Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.

Lysine Ubiquitylation Drives Rhodopsin Protein Turnover.

Rhodopsin is a G-protein-coupled receptor that is specifically and abundantly expressed in rod photoreceptors. Over 150 rhodopsin mutations cause autosomal dominant retinitis pigmentosa (adRP). The most common mutation in the United States is the conversion of proline to histidine at position 23 (P23H) in the N-terminal domain of rhodopsin. We previously found that P23H rhodopsin was misfolded, ubiquitinylated, and rapidly degraded. Here, we investigated the role of lysine residues on P23H rhodopsin ubiquitinylation and turnover. We transfected HEK293 cells with a P23H human rhodopsin construct where all 11 lysine residues were mutated to arginine (K-null P23H). We found that the K-null P23H rhodopsin was significantly less ubiquitylated than intact P23H rhodopsin. We found that K-null P23H protein turnover was significantly slower compared to P23H rhodopsin through cycloheximide chase analysis. Finally, we also generated a wild-type rhodopsin construct where all lysines were converted to arginine and found significantly reduced ubiquitylation. Our findings identify ubiquitinylation of lysine residues as an important posttranslational modification involved in P23H rhodopsin protein degradation.

Presentation and Management of Acute Mania in Fanconi-Bickel Syndrome, A Metabolic Genetic Disorder.

Fanconi-Bickel syndrome (FBS) is a rare metabolic disorder caused by decreased glucose transporter 2 (GLUT2) function due to several known mutations in the SLC2A2 gene. As of 2020, 144 cases of FBS have been described in the literature. Metabolic and somatic sequelae include dysglycemia and accumulation of glycogen in the kidney and liver. However, there are no descriptions in the literature of possible neuropsychiatric manifestations of FBS. This case report is to our knowledge the first in this regard, describing a patient with FBS who was admitted to our psychiatric inpatient unit while experiencing acute mania. We conceptualize the case as a novel psychiatric presentation of acute mania in FBS, which may inform our understanding of bipolar disorder pathophysiology because of the hypothesized functional changes in neural pathways involving the paraventricular thalamus induced by decreased GLUT2 activity in FBS.

The use of the Oral Health Impact Profile to measure the impact of mild, moderate and severe hypodontia on oral health-related quality of life in young adults.

There is limited understanding of the subjective impact of congenital absence of teeth in patients with hypodontia. This study aimed to investigate the impact of mild, moderate and severe hypodontia on oral health-related quality of life (OHRQoL) and its relationship to age, gender and extent of hypodontia prior to treatment. 82 patients (43 females and 39 males, age range from 16 to 34 years) with a confirmed diagnosis of non-syndromic hypodontia were recruited for this study prior to treatment. Demographic details were recorded and a clinical examination documented the number and location of missing teeth. Participants were also asked to complete an oral health-related quality of life measure, the OHIP-49. The impact was of hypodontia was significant, with appearance concerns being the most prevalent impacts on oral health-related quality of life. Gender was a significant predictor of the overall OHIP-49 score, with females having higher level of impacts. The number and location of missing permanent teeth was not a good predictor of quality of life. However, location of missing teeth was a predictor of the psychological discomfort subscale score. There was a positive correlation between age and the functional limitation and physical disability subscale scores. This study shows that the impact of hypodontia on oral health-related quality of life is substantial.

Prosthodontic rehabilitation of a patient using a swing-lock lower denture after segmental mandibulectomy.

A swing-lock denture is useful in partially dentate patients where the configuration of the remaining teeth means that either the retention or stability available for a conventional removable partial denture is compromised. Such removable prostheses can also prove to be extremely useful when providing prosthodontic rehabilitation following surgical resection of oral cancer. A 20 year-old patient was referred to the Restorative Department of Cork University Dental Hospital following segmental mandibulectomy to treat a calicifying epithelial odontogenic tumour (Pindborg Tumour). Initial treatment using a conventional lower partial denture failed. This paper outlines the successfully rehabilitation using a lower Cobalt-Chromium swing-lock partial denture.

Nigrostriatal dopamine modulates the striatal-amygdala pathway in auditory fear conditioning.

