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BackgroundHypersalivation and drooling are commonly reported in clozapine-treated patients. Current management strategies have been evaluated using subjective measures. Many case reports describe the successful use of atropine in the treatment of the condition.AimsTo measure the effect and safety of sublingual atropine on nocturnal unstimulated saliva secretion. Secondary aims were to evaluate the patient’s satisfaction with the atropine effect on hypersalivation (or sialorrhea), drooling, and sleep.MethodTwenty-one clozapine-treated patients with hypersalivation, or drooling, were randomised to take a single 600-μg dose of sublingual atropine drops or a matching placebo. The saliva secretion was measured over 5 min at baseline and 2 h after the administration of the study medication.ResultsSublingual atropine reduced the saliva secretion significantly more than the placebo (mean difference = − 57.21%, 95% CI: − 104.30, − 10.11, P = 0.02). A significant decrease in standing pulse rate was recorded in the participants in the atropine group (− 5.8 (− 9.54, − 2.15), P = 0.002). Subjectively, more patients in the atropine group found their pillow to have less saliva the following morning and found their sleep to be better.ConclusionsSublingual atropine drops significantly reduces nocturnal unstimulated clozapine-induced saliva secretion. More research is required to compare the effect of sublingual atropine with other anticholinergic medications and different dosage forms.Trial registrationACTRN12618000051246

ObjectivesTo assess the effect of sialendoscopy of the major salivary glands on salivary flow and xerostomia in patients with Sjögren’s syndrome (SS).MethodsForty-nine patients with SS were randomly assigned to a control group (n=15) and two intervention groups: irrigation of the major glands with saline (n=16) or with saline followed by triamcinolone acetonide (TA) in saline (n=18). Unstimulated whole saliva flow (UWS), chewing-stimulated whole saliva flow (SWS), citric acid-stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) score and the European League Against Rheumatism (EULAR) SS Patient-Reported Index (ESSPRI) were obtained 1 week (T0) before, and 1 (T1), 8 (T8), 16 (T16) and 24 (T24) weeks after sialendoscopy.ResultsMedian baseline UWS, SWS and SPF scores were 0.14, 0.46 and 0.22 mL/min, respectively. After intervention, significant increases in UWS and SWS were observed in the saline group (at T8 (P=0.013) and T24 (P=0.004)) and the saline/TA group (at T24 (P=0.03) and T=16 (P=0.035)). SPF was increased significantly in the saline/TA group at T24 (P=0.03). XI scores declined after sialendoscopy in both intervention groups. Compared with the control group, CODS, XI and ESSPRI improved in the intervention groups. UWS, SWS and SPF were higher in the intervention groups compared with the control group, but these differences were not significant except for SPF in the saline/TA group at T24 (P=0.005).ConclusionsIrrigation of the major salivary glands in patients with SS enhances salivary flow and reduces xerostomia up to 6 months after sialendoscopy.

Snus is a smokeless tobacco product traditionally used in Scandinavia and available in pouched or loose forms. The objective of this study was to determine nicotine absorption for current pouched and loose snus products in comparison with a cigarette and an over-the-counter nicotine gum. We conducted an open-label, randomized, 6-way, crossover study involving 20 healthy snus and cigarette users. One of 6 products (2 pouched snus, 2 weights of loose snus, a cigarette, and a nicotine gum) was administered at each of 6 visits. Blood samples were taken at intervals over 120 min and sensory perception assessed by questionnaire. For the 4 smokeless tobacco products and the nicotine gum, blood plasma levels of nicotine were ranked according to total nicotine content as follows: loose snus (27.1 mg nicotine) > pouched snus (14.7 mg nicotine) > loose snus (10.8 mg nicotine) = pouched snus (10.7 mg nicotine) > nicotine gum (4.2 mg nicotine). The area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) of nicotine ranged from 26.9 to 13.1 ng.h/ml and 17.9 to 9.1 ng.h/ml, respectively across all the products. Nicotine was absorbed more rapidly from the cigarette but systemic exposure was within the range of the smokeless tobacco products (AUC = 14.8 ng.h/ml; C(max) = 12.8 ng.h/ml). This study has generated new information on comparative nicotine absorption from a cigarette, loose snus, and pouched snus typical of products sold in Scandinavia. The similar nicotine absorption for 1 g portions of loose and pouched snus with approximately 11 mg of nicotine indicate that absorption kinetics were dependent on quantity of tobacco by weight and total nicotine content rather than product form.

