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Abstract Saliva serves multiple important functions within the body that we typically take for granted, such as helping prepare food for swallowing and defense against oral pathogens. Dry mouth is a primary symptom of Sjӧgren’s syndrome and is a side effect of many drug treatments. Cannabis users frequently report dry mouth, but the basis for this is still unknown. If the effects occur via the endogenous cannabinoid signaling system, then this may represent a novel mechanism for the regulation of salivation. We examined expression of cannabinoid CB1 receptors in submandibular salivary gland using immunohistochemistry and tested regulation of salivation by THC and cannabinoid-related ligands. We now report that CB1 receptors are expressed in the axons of cholinergic neurons innervating the submandibular gland. No staining is seen in submandibular gland epithelial cells (acinar and ductal), or myoepithelial cells (MECs). Treatment with THC (4 mg/kg, IP) or the cannabinoid receptor agonist CP55940 (0.5 mg/kg) reduced salivation in both male and female mice 1 h after treatment. CBD had no effect on its own but reversed the effect of THC in a concentration-dependent manner. Neither the CB1 receptor antagonist SR141716 (4 mg/kg) nor the CB2-selective agonist JWH133 (4 mg/kg) had an effect on salivation. We also found that fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide and related lipids, regulates salivation. Salivation was reduced in FAAH knockout mice as well as mice treated with the FAAH blocker URB597 (4 mg/kg). URB597 had no effect in CB1 knockout mice. FAAH protein is detected intracellularly in acinar but not ductal epithelial cells. In lipidomics experiments, we found that FAAH knockout mice chiefly had elevated levels of acylethanolamines, including anandamide, and reduced levels of acyglycines. Our results are consistent with a model wherein endocannabinoids activate CB1 receptors on cholinergic axons innervating the submandibular gland. THC likely acts by plugging into this system, activating CB1 receptors to reduce salivation, thus offering a mechanism underlying the dry mouth reported by cannabis users.

High-frequency stimulation resulted in increased event-related potentials (like in humans) and mechanical hypersensitivity (like in humans and rodents). Event-related potentials and mechanical hypersensitivity were correlated (novel). Supplemental Digital Content is Available in the Text. Translational models of the sensitized pain system are needed to progress the understanding of involved mechanisms. In this study, long-term potentiation was used to develop a mechanism-based large-animal pain model. Event-related potentials to electrical stimulation of the ulnar nerve were recorded by intracranial recordings in pigs, 3 weeks before, immediately before and after, and 3 weeks after peripheral high-frequency stimulation (HFS) applied to the ulnar nerve in the right forelimb (7 pigs) or in control animals (5 pigs). Event-related potential recordings and peripheral HFS were done during anesthesia. Two weeks before and after the HFS, behavioral responses reflecting mechanical and thermal sensitivity were collected using brush, noxious limb-mounted pressure algometer, and noxious laser stimuli. The HFS intervention limb was progressively sensitized to noxious mechanical stimulation in week 1 and 2 compared with baseline (P = 0.045) and the control group (P < 0.034) but not significantly to laser or brush stimulation. The first negative (N1) peak of the event-related potential was increased 30 minutes after HFS compared with before (P < 0.05). The N1 peak was also larger compared with control pigs 20 to 40 minutes after HFS (P < 0.031) but not significantly increased 3 weeks after. The relative increase in N1 30 minutes after HFS and the degree of mechanical hyperalgesia 2 weeks post-HFS was correlated (P < 0.033). These results show for the first time that the pig HFS model resembles the human HFS model closely where the profile of sensitization is comparable. Interestingly, the degree of sensitization was associated with the cortical signs of hyperexcitability at HFS induction. [ABSTRACT FROM AUTHOR]

