Comorbid Relationship Research Articles

Psychiatric predictors of quality of life in Parkinson's disease: A three-year longitudinal study

IntroductionParkinson's disease (PD) is associated with worsened quality of life (QOL) over time. Few longitudinal studies exist investigating the relationship of psychiatric comorbidities with QOL in people with PD (PwP). We sought to determine specific psychiatric symptoms associated with decreasing QOL in PwP over time. MethodsWe recruited PwP without dementia from a movement disorders clinic at an academic medical center. Participants were evaluated annually with motor and neuropsychological assessments at each visit. QOL was measured using the Parkinson's Disease Questionnaire-39 (PDQ-39). We assessed psychiatric symptoms, including depression (Beck Depression Inventory II, BDI-II), anxiety (Beck Anxiety Index, BAI), and apathy (Apathy Scale). Psychosis and impulse control disorders (ICDs) were recorded as present or absent. Using random coefficient regression, we analyzed psychiatric features associated with worsened QOL in PwP over three years. ResultsFrom the 105 participants enrolled at baseline, 67 completed three years of follow up. Mean PDQ-39 scores increased from 16.0 at baseline to 19.8 at year three. In multivariate analysis, higher BDI-II scores, BAI scores, and apathy scores were uniquely associated with worsened QOL over time (p < 0.001 for all measures), while presence of ICDs (p = 0.18) or psychosis (p = 0.10) were not. Changes in the BAI score and the BDI-II score exerted similar effects on the overall PDQ-39 score. ConclusionDepression, anxiety, and apathy are all associated with worsening quality of life over time in PwP, while presence of ICDs and psychosis are not. Treatment of these symptoms may lead to improved QOL in PwP.

Psychiatric, Neurological, and Somatic Comorbidities in Intermittent Explosive Disorder: a retrospective cohort study of electronic health records.

Intermittent Explosive Disorder (IED) is an understudied psychiatric condition that presents with repeated episodes of impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities will allow for enhanced screening, diagnosis, and treatment of patients. To investigate prevalence and associations of IED with psychiatric, neurological, and somatic disorders using real-world data. Matched cohorts of patients with or without IED diagnosis were identified using data from the TriNetX Research Network (until January 31, 2024). Cox proportional hazard models were used to estimate and compare the probabilities of acquiring other diagnoses using patients' available medical records. Analysis of electronic medical records from two patient populations. 30,357 individuals with IED and equal number of demographically matched individuals without IED from the TriNetX Research. IED diagnosis identified through the associated ICD codes. The main outcomes were ICD-10-CM diagnostic categories and root codes for disorders and health conditions in both cohorts. Main measures are total numbers and proportions of patients who had the diagnostic codes, as well as adjusted hazard ratios for IED diagnosis. Although only 0.03% of the total patient population had an IED diagnosis, we found extensive and widespread comorbidities with psychiatric, neurological and somatic conditions. A significant 95.7% of the individuals with IED had another psychiatric diagnosis. All psychiatric sub-categories and 95% of the psychiatric diagnoses were significantly associated with IED, with HRs ranging from 2 to 77. Among neurological conditions, neurodegenerative diseases and epilepsy had the highest HRs, followed by extrapyramidal and movement disorders, cerebral palsy and other paralytic syndromes, and sleep disorders. Notable associations with IED also includes conditions such as obesity, hyperlipidemia, hypertension, and GERD. Our findings illuminate the extensive comorbid relationships between IED and psychiatric, neurological, and somatic disorders. This underscores the necessity for an integrated diagnostic and treatment approach that addresses both the psychological and physical health aspects of IED. Additionally, our work highlights the need for more accurate and inclusive diagnosis of IED in patients with mental disorders.

The Relationship Between Pre-Pandemic Comorbidities With SARS-CoV-2 Infections and Hospitalizations in Black Versus White Military Service Members: A Retrospective Study.

