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Aims: In metal-on-metal (MoM) hip arthroplasties and resurfacings, mechanically induced corrosion can lead to elevated serum metal ions, a local inflammatory response, and formation of pseudotumours, ultimately requiring revision. The size and diametral clearance of anatomical (ADM) and modular (MDM) dual-mobility polyethylene bearings match those of Birmingham hip MoM components. If the acetabular component is satisfactorily positioned, well integrated into the bone, and has no surface damage, this presents the opportunity for revision with exchange of the metal head for ADM/MDM polyethylene bearings without removal of the acetabular component. Methods: Between 2012 and 2020, across two centres, 94 patients underwent revision of Birmingham MoM hip arthroplasties or resurfacings. Mean age was 65.5 years (33 to 87). In 53 patients (56.4%), the acetabular component was retained and dual-mobility bearings were used (DM); in 41 (43.6%) the acetabulum was revised (AR). Patients underwent follow-up of minimum two-years (mean 4.6 (2.1 to 8.5) years). Results: In the DM group, two (3.8%) patients underwent further surgery: one (1.9%) for dislocation and one (1.9%) for infection. In the AR group, four (9.8%) underwent further procedures: two (4.9%) for loosening of the acetabular component and two (4.9%) following dislocations. There were no other dislocations in either group. In the DM group, operating time (68.4 vs 101.5 mins, p < 0.001), postoperative drop in haemoglobin (16.6 vs 27.8 g/L, p < 0.001), and length of stay (1.8 vs 2.4 days, p < 0.001) were significantly lower. There was a significant reduction in serum metal ions postoperatively in both groups (p < 0.001), although there was no difference between groups for this reduction (p = 0.674 (cobalt); p = 0.186 (chromium)). Conclusion: In selected patients with Birmingham MoM hips, where the acetabular component is well-fixed and in a satisfactory position with no surface damage, the metal head can be exchanged for polyethylene ADM/MDM bearings with retention of the acetabular prosthesis. This presents significant benefits, with a shorter procedure and a lower risk of complications. Cite this article: Bone Jt Open 2024;5(6):514–523.

Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome.

Abstract Humans receive sensory information from the past, requiring the brain to overcome delays to perform daily motor skills such as standing upright. Because delays vary throughout the body and change over a lifetime, it would be advantageous to generalize learned control policies of balancing with delays across contexts. However, not all forms of learning generalize. Here, we use a robotic simulator to impose delays into human balance. When delays are imposed in one direction of standing, participants are initially unstable but relearn to balance by reducing the variability of their motor actions and transfer balance improvements to untrained directions. Upon returning to normal standing, aftereffects from learning are observed as small oscillations in control, yet they do not destabilize balance. Remarkably, when participants train to balance with delays using their hand, learning transfers to standing with the legs. Our findings establish that humans use experience to broadly update their neural control to balance with delays.

Background: Sepsis is a severe and life-threatening condition triggered by a dysregulated response to infection, leading to organ failure and, often, death. The syndrome is expensive to treat, with survivors frequently experiencing reduced quality of life and enduring various long-term disabilities. The increasing understanding of RNA, RNA biology, and therapeutic potential offers an unprecedented opportunity to develop innovative therapy. Objective: This study is a scoping review focusing on pre-clinical studies of microRNA (miRNA)-based therapies for sepsis. Methodology: A scoping review. The search strategy identified papers published in PubMed until 15 October 2023, using the keywords (microRNA) AND (sepsis) AND (animal model). Inclusion criteria included papers that used either gain- or loss-of-function approaches, excluding papers that did not focus on microRNAs as therapy targets, did not include animal models, did not show organ failure-specific assessments, and focused on microRNAs as biomarkers. The PRISMA-ScR guideline was used in this study. Results: A total of 199 articles were identified that featured the terms “microRNA/miRNA/miR”, “Sepsis”, and “animal model”. Of these, 51 articles (25.6%) employed miRNA-based therapeutic interventions in animal models of sepsis. Of these, 15 studies extended their inquiry to include or reference human clinical data. Key microRNAs of interest and their putative mechanisms of action in sepsis are highlighted. Conclusions: The body of work examined herein predominantly addresses various dimensions of sepsis-induced organ dysfunction, supporting the emerging role of miRNAs as potential therapeutic candidates. However, nearly 5% of papers on miR-based therapy have been retracted over the past 5 years, raising important concerns regarding the quality and complexity of the biology and models for assessing therapeutic potential.

