Salivary alpha-amylase stress reactivity in advanced-aged marmosets (Callithrix jacchus): Impacts of cognitive function and oral health status.

Salivary alpha-amylase (sAA) is an enzyme found in saliva and is considered a noninvasive biomarker for sympathetic nervous system activity. While a wide range of sAA activity in response to stress has been reported in nonhuman primates, the effects of stress on sAA activity in common marmosets are still unknown. We tested the hypothesis that advanced age and cognitive function may have an impact on stress-related sAA reactivity in marmosets. Thirteen marmosets (nine males and five females) had saliva samples collected during a stressful condition (manual restraint stress) at two different time points, with a 60-min interval. On the next day, the animals underwent the object recognition test (ORT, a type of cognitive test), and then oral examinations. The animals were categorized into two age groups: old (10-13 years), and very old (15-22 years). Irrespective of age, sAA levels showed a significant difference between T1 (mean 2.07 ± 0.86 U/mL) and T2 samples (mean 1.03 ± 0.67 U/mL), with higher values observed at T1 (p < 0.001). The intra-assay coefficients of variation (CV) for low and high sAA concentrations were 10.79% and 8.17%, respectively, while the interassay CVs for low and high sAA concentrations were 6.39% and 4.38%, respectively. Oral health issues were common but did not significantly impact sAA levels. The ORT indicated that the animals could recognize an object placed in the cage 6 h after familiarization. In conclusion, all marmosets showed a higher sAA concentration in the first saliva sample as compared to the second saliva sample collected 1 h later, indicating adaptation to stress. No significant differences in sAA levels were observed between sexes, ORT performance, or oral health. Our results indicate that autonomic responsivity and cognitive (memory) functions were preserved even in very old marmosets.

The use of natural language processing in palliative care research: A scoping review.

BACKGROUND: Natural language processing has been increasingly used in palliative care research over the last 5 years for its versatility and accuracy. AIM: To evaluate and characterize natural language processing use in palliative care research, including the most commonly used natural language processing software and computational methods, data sources, trends in natural language processing use over time, and palliative care topics addressed. DESIGN: A scoping review using the framework by Arksey and O'Malley and the updated recommendations proposed by Levac et al. was conducted. SOURCES: PubMed, Web of Science, Embase, Scopus, and IEEE Xplore databases were searched for palliative care studies that utilized natural language processing tools. Data on study characteristics and natural language processing instruments used were collected and relevant palliative care topics were identified. RESULTS: 197 relevant references were identified. Of these, 82 were included after full-text review. Studies were published in 48 different journals from 2007 to 2022. The average sample size was 21,541 (median 435). Thirty-two different natural language processing software and 33 machine-learning methods were identified. Nine main sources for data processing and 15 main palliative care topics across the included studies were identified. The most frequent topic was mortality and prognosis prediction. We also identified a trend where natural language processing was frequently used in analyzing clinical serious illness conversations extracted from audio recordings. CONCLUSIONS: We found 82 papers on palliative care using natural language processing methods for a wide-range of topics and sources of data that could expand the use of this methodology. We encourage researchers to consider incorporating this cutting-edge research methodology in future studies to improve published palliative care data.

Glutamate Within the Marmoset Anterior Hippocampus Interacts with Area 25 to Regulate the Behavioral and Cardiovascular Correlates of High-Trait Anxiety.

