The PilT retraction ATPase promotes both extension and retraction of the MSHA type IVa pilus in Vibrio cholerae.

Diverse bacterial species use type IVa pili (T4aP) to interact with their environments. The dynamic extension and retraction of T4aP is critical for their function, but the mechanisms that regulate this dynamic activity remain poorly understood. T4aP are typically extended via the activity of a dedicated extension motor ATPase and retracted via the action of an antagonistic retraction motor ATPase called PilT. These motors are generally functionally independent, and loss of PilT commonly results in T4aP hyperpiliation due to undeterred pilus extension. However, for the mannose-sensitive hemagglutinin (MSHA) T4aP of Vibrio cholerae, the loss of PilT unexpectedly results in a loss of surface piliation. Here, we employ a combination of genetic and cell biological approaches to dissect the underlying mechanism. Our results demonstrate that PilT is necessary for MSHA pilus extension in addition to its well-established role in promoting MSHA pilus retraction. Through a suppressor screen, we also provide genetic evidence that the MshA major pilin impacts pilus extension. Together, these findings contribute to our understanding of the factors that regulate pilus extension and describe a previously uncharacterized function for the PilT motor ATPase.

Nitric oxide stimulates type IV MSHA pilus retraction in Vibrio cholerae via activation of the phosphodiesterase CdpA.

Bacteria use surface appendages called type IV pili to perform diverse activities including DNA uptake, twitching motility, and attachment to surfaces. The dynamic extension and retraction of pili are often required for these activities, but the stimuli that regulate these dynamics remain poorly characterized. To address this question, we study the bacterial pathogen Vibrio cholerae, which uses mannose-sensitive hemagglutinin (MSHA) pili to attach to surfaces in aquatic environments as the first step in biofilm formation. Here, we use a combination of genetic and cell biological approaches to describe a regulatory pathway that allows V. cholerae to rapidly abort biofilm formation. Specifically, we show that V. cholerae cells retract MSHA pili and detach from a surface in a diffusion-limited, enclosed environment. This response is dependent on the phosphodiesterase CdpA, which decreases intracellular levels of cyclic-di-GMP to induce MSHA pilus retraction. CdpA contains a putative nitric oxide (NO)-sensing NosP domain, and we demonstrate that NO is necessary and sufficient to stimulate CdpA-dependent detachment. Thus, we hypothesize that the endogenous production of NO (or an NO-like molecule) in V. cholerae stimulates the retraction of MSHA pili. These results extend our understanding of how environmental cues can be integrated into the complex regulatory pathways that control pilus dynamic activity and attachment in bacterial species.

Bowel Emergencies in Patients With Cancer.

Cancer is the second most common cause of death worldwide. Bowel emergencies in patients with cancer are becoming increasingly more prevalent due to advances in cancer therapy and longer overall patient survival. When these patients present acutely, they are often frail and may have pre-existing co-morbidities. This article discusses the imaging features of bowel emergencies commonly encountered in oncological patients in clinical practice. These include chemotherapy related colitis, neutropenia enterocolitis and typhlitis, toxic megacolon, bowel perforation, malignant bowel obstruction and gastrointestinal haemorrhage. The radiologist plays a key role in identifying these oncological emergencies and guiding further management.

Paranoid About Androids: A Review of Robotics in Radiology.

