A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy.

Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP ( https://www.ncbi.nlm.nih.gov/snp/ ), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein-protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene-miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein-Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, L-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein-Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information.

General low alertness in people with obstructive sleep apnea.

STUDY OBJECTIVES: In patients with obstructive sleep apnea (OSA), a previous study using a Go/No-Go task reported an average attention deficit. However, the temporal dynamics of such a deficit are unknown. Here, we investigated whether attention deficits in different subdomains increased as the test progressed. We also investigated the effect of target frequency and speed of stimulus presentation on performance. METHODS: Twenty-seven untreated people with OSA and 27 age- and sex-matched controls underwent a 15-minute Go/No-Go task, divided into 6 blocks. Each block was subdivided into 3 different interstimulus intervals (1, 2, and 4 seconds). Three blocks had a low and three had a high target probability (20% and 80%, respectively). Reaction time (alertness), variability of reaction time (sustained attention), commission errors (response inhibition), and omission errors (focused attention) were measured. RESULTS: Alertness was lower in the group with OSA compared with controls, as evidenced by a significantly higher average reaction time. This effect was seen from the start of the task and continued until the end but did not increase in test progression. The temporal pattern of intrinsic alertness deficits in patients with OSA was found to be independent of target frequency or interstimulus interval. CONCLUSIONS: The primary attention problem in OSA is on the alertness subdomain irrespective of the number of required responses or speed of stimulus presentation. The present results support the notion that OSA is distinct from other neurological and psychiatric conditions, such as depression or chronic pain. The results also suggest significant concerns regarding daily life activities (eg, driving). CITATION: de Souza Bezerra ML, van Duinkerken E, Simões E, Schmidt SL. General low alertness in people with obstructive sleep apnea. J Clin Sleep Med. 2024;20(5):689-698.

Cognitive Performance in Asymptomatic Elderly People with Hepatitis C: The Role of Education.

BACKGROUND: Neurotropism of the hepatitis C virus (HCV) can be the source of subtle neuropsychological symptoms in non-cirrhotic patients. Age is a risk factor for cognitive impairment (CI). Thus, asymptomatic elderly people who carry HCV might be at a greater risk of CI. Education can influence test performance. OBJECTIVES: (1) To verify whether elderly people with HCV performed poorer than controls on cognitive tests. (2) To analyze how education affects performance. (3) To verify whether the extent of the effect of education on performance depends on the group (HCV vs. controls) and the type of cognitive test. METHODS: Asymptomatic HCV carriers older than 60 years (n = 41) were matched with 41 corresponding controls. All participants performed the following tests: Mini-Cog, Mini Mental State Examination, clock drawing test (CDT), and verbal fluency. RESULTS: (1) There were no significant differences in cognitive performance between the two groups. (2) Higher education was always associated with better performance. (3) There was a significant group difference in the slopes of the regression lines between years of education and CDT performance. No differences were found for the other three tests. CONCLUSION: Considering the scores on the CDT, the rate of improvement in performance when schooling increases is higher in HCV carriers.

Association between attention performance and the different dimensions of DSM-5 depression symptoms.

Objective: Depressive symptoms can be assessed with self-reported questionnaires, such as the Patient Health Questionary-9 (PHQ-9). Previous studies have suggested that the PHQ-9 items can be grouped into somatic and non-somatic clusters. However, the classification of the PHQ-9 item "concentration difficulties" into somatic or non-somatic is still controversial. This controversy may be explained by difficulties experienced by subjects in accurately evaluating their attention problems. The primary objective of this study was to determine the correlation between objective attentional performance and the two clusters of depressive symptoms in hospital employees working in stressful conditions. Methods: The participants filled out the PHQ-9 to identify their depressive symptoms. Based on the PHQ-9, the somatic or non-somatic symptoms were measured without considering the question about subjective concentration difficulties. Then, a brief version of the Continuous Visual Attention Test (CVAT) was applied to assess four attentional subdomains. The CVAT is a Go/No-go task that measures number of correct responses (focused attention), number of incorrect responses (behavior-inhibition), average reaction time of correct responses (RT-alertness), and variability of reaction time (VRT-sustained attention). The entire task lasted 90 s. Correlation analyses assessed the relationships between attentional performance and the two dimensions of depressive symptoms. Results: After applying the inclusion/exclusion criteria, 359 individuals were selected. Their age ranged from 20 to 70 years (mean = 40.5, SD = 10.37), and the majority was female (67.6%). A predominance in somatic depressive symptoms was present in 231 (64%) participants, whereas 59 (16%) showed a predominance of non-somatic symptoms. Sixty-nine participants (20%) did not show any predominance. Higher somatic scores were associated with higher RTs, whereas higher non-somatic scores were related to an increase in the number of incorrect responses. Conclusion: The predominance of the somatic cluster was related to lower alertness, whereas the predominance of non-somatic cluster was associated with impulsivity/hyperactivity. This result may explain the difficulties associated with correctly classifying the item concentration difficulties. A brief attentional task can be used as an auxiliary tool to correctly identify the different dimensions of attention that are associated with different clusters of depressive symptoms.