Objectives: To predict palatally impacted maxillary canines based on maxilla measurements through supervised machine learning techniques. Materials and Methods: The maxilla images from 138 patients were analysed to investigate intermolar width, interpremolar width, interpterygoid width, maxillary length, maxillary width, nasal cavity width and nostril width, obtained through cone beam computed tomography scans. The predictive models were built using the following machine learning algorithms: Adaboost Classifier, Decision Tree, Gradient Boosting Classifier, K‐Nearest Neighbours (KNN), Logistic Regression, Multilayer Perceptron Classifier (MLP), Random Forest Classifier and Support Vector Machine (SVM). A 5‐fold cross‐validation approach was employed to validate each model. Metrics such as area under the curve (AUC), accuracy, recall, precision and F1 Score were calculated for each model, and ROC curves were constructed. Results: The predictive model included four variables (two dental and two skeletal measurements). The interpterygoid width and nostril width showed the largest effect sizes. The Gradient Boosting Classifier algorithm exhibited the best metrics, with AUC values ranging from 0.91 [CI95% = 0.74–0.98] for test data to 0.89 [CI95% = 0.86–0.94] for crossvalidation. The nostril width variable demonstrated the highest importance across all tested algorithms. Conclusion: The use of maxillary measurements, through supervised machine learning techniques, is a promising method for predicting palatally impacted maxillary canines. Among the models evaluated, both the Gradient Boosting Classifier and the Random Forest Classifier demonstrated the best performance metrics, with accuracy and AUC values exceeding 0.8, indicating strong predictive capability. [ABSTRACT FROM AUTHOR]

Background/Aims: Most birth-related ambulance calls occur without difficulty, but in some cases, complications can arise. Paramedics' involvement in birth is infrequent; therefore, the knowledge and skills required to manage complications can atrophy over time, particularly without educational interventions. This may impact outcomes. The study's aims were to measure the knowledge, attitude, and practice of paramedics in managing obstetric cases. Methods: This cross-sectional questionnaire-based study was carried out with 264 paramedics. Spearman's measure of correlation was used to observe linear correlations between ranks of the observations. Results: The majority of participants were advanced care paramedics (81.1%). Participants reported infrequently attending births in the community, with under half feeling confident in managing these (44%). Antenatal complications and trauma in pregnancy were self-reported areas of weakness; this was consistent with assessed knowledge. Conclusions: Paramedics self-reported infrequently responding to obstetric calls and the majority lacked confidence in managing these. Few indicated an excellent level of obstetric knowledge, reporting a desire to receive more education in this area. Implications for practice: When paramedics lack confidence in managing obstetric emergencies, it can lead to delayed decision making, inadequate assessment, increased error rates and adverse maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Background: Numbers of people with an intellectual disability and dementia present a global health and social challenge with associated need to reduce stress or agitation and improve quality of life in affected individuals. This study aimed to identify effectiveness of psychosocial interventions in social care settings and, uniquely, explore use of photovoice methodology to develop dialogue about dementia. Methods: This mixed-method participatory action study used individualised goal-setting theory with 16 participants with intellectual disability and dementia, and 22 social care staff across 11 sites. Five co-researchers with intellectual disability were part of an inclusive research team collecting data using existing and bespoke tools including photovoice. Analysis used descriptive and inferential statistics and framework analysis. Results: Seventy four percentage of individual goals met or exceeded expectations with reduction in some "as required" medication. Qualitative findings include themes of enabling care and interventions as tools for practice. Photovoice provided insight into previously unreported fears about dementia. Conclusions: Individualized psychosocial interventions have potential to reduce distress or agitation.

BackgroundA pressure algometer is a valuable tool for assessing the mechanical nociceptive threshold (MNT) in clinical pain studies. Recent research has turned to large animal models of pain because of the closer anatomy and physiology to humans. Although the reliability and usefulness of the MNT have been extensively validated in humans, similar data from large animals is still sparse.ObjectiveTherefore, the aim of the current study was to evaluate the reliability (within- and between-session) of MNT in the forelimb of pigs using a pressure algometer.MethodsNine animals were used (23–40 kg), and MNTs were measured at both the right and left limbs at three different sessions, with three repetitions per session. The intraclass correlation coefficient (ICC) was used as a metric for relative reliability. The standard error of measurement (SEM) and coefficient of variation (CV) was used to assess absolute reliability. Systematic bias was also evaluated.ResultsThe average ICC was found to be 0.71 and 0.45 for the between-session and within-session, respectively. CV ranged from 17.9% to 20.5%, with a grand average of 19.1%. The grand average SEM was 249.5 kPa (16.6%). No systematic differences were found for the MNT between sessions, which suggests that there was no habituation to the stimulus.ConclusionThe reliability indices obtained in this study are comparable to results obtained in other species or anatomical regions and substantiate the use of the pressure algometer as a valuable tool to investigate the nociceptive system in pigs and translation to the human nociceptive withdrawal reflex.

Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure that might lead to severe adverse events. Post-ERCP pancreatitis (PEP) is the most common post-procedural complication, which is related to significant mortality and increasing healthcare costs. Up to now, the prevalent approach to prevent PEP consisted of employing pharmacological and technical expedients that have been shown to improve post-ERCP outcomes, such as the administration of rectal nonsteroidal anti-inflammatory drugs, aggressive intravenous hydration, and the placement of a pancreatic stent. However, it has been reported that PEP originates from a more complex interaction of procedural and patient-related factors. Appropriate ERCP training has a pivotal role in PEP prevention strategy, and it is not a chance that a low PEP rate is universally considered one of the most relevant indicators of proficiency in ERCP. Scant data on the acquisition of skills during the ERCP training are currently available, although some efforts have been recently done to shorten the learning curve by way of simulation-based training and demonstrate competency by meeting technical requirements as well as adopting skill evaluation scales. Besides, the identification of adequate indications for ERCP and accurate pre-procedural risk stratification of patients might help to reduce PEP occurrence regardless of the endoscopist’s technical abilities, and generally preserve safety in ERCP. This review aims at delineating current preventive strategies and highlighting novel perspectives for a safer ERCP focusing on the prevention of PEP.

Oligometastatic colorectal cancer (CRC) is a clinically relevant entity, and surgery is the gold standard therapeutic option. Current guidelines recommend evaluating other local ablative treatments (LATs) in patients not eligible for surgery. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and stereotactic body radiation therapy (SBRT) are emerging as highly beneficial less-invasive LATs in alternative to surgery. In our paper, we report the first case in literature of lymph node metastases from CRC treated sequentially with EUS-RFA and SBRT, providing evidence of their efficacy and safety. LATs combined with systemic chemotherapy might be included in a multimodal therapeutic approach to oligometastatic disease.

This study implements the use of Danish Landrace pigs as subjects for the long-term potentiation (LTP)-like pain model. This is accomplished by analyzing changes in the primary somatosensory cortex (S1) in response to electrical stimulation on the ulnar nerve after applying high-frequency electrical stimulation (HFS) on the ulnar nerve. In this study, eight Danish Landrace pigs were electrically stimulated, through the ulnar nerve, to record the cortically evoked response in S1 by a 16-channel microelectrode array (MEA). Six of these pigs were subjected to HFS (four consecutive, 15 mA, 100 Hz, 1000 µs pulse duration) 45 min after the start of the experiment. Two pigs were used as control subjects to compare the cortical response to peripheral electrical stimulation without applying HFS. Low-frequency components of the intracortical signals (0.3–300 Hz) were analyzed using event-related potential (ERP) analysis, where the minimum peak during the first 30–50 ms (N1 component) in each channel was detected. The change in N1 was compared over time across the intervention and control groups. Spectral analysis was used to demonstrate the effect of the intervention on the evoked cortical oscillations computed between 75 ms and 200 ms after stimulus. ERP analysis showed an immediate increase in N1 amplitude that became statistically significant 45 mins after HFS (p