In tandem with the ever-increasing global population, the demand for diagnostic radiology service provision is on the rise and at a disproportionate rate compared to the number of radiologists available to practice. The current "revolution in robotics" promises to alleviate personnel shortages in many sectors of industry, including medicine. Despite negative depictions of robots in popular culture, their multiple potential benefits cannot be overlooked, in particular when it comes to health service provision. The type of robots used for interventional procedures are largely robotic-assistance devices, such as the Da Vinci surgical robot. Advances have also been made with regards to robots for image-guided percutaneous needle placement, which have demonstrated superior accuracy compared to manual methods. It is likely that artificial intelligence will come to play a key role in the field of robotics and will result in an increase in the levels of robotic autonomy attainable. However, this concept is not without ethical and legal considerations, most notably who is responsible should an error occur; the physician, the robot manufacturer, software engineers, or the robot itself? Efforts have been made to legislate in order to protect against the potentially harmful effects of unexplainable "black-box" decision outputs of artificial intelligence systems. In order to be accepted by patients, studies have shown that the perceived level of trustworthiness and predictability of robots is crucial. Ultimately, effective, widespread implementation of medical robotic systems will be contingent on developers remaining cognizant of factors that increase human acceptance, as well as ensuring compliance with regulations.

Outcomes and Complications of Image-Guided Percutaneous Tumour Ablation for Hepatocellular Carcinoma at the Irish National Liver Transplant Centre.

Background: Image-guided tumour ablation is a minimally invasive treatment for early stage hepatocellular carcinoma (HCC). Our study reviews the complications and long term outcomes in patients treated at a tertiary referral centre. Methods: Retrospective study. All patients with HCC who underwent microwave ablation (MWA) or radiofrequency ablation (RFA) from 1st January 2014 to 31st December 2022 were identified. Treatment response of target lesion, complications, and survival were recorded. Results: One hundred seventy ablations were performed in 118 patients; 70% MWA, 30% RFA. Median radiological follow-up 21 months (range 3-107). Follow-up imaging was reported using LI-RADS and mRECIST. At first follow-up imaging, 94 patients had complete response (primary efficacy rate 80.3%) while 19.7% (n = 23) had residual disease. Fifteen of these had repeat ablation; 10 had complete response (secondary efficacy rate 85.6%). By end of study duration, 70.5% (n = 79) achieved sustained local complete response from single ablation without documented recurrence. 14.3% (n = 16) required more than one ablation of target lesion. Overall, 84.8% (n = 95) demonstrated long term local complete response to ablation. Complication occurred in 5.9% (n = 10); 40.0% Grade I, 40.0% Grade II, 10.0% Grade III, 10.0% Grade IV as per the CIRSE Classification. 1-, 3-, and 5-year overall survival (OS) rate was 97%, 68%, and 61% respectively. Mean OS was 5.3 years (median 4.7). No difference in OS (P = .7) or local progression free survival (P = .5) between patients treated with MWA versus RFA. Conclusion: This study demonstrates excellent long-term response to TA, with acceptable complication profile. No difference in survival between RFA versus MWA.

Prevalence of Ankle Charcot Neuroarthropathy Presenting in a Tertiary Care Center.

Charcot neuroarthropathy's (CN) anatomic classification was originally formulated by the Brodsky article and the Trepman et al modification, including midfoot (type 1), rearfoot (type 2), ankle (type 3a), calcaneus (type 3b), multiarticular (type 4), and forefoot (type 5). In these classic studies, ankle joint and multijoint CN are reported as 9% and 6% to 9%, respectively, but we believe ankle CN to be more common than that in a tertiary setting. We retrospectively reviewed patients presenting initially or as referral between 2004 and 2020. Initial presentation radiographs were reviewed and classified by 3 authors based on Brodsky's model with Trepman and colleagues' modification, and any discrepancies were reviewed by the fourth author. A total of 175 patients (205 feet) were assessed. This revealed 80 cases classified as type 1 (39.0%), 23 cases type 2 (11.2%), 17 cases type 3a (8.3%), 2 cases type 3b (1.0%), and 83 cases type 4 (40.5%). After subdividing type 4, total prevalence included 150 with type 1 anatomic location (73.2%), 103 type 2 (50.2%), 44 type 3a (21.5%), and still 2 type 3b (1.0%). This study revealed a similar prevalence of isolated ankle CN (8.5%) compared to the Trepman et al article (9%), however, in total, ankle CN (21.5%) occurred 2.4-times more than the original 9%. Our study also found there to be a higher prevalence of ankle CN in the setting of multiarticular CN, which has not been evaluated in past studies. The prevalence of multiarticular CN was found to be 4.5-fold greater than the Trepman article (6%-9%).