High-trait anxiety is a risk factor for the development of affective disorders and has been associated with decreased cardiovascular and behavioral responsivity to acute stressors in humans that may increase the risk of developing cardiovascular disease. Although human neuroimaging studies of high-trait anxiety reveals dysregulation in primate cingulate areas 25 and 32 and the anterior hippocampus (aHipp) and rodent studies reveal the importance of aHipp glutamatergic hypofunction, the causal involvement of aHipp glutamate and its interaction with these areas in the primate brain is unknown. Accordingly, we correlated marmoset trait anxiety scores to their postmortem aHipp glutamate levels and showed that low glutamate in the right aHipp is associated with high-trait anxiety in marmosets. Moreover, pharmacologically increasing aHipp glutamate reduced anxiety levels in highly anxious marmosets in two uncertainty-based tests of anxiety: exposure to a human intruder with uncertain intent and unpredictable loud noise. In the human intruder test, increasing aHipp glutamate decreased anxiety by increasing approach to the intruder. In the unpredictable threat test, animals showed blunted behavioral and cardiovascular responsivity after control infusions, which was normalized by increasing aHipp glutamate. However, this aHipp-mediated anxiolytic effect was blocked by simultaneous pharmacological inactivation of area 25, but not area 32, areas which when inactivated independently reduced and had no effect on anxiety, respectively. These findings provide causal evidence in male and female primates that aHipp glutamatergic hypofunction and its regulation by area 25 contribute to the behavioral and cardiovascular symptoms of endogenous high-trait anxiety.SIGNIFICANCE STATEMENT High-trait anxiety predisposes sufferers to the development of anxiety and depression. Although neuroimaging of these disorders and rodent modeling implicate dysregulation in hippocampal glutamate and the subgenual/perigenual cingulate cortices (areas 25/32), the causal involvement of these structures in endogenous high-trait anxiety and their interaction are unknown. Here, we demonstrate that increased trait anxiety in marmoset monkeys correlates with reduced hippocampal glutamate and that increasing hippocampal glutamate release in high-trait-anxious monkeys normalizes the aberrant behavioral and cardiovascular responsivity to potential threats. This normalization was blocked by simultaneous inactivation of area 25, but not area 32. These findings provide casual evidence in primates that hippocampal glutamatergic hypofunction regulates endogenous high-trait anxiety and the hippocampal-area 25 circuit is a potential therapeutic target.

Periodontal and peri-implant wound healing following laser therapy.

Laser irradiation has numerous favorable characteristics, such as ablation or vaporization, hemostasis, biostimulation (photobiomodulation) and microbial inhibition and destruction, which induce various beneficial therapeutic effects and biological responses. Therefore, the use of lasers is considered effective and suitable for treating a variety of inflammatory and infectious oral conditions. The CO2 , neodymium-doped yttrium-aluminium-garnet (Nd:YAG) and diode lasers have mainly been used for periodontal soft-tissue management. With development of the erbium-doped yttrium-aluminium-garnet (Er:YAG) and erbium, chromium-doped yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers, which can be applied not only on soft tissues but also on dental hard tissues, the application of lasers dramatically expanded from periodontal soft-tissue management to hard-tissue treatment. Currently, various periodontal tissues (such as gingiva, tooth roots and bone tissue), as well as titanium implant surfaces, can be treated with lasers, and a variety of dental laser systems are being employed for the management of periodontal and peri-implant diseases. In periodontics, mechanical therapy has conventionally been the mainstream of treatment; however, complete bacterial eradication and/or optimal wound healing may not be necessarily achieved with conventional mechanical therapy alone. Consequently, in addition to chemotherapy consisting of antibiotics and anti-inflammatory agents, phototherapy using lasers and light-emitting diodes has been gradually integrated with mechanical therapy to enhance subsequent wound healing by achieving thorough debridement, decontamination and tissue stimulation. With increasing evidence of benefits, therapies with low- and high-level lasers play an important role in wound healing/tissue regeneration in the treatment of periodontal and peri-implant diseases. This article discusses the outcomes of laser therapy in soft-tissue management, periodontal nonsurgical and surgical treatment, osseous surgery and peri-implant treatment, focusing on postoperative wound healing of periodontal and peri-implant tissues, based on scientific evidence from currently available basic and clinical studies, as well as on case reports.

Assessing bioequivalence of antiepileptic drugs: are the current requirements too permissive?