Comorbidities such as hypertension, diabetes mellitus, asthma, and cardiovascular conditions have been reported to worsen the clinical progression of coronavirus disease 2019 (COVID-19) and related hospitalizations. Furthermore, the COVID-19 pandemic has disproportionately affected the historically marginalized groups, i.e., Black, Hispanic, and Asian individuals have substantially higher rates of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, COVID-19 hospitalization, and death compared to White individuals. Despite these findings in civilian populations, the impact of comorbidities and race in SARS-CoV-2 infection and COVID-19 hospitalizations in military populations is unknown. We evaluated the relationship of pre-selected pre-pandemic comorbidities and race with SARS-CoV-2 infections and COVID-19 hospitalizations in U.S. military service members (SMs). We conducted a systematic review of Military Health System beneficiaries' records by accessing the Defense Medical Epidemiological Database. Our inclusion criteria were being an active duty SM and having at least one pre-COVID-19 pandemic comorbidity. Retired as well as uninfected healthy active duty SMs and beneficiaries were excluded from the study. A total population of 1.334 million active duty SM records was drawn from Defense Medical Epidemiological Database. The data were stratified, by race (primary outcome), as well as gender, age, and military service branches (secondary outcomes). We found higher trends in SARS-CoV-2 infection and COVID-19 hospitalization rates in Black compared to White SMs. This seamless inequality was also seen in other viral infections affecting SMs including human immunodeficiency virus and viral hepatitis. We hypothesized this disparity to some extent be associated with the presence of pre-pandemic comorbidities that is affecting this military subpopulation. Supporting our hypothesis, we found trends toward the higher pre-pandemic prevalence of diabetes mellitus, asthma, hypertension, and ischemic heart disease, in Black compared to White military SMs, especially in Black older male adults. Our results highlight the role of pre-pandemic comorbidities and race likely enhancing the frequency of SARS-CoV-2 infections and COVID-19 hospitalizations in military SMs. These preliminary findings underscore the need for future retrospective studies using additional Military Health System data bases reporting data on this military subpopulation, especially in the setting of future pathogens outbreaks or pandemics affecting military populations.

Investigating Genetic Overlap between Alzheimer's Disease, Lipids, and Coronary Artery Disease: A Large-Scale Genome-Wide Cross Trait Analysis.

There is evidence to support a link between abnormal lipid metabolism and Alzheimer's disease (AD) risk. Similarly, observational studies suggest a comorbid relationship between AD and coronary artery disease (CAD). However, the intricate biological mechanisms of AD are poorly understood, and its relationship with lipids and CAD traits remains unresolved. Conflicting evidence further underscores the ongoing investigation into this research area. Here, we systematically assess the cross-trait genetic overlap of AD with 13 representative lipids (from eight classes) and seven CAD traits, leveraging robust analytical methods, well-powered large-scale genetic data, and rigorous replication testing. Our main analysis demonstrates a significant positive global genetic correlation of AD with triglycerides and all seven CAD traits assessed-angina pectoris, cardiac dysrhythmias, coronary arteriosclerosis, ischemic heart disease, myocardial infarction, non-specific chest pain, and coronary artery disease. Gene-level analyses largely reinforce these findings and highlight the genetic overlap between AD and three additional lipids: high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and total cholesterol. Moreover, we identify genome-wide significant genes (Fisher's combined p value [FCPgene] < 2.60 × 10-6) shared across AD, several lipids, and CAD traits, including WDR12, BAG6, HLA-DRA, PHB, ZNF652, APOE, APOC4, PVRL2, and TOMM40. Mendelian randomisation analysis found no evidence of a significant causal relationship between AD, lipids, and CAD traits. However, local genetic correlation analysis identifies several local pleiotropic hotspots contributing to the relationship of AD with lipids and CAD traits across chromosomes 6, 8, 17, and 19. Completing a three-way analysis, we confirm a strong genetic correlation between lipids and CAD traits-HDL and sphingomyelin demonstrate negative correlations, while LDL, triglycerides, and total cholesterol show positive correlations. These findings support genetic overlap between AD, specific lipids, and CAD traits, implicating shared but non-causal genetic susceptibility. The identified shared genes and pleiotropic hotspots are valuable targets for further investigation into AD and, potentially, its comorbidity with CAD traits.

Antidepressant effect of carvedilol on streptozotocin-induced diabetic peripheral neuropathy mice by altering gut microbiota

RationaleAlthough diabetic peripheral neuropathic pain (DPNP) and depression have been recognized for many years, their co-morbidity relationship and effective treatment choices remain uncertain. ObjectivesTo evaluate the antidepressant effect of carvedilol on streptozotocin-induced DPNP mice, and the relationship with gut microbiota. MethodsThe hyperalgesia and depressive behaviors of mice with comorbidity of DPNP and depression were confirmed by pain threshold of the mechanical sensitivity test (MST), immobility time of the tail suspension test (TST) and the forced swimming test (FST). The anti-depressive effect and fecal gut microbiota composition were studied in DPNP mice treated with carvedilol (10 mg/kg/day), and the relationships between them were analyzed by Spearman's correlation. ResultsDepression was successfully induced in DPNP mice. Carvedilol can reverse the decreased mechanical pain threshold and relieve the depressive behaviors of DPNP mice, while increasing the abundance of Prevotella, Ruminococcus, Helicobacter and Desulfovibrio, and decreasing the abundance of Akkermansia and Allobaculum. ConclusionsCarvedilol can alleviate the mechanical hyperalgesia and alter gut microbiota to ameliorate the depression-like behaviors which induced by DPNP.