IntroductionThe Centre of Pressure (COP) is the single point summarising all forces transferred to the hoof during the stance phase of a stride. COP path (COPp) is the trajectory that COP follows from footstrike to lift-off. Aim of the present study was to characterize the COP and COPp in horses affected by osteoarthritis and chronic lameness.Materials and methodsSeventeen adult horses with a diagnosis of osteoarthritis and single limb chronic lameness were recruited. The COP was recorded using a wireless pressure measuring system (TekScan®) with sensors taped to the hooves (either fore- or hind limb, depending on lameness location). The COPp coordinates were further processed. Procrustes analysis was performed to assess the variability of single strides COPp and average COPp among strides, gaits, and limbs by calculating Procrustes distances (D-values). A linear mixed-effects model was run to analyse D-values differences for lame and sound limbs. Additionally, average COPp D-values and COPp hoofprint shape indices were compared for lame and sound limbs with the Signed Rank Test.ResultsAt walk and trot the single-stride COPp D-values were significantly lower in lame than in sound limbs (marginal effects pConclusionOur findings are in line with previous observations that COPp are highly repetitive and characteristic for each horse and limb. There seems to be a further decrease in COPp variability in the presence of a painful limb pathology.

Equipe Editorial e Avaliadores Ad hoc da REMAT, v. 8, n. 2, 2022.

Apresentação da REMAT, v. 8, n. 2, 2022. Publicação contínua: 01/07/2022 a 31/12/2022.

IntroductionInflammatory bowel disease (IBD), namely ulcerative colitis and Crohn’s disease, is a chronic relapsing immune-mediated condition that may cause an impairment of social functions due to stigmatisation. Resilience instead is associated with an improvement in coping with adversities and thus may counteract the detrimental effects of stigmatisation. We herein sought to determine the fluctuation of stigmatisation and resilience in a cohort of patients with IBD at 1-year follow-up.MethodsThis is a prospective, monocentric study conducted in a tertiary referral centre. All patients with IBD were assessed at enrolment and at oneyear follow-up. Several clinical and demographic variables were collected. Stigmatisation was assessed through a validated Italian version of the Perceived Stigma Scale for IBD (PSS-IBD), while resilience was assessed through the 25-item Connor Davidson Resilience Scale (CD-RISC25). Also, self-efficacy (SEF) and self-esteem (SES) scales were assessed.ResultsIn this study, 105 patients were included (46 Crohn’s disease, 59 ulcerative colitis; overall mean age 47 years ±11, M:F ratio 1:1.2). None of the 4 scales showed a statistically significant variation at one year compared to baseline (median CD-RISC25 64 at baseline vs 61 at follow-up; SEF 31 vs 30; SES 32.5 vs 32; PSS-IBD 0.45 vs 0.45). A statistically significant and inverse correlation was found between CD-RISC25 and PSS-IBD (rho -0.222, p=0.01), SEF and PSS-IBD (rho -0.219, p= 0.01), SES and PSS-IBD (-0.316, p=0.003). CD-RISC25 was found to be positively associated with inactive IBD (p=0.05).DiscussionIn this prospective study we have shown for the first time that stigmatisation, resilience, SEF and SEM did not change over a one-year time span, suggesting that, based on the information gathered, these characteristics may be independent from IBD severity or IBD flares. Furthermore, we found an inverse correlation of stigma with resilience, SEF and SES, suggesting an important role that these variables may have on preventing stigmatisation.

EUS-FNB has been introduced in clinical practice as a less invasive diagnostic approach with respect to surgery. We performed a single-center retrospective study on the diagnostic efficacy of EUS-guided FNB, including 171 patients with lymph nodes, splenic, and extranodal lesions that underwent EUS for FNB at our institution. Excluding 12 patients who did not undergo FNB and 25 patients with a previous diagnosis of a solid tumor, we included 134 patients with clinical/radiological suspect of a lymphoproliferative disease, including 20 patients with a previous history of lymphoma. Out of the 134 biopsies, material of diagnostic quality was obtained in 111 procedures (84.3%). Histological examination of the EUS-FNB samples produced an actionable diagnosis in 100 cases (74.6%). Among the patients without an actionable diagnosis, a second, different diagnostic procedure produced a further eight diagnoses of lymphoma. Therefore, the sensitivity of EUS-FNB for diagnosing lymphomas was calculated to be 86.4% (51/59). Assignment of lymphomas to WHO classification subtypes was possible in 47/51 (92%) of the cases. In conclusion, EUS-FNB is an effective procedure for the histological characterization of lesions that are suspected to be lymphoproliferative disease, allowing for an actionable diagnosis in 75% of cases.