PURPOSE: In order to evaluate the permissiveness of current bioequivalence requirements for antiepileptic drugs we investigated how accurate Cmax and AUC0-t of generic antiepileptic drugs approved in Brazil are in comparison to reference products. METHODS: Data collected from assessment reports of approved bioequivalence studies archived in the Brazilian regulatory agency in 2007-2012 were: geometric mean ratios and 90% confidence intervals (CI) for Cmax and AUC0-t, intra-subject variability (CV) of Cmax and AUC0-t and number of subjects. RESULTS: The average difference in Cmax and AUC0-t between generic and reference products was 5% and 3%, respectively. Maximum deviation from 1.00 of the CI of Cmax can achieve 15-20% (demonstrated in 27% of studies); for AUC0-t, 25% of studies showed the deviation can be >10%. All studies that used adequate number of subjects for a 90% CI of 0.90-1.11 complied with it for AUC0-t, except one of carbamazepine, but only 33% complied with it for both AUC0-t and Cmax. The CV was strongly correlated to the maximum CI deviation for AUC0-t (CV of approximately 15% corresponding to deviation of 10%). Studies that presented maximum CI deviation ≤ 10 % together with CV ≤ 15% for AUC0-t represented 65% of the total. Weaker correlation was observed for Cmax and no correlation was seen between maximum CI deviation and number of subjects. CONCLUSIONS: Modification in legislation for bioequivalence of antiepileptic drugs is suggested, not only with constraint of AUC0-t 90% CI to 0.90-1.11, but also with limitation of the CV to 15%, as to assure similar variance in pharmacokinetics and diminish the risk of critical plasma-level fluctuation when switching between generic and reference formulations. Although most generics presented differences ≤ 10% in AUC0-t compared to their references, some narrow therapeutic index drugs displayed differences that could be clinically significant after product substitution.

Stress-induced modulation of nociceptive responses in the rat anterior cingulate cortex.

In the limbic system, the anterior cingulate cortex (ACCX) is one of the key areas involved in the close association between pain and emotion. However, neuronal changes in ACCX nociceptive responses after stress conditioning have not yet been quantitatively investigated. We investigated the modulation of nociceptive responses in the ACCX neurons following restraint stress in rats. The present study demonstrated that stress-conditioning enhanced excitatory nociceptive responses in the ACCX following tail stimuli in the mid-term (7 days). Short-term (3 days) and long-term (21 days) of stress conditioning did not affect these responses significantly. Nociceptive responses evoked by other sites of the body (nose, back and four paws) stimulation were not changed by stress-conditioning, indicating that neural information from the tail is important for emotional system modulation. It is suggested that the emotional/affective part of the pain sensation is strongly modified by stress through neuroplasticity in the ACCX.

Respiratory support effect on pharyngeal area in patients with amyotrophic lateral sclerosis: A fluoroscopic comparison of NIV, helmet/CPAP, and high-flow nasal cannula.

The global use of noninvasive respiratory support provided by different supportive ventilation delivery methods (SVDMs) has increased, but the impact of these devices on the upper airway structures of patients with amyotrophic lateral sclerosis (ALS) is not known. We aimed to compare the pharyngeal cross-sectional area during spontaneous breathing with four different SVDMs: intranasal masks, oronasal masks, high-flow nasal cannula (HFNC), and helmet in patients with ALS. We compared measures of the pharyngeal area during spontaneous breathing and SVDM use. The greatest increase was observed with intranasal mask use, followed by HFNC, oronasal mask, and helmet respectively. In conclusion, upper airway opening in patients with ALS is enhanced by positive pressure with intranasal masks and HFNC, showing promise for increasing pharyngeal patency. Future studies should explore its applicability and effectiveness in maintaining long-term pharyngeal patency, especially in this population with bulbar weakness.

Hypergravity conditioning on ileal movements in rats.

INTRODUCTION: Stress is a common trigger for various physiological disturbances, including feeding disorders. One of the possible mechanisms for feeding disorders may be linked to changes in intestinal movement caused by stress. Therefore, here we investigated in vitro stress-induced changes in ileal movement. METHODS: Rats (female Wistar, SPF) were divided into Control (1 G) and hypergravity (hyperG) groups. HyperG stress was applied daily for 10 min by a centrifugal apparatus for 1 to 30 d. Under barbiturate anesthesia, a 1-cm long section of the ileum was isolated and fixed in a Magnus-type chamber filled with tyrode solution. Intestinal movement was evoked by applying acetylcholine (Ach, 10(-7)-10(-5) g x ml(-1)). Antagonistic effects of adrenalin (Adr, 10(-4) g x ml(-1)) on the Ach-evoked movements were also observed. RESULTS: Clear ileum movements were observed after Ach application. The movement pattern was phasic (early) and tonic (late). Peak amplitude of the phasic wave was dose-dependent on the Ach concentration. No significant differences in the averaged peak amplitude between control and hyperG groups were observed. The peak amplitude was decreased by Adr application in both the control and hyperG groups; however, the degree of the decrement was higher in hyperG than in control at 1 d after stress loading. DISCUSSION: The present study indicates that gravity stress modified ileal movement. Although basic ileum movements evoked by Ach were not influenced by stress, they were modified by Adr at a quite early stage after stress loading, suggesting an increase in the sensitivity of Adr receptors, but not of Ach receptors in the ileum.