Salivation to food cues is typically explained in terms of mere stimulus-response links. However, food cues seem to especially increase salivation when food is attractive, suggesting a more complex psychological process. Adopting a grounded cognition perspective, we suggest that perceiving a food triggers simulations of consuming it, especially when attractive. These simulations then induce salivation, which effectively prepares the body for eating the food. In two experiments, we systematically examined the role of simulations on salivation to food cues. As stimuli, both experiments used an attractive, a neutral, and a sour food, as well as a non-food control object. In Experiment 1, participants were instructed to simulate eating every object they would be exposed to. We then exposed them to each object separately. Salivation was assessed by having participants spit their saliva into a cup after one minute of exposure. In Experiment 2, we instructed half of participants to simulate eating each object, and half to merely look at them, while measuring salivation as in Experiment 1. Afterwards, participants rated their simulations and desire to eat for each object separately. As predicted, foods increased salivation compared to the non-food control object, especially when they were attractive or sour (Exp. 1 and 2). Importantly, attractive and sour foods especially increased salivation when instructed to simulate (Exp. 2). These findings suggest that consumption simulations play an important role in inducing salivary responses to food cues. We discuss directions for future research as well as the role of simulations for other appetitive processes.

Screening tests can be performed to identify stroke patients who require further assessment of swallowing function. The Repetitive Saliva Swallowing Test (RSST) is a screening test during which the patient is asked to swallow saliva as many times as possible for 30 s, while deglutition is counted through palpation of the larynx. This study aimed to establish normative values for three age groups of non-patients (total N = 120) on RSST. One patient group (N = 40) was also recruited from a geriatric stroke unit to assess whether RSST scores predicted outcomes on the Standardised Swallowing Assessment—Svenska (SSA-S), a clinical screening tool here used as a reference test. Since the RSST involves the swallowing of saliva, this study also measured the participants’ saliva secretion in order to examine its effect on RSST performance. This study showed that RSST results vary with age (lower among older) and gender (higher for men than women), while the number of doctor-prescribed medications, objective saliva secretion and self-assessed dryness of mouth did not affect the performance significantly. In comparison to a more extensive clinical screening procedure (SSA-S), the RSST correctly predicted 93% of negative cases and 69% of positive cases. This suggests that patients who show signs of aspiration according to SSA-S have a lower probability of detection with RSST.

Narcolepsy type 1 (NT1) is caused by a significant loss of orexin-producing neurons. In clinical trials, multiple orexin receptor 2 (OX2R)-selective agonists (e.g., danavorexton, TAK-994, and oveporexton) improved wakefulness and decreased cataplexy in individuals with NT1. However, OX2R-selective agonists were also reported to induce hypersalivation as an adverse event in a small number of healthy volunteers and in individuals with NT1. Importantly, no objective data supporting these observations are available, and multiple factors can indirectly affect saliva secretion. In this study, we assessed the effect of an OX2R-selective agonist, OX-202, on salivary secretion in anesthetized or freely moving rats using a muscarinic acetylcholine receptor agonist, pilocarpine, as a positive control. Subcutaneous administration of pilocarpine at 1 mg/kg significantly increased the amount of saliva in the oral cavity in both anesthetized and freely moving rats. In contrast, intraperitoneal administration of OX-202 at 100 mg/kg under anesthetized conditions did not increase salivary secretion in rats. Moreover, oral administration of OX-202 (30 and 100 mg/kg) at zeitgeber time 6 (sleep phase) or zeitgeber time 15 (active phase) did not increase salivary secretion in the oral cavity in freely moving rats. In conclusion, OX2R-selective agonists may not directly induce salivary secretion in rats.

Background Drooling, defned as the unintentional loss of saliva from the anterior oral cavity, remains poorly understood in terms of the underlying clinical factors in people with Parkinson’s disease (PwP). This study aims to clarify these factors by analyzing predictors and secondarily the correlates with the severity of drooling in PwP. Methods We conducted a cross-sectional study involving 42 PwP with drooling and 59 without drooling. Clinical assess ments were performed, and the primary outcome was the item 2.2 Saliva and drooling of the Movement Disorder Society Unifed Parkinson’s Disease Rating Scale. The Mann–Whitney test was used to compare the distribution diferences in clinical variables between PwP with and without drooling. The Spearman test was used to examine correlations with drooling, and ordinal logistic regression was used to examine predictors of drooling. Results PwP with drooling showed signifcantly greater impairments in axial signs, posture, facial expression, speech, swallowing, oromotor, motor and non-motor domains than PwP without drooling. Longer disease duration, higher disease severity, levodopa equivalent daily dose, axial signs, unstimulated salivary fow rate, and impairments in speech, posture, facial expression, swallowing, oromotor, motor and non-motor domains were signifcantly correlated with a higher score on the item 2.2. Male sex, poorer swallowing, oromotor and speech functions were strong predictors of higher scores on the item 2.2 Saliva and drooling. Conclusions Male PwP with swallowing disorders, oromotor and speech impairments are signifcantly more likely to have severe drooling. Targeted interventions aimed at these swallowing, oromotor, and speech impairments may ofer promising approaches to reducing drooling severity in PwP.