The auditory striatum, a sensory portion of the dorsal striatum, plays an essential role in learning and memory. In contrast to its roles and underlying mechanisms in operant conditioning, however, little is known about its contribution to classical auditory fear conditioning. Here, we reveal the function of the auditory striatum in auditory-conditioned fear memory. We find that optogenetically inhibiting auditory striatal neurons impairs fear memory formation, which is mediated through the striatal-amygdala pathway. Using calcium imaging in behaving mice, we find that auditory striatal neuronal responses to conditioned tones potentiate across memory acquisition and expression. Furthermore, nigrostriatal dopaminergic projections plays an important role in modulating conditioning-induced striatal potentiation. Together, these findings demonstrate the existence of a nigro-striatal-amygdala circuit for conditioned fear memory formation and expression.

Nigrostriatal dopamine pathway regulates auditory discrimination behavior.

The auditory striatum, the tail portion of dorsal striatum in basal ganglia, is implicated in perceptual decision-making, transforming auditory stimuli to action outcomes. Despite its known connections to diverse neurological conditions, the dopaminergic modulation of sensory striatal neuronal activity and its behavioral influences remain unknown. We demonstrated that the optogenetic inhibition of dopaminergic projections from the substantia nigra pars compacta to the auditory striatum specifically impairs mouse choice performance but not movement in an auditory frequency discrimination task. In vivo dopamine and calcium imaging in freely behaving mice revealed that this dopaminergic projection modulates striatal tone representations, and tone-evoked striatal dopamine release inversely correlated with the evidence strength of tones. Optogenetic inhibition of D1-receptor expressing neurons and pharmacological inhibition of D1 receptors in the auditory striatum dampened choice performance accuracy. Our study uncovers a phasic mechanism within the nigrostriatal system that regulates auditory decisions by modulating ongoing auditory perception.

Creating a patient-based condition-specific outcome measure for Temporomandibular Disorders (TMDs): Oral Health Impact Profile for TMDs (OHIP-TMDs).

The aim of this study was to generate a putative patient-based outcome measure specifically for Temporomandibular Disorders (TMDs) using a mixed-method approach. A combined quantitative-qualitative methodology was used to identify the most relevant items in the Oral Health Impact Profile (OHIP-49) for TMDs. The quantitative study involved 110 patients with TMDs diagnosed using the Research Diagnostic Criteria for TMDs (RDC/TMD) and 110 age- and sex-matched controls. All subjects completed the OHIP-49. The qualitative study involved semi-structured interviews with a separate sample of patients with TMDs (n = 29). The two resultant data sets were analysed blinded and separately. Each data set used predetermined rules to select candidate items for the putative OHIP for TMDs. The two sets of selected items were then compared using a priori rules to make a final item selection for OHIP TMDs. Eighteen pre-existing items were selected through the quantitative process and fourteen by the qualitative process. On comparison of the two selections all but two of the items selected by the qualitative process had also been selected by the quantitative process. Two new candidate items emerged from the qualitative data that were not covered by OHIP-49. A 22 item putative OHIP-TMDs outcome measure emerged from the final selection process. A putative OHIP-TMDs outcome measure has been generated which requires further testing especially in relation to its responsiveness to change.

Aerosol-generating dental procedures: a reappraisal of analysis methods and infection control measures.

BACKGROUND: Dental aerosol-generating procedures (AGPs) have been associated with risk for transmitting infectious agents. However, existing infection control monitoring studies potentially underestimate the extent of contamination, due to methodological inadequacies. These studies employed settle plate methodology which only captures droplets that land on agar plates, but not those suspended in air. Furthermore, bacterial culture was used to determine the extent of contamination, without accounting for non-bacterial sources of contamination. AIMS: This study sought to bridge these gaps by establishing a monitoring protocol involving active aerosol sampling and analysis of two dental AGPs, root canal treatment (RCT) and scaling. METHODS: RCT and scaling were performed with standard aerosol mitigation precautions. Aerosols generated throughout each procedure were sampled using the air sampler device, while contamination of operatory fomites and personal protective equipment was sampled using surface swabs, before and post-treatment. The amount of contamination was quantified using bacterial culture and adenosine triphosphate (ATP) assay. FINDINGS: RCT generated insignificant aerosol and splatter, supporting the infection control procedures' effectiveness. Conversely, scaling significantly increased the amount of aerosol and splatter. When comparing bacterial culture and ATP assay, the magnitude of contamination obtained with ATP assay was greater, suggesting that ATP assay may have detected additional contamination of human origin and bacteria that was not recovered by the culture conditions employed. CONCLUSIONS: This monitoring protocol is feasible in the dental setting and determines the extent of contamination generated during AGPs. This could be adopted in future studies to overcome the limitations of the existing literature.

Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease.

Dopamine (DA) is a behaviorally and clinically diverse neuromodulator that controls CNS function. DA plays major roles in many behaviors including locomotion, learning, habit formation, perception, and memory processing. Reflecting this, DA dysregulation produces a wide variety of cognitive symptoms seen in neuropsychiatric diseases such as Parkinson's, Schizophrenia, addiction, and Alzheimer's disease. Here, we review recent advances in the DA systems neuroscience field and explore the advancing hypothesis that DA's behavioral function is linked to disease deficits in a neural circuit-dependent manner. We survey different brain areas including the basal ganglia's dorsomedial/dorsolateral striatum, the ventral striatum, the auditory striatum, and the hippocampus in rodent models. Each of these regions have different reported functions and, correspondingly, DA's reflecting role in each of these regions also has support for being different. We then focus on DA dysregulation states in Parkinson's disease, addiction, and Alzheimer's Disease, emphasizing how these afflictions are linked to different DA pathways. We draw upon ideas such as selective vulnerability and region-dependent physiology. These bodies of work suggest that different channels of DA may be dysregulated in different sets of disease. While these are great advances, the fine and definitive segregation of such pathways in behavior and disease remains to be seen. Future studies will be required to define DA's necessity and contribution to the functional plasticity of different striatal regions.

A deep learning approach for monitoring parietal-dominant Alzheimer's disease in World Trade Center responders at midlife.

Little is known about the characteristics and causes of early-onset cognitive impairment. Responders to the 2001 New York World Trade Center disaster represent an ageing population that was recently shown to have an excess prevalence of cognitive impairment. Neuroimaging and molecular data demonstrate that a subgroup of affected responders may have a unique form of parietal-dominant Alzheimer's Disease. Recent neuropsychological testing and artificial intelligence approaches have emerged as methods that can be used to identify and monitor subtypes of cognitive impairment. We utilized data from World Trade Center responders participating in a health monitoring program and applied a deep learning approach to evaluate neuropsychological and neuroimaging data to generate a cortical atrophy risk score. We examined risk factors associated with the prevalence and incidence of high risk for brain atrophy in responders who are now at midlife. Training was conducted in a randomly selected two-thirds sample (N = 99) enrolled using of the results of a structural neuroimaging study. Testing accuracy was estimated for each training cycle in the remaining third subsample. After training was completed, the scoring methodology that was generated was applied to longitudinal data from 1441 World Trade Center responders. The artificial neural network provided accurate classifications of these responders in both the testing (Area Under the Receiver Operating Curve, 0.91) and validation samples (Area Under the Receiver Operating Curve, 0.87). At baseline and follow-up, responders identified as having a high risk of atrophy (n = 378) showed poorer cognitive functioning, most notably in domains that included memory, throughput, and variability as compared to their counterparts at low risk for atrophy (n = 1063). Factors associated with atrophy risk included older age [adjusted hazard ratio, 1.045 (95% confidence interval = 1.027-1.065)], increased duration of exposure at the WTC site [adjusted hazard ratio, 2.815 (1.781-4.449)], and a higher prevalence of post-traumatic stress disorder [aHR, 2.072 (1.408-3.050)]. High atrophy risk was associated with an increased risk of all-cause mortality [adjusted risk ratio, 3.19 (1.13-9.00)]. In sum, the high atrophy risk group displayed higher levels of previously identified risk factors and characteristics of cognitive impairment, including advanced age, symptoms of post-traumatic stress disorder, and prolonged duration of exposure to particulate matter. Thus, this study suggests that a high risk of brain atrophy may be accurately monitored using cognitive data.

Genetic targeting of astrocytes to combat neurodegenerative disease.

Astrocytes, glial cells that interact extensively with neurons and other support cells throughout the central nervous system, have recently come under the spotlight for their potential contribution to, or potential regenerative role in a host of neurodegenerative disorders. It is becoming increasingly clear that astrocytes, in concert with microglial cells, activate intrinsic immunological pathways in the setting of neurodegenerative injury, although the direct and indirect consequences of such activation are still largely unknown. We review the current literature on the astrocyte's role in several neurodegenerative diseases, as well as highlighting recent advances in genetic manipulation of astrocytes that may prove critical to modulating their response to neurological injury, potentially combatting neurodegenerative damage.

