Gene content, phage cycle regulation model and prophage inactivation disclosed by prophage genomics in the Helicobacter pylori Genome Project.

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified genome rearrangements and assessed the impact of prophage presence on bacterial gene disruption and methylome. We found that 29.5% (298) of the HpGP genomes contain prophages, of which only 32.2% (96) were complete, minimizing the burden of prophage carriage. The prevalence of H. pylori prophage sequences was variable by geography and ancestry, but not by disease status of the human host. Prophage insertion occasionally results in gene disruption that can change the global bacterial epigenome. Gene function prediction allowed the development of the first model for lysogenic-lytic cycle regulation in H. pylori. We have disclosed new prophage inactivation mechanisms that appear to occur by genome rearrangement, merger with other mobile elements, and pseudogene accumulation. Our analysis provides a comprehensive framework for H. pylori prophage biological and genomics, offering insights into lysogeny regulation and bacterial adaptation to prophages.

Evidence to support cultivated fruiting body of Ophiocordyceps sinensis (Ascomycota)'s role in relaxing airway smooth muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps sinensis (O. sinensis) is a genus of Ascomycete fungus that is endemic to the alpine meadows of the Tibetan Plateau and adjoining Himalayas. It has been used traditionally as a tonic to improve respiratory health in ancient China as well as to promote vitality and longevity. Bioactive components found in O. sinensis such as adenosine, cordycepin, 3-deoxyadenosine, L-arginine and polysaccharides have gained increasing interest in recent years due to their antioxidative and other properties, which include anti-asthmatic, antiviral, immunomodulation and improvement of general health. AIM OF THE STUDY: This study's primary aim was to investigate the effect of a cultivated fruiting body of O. sinensis strain (OCS02®) on airways patency and the secondary focus was to investigate its effect on the lifespan of Caenorhabditis elegans. MATERIALS AND METHODS: A cultivated strain, OCS02®, was employed and the metabolic profile of its cold-water extract (CWE) was analysed through liquid chromatography-mass spectrometry (LC-MS). Organ bath approach was used to investigate the pharmacological properties of OCS02® CWE when applied on airway tissues obtained from adult male Sprague-Dawley rats. The airway relaxation mechanisms of OCS02® CWE were explored using pharmacological tools, where the key regulators in airway relaxation and constriction were investigated. For the longevity study, age-synchronised, pos-1 RNAi-treated wild-type type Caenorhabditis elegans at the L4 stage were utilised for a lifespan assay. RESULTS: Various glycopeptides and amino acids, particularly a high concentration of L-arginine, were identified from the LC-MS analysis. In airway tissues, OCS02® CWE induced a significantly greater concentration-dependent relaxation when compared to salbutamol. The relaxation response was significantly attenuated in the presence of NG-Nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and several K+ channel blockers. The longevity effect induced by OCS02® CWE (5 mg/mL and above) was observed in C. elegans by at least 17%. CONCLUSIONS: These findings suggest that the airway relaxation mechanisms of OCS02® CWE involved cGMP-dependent and cGMP-independent nitric oxide signalling pathways. This study provides evidence that the cultivated strain of OCS02® exhibits airway relaxation effects which supports the traditional use of its wild O. sinensis in strengthening respiratory health.

Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease with limited survival. Herein, we propose the pharmacological inhibition of Gq proteins as a novel concept to counteract pulmonary vasoconstriction and proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in PAH. We demonstrate that the specific pan-Gq inhibitor FR900359 (FR) induced a strong vasorelaxation in large and small pulmonary arteries in mouse, pig, and human subjects ex vivo. Vasorelaxation by FR proved at least as potent as the currently used triple therapy. We also provide in vivo evidence that local pulmonary application of FR prevented right ventricular systolic pressure increase in healthy mice as well as in mice suffering from hypoxia (Hx)-induced pulmonary hypertension (PH). In addition, we demonstrate that chronic application of FR prevented and also reversed Sugen (Su)Hx-induced PH in mice. We also demonstrate that Gq inhibition reduces proliferation and migration of PASMCs in vitro. Thus, our work illustrates a dominant role of Gq proteins for pulmonary vasoconstriction as well as remodeling and proposes direct Gq inhibition as a powerful pharmacological strategy in PH.