Background Radiation-induced hyposalivation is a common and debilitating side effect of head and neck radiotherapy, significantly impairing patients’ quality of life. Alpha-lipoic acid (ALA), a potent antioxidant, is hypothesized to enhance salivary secretion and promote the regeneration of acinar cells. Our study aimed to evaluate the effect of ALA on unstimulated salivary flow rate in patients undergoing head and neck radiotherapy. Methods This double-blind, randomized controlled clinical trial included 20 patients undergoing head and neck radiotherapy. Participants were randomly assigned to the intervention group (receiving 1200 mg/day ALA) or to the control group (receiving placebo) for three months. Unstimulated whole salivary flow rate (mL/min) was measured using the spitting method at baseline (pre-radiotherapy) and at weeks 2, 6, 8, and 12 post-radiotherapy. Xerostomia severity was assessed using the Numeric Rating Scale (NRS), alongside clinical signs of hyposalivation (e.g., frothy saliva, mucosal adherence). Data were analyzed using t-tests and Fisher’s exact test in SPSS version 25.00, with a significance level of 0.05. Results Although both groups indicated a decline in salivary flow over time, no significant intergroup differences were observed at any follow-up point ( P  > 0.05). Within the ALA group, pairwise comparisons revealed a significant reduction in salivary flow from baseline to weeks 6, 8, and 12 ( P  = 0.02, P  = 0.01, and P  = 0.003, respectively). Additionally, a significant reduction was observed between weeks 2 and 6 ( P  = 0.011). No significant differences between groups were found in NRS scores or clinical indicators of hyposalivation during any follow-up session ( P  > 0.05). Conclusions Administration of 1200 mg/day ALA may temporarily delay the onset of salivary gland dysfunction in the early phases of radiotherapy. However, this effect was not statistically significant and may not have a sustained clinical benefit. Trial registration This clinical trial was approved by the Research Ethics Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.DRC.REC.1401.062) and registered in the Iranian Registry of Clinical Trials (IRCT20221219056864N1, registered on December 19, 2022).

Radiotherapy serves as an essential therapeutic modality for head and neck malignancies. However, many patients who undergo head and neck radiation (HNR) frequently experience different severities of xerostomia. Berberine (BBR) has a variety of pharmacological functions and has shown favorable clinical efficacy. However, its therapeutic potential and mechanistic basis in xerostomia have not been explored. The histological expressions of Aquaporin 5 (AQP5), Na-K-Cl cotransporter 1 (NKCC1), Muscle intestine stomach expression 1 (MIST1), Proliferating cell nuclear antigen (PCNA), Phospho-GSK-3beta (p-GSK3β) and β-Catenin were examined by immunohistochemistry (IHC). Mucin2 (MUC2), were examined by immunofluorescence. The degree of apoptosis was assessed by TUNEL. The mRNA expression levels of AQP5, NKCC1, PCNA, MUC2, and MIST1 were detected by qRT-PCR assay. The degree of inflammatory was evaluated by detecting the mRNA expression levels of , , , and . The Proliferation level was performed by salivary gland organoids. BBR significantly enhanced saliva secretion in normal physiological conditions and after radiation injury. Mechanistically, BBR upregulated the expression of AQP5, NKCC1 and MIST1. Moreover, BBR conferred its protection via the upregulation of mucin 2 (MUC2) expression, and qPCR analysis revealed elevated levels. Additionally, BBR preserved cellular proliferation, decreased TUNEL apoptotic cells and the inflammatory response in SMG tissues and organoids in HNR-induced xerostomia models. In conclusion, this study demonstrates that BBR can increase saliva secretion in healthy and HNR mice, indicating its potentiality for the treatment of radiation-induced xerostomia.

Ruiqiang Li and colleagues report the whole-genome sequencing of a Tibetan female wild boar, as well as resequencing of 48 domestic pigs and wild boar from Tibet and China. Their analysis provides insights into the genetic diversity, population structure and evolution of the wild boar. We report the sequencing at 131× coverage, de novo assembly and analyses of the genome of a female Tibetan wild boar. We also resequenced the whole genomes of 30 Tibetan wild boars from six major distributed locations and 18 geographically related pigs in China. We characterized genetic diversity, population structure and patterns of evolution. We searched for genomic regions under selection, which includes genes that are involved in hypoxia, olfaction, energy metabolism and drug response. Comparing the genome of Tibetan wild boar with those of neighboring Chinese domestic pigs further showed the impact of thousands of years of artificial selection and different signatures of selection in wild boar and domestic pig. We also report genetic adaptations in Tibetan wild boar that are associated with high altitudes and characterize the genetic basis of increased salivation in domestic pig.