How long should a shortened dental arch be?

UNLABELLED: Increasing numbers of older adults are retaining teeth into old age. Many of these patients refuse to wear removable partial dentures, and have a high prevalence of dental disease and heavily restored teeth. The shortened dental arch (SDA) concept is a potentially cost-effective way of managing older, partially dentate adults. However, case selection is critical and long term preservation of a functional dentition may not be possible in certain patients. This paper highlights the critical treatment planning issues and outlines treatment strategies aimed at avoiding occlusal instability in patients with shortened dental arches. CLINICAL RELEVANCE: Appropriate application of the shortened dental arch concept will provide satisfactory oral function in the long term for partially dentate adults.

An RCT of atraumatic restorative treatment for older adults: 5 year results.

OBJECTIVES: to compare the survival of ART and a conventional restorative technique (CT) for restoring carious lesions in older adults after 5 years. METHODS: In this parallel randomised controlled clinical trial, 219 independently-living adults were recruited from a dental hospital/community and a geriatric day hospital. Ninety-nine patients who met the inclusion criteria and presented with carious lesions were randomly allocated to receive either ART or conventional restorations (anaesthesia, rotary instruments and resin-modified glass ionomer). The status of restorations was assessed 6 months, 1, 2 and 5 years after restoration placement. Estimates of cumulative survival were calculated for each interval between assessments and a Cox Proportional Hazards (PH) model was fitted to the interval-censored survival time. RESULTS: Three hundred restorations (ART n=142; CT n=158) were placed on 99 patients, 46 males and 53 females, with a mean age of 73.2, SD: 6.8 (65-90 yrs). After 5 years, ART and CT presented cumulative probability of survival of 85% and 79% (p=0.8095), respectively. CONCLUSIONS: ART presents survival rates comparable to a conventional technique, when treating older adults after 5 years. The ART approach could be a useful tool to provide dental care for older adults particularly in the nonclinical setting. (Trial Registration number: ISRCTN 76299321). CLINICAL RELEVANCE: This study shows that ART presents survival rates comparable to conventional techniques to treat carious lesions in older patients after 5 years. It is well accepted by this age cohort, and therefore could be an alternative to treat the elderly, especially those who are homebound or cannot attend the dentist.

Perceived chewing ability and intake of fruit and vegetables.

Edentulous individuals have reduced chewing ability and lower fruit and vegetable consumption compared with dentate individuals. It has been suggested that the two are causally related. However, psychosocial factors such as attitude, self-identity, and knowledge of recommendations are predictive of intake in non-edentulous persons. The aims of this study were to: determine if perceived chewing ability was predictive of fruit and vegetable intake; explore the predictive ability of knowledge, attitude, and self-identity; and compare intake between edentulous and dentate individuals. Full denture-wearing (N = 79) and dentate persons (N = 52) completed a three-day food diary. Perceived chewing ability, sociodemographic, and psychosocial factors were assessed via self-administered questionnaire. The dentate persons consumed significantly more fruit and vegetables, but differences were not significant when juices were excluded. Perceived chewing ability explained approximately 4% variance in intake. Attitude, self-identity, and knowledge explained a further approximately 20%. If the diet of denture-wearers is to be improved, psychosocial factors, as well as perceived chewing ability, must be addressed.

A randomized-controlled trial of food choices made by edentulous adults.

AIM: The aim of this study was to conduct a randomized-controlled trial to compare food choices of edentulous adults provided with implant-supported mandibular overdentures and conventional dentures. METHODS: Edentulous patients were randomly allocated to an implant group (IG) or a denture group (DG). IG subjects (n=49) were provided with conventional maxillary dentures and implant-retained mandibular overdentures. Subjects in this group refusing implants were retained using the 'intention-to-treat principle' and provided with conventional dentures. DG subjects (n=48) were provided with conventional dentures. Subjects indicated whether they consumed any of seven test foods and the level of chewing difficulty experienced. Data were collected pre-treatment and 3 months post treatment. RESULTS: IG subjects reported increased consumption of carrots, apples and nuts post-treatment (P<0.05) and decreased post-treatment difficulty in chewing apples and nuts. DG subjects reported decreased post-treatment difficulty in chewing carrots, bacon and nuts (P<0.05). Between group differences for chewing difficulty were detected for nuts that DG subjects found easier to chew than IG subjects (P=0.002). CONCLUSION: Food selection and perceived chewing difficulty improved in both groups, with no significant differences between groups. Successful rehabilitation may not result in different food selection, which may require concurrent tailored dietary interventions, but may increase available food choices.