Artificial Intelligence as a Consent Aid for Carpal Tunnel Release.

Background Hand surgeons have been charged with the use of diverse modalities to enhance the consenting process following the Montgomery ruling. Artificial Intelligence language models have been suggested as patient education tools that may aid consent. Methods We compared the quality and readability of the Every Informed Decision Online (EIDO) patient information leaflet for carpal tunnel release with the artificial intelligence language model Chat Generative Pretrained Transformer (GPT). Results The quality of information by ChatGPT was significantly higher using the DISCERN score, 71/80 for ChatGPT compared to 62/80 for EIDO (p=0.014). DISCERN interrater observer reliability was high (0.65) using the kappa statistic. Flesch-Kincaid readability scoring was 12.3 for ChatGPT and 7.5 for EIDO, suggesting a more complex reading age for the ChatGPT information. Conclusion The artificial intelligence language model ChatGPT produces high-quality information at the expense of readability when compared to EIDO information leaflets for carpal tunnel release consent.

Proxi-RIMS-seq2 applied to native microbiomes uncovers hundreds of known and novel m5C methyltransferase specificities.

Methylation patterns in bacteria can be used to study Restriction-Modification (RM) or other defense systems with novel properties. While m4C and m6A methylation is well characterized mainly through PacBio sequencing, the landscape of m5C methylation is under-characterized. To bridge this gap, we performed RIMS-seq2 on microbiomes composed of resolved assemblies of distinct genomes through proximity ligation. This high-throughput approach enables the identification of m5C methylated motifs and links them to cognate methyltransferases directly on native microbiomes without the need to isolate bacterial strains. Methylation patterns can also be identified on viral DNA and compared to host DNA, strengthening evidence for virus-host interaction. Applied to three different microbiomes, the method unveils over 1900 motifs that were deposited in REBASE. The motifs include a novel 8-base recognition site (CATm5CGATG) that was experimentally validated by characterizing its cognate methyltransferase. Our findings suggest that microbiomes harbor arrays of untapped m5C methyltransferase specificities, providing insights to bacterial biology and biotechnological applications.

Identification of an endonuclease and N6-adenine methyltransferase from Ureaplasma parvum SV3F4 strain.

Here, we report a novel endonuclease and N6-adenine DNA methyltransferase (m6A methyltransferase) in the Ureaplasma parvum SV3F4 strain. Our previous study found that the SV3F4 strain carries 17 unique genes, which are not encoded in the two previously reported U. parvum serovar 3 strain, OMC-P162 and ATCC 700970. Of these 17 unique genes, UP3_c0261 and UP3_c0262, were originally annotated as encoding hypothetical proteins. Comparative genomics analyses more recently indicated they encode a Type II restriction endonuclease and an m6A methyltransferase, respectively. The UP3_c0261 and UP3_c0262 genes were individually expressed and purified in Escherichia coli. The UP3_c0261 recombinant protein showed endonuclease activity on the pT7Blue vector, recognizing and cleaving a GTNAC motif, resulting in a 5 base 5' extension. The UP3_c0261 protein digested a polymerase chain reaction (PCR) product harboring the GTNAC motif. The endonuclease UP3_c0261 was designated as UpaF4I. Treatment of the PCR product with the recombinant protein UP3_c0262 completely blocked the restriction enzyme activity of UpaF4I. Analysis of the treated PCR product harboring a modified nucleotide by UP3_c0262 with HPLC-MS/MS and MS/MS showed that UP3_c0262 was an m6A methyltransferase containing a methylated A residue in both DNA strands of the GTNAC motif. Whole genome methylation analysis of SV3F4 showed that 99.9 % of the GTNAC motif was m6A modified. These results suggest the UP3_c0261 and UP3_c0262 genes may act as a novel Type II restriction-modification system in the Ureaplasma SV3F4 strain.