Chronic respiratory failure negatively affects speech function in patients with bulbar and spinal onset amyotrophic lateral sclerosis: retrospective data from a tertiary referral center.

Background: Although dysarthria and respiratory failure are widely described in literature as part of the natural history of Amyotrophic lateral sclerosis (ALS), the specific interaction between them has been little explored.Aim: To investigate the relationship between chronic respiratory failure and the speech of ALS patients.Materials and methods: In this cross-sectional retrospective study we reviewed the medical records of all patients diagnosed with ALS that were accompanied by a tertiary referral center. In order to determine the presence and degree of speech impairment, the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) speech sub-scale was used. Respiratory function was assessed through spirometry and through venous blood gasometry obtained from a morning peripheral venous sample. To determine whether differences among groups classified by speech function were significant, maximum and mean spirometry values of participants were compared using multivariate analysis of variance (MANOVA) with Tukey's post hoc test.Results: Seventy-five cases were selected, of which 73.3% presented speech impairment and 70.7% respiratory impairment. Respiratory and speech functions were moderately correlated (seated FVC r = 0.64; supine FVC r = 0.60; seated FEV1 r = 0.59 and supine FEV1 r = 0.54, p < .001). Multivariable logistic regression revealed that the following variables were significantly associated with the presence of speech impairment after adjusting for other risk factors: seated FVC (odds ratio [OR] = 0.862) and seated FEV1 (OR = 1.106). The final model was 81.1% predictive of speech impairment. The presence of daytime hypercapnia was not correlated to increasing speech impairment.Conclusion: The restrictive pattern developed by ALS patients negatively influences speech function. Speech is a complex and multifactorial process, and lung volume presents a pivotal role in its function. Thus, we were able to find that lung volumes presented a significant correlation to speech function, especially in those with bulbar onset and respiratory impairment. Neurobiological and physiological aspects of this relationship should be explored in further studies with the ALS population.

Migrated maxillary implant removed via semilunar hiatus by transnasal endoscope.

Endoscopic surgery via nasal approach to remove the implant body from the semilunar hiatus is presented with the images of the computed tomography and the intraoperative endoscopic findings.

Effect of celecoxib on emotional stress and pain-related behaviors evoked by experimental tooth movement in the rat.

OBJECTIVE: To test the efficacy of an animal model of pain and stress and evaluate the effects of celecoxib administered when orthodontic force is applied. MATERIALS AND METHODS: A 20-g reciprocal force was applied via an orthodontic appliance to the maxillary left first and second molars of 7-week-old male Sprague-Dawley rats. Rat behavior was evaluated at 5, 24, and 48 hours after the appliance was set. Behavior was assessed in a test field by the number of lines crossed in the first 30 seconds and 5 minutes following force application; number of lines crossed to the center; rearing time; and facial grooming time. Experimental group 1 received intraperitoneal administration of 30 mg/kg celecoxib before every behavioral test. Experimental group 2 received 90 mg/kg before the first behavioral test, and physiologic saline was administered before the remaining behavioral tests. Control groups received saline before every behavioral test and were given passive (passive control group) and active (active control group) appliances, respectively. RESULTS: Parameters related to pain increased in the active controls, whereas the parameters in the experimental groups decreased to the level seen in the passive controls. Statistically significant differences in pain-related behavior between control and experimental groups were found at 5 and 24 hours after placing the appliance. Stress-related behavior was significantly less in the experimental groups compared to the active control group during experimental periods. CONCLUSIONS: The administration of celecoxib relieves pain- and stress-related behavior evoked by orthodontic tooth movement in the rat. This model might be a useful tool for the evaluation of pain and stress.

Characterization of oral microbiota in marmosets: Feasibility of using the marmoset as a human oral disease model.

