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.

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.

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.

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.

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.

Cineradiographic analysis of mouse postural response to alteration of gravity and jerk (gravity deceleration rate).

The ability to maintain the body relative to the external environment is important for adaptation to altered gravity. However, the physiological limits for adaptation or the disruption of body orientation are not known. In this study, we analyzed postural changes in mice upon exposure to various low gravities. Male C57BL6/J mice (n = 6) were exposed to various gravity-deceleration conditions by customized parabolic flight-maneuvers targeting the partial-gravity levels of 0.60, 0.30, 0.15 and µ g (<0.001 g). Video recordings of postural responses were analyzed frame-by-frame by high-definition cineradiography and with exact instantaneous values of gravity and jerk. As a result, the coordinated extension of the neck, spine and hindlimbs was observed during the initial phase of gravity deceleration. Joint angles widened to 120%-200% of the reference g level, and the magnitude of the thoracic-curvature stretching was correlated with gravity and jerk, i.e., the gravity deceleration rate. A certain range of jerk facilitated mouse skeletal stretching efficiently, and a jerk of -0.3~-0.4 j (g/s) induced the maximum extension of the thoracic-curvature. The postural response of animals to low gravity may undergo differential regulation by gravity and jerk.

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.

Comparison of stress-induced modulation of smooth-muscle activity between ileum and colon in male rats.

Stress is a well-known cause of numerous digestive conditions, including gastrointestinal-function disorders. The autonomic nervous system regulates intestinal movements via cholinergic and adrenergic efferent fibers; however it is not clear how stress could affect these control mechanisms and in particular whether in a site-dependent manner. In this study we tested in vitro the effects of topical application of acetylcholine (Ach) and adrenalin (Adr) on smooth-muscle contractions of intestinal segments isolated from stress-conditioned rats. Stress was loaded by hypergravity stimulation (10min/day) for periods of 1, 6 or 30days. As a result, stress-conditioning affected intestinal sensitivity to Ach and Adr differently at sections of the ileum and colon. In the ileum no significant differences were found between control and stress-conditioned rats, whereas in the colon, samples from 6- and 30-day stress-conditioned rats showed larger amplitudes of Ach-induced contraction, as well as greater antagonization by Adr application. These results suggest that stress conditioning can modify autonomic control of intestinal movements by altering smooth-muscle sensitivity to Ach and Adr.

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.

Influence of malocclusion on the development of masticatory function and mandibular growth.

OBJECTIVE: To verify the hypothesis that appropriate acquisition of masticatory function and normal growth of the mandible are modified by malocclusion. MATERIALS AND METHODS: Eighteen Jcl:ICR mice were divided into two groups. In one group we shifted the mandible laterally using an occlusal guidance appliance, creating a posterior crossbite at 5 weeks of age. The other group served as control. After 10 weeks, three-dimensional jaw movements and muscle activities were recorded simultaneously during mastication. Microcomputed tomography scans were obtained in vivo to evaluate morphometric changes in the mandible. RESULTS: (1) The jaw movement pattern in the sagittal plane showed significantly less anteroposterior excursion in the malocclusion group during the late-closing phase (power phase). (2) Electromyography showed significantly less masseter activity in the malocclusion group. (3) The condylar width and mandibular bone mineral density (BMD) were significantly reduced in the malocclusion mice compared to the normal mice. CONCLUSIONS: These findings suggest that optimization of the chewing pattern and acquisition of appropriate masticatory function is impeded by malocclusion. Altered mechanical loading to the mandible may cause significant reduction of condylar width and mandibular BMD.

Behavioral responses to partial-gravity conditions in rats.

The effects of microgravity or hypergravity on living organisms have been studied extensively; however, thus far no studies have addressed the effects of "partial-gravity", that is, the low-gravity levels between the unit gravity (1G) on Earth and zero gravity (0 G) in space. The purpose of the present study was to examine behavioral responses in rats under partial-gravity conditions. Rat behavior was monitored by video cameras during parabolic flights. The flight trajectory was customized in order to generate graded levels of partial gravity. Gravity-dependent behavior patterns were observed in rats. In the conditions of 0.4 G through 0.2G, rats showed startle and crouching. Hindlimb stretching emerged at 0.15 G and was more frequently observed toward 0.01 G. Different thresholds may exist for emotional and balance/posture-related behaviors.