Application of Calcium Kinetics Characterization in Cardiac Disease Modeling and Drug Discovery.

Calcium regulation is essential in virtually any cell due to its critical role as a second messenger in multiple signaling pathways [...].

Surgical management of the diabetic foot: The current evidence.

The prevalence of diabetes mellitus and its associated complications, particularly diabetic foot pathologies, poses significant healthcare challenges and economic burdens globally. This review synthesises current evidence on the surgical management of the diabetic foot, focusing on the interplay between neuropathy, ischemia, and infection that commonly culminates in ulcers, infections, and, in severe cases, amputations. The escalating incidence of diabetes mellitus underscores the urgency for effective management strategies, as diabetic foot complications are a leading cause of hospital admissions among diabetic patients, significantly impacting morbidity and mortality rates. This review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers, infections, and skeletal pathologies such as Charcot arthropathy, emphasising the critical role of early diagnosis, comprehensive management strategies, and interdisciplinary care in mitigating adverse outcomes. In addressing surgical interventions, this review evaluates conservative surgeries, amputations, and reconstructive procedures, highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot pathologies. The integration of advanced diagnostic tools, novel surgical techniques, and postoperative care, including offloading and infection control, are discussed in the context of optimising healing and preserving limb function.

Antibiotic resistance and tolerance: What can drug delivery do against this global threat?

Antimicrobial resistance and tolerance (AMR&T) are urgent global health concerns, with alarmingly increasing numbers of antimicrobial drugs failing and a corresponding rise in related deaths. Several reasons for this situation can be cited, such as the misuse of traditional antibiotics, the massive use of sanitizing measures, and the overuse of antibiotics in agriculture, fisheries, and cattle. AMR&T management requires a multifaceted approach involving various strategies at different levels, such as increasing the patient's awareness of the situation and measures to reduce new resistances, reduction of current misuse or abuse, and improvement of selectivity of treatments. Also, the identification of new antibiotics, including small molecules and more complex approaches, is a key factor. Among these, novel DNA- or RNA-based approaches, the use of phages, or CRISPR technologies are some potent strategies under development. In this perspective article, emerging and experienced leaders in drug delivery discuss the most important biological barriers for drugs to reach infectious bacteria (bacterial bioavailability). They explore how overcoming these barriers is crucial for producing the desired effects and discuss the ways in which drug delivery systems can facilitate this process.

Revised whole genome and DNA methylome of Mycobacterium marinum type strain ATCC 927T.

Mycobacterium marinum, a slow-growing Actinobacterium, typically induces tuberculosis-like disease in fish. Here, we report a new reference sequence for M. marinum ATCC 927T, along with its DNA methylome. This aims to maximize the research potential of this type strain and facilitates investigations into the pathomechanisms of human tuberculosis.

Probabilities of Isolated and Co-Occurring Vestibular Disorder Symptom Clusters Identified Using the Dizziness Symptom Profile.