Health professionals' initial experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic paediatric early warning system (the DETECT study): a qualitative interview study.

BACKGROUND: Paediatric early warning systems (PEWS) alert health professionals to signs of a child's deterioration with the intention of triggering an urgent review and escalating care. They can reduce unplanned critical care transfer, cardiac arrest, and death. Electronic systems may be superior to paper-based systems. The objective of the study was to critically explore the initial experiences and perceptions of health professionals about the acceptability of DETECT e-PEWS, and what factors influence its acceptability. METHODS: A descriptive qualitative study (part of The DETECT study) was undertaken February 2020-2021. Single, semi-structured telephone interviews were used. The setting was a tertiary children's hospital, UK. The participants were health professionals working in study setting and using DETECT e-PEWS. Sampling was undertaken using a mix of convenience and snowballing techniques. Participants represented two user-groups: 'documenting vital signs' (D-VS) and 'responding to vital signs' (R-VS). Perceptions of clinical utility and acceptability of DETECT e-PEWS were derived from thematic analysis of transcripts. RESULTS: Fourteen HPs (12 nurses, 2 doctors) participated; seven in D-VS and seven in the R-VS group. Three main themes were identified: complying with DETECT e-PEWS, circumventing DETECT e-PEWS, and disregarding DETECT e-PEWS. Overall clinical utility and acceptability were deemed good for HPs in the D-VS group but there was diversity in perception in the R-VS group (nurses found it more acceptable than doctors). Compliance was better in the D-VS group where use of DETECT e-PEWS was mandated and used more consistently. Some health professionals circumvented DETECT e-PEWS and fell back into old habits. Doctors (R-VS) did not consistently engage with DETECT e-PEWS, which reduced the acceptability of the system, even in those who thought the system brought benefits. CONCLUSIONS: Speed and accuracy of real-time data, automation of triggering alerts and improved situational awareness were key factors that contributed to the acceptability of DETECT e-PEWS. Mandating use of both recording and responding aspects of DETECT e-PEWS is needed to ensure full implementation.

PilT and PilU are homohexameric ATPases that coordinate to retract type IVa pili.

Bacterial type IV pili are critical for diverse biological processes including horizontal gene transfer, surface sensing, biofilm formation, adherence, motility, and virulence. These dynamic appendages extend and retract from the cell surface. In many type IVa pilus systems, extension occurs through the action of an extension ATPase, often called PilB, while optimal retraction requires the action of a retraction ATPase, PilT. Many type IVa systems also encode a homolog of PilT called PilU. However, the function of this protein has remained unclear because pilU mutants exhibit inconsistent phenotypes among type IV pilus systems and because it is relatively understudied compared to PilT. Here, we study the type IVa competence pilus of Vibrio cholerae as a model system to define the role of PilU. We show that the ATPase activity of PilU is critical for pilus retraction in PilT Walker A and/or Walker B mutants. PilU does not, however, contribute to pilus retraction in ΔpilT strains. Thus, these data suggest that PilU is a bona fide retraction ATPase that supports pilus retraction in a PilT-dependent manner. We also found that a ΔpilU mutant exhibited a reduction in the force of retraction suggesting that PilU is important for generating maximal retraction forces. Additional in vitro and in vivo data show that PilT and PilU act as independent homo-hexamers that may form a complex to facilitate pilus retraction. Finally, we demonstrate that the role of PilU as a PilT-dependent retraction ATPase is conserved in Acinetobacter baylyi, suggesting that the role of PilU described here may be broadly applicable to other type IVa pilus systems.

A trial of antithrombotic therapy in patients with refractory migraine and antiphospholipid antibodies: A retrospective study of 75 patients.