With rapid aging of the world's population, the demand for research, for a better understanding of aging and aging-related disorders, is increasing. Ideally, such research should be conducted on human subjects. However, due to ethical considerations, animals such as rodents and monkeys are used as alternatives. Among these alternative models, non-human primates are preferred because of their similarities with humans. The small South American common marmoset (Callithrix jacchus) may offer several advantages over other non-human primates in terms of its smaller size, shorter life-span, and dental anatomy identical to humans. The purpose of this study was to determine the viability of using the marmoset as a human oral disease model. We collected saliva samples from eight marmosets and eight human subjects. Prokaryotic DNA was extracted from the saliva samples, and 16S bacterial rRNA gene sequencing was performed on each of the samples. Our results indicated that the types of oral microbiomes detected among human and marmoset samples were nearly indistinguishable. In contrast, the oral microbiomes of our human and marmoset subjects were distinctly different from those reported for rats and dogs, which are currently popular research animals. The oral microbiomes of marmosets showed greater diversity than those of humans. However, the oral microbiota of marmosets exhibited less variation than those of humans, which may be attributed to the fact that the marmoset subjects were kept in a controlled environment with identical lifestyles. The characteristics of its oral microbiota, combined with other technical advantages, suggest that the marmoset may provide the best animal model thus far for the study of oral health. This study characterized the oral microbes of the marmoset, thereby providing information to support future application of the marmoset as a model for age-related oral disease.

Disinhibitory involvement of the anterior cingulate cortex in the descending antinociceptive effect induced by electroacupuncture stimulation in rats.

The present study was conducted to clarify the role of the anterior cingulate cortex (ACCX) in acupuncture analgesia. Experiments were performed on 35 female Wistar albino rats weighing about 300 g. Single unit recordings were made from ACCX neurons with a tungsten microelectrode. Descending ACCX neurons were identified by antidromic activation from electrical shocks applied to the ventral part of the ipsilateral PAG through a concentric needle electrode. Cathodal electroacupuncture stimulation of Ho-Ku (0.1 ms in duration, 45 Hz) for 15 min was done by inserting stainless steel needles bilaterally. An anodal silver-plate electrode (30 mm x 30 mm) was placed on the center of the abdomen. Naloxone (1.0 mg/kg, i.v.) was used to test whether changes of ACCX activities were induced by the endogenous opioid system. Data were collected from a total of 73 ACCX neurons. Forty-seven neurons had descending projection to the PAG, and the other 26 had no projections to the PAG. A majority of descending ACCX neurons were inhibited by electroacupuncture stimulation. By contrast, non-projection ACCX neurons were mainly unaffected by electroacupuncture. Naloxone did not reverse acupuncture effects on the changes of ACCX neuronal activities. Acupuncture stimulation had predominantly inhibitory effects on the activities of descending ACCX neurons. Since the functional connection between ACCX and PAG is inhibitory, electroacupuncture caused disinhibition of PAG neurons, whose activity is closely related to descending antinociception to the spinal cord. This disinhibitory effect elicited by acupuncture stimulation is thought to play a significant role in acupuncture analgesia.

Emotional stress- and pain-related behaviors evoked by experimental tooth movement.

OBJECTIVE: To investigate by behavioral methods the relationship between emotional stress and pain during experimental tooth movement in rats. MATERIALS AND METHODS: Sixteen male Sprague-Dawley rats (210 to 250 g) were divided into two groups. The experimental group was treated with an active Ti-Ni appliance, and the control group received a passive appliance. A force of 20 gf was delivered by the active appliance between the maxillary first and second molars for 3 days. During this period the rat's behavior was evaluated eight times by means of open-field test and resistance-to-capture test. The specific parameters of animal activity were facial grooming, rearing, and locomotor activity, movement into the center of the open field, and response to capture. RESULTS: Parameters related to stress and pain were higher in the group carrying active appliance, compared to the group with a passive appliance. Statistically significant differences in stress-related behavior between control and experimental groups were found 8 hours after placing the appliance and were most evident on the second day. Pain-related behavior was significantly greater in the experimental group than in the control group at 24 hours. CONCLUSIONS: The increase in emotional stress evoked by orthodontic tooth movement may precede the appearance of periodontal pain.

Splenius muscle activities induced by temporomandibular joint stimulation in rats.