OBJECTIVES: Dizziness is among the most common reasons people seek medical care. There are data indicating patients with dizziness, unsteadiness, or vertigo may have multiple underlying vestibular disorders simultaneously contributing to the overall symptoms. Greater awareness of the probability that a patient will present with symptoms of co-occurring vestibular disorders has the potential to improve assessment and management, which could reduce healthcare costs and improve patient quality of life. The purpose of the current investigation was to determine the probabilities that a patient presenting to a clinic for vestibular function testing has symptoms of an isolated vestibular disorder or co-occurring vestibular disorders. DESIGN: All patients who are seen for vestibular function testing in our center complete the dizziness symptom profile, a validated self-report measure, before evaluation with the clinician. For this retrospective study, patient scores on the dizziness symptom profile, patient age, and patient gender were extracted from the medical record. The dizziness symptom profile includes symptom clusters specific to six disorders that cause vestibular symptoms, specifically: benign paroxysmal positional vertigo, vestibular migraine, vestibular neuritis, superior canal dehiscence, Meniere disease, and persistent postural perceptual dizziness. For the present study, data were collected from 617 participants (mean age = 56 years, 376 women, and 241 men) presenting with complaints of vertigo, dizziness, or imbalance. Patients were evaluated in a tertiary care dizziness specialty clinic from October 2020 to October 2021. Self-report data were analyzed using a Bayesian framework to determine the probabilities of reporting symptom clusters specific to an isolated disorder and co-occurring vestibular disorders. RESULTS: There was a 42% probability of a participant reporting symptoms that were not consistent with any of the six vestibular disorders represented in the dizziness symptom profile. Participants were nearly as likely to report symptom clusters of co-occurring disorders (28%) as they were to report symptom clusters of an isolated disorder (30%). When in isolation, participants were most likely to report symptom clusters consistent with benign paroxysmal positional vertigo and vestibular migraine, with estimated probabilities of 12% and 10%, respectively. The combination of co-occurring disorders with the highest probability was benign paroxysmal positional vertigo + vestibular migraine (~5%). Probabilities decreased as number of symptom clusters on the dizziness symptom profile increased. The probability of endorsing vestibular migraine increased with the number of symptom clusters reported. CONCLUSIONS: Many patients reported symptoms of more than one vestibular disorder, suggesting their symptoms were not sufficiently captured by the symptom clusters used to summarize any single vestibular disorder covered by the dizziness symptom profile. Our results indicate that probability of symptom clusters indicated by the dizziness symptom profile is comparable to prior published work on the prevalence of vestibular disorders. These findings support use of this tool by clinicians to assist with identification of symptom clusters consistent with isolated and co-occurring vestibular disorders.

Can Large Language Models Generate Outpatient Clinic Letters at First Consultation That Incorporate Complication Profiles From UK and USA Aesthetic Plastic Surgery Associations?

The importance of written communication between clinicians and patients, especially in the wake of the Supreme Court case of Montgomery vs Lanarkshire, has led to a shift toward patient-centric care in the United Kingdom. This study investigates the use of large language models (LLMs) like ChatGPT and Google Bard in enhancing clinic letters with gold-standard complication profiles, aiming to improve patients' understanding and save clinicians' time in aesthetic plastic surgery. The aim of this study is to assess the effectiveness of LLMs in integrating complication profiles from authoritative sources into clinic letters, thus enhancing patient comprehension and clinician efficiency in aesthetic plastic surgery. Seven widely performed aesthetic procedures were chosen, and complication profiles were sourced from the British Association of Aesthetic Plastic Surgeons (BAAPS) and the American Society of Plastic Surgeons (ASPS). We evaluated the proficiency of the ChatGPT4, ChatGPT3.5, and Google Bard in generating clinic letters which incorporated complication profiles from online resources. These letters were assessed for readability using an online tool, targeting a recommended sixth-grade reading level. ChatGPT4 achieved the highest compliance in integrating complication profiles from BAAPS and ASPS websites, with average readability grades between eighth and ninth. ChatGPT3.5 and Google Bard showed lower compliance, particularly when accessing paywalled content like the ASPS Informed Consent Bundle. In conclusion, LLMs, particularly ChatGPT4, show promise in enhancing patient communications in aesthetic plastic surgery by effectively incorporating standard complication profiles into clinic letters. This aids in informed decision making and time saving for clinicians. However, the study underscores the need for improvements in data accessibility, search capabilities, and ethical considerations for optimal LLM integration into healthcare communications. Future enhancements should focus on better interpretation of inaccessible formats and a Human in the Loop approach to combine Artifical Intelligence capabilities with clinician expertise.

The cross-cutting edge: Medical selection and education viewed through the lens of emotional intelligence.