VALIDATION OF THE DIABETES SCREENING QUESTIONNAIRE USE ON THE INITIAL APPOINTMENT DAY, AFTER 6 AND 12 MONTHS

Background. Psoriasis is an immune-mediated inflammatory disease affecting the skin, characterized by keratinocyte hyperproliferation and T-lymphocyte inflammation, with a worldwide prevalence of 2–4% [1]. Proinflammatory molecules released during chronic inflammation can lead to one or more comorbidities such as atherosclerosis, insulin resistance, hypertension, obesity, dyslipidemia, metabolic syndrome, and type 2 diabetes mellitus [2–4]. Given the close comorbid relationship between psoriasis and type 2 diabetes mellitus, we recommend screening patients using a previously developed diabetes screening questionnaire. Purpose. To determine the results of validation of the diabetes screening test from October 2021 to October 2022 and to conduct a single-center cohort retrospective continuous study of 100 people with psoriasis. Materials and Methods. Data collection, its subsequent correction, systematization of initial information and visualization of the results obtained were carried out in Microsoft Office Excel (2016) spreadsheets. Statistical processing of the results was carried out using the Python language (Python 3.8.). For calculations, built-in functions from the Statsmodels.api and Scipy modules were used. Quantitative indicators were assessed for compliance with normal distribution, using the Shapiro-Wilk test. Results. A test for normal distribution showed that the data in the study were not normally distributed. Therefore, further calculations were made using nonparametric statistics methods. The median was calculated as the center of distribution, and quartiles were calculated as indicators of variation (Me [Q1; Q3]). Mann-Whitney U test was used to compare unrelated samples. Conclusion. The validation stage showed that the use of screening questionnaires developed by the authors is a simple and low- cost method that is effective in identifying the pathology of type 2 diabetes, which makes it possible to recommend them for testing psoriasis patients at annual medical examinations.

Associations between stroke risk factors and left atrial low-voltage areas in patients with atrial fibrillation undergoing catheter ablation from the REAL-AF registry

Abstract Background Prior research indicates that increased left atrial low-voltage areas (LA LVA) are linked to comorbidities and CHA2DS2-VASc score in patients with persistent atrial fibrillation (PerAF) undergoing catheter ablation. However, given the heterogeneity of AF where patients may transition between paroxysmal AF (PAF) and PerAF types, it is biologically plausible that these associations span all forms of AF. Purpose To investigate the relationship of stroke demographics and comorbidities to LA LVA and AF type in a multicenter registry of patients undergoing catheter ablation. Methods The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic PAF and PerAF Using Novel Contact Force Technologies registry (REAL-AF) is a prospective, observational multicenter registry of patients undergoing catheter ablation. We evaluated 6053 patients undergoing first-time catheter ablation for both PAF and PerAF to identify associations between stroke risk factors and LA LVA. LA LVA was determined in contact maps as bipolar voltage &amp;lt;0.50 mV. Mapping was completed using 5-spline high-density catheters before ablation. LA LVA was categorized into low (&amp;lt;5%) vs. high (≥5%) based on preliminary data. Analyses were conducted using independent samples t-test and Chi-square test. Results LA LVA was associated with greater CHA2DS2-VASc score (3.2 vs. 2.5, p &amp;lt;0.001). Age 75+ (Odds ratio (OR): 2.22, p&amp;lt;0.001), congestive heart failure (CHF) (OR: 2.01, p&amp;lt;0.001), female sex (OR): 1.51, p&amp;lt;0.001), vascular disease (OR: 1.50, p&amp;lt;0.001), age 65-74 (OR: 1.20, p=0.001), hypertension (OR: 1.38, p&amp;lt;0.001), history of stroke (OR: 1.29, p=0.004) and diabetes (OR: 1.25, p=0.001) were also associated with LA LVA (Table 1). These associations remained significant among a subgroup of those presenting in normal sinus rhythm (N = 3546). Patients with CHF (OR: 2.09, p&amp;lt;0.001), hypertension (OR: 1.89, p&amp;lt;0.001) and male sex (OR: 0.60, p&amp;lt;0.001) were more likely to have PerAF in the LVA ≥5% subgroup (n=1594) (Table 2). All other components of the CHA2DS2-VASc score were not significantly associated with AF type in this subgroup. While there was a significant association between AF type and CHA2DS2-VASc score (PAF: 3.15, PerAF: 3.42, p&amp;lt;0.001) in the LA LVA ≥5% subgroup, the effect size was small (Cohen’s d = -0.179). Conclusion LA LVA ≥5% was associated with all separate components and overall CHA2DS2-VASc score. In patients with LA LVA ≥5%, there were only associations between PerAF and CHF, hypertension, and male sex, implying a special role in substrate progression. Our findings suggest that LA LVA may represent a more sensitive clinical phenotyping tool of AF rather than current duration-based ones. This is the largest study to our knowledge in elucidating the relationship between increased LA LVA and stroke risk factors in the AF population.