Spirituality as a protective factor for chronic and acute anxiety in Brazilian healthcare workers during the COVID-19 outbreak.

BACKGROUND: Anxiety symptoms (AS) are exacerbated in healthcare workers (HCWs) during the COVID-19 pandemic. Spirituality is known to protect against AS in the general population and it is a construct that differs from religion. It can be assessed using structured questionnaires. A validated questionnaire disclosed three spirituality dimensions: peace, meaning, and faith. In HCWs we investigated the predictors of chronic anxiety (pre-COVID-19 and during the pandemic) and acute anxiety (only during the pandemic), including spirituality in the model. Then, we verified which spirituality dimensions predicted chronic and acute anxiety. Lastly, we studied group differences between the mean scores of these spirituality dimensions. MATERIAL AND METHODS: The study was carried out in a Brazilian Hospital. HCWs (n = 118) were assessed for spirituality at a single time-point. They were also asked about AS that had started pre-COVID-19 and persisted during the pandemic (chronic anxiety), and AS that had started only during the pandemic (acute anxiety). The subjects without chronic anxiety were subdivided into two other groups: acute anxiety and without chronic and acute anxiety. Forward stepwise logistic regressions were used to find the significant AS predictors. First, the model considered sex, age, religious affiliation, and spirituality. Then, the analysis were performed considering only the three spirituality dimensions. Group means differences in the spirituality dimensions were compared using univariate ANCOVAS followed by T-tests. RESULTS: Spirituality was the most realible predictor of chronic (OR = 0.818; 95%CI:0.752-0.890; p<0.001) and acute anxiety (OR = 0.727; 95%CI:0.601-0.881; p = 0.001). Peace alone predicted chronic anxiety (OR = 0.619; 95%CI:0.516-0.744; p<0.001) while for acute anxiety both peace (OR:0.517; 95%CI:0.340-0.787; p = 0.002), and faith (OR:0.674; 95%CI:0.509-0.892; p = 0.006) significantly contributed to the model. Faith was significantly higher in subjects without AS. CONCLUSION: Higher spirituality protected against chronic and acute anxiety. Faith and peace spirituality dimensions conferred protection against acute anxiety during the pandemic.

Post-COVID-19 olfactory dysfunction: carbamazepine as a treatment option in a series of cases.

Olfactory dysfunction is reported frequently in patients with coronavirus disease 2019. However, an effective treatment for this dysfunction is unknown. The present study evaluated carbamazepine as a treatment option for olfactory dysfunction based on its use in cases of neuralgia, especially of the V cranial nerve. The study included 10 patients with coronavirus disease with olfactory complaints who were part of a cohort of 172 coronavirus disease patients monitored for late neurological manifestations. Carbamazepine was administered for 11 weeks. The adverse effects reported were drowsiness (9/10) and dizziness (2/10); 9 of the 10 patients reported improved olfactory function after carbamazepine treatment. While the role of carbamazepine in the control of post-coronavirus disease olfactory dysfunction could not be confirmed in this study, the satisfactory response observed in most patients in this series suggests that further studies are warranted.

Attention profile of physically recovered COVID-19 inpatients on the day of discharge.