Attitudes, awareness and oral health-related quality of life in patients with diabetes.

The purpose of this study was to assess the knowledge diabetic patients have of their risk for periodontal disease, their attitude towards oral health and their oral health-related quality of life (OHRQL). One hundred and one consecutive patients (age range 31-79 years) recruited from a diabetic outpatient clinic participated in the study. Twenty-seven per cent of participants had type 1 diabetes, 66% type 2 and 7% did not know what type of diabetes they had. The length of time since participants were diagnosed as diabetic ranged from 1 to 48 years. Metabolic control of diabetes as determined by HbA1c levels ranged from 6.2% to 12.0% compared with the normal range of 4.5-6.0%. Thirty-three per cent of participants were aware of their increased risk for periodontal disease, 84% of their increased risk for heart disease, 98% for eye disease, 99% for circulatory problems and 94% for kidney disease. Half of the participants who were aware of their increased risk for periodontal disease had received this information from a dentist. Dental attendance was sporadic, with 43% reporting attendance within the last year. OHRQL was not significantly affected by the presence of diabetes in the group surveyed, in comparison with a previous survey of non-diabetic patients. A significant association was found between metabolic control and dentate status. Awareness of the potential associations between diabetes, oral health and general health needs to be increased in diabetic patients.

Evaluation of the Cariogram for root caries prediction.

OBJECTIVES: The aim of this study was to evaluate complete and reduced Cariogram models in predicting root caries risk in independently living older adults by comparing the caries risk assessment of the programme to observed root caries increment over a two-year period. METHODS: A prospective study recording root caries incidence was conducted on 334 dentate older adults. Data were collected on participant's medical history, fluoride exposure, and diet. Saliva samples were collected to measure salivary flow rate, buffer capacity and bacterial counts. Clinical examination was completed to record decayed, missing and filled teeth (DMFT) and also exposed, filled and decayed root surfaces (RDFS). This was repeated after 12 and 24 months. Scores were entered into the Cariogram and baseline risk category was recorded. Reduced Cariogram models were generated by omitting individual salivary variables and all salivary variables. The performance of the complete and reduced Cariogram models in predicting root caries incidence were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: 280 participants were examined at two year follow up. 55.6% of those in the highest risk group developed new caries compared to 3.8% in the lowest risk group. The mean root caries increment in the highest risk group was 2.00 (SD 3.20) compared to 0.04 (SD 0.20) in the lowest risk group. The area under the ROC curve for the complete Cariogram model was 0.77 (95% CI 0.70-0.83) indicating a fair performance in predicting root caries. Omitting individual or all salivary variables did not significantly alter the predictive ability of the Cariogram. CONCLUSION: Within the limitations of this study, the Cariogram was clinically useful in identifying individuals with a high risk of developing root caries. CLINICAL SIGNIFICANCE: Identification of a caries risk assessment tool which could reliably select high-risk individuals for root caries prevention strategies would maximise the cost effectiveness of professionally delivered prevention measures.

A randomized controlled trial of implant-retained mandibular overdentures.

Evidence from randomized clinical trials of implant-retained overdentures is very limited at the present time. The aim of this study was to compare implant-retained mandibular overdentures and conventional complete dentures in a randomized controlled trial (RCT). Our a priori hypothesis was that implant-retained mandibular overdentures would be significantly better than conventional complete dentures. Edentulous patients (n = 118) were randomly allocated to either an Implant Group (n = 62) or a Denture Group (n = 56). Patients completed the Oral Health Impact Profile (OHIP) and a denture satisfaction scale pre-treatment and three months post-treatment. Upon completion of treatment, both groups reported improvement (p < 0.001, Wilcoxon Ranks Sum test) in oral-health-related quality of life and denture satisfaction. There were no significant post-treatment differences between the groups, but a treatment effect may be masked by application of "intention to treat" analysis. The OHIP change scores were significantly greater for patients receiving implants than for those who refused them.