Epidemiology of DSM-5 psychiatric disorders in Kenyan youth with low and high psychosis risk

IntroductionThere are few psychiatric epidemiology studies among Kenyan youth and fewer among those at high psychosis risk (HR). MethodsThis study assessed the epidemiology of DSM-5 psychiatric disorders in HR and low-risk (LR) individuals to inform research and mental health services. 567 participants (aged 15–25) in HR (n = 246) and LR (n = 260) groups based on Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen scores. Diagnostic Interview Schedule, version 5 (DIS-5) assessed DSM-5 psychiatric disorder prevalence. Diagnostic comorbidity and demographic relationships were investigated. ResultsA higher prevalence was observed for all DSM-5 disorders in the HR group, significantly for gambling disorder (13% vs. 5.8%), major depressive disorder (9.8% vs. 3.8%), antisocial personality disorder (5.7% vs. 2.3%), general anxiety disorder (4.9% vs. 0.4%), oppositional defiant disorder (3.3% vs. 0.4%), panic disorder (2.8% vs. 0.8%), and anorexia nervosa (2.8% vs. 0%). Gambling disorder was the most prevalent and showed significant gender effects (males>females). DiscussionPsychiatric disorders occur at increased rates among HR compared to LR. Prevalence rates found are lower than in US studies, except for gambling disorder which was highly prevalent. Large-population-based epidemiology studies in Africa are needed to estimate rates, particularly of disorders such as schizophrenia, accurately.

Pretreatment relationship characteristics predict outcomes from an uncontrolled trial of intensive, multicouple group PTSD treatment.

Cognitive behavioral conjoint therapy for posttraumatic stress disorder (CBCT for PTSD; Monson & Fredman, 2012) is associated with improvements in patients' and partners' mental health and relationship satisfaction. Some pretreatment relationship characteristics have predicted CBCT for PTSD outcomes for patients, but findings were limited to a single community sample consisting primarily of female patients with male partners. A better understanding of whether pretreatment relationship characteristics predict outcomes in other patient populations and whether there are partners who may be particularly responsive to couple therapy for PTSD could optimize treatment matching. This study investigated whether pretreatment partner accommodation and relationship satisfaction predicted patient and partner treatment outcomes from an uncontrolled trial of an abbreviated, intensive, multicouple group version of CBCT for PTSD conducted with 24 active-duty military or veteran couples (96% male patients/female partners). In general, changes in patients' PTSD and comorbid symptoms and relationship satisfaction did not vary by pretreatment partner accommodation or patients' own pretreatment relationship satisfaction. In contrast, pretreatment relationship characteristics predicted partner outcomes. Partners who engaged in higher levels of accommodation pretreatment and partners who reported lower levels of pretreatment relationship satisfaction experienced greater declines in psychological distress following treatment. Also, partners who began the study relationally distressed exhibited significant increases in relationship satisfaction following treatment, whereas those who were not relationally distressed did not. Findings suggest that improvements generally do not vary by pretreatment relationship characteristics for patients, whereas partners who begin treatment with elevated relationship risk factors may be especially likely to experience improvement across outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prevalence and temporal relationship of clinical co-morbidities in idiopathic dystonia: a UK linkage-based study