Few studies have reported specific attention deficits in post-COVID-19 patients. Attention consists of different subdomains. Disruptions to specific attention subdomains might impair a wide range of everyday tasks, including road safety. As there are millions of COVID-19 patients with different socio-economic backgrounds, screening of attentional performance less dependent on education is needed. Here, we verified if physically recovered COVID-19 inpatients showed specific attention decrements at discharge. The Continuous Visual Attention Test (CVAT) is a Go/No-go task which is independent of participants' schooling. It detects visuomotor reaction time (RT = intrinsic alertness), variability of reaction time (VRT = sustained attention), omission (focused-attention), and commission errors (response-inhibition). Thirty physically functional COVID-19 inpatients at discharge and 30 non-infected controls underwent the CVAT. A MANCOVA was performed to examine differences between controls and patients, followed by post-hoc ANCOVAs. Then, we identified the percentile score for each patient within the distribution of the CVAT performance of 211 subjects mentally capable of driving (reference group). COVID-19 patients at discharge showed greater RT and VRT, and more omission errors than controls. Twenty-two patients (73%) had performance below the 5th percentile of the reference group in one or more subdomains. As slow visuomotor RT, deficits in focusing and difficulties in keeping visual attention are associated with traffic accidents, we concluded that most COVID-19 patients at discharge had deficits that may increase the risk of road injuries. As these deficits will probably affect other daily activities, a routine assessment with the CVAT could provide useful information on whom to send to post-COVID centers.

Is Asian type MS an MS phenotype, an NMO spectrum disorder, or a MOG-IgG related disease?

BACKGROUND: A specific particularity of neurological diseases in Asia is the relative commonality of neuromyelitis optica (NMO) and Asian type MS (OSMS). Both conditions also occur in South American patients. The Brazilian population differs from the European and the Asian populations due to the mixture of ancestralities between European colonizers and African slaves. To better know the clinical characteristics of Brazilian patients with Asian type MS this study aimed to analyze the clinical, radiological and serological data that would help to distinguish between OSMS and NMO and clarify, in a Non-Asian population, if OSMS is an MS phenotype, an NMO spectrum disorder by 2015 classification, or a complement activating antibody to myelin oligodendrocyte glycoprotein (MOG-IgG) antibody-related disease. METHODS: We selected cases retrospectively with NMO and OSMS in the medical registry of patients with idiopathic inflammatory demyelinating diseases under follow-up since 1997 in Federal Hospital da Lagoa, the principal reference center for MS treatment in Rio de Janeiro, Brazil. OSMS has selective involvement of the optic nerve and spinal cord with no cerebral or cerebellar symptoms associated with small spinal cord lesions and negativity for the aquaporin-4 antibody (AQP4-IgG). NMO full-filled the revised criteria (2006) associated with longitudinally extensive transverse myelitis (LETM). We recorded the following data: ethnicity/skin color, neurologic impairment "at nadir" and "at recovery" of the index events (optic neuritis and transverse myelitis), long term disability, mortality, health quality of life scores by the SF-36 questionnaire, CSF IgG oligoclonal bands and serological AQP4-IgG and MOG-IgG antibodies tested by Cell-based assay. The last brain MRIs were classified as either satisfying or not satisfying MAGNIMS radiologic criteria for MS or typical or not typical for NMOSD. The new classification of NMO spectrum disorders (2015) was applied. RESULTS: Forty-one OSMS and 122 NMO cases were analyzed. OSMS affected mainly young white women, causing unilateral optic neuritis and partial myelitis with excellent recovery. After a mean disease duration of 20 years, 90% of the patients had free ambulation, and 70% had a mild disability or no disability. Only 7.2% presented a secondary progressive course, and no deaths occurred. All cases had negativity to AQP4-IgG and MOG-IgG biomarkers. 95% had resonance criteria for MS. OSMS differed from NMO by ethnicity, morbidity, and mortality: most were African descendants, with severe motor and visual dysfunction, and one third died. Only NMO cases full-filled the new NMOSD classification (52 AQP4-IgG positive, 29 AQP4-IgG negative, and 41 AQP4-IgG unknown). CONCLUSION: In Brazilian patients, OSMS and NMO are different immune-mediated diseases. OSMS is a milder MS phenotype.

Association Between Auditory and Visual Continuous Performance Tests in Students With ADHD.