ABSTRACTBackground Anesthesia for transjugular intrahepatic portosystemic shunt (TIPS) for lowering raised portal pressure is clinically challenging. As patients, candidates for TIPS are medically complex due to chronic liver disease, adding to remote area anesthesia’s complexities. Multimodal analgesia, including erector spinae plane block (ESPB), can improve anesthesia quality with patient satisfaction.Methods Fifty-six patients scheduled for TIPS, aged 18–60 years and with Child classification A or B, were randomly allocated into two groups. The ESPB group experienced ESPB (n = 24), while the control group was introduced with sedation spontaneously breathing (n = 24). Primarily, we investigated the records of the hemodynamic profile and analgesia nociceptive index (ANI). As a secondary aim, we recorded the opioid consumption, complication incidence, and patient and interventional radiologist satisfaction scores.Results Heart rate was significantly lower in the ESPB group at the beginning of the procedure, liver puncture, and balloon dilatation events, while there were no significant differences in mean blood pressure. Analgesia assessment by ANI was significantly higher in the ESPB group indicating adequate analgesia. Opioid consumption was significantly lower in the ESPB group than in the control group. Statistical analysis for patient satisfaction showed better results in the ESPB group, while the surgeon satisfaction score showed no significant statistical differences.Conclusion ESPB could be recommended as an alternative to analgesia in TIPS and its vulnerable patients to improve safety by reducing sedation-related morbidity and complications with improving the patient’s degree of satisfaction.

ABSTRACTBackground Spinal anesthesia is a widely used technique for cesarean delivery, but it often results in hypotension, bradycardia, and reduced cardiac output (CO). Atropine has a potent muscarinic receptor antagonist activity in the heart. It may be a good choice to prevent post-spinal bradycardia and minimize the marked CO reduction.Methods Sixty pregnant women between the ages of 18 and 40 who were ASA-PS II and planned for elective cesarean delivery were divided into two equal groups at random. Both groups received spinal anesthesia. Atropine group (I) (n = 30): patients received 0.01 mg/kg atropine, while control group (II) (n = 30): patients received the same volume of saline. CO measured by electrical cardiometry (EC) was the primary outcome where, heart rate (HR), mean blood pressure (MBP), stroke volume (SV), systemic vascular resistance (SVR), and neonatal outcomes were the secondary outcomes.Results CO after the intervention was higher in the atropine (group I) than in the control (group II). Also, CO reduction at 5 and 10 min following spinal anesthesia was less in the group I than in the group II. Except for baseline reading, HR was significantly higher in the atropine group versus the control group. MBP was higher in the atropine group than in the control group in all readings. SV and SVR were similar in both groups. Neonatal outcomes were equivalent in both groups.Conclusion Pre-spinal atropine was effective in preventing post-spinal bradycardia and minimized CO reduction in patients undergoing elective cesarean delivery under spinal anesthesia.

Diabetic bladder dysfunction (DBD) comprises a wide spectrum of lower urinary tract symptoms that impact diabetic patients’ lives, including urinary frequency, urgency, incontinence, and incomplete bladder emptying. To relieve symptoms, anticholinergics have been widely prescribed and are considered an effective treatment. There is increasing evidence that diabetic patients may benefit from the use of phosphodiesterase 5 (PDE5) inhibitors. This narrative review aims to provide a brief overview of the pathophysiology of DBD along with a focus on cholinergic and phosphodiesterase inhibitors as therapies that benefit DBD. An examination of the literature suggests compelling avenues of research and underscores critical gaps in understanding the mechanisms underlying DBD. New tools and models, especially rodent models, are required to further elucidate the mechanisms of action of current therapies in the treatment of DBS.