OBJECTIVE: It has been reported that patients with antiphospholipid antibodies (aPL) and refractory migraine may experience symptomatic improvement with antithrombotic therapy, but this phenomenon has not been well studied. This study was undertaken to detail the response to trials of antithrombotic therapy in these patients. METHODS: This is a retrospective study of 75 patients with refractory migraine and aPL who were given a 2-4 week trial of aspirin, clopidogrel and/or anticoagulation. Major response was defined as 50-100% improvement in frequency and/or severity of migraine; minor response: 25-49% improvement; no response: <25% improvement. RESULTS: 66 patients were given a trial of aspirin: 47% responded (21% major); 60 patients were given a trial of clopidogrel: 83% responded (67% major); and 34 patients were given a trial of anticoagulation (usually apixaban): 94% responded (85% major). The response rate to any anti-thrombotic therapy was 89% (83% major). Many patients also noted improvement in non-headache symptoms. No patient experienced stroke. There was no major bleeding during any 2-4 week treatment trial and only 3 of 69 patients maintained on an antithrombotic regimen for a median follow up of 29.9 months (5-100) experienced major bleeding. CONCLUSIONS: There was a high rate of symptomatic response to antithrombotic therapy in this context and long-term follow up suggested an individualized symptom-derived antithrombotic regimen may be associated with a low bleeding risk. Our data support consideration of a 2-4 week trial of antithrombotic therapy, usually starting with antiplatelet therapy, in aPL-positive patients with refractory migraine, particularly if other treatment options have been exhausted. As a retrospective study, our data provide only Class IV level of evidence, but they suggest randomized controlled trials are warranted to validate these encouraging findings.

Comforting Versus Distressing Dreams of the Deceased: Relations to Grief, Trauma, Attachment, Continuing Bonds, and Post-Dream Reactions.

Why are some dreams of the deceased experienced as comforting, while others are distressing? We propose that there are different types of dreams serving diverse functions. In particular, we considered three: processing trauma, maintaining a continuing bond, and regulating emotion. We also examined the impact of post-dream reactions on the bereaved's experience of their dreams. Participants were 216 individuals whose romantic partner or spouse had died. They provided reports of dreams of the deceased that were content analyzed and completed measures of grief intensity, posttraumatic symptoms, attachment style, internalized versus externalized continuing bonds, as well as questions about the death, and ratings of how they experienced the dream after awakening. Support was found for the three proposed functions, suggesting dreams of the deceased can actively facilitate adjustment to bereavement. In addition, there was evidence that post-dream reactions can impact both the perception of the dream and grief.

Racial disparities and the use of technology for self-management in blacks with heart failure: a literature review.

Heart failure is a debilitating illness that requires patients to be actively engaged in self-management. Self-management practices, including maintenance and management of an evidence-based medication regimen, are associated with improved outcomes. Yet, sustained engagement with self-management practices remains a challenge. Both self-management practices and clinical outcomes differ by race, with the poorest self-management and clinical outcomes reported in Blacks. Contemporary interventions to address self-management and reverse current trends in outcomes have evaluated the use of technology. Technological innovations, such as text messaging, social networking, and online learning platforms may provide a more accessible means for self-management of heart failure, yet these innovations have been understudied in the population at greatest risk - Blacks with heart failure. We conducted a review and discovered only four studies evaluating use of technology for self-management in Blacks. More studies are needed to close the gap on racial disparities and use of technology for self-management.

Rate and Location of Reulceration and Reamputation After Partial First-Ray Amputation versus Hallux Amputation in Diabetic and Nondiabetic Populations.