OBJECTIVE: Continuous Performance Tests (CPTs) are known to measure inattention and impulsivity in students with ADHD. Many CPTs utilize a visual format. It is accepted that auditory tasks reflect attentional demand more closely in the classroom. Thus, the association between deficits found by auditory and visual CPTs needs to be studied. We hypothesized that impulsivity would be dependent on sensory modality and inattention would be a unitary cross-modal construct. METHOD: Forty-four students with ADHD performed two CPTs (visual and auditory). We analyzed correlations between the variables examined by the two tasks. RESULTS: There were strong correlations between variables measuring inattention. Correlations between auditory and visual measures of impulsivity were weak. CONCLUSION: Inattention is partially independent of modality. In contrast, response inhibition is modality-specific. Although ADHD is defined regardless of modality, hyperactive students may exhibit deficits in the auditory modality but not in the visual modality or vice versa.

Validity and reliability of a teacher's scale developed in Brazil for assessment of hyperactive: impulsive behavior and inattention in children and adolescents / Validade e confiabilidade de uma escala para professores desenvolvida no Brasil para avaliação de comportamento hiperativo: impulsivo e desatenção em crianças e adolescentes

This study was designed to develop and assess the internal consistency and factor structure of a teacher's scale for the assessment of hyperactive/impulsive and inattentive behavior in a sample of 221 children from different cities in the State of Rio de Janeiro, Brazil. Forty-five teachers rated the children. The internal consistency of the scale was evaluated using Cronbach's alpha. An orthogonal varimax rotation that maximizes the variance of the squared loadings for each factor was used to find the simplest possible factor structure. There is no internal discrepancy in the item content of the scale. Exploratory factor analysis showed four primary factors (hyperactivity/impulsivity; inattention; social isolation; self-confidence) that are psychologically meaningful. When factor analysis was carried out there was no substantial difference from other studies when compared with the results of other western and oriental countries. It was concluded that this teacher's scale can be a useful aid to clinicians in the identification of children with hyperactivity/impulsivity and inattention problems.

Este estudo foi elaborado para avaliar a consistência interna e a estrutura fatorial de uma escala para professores, destinada à avaliação de comportamento hiperativo/impulsivo e desatenção em uma amostra de 221 crianças de diferentes cidades do Estado do Rio de Janeiro. Quarenta e cinco professores avaliaram as crianças. A consistência interna da escala foi avaliada usando o coeficiente alfa de Cronbach. Uma rotação Varimax (ortogonal), que maximiza a variância ao quadrado das cargas para cada fator, foi usada para encontrar a estrutura fatorial mais simples. Não houve discrepâncias no conteúdo dos itens da escala. A análise fatorial exploratória indicou quatro fatores primários (hiperatividade/impulsividade; desatenção; isolamento social; autoconfiança) com significado psicológico. Os resultados obtidos neste estudo não diferem daqueles realizados em outros países ocidentais e orientais. Conclui-se que esta escala para professores pode auxiliar na identificação de crianças com queixas de hiperatividade/impulsividade e desatenção.

Acurácia do mini exame do estado mental no diagnóstico de portadores de transtorno cognitivo leve / Accuracy of the mini mental state examination in the diagnosis of individuals with mild cognitive impairment

Vários fatores da sociedade moderna têm contribuído para o aumento da população de idosos no mundo. Um dos primeiros transtornos que acometem essa população é o transtorno cognitivo leve (TCL). O objetivo desse estudo foi verificar a acurácia diagnóstica do teste mini exame do estado mental (MEEM) em portadores de TCL. A amostra do estudo foi composta por idosos com mais de 65 anos, divididos em dois grupos, o grupo controle (N = 23) e o grupo TCL (N = 38). Todos os indivíduos foram submetidos ao teste MEEM e os resultados obtidos foram analisados através do pacote estatístico SPSS 14.0 e fixado grau de significância em p < 0,05. Os resultados mostraram escores inferiores dos indivíduos TCL em relação aos indivíduos do grupo controle no teste MEEM e que o único parâmetro deste instrumento capaz de predizer o TCL foi o referente à memória de evocação. Conclui-se que para essa amostra o instrumento MEEM foi eficaz no rastreio dos indivíduos portadores de TCL e que o parâmetro que melhor prediz o TCL nesse teste é a memória de evocação. Apesar deste fato, recomenda-se que não se deve aplicar o teste isoladamente.