CONTEXT: Evidence suggesting the benefits of compassionate, person-centred care, for both patients and physicians is accruing. Medical selection, for example, aims to choose future health professionals that possess the correct attitudes, beliefs and personal attributes to deliver such care. Moreover, once in training, these desirable personal qualities should be developed and maintained, sometimes in the face of adverse health care service conditions. However, advances in selecting for, and developing, these abilities and attributes in health care have been hindered by a lack of clarity regarding how the relevant skills and traits should be defined, measured, developed and maintained in clinicians. METHODS: In this article, we demonstrate how developments in the emotional intelligence (EI) field can be applied to the challenge of selecting for, and developing, relevant interpersonal care skills in medical students and physicians. The concept of EI itself has been somewhat controversial. However, a more nuanced understanding of EI has evolved in the light of research findings that can be applied to medical selection and education. Specifically, we propose modifications to the existing 'cascading' model of EI. This model identifies, and relates, several key socioemotional skills and traits that could be considered as 'the elementary particles' of EI required to deliver compassionate, person-centred care. CONCLUSIONS: Our model of EI, which is relevant to care delivery, identifies putative targets for both medical selection and training. Selection for medical school and subsequent clinical education should focus on screening out those with low levels of the traits and abilities less amenable to training. Conversely, medical education should be concerned with developing and maintaining the socioemotional skills, attitudes and behaviours critical to the delivery of compassionate, person-centred care. This is especially important for specialties characterised by high levels of emotional labour and possible resultant compassion fatigue.

Self-Reported Symptoms of Vertigo and Imbalance Are Prevalent Among Adults With Chronic Moderate-Severe Traumatic Brain Injury: A Preliminary Analysis.

PURPOSE: Dizziness and imbalance are common symptoms during the acute phase of traumatic brain injury (TBI). However, there is evidence to suggest that these symptoms persist into the chronic phase of injury. Few prospective studies have examined the frequency and type of dizziness and imbalance in adults with chronic moderate-severe TBI. The aim of this preliminary analysis was to investigate the prevalence of these symptoms in adults with chronic moderate-severe TBI. METHOD: Twenty-four adults with chronic moderate-severe TBI and a group of 19 age-, sex-, and education-matched noninjured comparison participants were recruited. Self-reported dizziness and imbalance were measured using a modified version of a standard case history form. Significant associations between group (TBI group or noninjured comparison [NC] participants) and self-reports of dizziness, imbalance, and related symptoms (endorsed "yes" or "no") were explored. RESULTS: The TBI group most reported lightheadedness (75%), vertigo (38%), and imbalance and/or falling (46%). The most common related symptom reported by the TBI group was headache (63%) and nausea (46%). Significant associations revealed that the TBI group responded "yes" in higher percentages than the NC group across all categories (dizziness, imbalance, and related symptoms). There were no statistically significant relationships among dizziness, imbalance, or headache symptoms within the TBI group. CONCLUSIONS: These preliminary findings suggest that dizziness and imbalance are prevalent in adults with chronic moderate-severe TBI. Persistent vertiginous symptoms may point to an underlying vestibular impairment. However, further research is needed to characterize vestibular function in chronic moderate-severe TBI.

Benefits in routinely measured liver function tests following bariatric surgery: a retrospective cohort study.

Background: Bariatric surgery is well-established to support long-term metabolic health benefits associated with considerable weight loss. Here, we aim to determine the longer-term impact of bariatric surgery on liver enzymes and associations with other metabolic improvements. Methods: One hundred patients who underwent bariatric surgery between 2007 and 2014 were included, and changes in liver enzymes, anthropometric measures and other parameters were observed over a mean 9.8 years. Results: At the time of surgery, the mean age was 45.4 ± 9.6 years, weight 141.2 ± 31.6 kg, and body mass index (BMI) 50.2 ± 10.1 kg/m2. Most patients underwent sleeve gastrectomy [n = 71] with a mean follow-up duration 9.8 ± 2.3 years. From baseline, alanine transaminase (ALT) reduced by 41.3% within 12 months post-operatively (36.6 ± 29.2 U/L to 21.5 ± 14.9 U/L, p < 0.001), which was sustained at recent follow-up (20.2 ± 10.7 U/L, p < 0.001). There were associated reductions in body weight, BMI, HbA1c, blood pressure and triglycerides. Patients with greater baseline ALT had the greatest reduction in ALT over follow-up. Conclusions: Bariatric surgery is associated with rapid and sustained improvements in routine liver enzymes at 10 years, and sustained improvements in features of the metabolic syndrome. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01311-4.