BACKGROUND: We sought to determine the rates of reulceration and reamputation in individuals who underwent partial first-ray amputations versus hallux amputations in diabetic and nondiabetic populations. METHODS: Eighty-four amputations were reviewed in a retrospective fashion. A retrospective medical record review was performed to determine patients who underwent a hallux amputation, both partial and complete, and patients who underwent a partial first-ray amputation. Only patients from 2007 to 2019 were reviewed. The reulceration rate of hallux amputations was 61% compared with a partial first-ray amputation reulceration rate of 74%. RESULTS: The reamputation rate of hallux amputation versus partial first-ray amputation was 43% versus 51%. At final follow-up, it was statistically significant that patients who underwent hallux amputation were more likely to be healed than those who underwent partial first-ray amputation, regardless of reulceration or reamputation. In addition, patients who underwent hallux amputation went on to digital amputation, and those who underwent partial first-ray amputation went on to transmetatarsal amputation. CONCLUSIONS: Comparing partial first-ray amputation to hallux amputation, hallux amputation patients are more prone to subsequent digital ulceration. Patients who initially undergo hallux amputation have variable subsequent amputations, often digital. Reulceration primarily occurs at the incision site for partial first-ray amputations, with a higher likelihood of subsequent transmetatarsal amputation. Patients with a medical history of diabetes and staged procedures are more likely to receive partial first-ray amputations. However, hallux amputation patients have a lower risk of reulceration and reamputation, regardless of subsequent events. These findings underscore the importance of discussing risks and preventive measures with patients undergoing such amputations, emphasizing postoperative examinations for specific areas of concern. Hallux amputation appears to offer greater protection against reulceration and reamputation for both diabetic and nondiabetic populations.

GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.

The microcircuitry within superficial layers of the dorsolateral prefrontal cortex (DLPFC), composed of excitatory pyramidal neurons and inhibitory GABAergic interneurons, has been suggested as the neural substrate of working memory performance. In schizophrenia, working memory impairments are thought to result from alterations of microcircuitry within the DLPFC. GABAergic interneurons, in particular, are crucially involved in synchronizing neural activity at gamma frequency, the power of which increases with working memory load. Alterations of GABAergic interneurons, particularly parvalbumin (PV) and somatostatin (SST) subtypes, are frequently observed in schizophrenia. Abnormalities of GABAergic neurotransmission, such as deficiencies in the 67 kDA isoform of GABA synthesis enzyme (GAD67), vesicular GABA transporter (vGAT), and GABA reuptake transporter 1 (GAT1) in presynaptic boutons, as well as postsynaptic alterations in GABA A receptor subunits further contribute to impaired inhibition. This review explores GABAergic abnormalities of the postmortem DLPFC in schizophrenia, with a focus on the roles of interneuron subtypes involved in cognition, and GABAergic neurotransmission within presynaptic boutons and postsynaptic alterations. Where available, comparisons between schizophrenia and affective disorders that share cognitive pathology such as bipolar disorder and major depressive disorder will be made. Challenges in directly measuring GABA levels are addressed, emphasizing the need for innovative techniques. Understanding GABAergic abnormalities and their implications for neural circuit dysfunction in schizophrenia is crucial for developing targeted therapies.

The Attitudes of Patients Toward Orthopaedic Post-surgical Scars.

Background Post-surgical scars (PSS) are an expected consequence of surgery. Several factors have previously been associated with PSS satisfaction including patient age and time elapsed post-operative. Little data are available regarding patient attitudes toward orthopaedic PSS. Knowledge of patient attitudes and the various associated factors may allow physicians to administer peri-operative care to mitigate the potential negative effects of PSS. Our study aims to investigate the attitudes of patients toward their PSS using quantitative scar assessment scales and to identify factors associated with PSS satisfaction. Methods We conducted a retrospective study with a follow-up. We included all patients with orthopaedic PSS on their upper or lower limbs between two and 18 weeks postoperative attending Cork University Hospital, Ireland, between February and August 2022. Patients completed an initial baseline questionnaire and then a follow-up questionnaire six months post-operative. The Patient and Observer Scar Assessment Scale (POSAS) evaluated PSS satisfaction. The European Quality of Life 5 Domain (EQ-5D), alongside several Likert scales, evaluated the patient's quality of life (QoL). Results In total, 91 patients were included. The mean POSAS score was 28.41 (95% CI, 25.85-30.97). Younger patient age (p=0.045) and decreased time passed post-operatively (p=0.002) were associated with poorer PSS satisfaction. Patients reporting their PSS appearing worse than expected were more likely to agree that their QoL had been adversely affected by it (p=0.001). Conclusion Most patients were satisfied with their orthopaedic PSS. This study identified several factors associated with poor PSS satisfaction. Our finding, which associated patient scar expectations and QoL, is novel and has not been previously examined. Accordingly, peri-operative interventions, including scar expectation management, may be implemented to mitigate scar-related QoL impact.