Many factors of modern society have contributed to the growing population of elderly people in the world. One of the primary disorders that affect this population is mild cognitive impairment (MCI). The aim of this study was to assess the diagnostic accuracy of the Mini Mental State Examination (MMSE) in patients with MCI. The sample was composed of elderly over 65 years, divided into two groups, control group (N = 23) and MCI group (N = 38). All subjects underwent MMSE test and results were analyzed using the statistical package SPSS 14.0 and level of significance set at p < 0.05. The results showed that the MCI subjects showed lower results in the MMSE test than individuals of the control group and that the only parameter of the MMSE test capable of predicting the MCI was the parameter memory recall. It is concluded that for this sample the MMSE instrument was effective in screening of individuals with MCI and that the parameter that best predicts the TCL in this test is the evocation of memory. However, the test should not be applied alone.

Low level methylmercury exposure affects neuropsychological function in adults.

BACKGROUND: The neurotoxic effects of methylmercury (MeHg) have been demonstrated in both human and animal studies. Both adult and fetal brains are susceptible to the effects of MeHg toxicity. However, the specific effects of adult exposures have been less well-documented than those of children with prenatal exposures. This is largely because few studies of MeHg exposures in adults have used sensitive neurological endpoints. The present study reports on the results of neuropsychological testing and hair mercury concentrations in adults (>17 yrs) living in fishing communities of Baixada Cuiabana (Mato Grosso) in the Pantanal region of Brazil. METHODS: A cross-sectional study was conducted in six villages on the Cuiaba River. Participants included 129 men and women older than 17 years of age. They were randomly selected in proportion to the age range and number of inhabitants in each village. Questionnaire information was collected on demographic variables, including education, occupation, and residence history. Mercury exposure was determined by analysis of hair using flameless atomic absorption spectrophotometry. The neurocognitive screening battery included tests from the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale, Concentrated Attention Test of the Toulouse-Pierron Factorial Battery, the Manual Ability Subtests of the Tests of Mechanical Ability, and the Profile of Mood States. RESULTS: Mercury exposures in this population were associated with fish consumption. The hair mercury concentration in the 129 subjects ranged from 0.56 to 13.6 microg/g; the mean concentration was 4.2 +/- 2.4 micrograms/g and the median was 3.7 microg/g. Hair mercury levels were associated with detectable alterations in performance on tests of fine motor speed and dexterity, and concentration. Some aspects of verbal learning and memory were also disrupted by mercury exposure. The magnitude of the effects increased with hair mercury concentration, consistent with a dose-dependent effect. CONCLUSIONS: This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures.

Testosterone and free thyroxin blood in congenitally acallosal male BALB/cCF mice.

OBJECTIVES: Approximately 20% of BALB/cCF mice are born with partial or total absence of the corpus callosum. Here, we analyzed testosterone and free thyroxin blood levels in adult male mice of this strain in order to see if these hormones are related to the incidence of callosal defects. METHODS: Blood collected from the axillary blood vessels of 12 normal and 10 acallosal deeply anesthetized adult male mice was used in order to determine testosterone and free thyroxin levels through chemiluminescence (IMMULITE, Diagnostics Products Corporation, USA). RESULTS: No significant difference (one-way ANOVA: F = 0.11, df = 1, p > 0.10) was found between normal ((-)X= 1.95, SD = 0.62) and acallosal ((-)X= 1.86, SD = 0.62) mice for free thyroxin level. On the other hand, in those mice that had detectable testosterone levels (above 0.2 ng/ml), a significant difference was found (t = 2.8, df = 6.06, p = 0.03): normal mice (n = 7, (-)X= 8.73, SD = 7.64) had a higher level than acallosal mice (n = 4, (-)X= 0.62, SD = 0.41). CONCLUSIONS: The present results indicate that the incidence of callosal agenesis is not related to free thyroxin levels in the blood of adult BALB/cCF mice. On the other hand, in spite of the fact that low testosterone levels seems to be frequent in male mice of this strain, acallosal mice tend to have lower levels of this hormone than normal mice.