 5 weeks of life, nursery-reared rhesus monkeys (Macaca mulatta; N = 12) were rated using the standardized Infant Behavior Assessment Scale for nonhuman primates on measures related to BI (consolability, irritability, struggle, and predominant state). Three months later, behavioral assessments were made in relation to a novel playroom, an unfamiliar peer, and a variety of attention-grabbing, unfamiliar stimuli, followed by the introduction of a human stranger. Behaviors from Kagan's studies of BI in toddlers (freezing, exploration, and latency to approach) and physiological measures related to BI (heart rate) were assessed. Random effects models showed that subjects rated high in temperamental BI spent less time exploring the environment and socializing with peers and more time freezing (an indication of anxiety in rhesus monkeys). These findings suggest that Kagan's paradigm is readily adapted for use in nonhuman primates and support the utility of rhesus monkeys as translational models for assessing the causes and consequences of human BI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Controlling Genome Topology with Sequences that Trigger Post-replication Gap Formation During Replisome Passage: The E. coli RRS Elements.

We report that the Escherichia coli chromosome includes novel GC-rich genomic structural elements that trigger formation of post-replication gaps upon replisome passage. The two nearly perfect 222 bp repeats, designated Replication Risk Sequences or RRS, are each 650 kb from the terminus sequence dif and flank the Ter macrodomain. RRS sequence and positioning is highly conserved in enterobacteria. At least one RRS appears to be essential unless a 200 kb region encompassing one of them is amplified. The RRS contain a G-quadruplex on the lagging strand which impedes DNA polymerase extension producing lagging strand ssDNA gaps, ≤2000 bp long, upon replisome passage. Deletion of both RRS elements has substantial effects on global genome structure and topology. We hypothesize that RRS elements serve as topological relief valves during chromosome replication and segregation. There have been no screens for genomic sequences that trigger transient gap formation. Functional analogs of RRS could be widespread, possibly including some enigmatic G-quadruplexes in eukaryotes.