Screening and Assessment of Suicidal Behavior in Transition-Age Youth with Foster Care Involvement.

Transition-age youth with foster care involvement (TAY, ages 17-22) are at heightened risk for suicidal behavior. Despite this, mental health screenings are not standardized across child welfare (CW) systems and existing assessment tools are not designed for use with this specific population. As such, TAY are unlikely to be adequately screened for suicide risk and connected with needed services. In this paper, we sought to identify screening and assessment tools that could be effective for use with TAY in CW settings. Using PubMed and PsycINFO, we conducted a search of the current literature to identify some of the most commonly used screening and assessment tools for youth. We then narrowed our focus to those tools that met predefined inclusion criteria indicating appropriateness of use for TAY in CW settings. As a result of this process, we identified one brief screening tool (the ASQ) and four assessments (the SIQ-JR, the C-SSRS, the SHBQ, and the SPS) that demonstrated specific promise for use with TAY. The strengths and limitations of the tools are discussed in detail, as well as the ways that each could be used most effectively in CW settings. We highlight three key points intended to guide social work practice and policy: (1) systematic, routine assessment of mental health and suicide risk across CW settings is critical; (2) the protocol for assessing suicidal behavior in TAY must account for the wide variations in context and service provision; and (3) CW workers administering assessments must be thoughtfully trained on risk identification and the protocol implementation.

Genome and characteristics of Arthrobacter globiformis AZ cluster phage London.

London is a predicted temperate bacteriophage with siphovirus morphology infecting Arthrobacter globiformis NRRL strain B-2880. Sequencing of the genome revealed a length of 43,599 bp comprising 69 predicted open-reading frames and no tRNA genes. It is categorized as a cluster AZ1 phage along with closely related actinobacteriophages Elezi, Eraser, and Niobe.

Parents' experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic pediatric early warning system (the DETECT study): A qualitative interview study.

Background: Failure to recognize and respond to clinical deterioration in a timely and effective manner is an urgent safety concern, driving the need for early identification systems to be embedded in the care of children in hospital. Pediatric early warning systems (PEWS) or PEW scores alert health professionals (HPs) to signs of deterioration, trigger a review and escalate care as needed. PEW scoring allows HPs to record a child's vital signs and other key data including parent concern. Aim: This study aimed to explore the experiences and perceptions of parents about the acceptability of a newly implemented electronic surveillance system (the DETECT surveillance system), and factors that influenced acceptability and their awareness around signs of clinical deterioration and raising concern. Methods: Descriptive, qualitative semi-structured telephone interviews were undertaken with parents of children who had experienced a critical deterioration event (CDE) (n = 19) and parents of those who had not experienced a CDE (non-CDE parents) (n = 17). Data were collected between February 2020 and February 2021. Results: Qualitative data were analyzed using generic thematic analysis. Analysis revealed an overarching theme of trust as a key factor that underpinned all aspects of children's vital signs being recorded and monitored. The main themes reflect three domains of parents' trust: trust in themselves, trust in the HPs, and trust in the technology. Conclusion: Parents' experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic pediatric early warning system (The DETECT system) were positive; they found it acceptable and welcomed the use of new technology to support the care of their child.