A Survey of Archaeal Restriction-Modification Systems.

When compared with bacteria, relatively little is known about the restriction-modification (RM) systems of archaea, particularly those in taxa outside of the haloarchaea. To improve our understanding of archaeal RM systems, we surveyed REBASE, the restriction enzyme database, to catalog what is known about the genes and activities present in the 519 completely sequenced archaeal genomes currently deposited there. For 49 (9.4%) of these genomes, we also have methylome data from Single-Molecule Real-Time (SMRT) sequencing that reveal the target recognition sites of the active m6A and m4C DNA methyltransferases (MTases). The gene-finding pipeline employed by REBASE is trained primarily on bacterial examples and so will look for similar genes in archaea. Nonetheless, the organizational structure and protein sequence of RM systems from archaea are highly similar to those of bacteria, with both groups acquiring systems from a shared genetic pool through horizontal gene transfer. As in bacteria, we observe numerous examples of "persistent" DNA MTases conserved within archaeal taxa at different levels. We experimentally validated two homologous members of one of the largest "persistent" MTase groups, revealing that methylation of C(m5C)WGG sites may play a key epigenetic role in Crenarchaea. Throughout the archaea, genes encoding m6A, m4C, and m5C DNA MTases, respectively, occur in approximately the ratio 4:2:1.

Enhanced transformation efficiency in Treponema denticola enabled by SyngenicDNA-based plasmids lacking restriction-modification target motifs.

Oral spirochetes are among a small group of keystone pathogens contributing to dysregulation of tissue homeostatic processes that leads to breakdown of the tissue and bone supporting the teeth in periodontal disease. Additionally, our group has recently demonstrated that Treponema are among the dominant microbial genera detected intracellularly in tumor specimens from patients with oral squamous cell carcinoma. While over 60 species and phylotypes of oral Treponema have been detected, T. denticola is one of the few that can be grown in culture and the only one in which genetic manipulation is regularly performed. Thus, T. denticola is a key model organism for studying spirochete metabolic processes, interactions with other microbes, and host cell and tissue responses relevant to oral diseases, as well as venereal and nonvenereal treponematoses whose agents lack workable genetic systems. We previously demonstrated improved transformation efficiency using an Escherichia coli-T. denticola shuttle plasmid and its utility for expression in T. denticola of an exogenous fluorescent protein that is active under anaerobic conditions. Here, we expand on this work by characterizing T. denticola Type I and Type II restriction-modification (R-M) systems and designing a high-efficiency R-M-silent "SyngenicDNA" shuttle plasmid resistant to all T. denticola ATCC 35405 R-M systems. Resequencing of the ATCC 33520 genome revealed an additional Type I R-M system consistent with the relatively low transformation efficiency of the shuttle plasmid in this strain. Using SyngenicDNA approaches, we optimized shuttle plasmid transformation efficiency in T. denticola and used it to complement a defined T. denticola ΔfhbB mutant strain. We further report the first high-efficiency transposon mutagenesis of T. denticola using an R-M-silent, codon-optimized, himarC9 transposase-based plasmid. Thus, use of SyngenicDNA-based strategies and tools can enable further mechanistic examinations of T. denticola physiology and behavior.

Comparative study of ChatGPT and human evaluators on the assessment of medical literature according to recognised reporting standards.