Padrões de movimentos mastigatórios na respiração oral e nasal / Patterns of masticatory movements in nasal and oral breathing

Objetivo: comportamento alimentar requer aperfeiçoamentoquanto à coordenação entre a mastigação, a respiração e adeglutição. No entanto, os detalhes desta interação não são totalmentecompreendidos. Neste estudo, analisaram-se os movimentos damastigação na presença e na ausência de respiração nasal normal.Método: cinco voluntários saudáveis participaram deste estudo. Movimentosda cabeça e da mandíbula foram registrados em três eixospor um sistema de captura de movimento, o Qualisys Motion CaptureSystem (Quaüsys AB, Suécia), em quatro condições experimentais:quando os participantes comiam goma (alimento mole/pegajoso)e castanha-de-caju (alimento duro), com e sem obstrução nasal. Astrajetórias dos referidos movimentos, bem como as suas velocidades,foram então analisadas com um software de computação de alto níveltécnico. Resultado: a partir da análise dos dados constatou-se queos movimentos mastigatórios foram afetados pela consistência dosalimentos (mole e duro) e o modo de respiração (nasal e bucal). Comparadocom o alimento mole, o alimento duro foi associado com maiorsequência mastigatória e com maior número de ciclos mastigatórios.Comparado com a respiração nasal, movimentos mastigatórios emrespiração bucal, mostraram uma sequência mastigatória mais curtae irregular e maior extensão dos movimentos de cabeça. A obstruçãonasal causou maiores mudanças na mastigação de alimentos duros doque na mastigação dos alimentos moles. Conclusão: estes resultadossugerem que mecanismos de retroalimentação sensoriais envolvidosno controle dos movimentos da mastigação podem ser moduladospelo modo da respiração.

Objective: feeding behavior requires tine-tuned coordinationbetween mastication, breathing, and swallowing. However, detailsof this interaction are not fully understood. In this study, we analyzedmasticatory movements in the presence or absence of normal nasalbreathing. Method: tive normal, healthy volunteers participated in thisstudy. Head and jaw movements were recorded in 3 axes bya motioncapturing system (Qualisys, SwedenJ in four experimental conditions:when the subjects ate either a soit gummy (soft/sticky foodJ or a cashewnut (hardjbriffle iood), with and without nasal obstruction. Trajectoriesof those movements, as well as their velocities, were then analyzedwith a high-Ievel technical computing software. Result: fram the dataanalysis it was found that masticatory movements were affected byfood consistency (soft vs. hardJ and mode of breathing (nasal vs. ora/).Compared with sott food, hard food was associated with longer chewingsequences and greater number of chewing cycles. Compared with nasalbreathing, masticatory movements in oral breathing showed shorter andirregular chewing sequences, and greater extent of head movements.Nasal obstruction caused greater changes in the chewing of hard foodthan sott food. Conclusion: these results suggest that sensory feedbackmechanisms involved in the contrai of masticatory movements may bemodulated by the mode of breathing.

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.

Response properties of nucleus reticularis lateralis neurons after electroacupuncture stimulation in rats.

A descending inhibitory mechanism from the periaqueductal gray (PAG) to the spinal cord through the nucleus raphe magnus (NRM) is strongly involved in endogenous analgesic system produced by acupuncture stimulation. In addition to the PAG to NRM system which descends in the medial pathway of the brain stem, the nucleus reticularis lateralis (NRL) situated in the lateral part of the brain stem is reported to play an important role in modulating centrifugal antinociceptive action. In the present study, to clarify the role of NRL in acupuncture analgesia, we investigated the response properties of NRL neurons to acupuncture stimulation. The majority of NRM-projecting NRL neurons were inhibited by electroacupuncture stimulation. This effect was antagonized by ionophoretic application of naloxone, indicating that endogenous opioids act directly onto these NRL neurons. By contrast, about half of spinal projecting NRL neurons were excited by electroacupuncture stimulation, suggesting that part of the NRL neurons may modulate pain transmission directly at the spinal level.

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.