Recent studies show that temporomandibular joint disorders cause hyperalgesia and deficits in the postural control of cervical region. However, the effects of specific modalities of receptors in the temporomandibular joint area on these phenomena are still unclear. In this study, we investigated the neck muscle activities while natural mechanical stimulation was applied to the temporomandibular joint. Single motor unit activities were recorded bilaterally from the splenius muscles in 22 Wistar rats. Mechanical stimulation applied to the left temporomandibular joint elicited tonic discharges in the left or right splenius muscle. The mean threshold values for mechanical stimulation were 48.1 (+/-16.2 S.E.M.) and 54.1 mN (+/-16.3 S.E.M.) for left and right sides, respectively. It is suggested that the temporomandibular joint mechanoreceptors not only affect the motor unit activities of neck muscles, but also are concerned in the regulation of postural control of the head.

Periodontal masseteric reflex is changed by periodontal sensory modification during occlusal hypofunction in rats.

The purpose of this study was to investigate changes in the periodontal masseteric reflex (PMR) after experimentally induced occlusal hypofunction. Wistar rats were divided into control groups (CGs) and hypofunction groups (HGs). Rats in the HGs had their lower incisors cut down every other day for 6 weeks. Electrical stimulation was given to the periodontal ligaments of an upper incisor or the left trigeminal mesencephalic nucleus (MeV) in the CGs and HGs. Recordings of masseter motor unit responses were performed at 0, 1, 2, 4 and 6 weeks after hypofunction. Compared with the CGs, significant longer latencies in the PMR were found in the 4w- and 6w- HGs. After MeV stimulation, no significant difference in latency was found between HGs and CGs. After periodontal stimulation, the threshold value of masseteric motor-unit responses was higher in HGs than in CGs in 4and 6 weeks respectively. These results suggest that the PMR can be changed by periodontal sensory modification during occlusal hypofunction.

Functional changes of the temporomandibular joint mechanoreceptors induced by a lateral mandibular shift in rats.

OBJECTIVE: To investigate changes in functional characteristics of the temporomandibular joint (TMJ) mechanoreceptors under mandibular lateral shift. MATERIALS AND METHODS: Forty 7-week-old male Wistar rats were divided into control and experimental groups. Rats in the experimental group received a modified guiding appliance (MGA) that was designed to shift the mandible to the left side in the occlusal position. Single-unit activities of the TMJ mechanoreceptors were evoked by indirect stimulation of passive jaw movement. Electrophysiologic recordings of TMJ units were obtained 1, 3, 5, 7, and 9 weeks after MGA setting from the gasserian ganglion. RESULTS: At 1 week after mandibular shift, the firing thresholds were the lowest and the maximum instantaneous frequencies were the highest in TMJ units. At 5 weeks, the firing thresholds in the nonshifted side were significantly lower than those in the shifted side. The maximum instantaneous frequencies in the nonshifted side were significantly higher than those in the shifted side at 1, 5, and 7 weeks. CONCLUSION: These results suggest that the functional lateral shift of the mandible could alter the response properties of TMJ mechanoreceptors, particularly on the nonshifted side.

Cardiac nociceptors innervated by vagal afferents in rats.

It is reported that cardiac afferent information is transmitted through at least three different pathways to the CNS: sympathetic, parasympathetic, and somatic; however, there are few studies concerning the role of afferent fibers of vagus nerves for eliciting cardiac sensation including pain. Especially, receptive field properties innervated by single vagal nerve fiber and mechanical threshold of nociceptors on the cardiac surface are not yet quantitatively studied. Therefore, in this study, we systematically investigated characteristics of vagal units innervating cardiac nociceptors in rats. Using anesthetized and artificially ventilated rats, 37 single unit recordings were made from fine nerve filaments of the left vagal nerve. For quantitative mechanical stimulation, the cardiac surface was stimulated by a von Frey type device. In addition, bradykinin was used for checking the chemical sensitivity of the nociceptor. Electrical stimulation was used to estimate the conduction velocity of the recorded nerve fiber. All units recorded from the vagal nerve were either Adelta- or C-polymodal nociceptors. About 70% of the afferents had conduction velocities in the C-fiber range. In 60% of the units, the peripheral receptive field covered spot-like areas, but we also found larger and continuous receptive fields. Our results show that a majority of nociceptors innervated by vagal afferents are the C-polymodal type with spot-like receptive fields. We consider it to relate to the ambiguous and dull pain of angina pectoris.