A 'Hub and Spoke' Shared Care initiative for CTEV Ponseti service.

Aims: The Ponseti method is the gold standard treatment for congenital talipes equinovarus (CTEV), with the British Consensus Statement providing a benchmark for standard of care. Meeting these standards and providing expert care while maintaining geographical accessibility can pose a service delivery challenge. A novel 'Hub and Spoke' Shared Care model was initiated to deliver Ponseti treatment for CTEV, while addressing standard of care and resource allocation. The aim of this study was to assess feasibility and outcomes of the corrective phase of Ponseti service delivery using this model. Methods: Patients with idiopathic CTEV were seen in their local hospitals ('Spokes') for initial diagnosis and casting, followed by referral to the tertiary hospital ('Hub') for tenotomy. Non-idiopathic CTEV was managed solely by the Hub. Primary and secondary outcomes were achieving primary correction, and complication rates resulting in early transfer to the Hub, respectively. Consecutive data were prospectively collected and compared between patients allocated to Hub or Spokes. Mann-Whitney U test, Wilcoxon signed-rank test, or chi-squared tests were used for analysis (alpha-priori = 0.05, two-tailed significance). Results: Between 1 March 2020 and 31 March 2023, 92 patients (139 feet) were treated at the service (Hub 50%, n = 46; Spokes 50%, n = 46), of whom nine were non-idiopathic. All patients (n = 92), regardless of allocation, ultimately achieved primary correction, with idiopathic patients at the Hub requiring fewer casts than the Spokes (mean 4.0 (SD 1.4) vs 6.9 (SD 4.4); p < 0.001). Overall, 60.9% of Spokes' patients (n = 28/46) required transfer to the Hub due to complications (cast slips Hub n = 2; Spokes n = 17; p < 0.001). These patients ultimately achieved full correction at the Hub. Conclusion: The Shared Care model was found to be feasible in terms of providing primary correction to all patients, with results comparable to other published services. Complication rates were higher at the Spokes, although these were correctable. Future research is needed to assess long-term outcomes, parents' satisfaction, and cost-effectiveness.

Scoring systems for the management of oncological hepato-pancreato-biliary patients.

Oncological scoring systems in surgery are used as evidence-based decision aids to best support management through assessing prognosis, effectiveness and recurrence. Currently, the use of scoring systems in the hepato-pancreato-biliary (HPB) field is limited as concerns over precision and applicability prevent their widespread clinical implementation. The aim of this review was to discuss clinically useful oncological scoring systems for surgical management of HPB patients. A narrative review was conducted to appraise oncological HPB scoring systems. Original research articles of established and novel scoring systems were searched using Google Scholar, PubMed, Cochrane, and Ovid Medline. Selected models were determined by authors. This review discusses nine scoring systems in cancers of the liver (CLIP, BCLC, ALBI Grade, RETREAT, Fong's score), pancreas (Genç's score, mGPS), and biliary tract (TMHSS, MEGNA). Eight models used exclusively objective measurements to compute their scores while one used a mixture of both subjective and objective inputs. Seven models evaluated their scoring performance in external populations, with reported discriminatory c-statistic ranging from 0.58 to 0.82. Selection of model variables was most frequently determined using a combination of univariate and multivariate analysis. Calibration, another determinant of model accuracy, was poorly reported amongst nine scoring systems. A diverse range of HPB surgical scoring systems may facilitate evidence-based decisions on patient management and treatment. Future scoring systems need to be developed using heterogenous patient cohorts with improved stratification, with future trends integrating machine learning and genetics to improve outcome prediction.

Targeted activation of the hippocampal CA2 area strongly enhances social memory.

Social cognition enables individuals to understand others' intentions. Social memory is a necessary component of this process, for without it, subsequent encounters are devoid of any historical information. The CA2 area of the hippocampus, particularly the vasopressin 1b receptor (Avpr1b) expressed there, is necessary for memory formation. We used optogenetics to excite vasopressin terminals, originating from the hypothalamic paraventricular nucleus, in the CA2 of mice. This markedly enhanced their social memory if the stimulation occurred during memory acquisition, but not retrieval. This effect was blocked by an Avpr1b antagonist. Finally, this enhanced memory is resistant to the social distraction of an introduced second mouse, important for socially navigating populations of individuals. Our results indicate the CA2 can increase the salience of social signals. Targeted pharmacotherapy with Avpr1b agonists or deep brain stimulation of the CA2 are potential avenues of treatment for those with declining social memory as in various dementias.

Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model.

Antidepressant medication constitutes the first line pharmacological treatment for posttraumatic stress disorder (PTSD), however, because many patients display no beneficial drug effects it has been suggested that combinations of antidepressants with additional drugs may be necessary. The defining symptoms of PTSD include re-experiencing, avoidance and hyperarousal. In addition, PTSD patients were shown to become easily distracted and often suffer from poor concentration together with indications of comorbidity with attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) is the most common and effective drug treatment for ADHD, thus we aimed to investigate the effects of MPH treatment, by itself or in combination with the antidepressants fluoxetine (FLU) or desipramine (DES). We modified an animal model of PTSD by exposing rats to chronic stress and evaluating the subsequent development of behavioral PTSD-like symptoms, as well as the effects on proinflammatory cytokines, which were implicated in PTSD. We report that while FLU or DES had a beneficial effect on avoidance and hyperarousal symptoms, MPH improved all three symptoms. Moreover, the combination of MPH with DES produced the most dramatic beneficial effects. Serum levels of interleukin-1ß (IL-1ß) and IL-6 were elevated in the PTSD-like group compared with the control group, and were decreased by MPH, FLU, DES or the combination drug treatments, with the combination of DES+MPH producing the most complete rescue of the inflammatory response. Considering the versatile symptoms of PTSD, our results suggest a new combined treatment for PTSD comprising the antidepressant DES and the psychostimulant MPH.

Plant-derived nanoparticle treatment with cocc 30c ameliorates attention and motor abilities in sleep-deprived rats.

Sleep is an essential physiological process that underlies crucial cognitive functions as well as emotional reactivity. Thus, sleep deprivation (SD) may exert various deleterious effects. In this study, we aimed to examine the adverse behavioral and hormonal effects of SD and a potential treatment with Plant-derived nanoparticle treatment - cocc 30c. The study was a 4-arm trial with randomization and double-blinding of verum and placebo treatments. SD was induced by using the Multiple Platform Method for 48 h. The effects of SD were evaluated behaviorally (pre-pulse inhibition (PPI), startle response and rotor-rod) at baseline as well as at 6, 12, 24h, and 14 days post deprivation. cocc 30c treatment was administrated Per Os every three hours starting immediately after baseline tests and for a period of 24h. On day 14, blood samples were taken and serum levels of corticosterone, testosterone, serotonin and leptin were tested. We found that cocc 30c improved PPI 12 and 24h post deprivation, likewise, cocc 30c improved motor learning. On day 14 SD led to increased startle response that was ameliorated by cocc 30c. Likewise, SD led to increased levels of corticosterone and serotonin while decreasing testosterone and leptin. Interestingly, cocc 30c treatment has moderated these hormonal alterations. We conclude that the treatment with cocc 30c recovers both short-term behavioral and the long-term hormonal modulations following SD.

Selective melanocortin MC4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage.

BACKGROUND AND PURPOSE: In circulatory shock, melanocortins have life-saving effects likely to be mediated by MC4 receptors. To gain direct insight into the role of melanocortin MC4 receptors in haemorrhagic shock, we investigated the effects of two novel selective MC4 receptor agonists. EXPERIMENTAL APPROACH: Severe haemorrhagic shock was produced in rats under general anaesthesia. Rats were then treated with either the non-selective agonist [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP--MSH) or with the selective MC4 agonists RO27-3225 and PG-931. Cardiovascular and respiratory functions were continuously monitored for 2 h; survival rate was recorded up to 24 h. Free radicals in blood were measured using electron spin resonance spectrometry; tissue damage was evaluated histologically 25 min or 24 h after treatment. KEY RESULTS: All shocked rats treated with saline died within 30-35 min. Treatment with NDP--MSH, RO27-3225 and PG-931 produced a dose-dependent (13-108 nmol kg-1 i.v.) restoration of cardiovascular and respiratory functions, and improved survival. The three melanocortin agonists also markedly reduced circulating free radicals relative to saline-treated shocked rats. All these effects were prevented by i.p. pretreatment with the selective MC4 receptor antagonist HS024. Moreover, treatment with RO27-3225 prevented morphological and immunocytochemical changes in heart, lung, liver, and kidney, at both early (25 min) and late (24 h) intervals. CONCLUSIONS AND IMPLICATIONS: Stimulation of MC4 receptors reversed haemorrhagic shock, reduced multiple organ damage and improved survival. Our findings suggest that selective MC4 receptor agonists could have a protective role against multiple organ failure following circulatory shock.