INTRODUCTION: Amid clinicians' challenges in staying updated with medical research, artificial intelligence (AI) tools like the large language model (LLM) ChatGPT could automate appraisal of research quality, saving time and reducing bias. This study compares the proficiency of ChatGPT3 against human evaluation in scoring abstracts to determine its potential as a tool for evidence synthesis. METHODS: We compared ChatGPT's scoring of implant dentistry abstracts with human evaluators using the Consolidated Standards of Reporting Trials for Abstracts reporting standards checklist, yielding an overall compliance score (OCS). Bland-Altman analysis assessed agreement between human and AI-generated OCS percentages. Additional error analysis included mean difference of OCS subscores, Welch's t-test and Pearson's correlation coefficient. RESULTS: Bland-Altman analysis showed a mean difference of 4.92% (95% CI 0.62%, 0.37%) in OCS between human evaluation and ChatGPT. Error analysis displayed small mean differences in most domains, with the highest in 'conclusion' (0.764 (95% CI 0.186, 0.280)) and the lowest in 'blinding' (0.034 (95% CI 0.818, 0.895)). The strongest correlations between were in 'harms' (r=0.32, p<0.001) and 'trial registration' (r=0.34, p=0.002), whereas the weakest were in 'intervention' (r=0.02, p<0.001) and 'objective' (r=0.06, p<0.001). CONCLUSION: LLMs like ChatGPT can help automate appraisal of medical literature, aiding in the identification of accurately reported research. Possible applications of ChatGPT include integration within medical databases for abstract evaluation. Current limitations include the token limit, restricting its usage to abstracts. As AI technology advances, future versions like GPT4 could offer more reliable, comprehensive evaluations, enhancing the identification of high-quality research and potentially improving patient outcomes.

Diabetes management in older adults who fall: a study amongst older adults presenting to the emergency department.

INTRODUCTION: Type 2 diabetes mellitus (T2D) is associated with poor health outcomes whilst tight glycaemic targets are questionable in those aged over 70 years with increased frailty. Our aim was to examine whether people with T2D admitted to hospital with a fall, were more likely to have greater frailty, increased mortality and co-morbidity burden, or risk factors for falls than people without T2D, and whether these differences were associated with medications used for the treatment of T2D. METHODS: The Older Persons Assessment Service (OPAS) is a local emergency department (ED) service, which accepts patients on frailty criteria. The OPAS accepts patients primarily aged over 70 years who present with frailty and geriatric syndromes such as falls, with retrieval from the ED department directly to the service from triage. The OPAS databank was analysed for people with T2D admitted with a fall between June 2020-September 2022. We examined clinical outcomes relating to medication, age, Charlson co-morbidity index (CCI) and clinical frailty score (CFS). RESULTS: 1081 patients were included: 294 (27.2%) with T2D and a mean HbA1c of 53.9 (± 15.8) mmol/mol [7.1%]. People with T2D had a similar mean CFS and age compared to those without T2D, but higher mean CCI (7.0 ± 2.2 vs 5.9 ± 2.1, p < 0.001). Of those people with T2D, 175 (59.5%) and 240 (81.6%) had a HbA1c ≤ 53 mmol/mol [7.0%] and ≤ 64 mmol/mol [8.0%], respectively. In total, 48 (16.3%) people with T2D were identified to have a capillary blood glucose below 4.0 mmol/L on admission to the ED. At 12 months' follow-up, 831 (76.9%) patients were alive and 250 (23.1%) had died. People with T2D treated with insulin and/or gliclazide had a greater 1-year mortality (36.6% vs 23.6%, p < 0.05), greater frequency of hypoglycaemia (35.4% vs 11.8%, p < 0.001), and greater HbA1c (65.5 ± 17.2 mmol/mol [8.2] vs 48.9 ± 12.1 mmol/mol [6.6%]) compared to those who used other agents. Logistic regression confirmed a diagnosis of T2D was associated with 1-year mortality, but mortality was not significantly associated with hypoglycaemic-inducing agents. People with T2D were not more likely to live in deprived areas. CONCLUSIONS: A diagnosis of T2D is associated with greater 1-year mortality, and may be influenced by use of hypoglycaemia-inducing diabetes medications. Clinician awareness can support de-prescribing for patients with frailty and HbA1c < 64 mmol/mol.