While motor and psychiatric phenotypes in idiopathic dystonia are increasingly well understood, a few studies have examined the rate, type, and temporal pattern of other clinical co-morbidities in dystonia. Here, we determine the rates of clinical diagnoses across 13 broad systems-based diagnostic groups, comparing an overall idiopathic dystonia cohort, and sub-cohorts of cervical dystonia, blepharospasm, and dystonic tremor, to a matched-control cohort. Using the SAIL databank, we undertook a longitudinal population-based cohort study (January 1st 1994–December 31st 2017) using anonymised electronic healthcare records for individuals living in Wales (UK), identifying those diagnosed with dystonia through use of a previously validated algorithm. Clinical co-morbid diagnoses were identified from primary health care records, with a 10% prevalence threshold required for onward analysis. Using this approach, 54,166 dystonia cases were identified together with 216,574 matched controls. Within this cohort, ten of the main ICD-10 diagnostic codes exceeded the 10% prevalence threshold over the 20-year period (infection, neurological, respiratory, gastrointestinal, genitourinary, dermatological, musculoskeletal, circulatory, neoplastic, and endocrinological). In the overall dystonia cohort, musculoskeletal (aOR: 1.89, aHR: 1.74), respiratory (aOR: 1.84; aHR: 1.65), and gastrointestinal (aOR: 1.72; aHR: 1.6) disorders had the strongest associations both pre- and post-dystonia diagnosis. However, variation in the rate of association of individual clinical co-morbidities was observed across the cervical, blepharospasm, and tremor dystonia groups. This study suggests an increased rate of specific co-morbid clinical disorders both pre- and post-dystonia diagnosis which should be considered during clinical assessment of those with dystonia to enable optimum symptomatic management.

Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry.

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

The effect of simultaneous administration of occipital nerve block and cervical myofascial trigger point injection (MTrPI) on headache parameters in chronic migraine patients.

Peripheral myofascial mechanisms have been identified as contributors to migraine pathophysiology. The specific comorbid relationship between migraine and cervical trigger points may exacerbate the occurrence and severity of migraine attacks. Trigger point injections (TPIs) are frequently employed to address headaches and alleviate migraine symptoms. The current study explores the impact of concurrent myofascial trigger point injection (MTrPI) and occipital nerve block (greater occipital nerve block [GONB] + lesser occipital nerve block [LONB]) on the severity of headaches and the number of migraine attacks in individuals with chronic migraine (CM) and cervical myofascial trigger points (MTrPs), with a comparison of occipital nerve block alone (GONB + LONB). During trigger point examination and injection, trapezius, levator scapulae, splenius capitis, temporalis, and sternocleidomastoid muscles were targeted. We planned the treatment based on whether they were in the muscle groups we determined, rather than the number of trigger points. This study enrolled 62 individuals experiencing CM with bilateral headache and cervical MTrP who sought care at the Algology Unit within the Departments of Neurology and Physical Therapy and Rehabilitation at Siirt Training and Research Hospital between 2020 and 2022. The CM cohort was stratified into two groups: group 1 received trigger point injections (TrPI), while group 2 underwent concurrent bilateral occipital nerve block (GONB + LONB) and TrPI. Both groups underwent three treatment sessions with bupivacaine 0.5% (1ml = 5mg) in weeks 1, 2, and 4. Visual analog scale (VAS) was used to measure the patients' pain intensity. The evaluation included the assessment of the monthly migraine frequency and visual analog scale (VAS) p score for pain before treatment (BT) and after treatment (AT), conducted at baseline and during follow-up visits. Analysis of the data was conducted utilizing IBM SPSS Statistics for Windows version 28.0 software. Among patients diagnosed with CM and MTrPs, 32 individuals (51.6%) underwent GONB and LONB, while 30 patients (48.4%) received simultaneous GONB, LONB, and cervical MTrPI. Within the entire sample, 51 participants (82.3%) were female, and 11 (17.7%) were male, with a mean age of 32.81 ± 10.75years. With an average age of 32.81 ± 10.75years, there was no statistically significant variance between the two groups (p = 0.516). Of the total cohort, 45 individuals (72.6%) reported experiencing headaches persisting for 12months or longer. Among CM patients, 80% had active trigger points, while 20% had latent trigger points. No statistically significant difference was observed between the groups concerning TrPs (p = 0.158), and the distribution of TrPs was homogenous across the two groups. In group 1, the median (min-max) monthly frequency of migraines reduced from 18.5days (range: 15.0 to 25.0days) before treatment to 12.0days (range: 7.0 to 17.0days) after treatment (p = 0.000). In group 2, the median monthly frequency of migraines reduced from 16.5days (range: 15.0 to 22.0days) before treatment to 4.0days (range: 2.0 to 8.0days) after treatment (p = 0.000). The median (min-max) VAS score in group 1 was 8.0 (range: 5.0 to 9.0) before treatment, 4.0 (range: 2.0 to 6.0) at week 1, and 5.0 (range: 4.0 to 8.0) at week 4 (p = 0.000). In group 2, the median VAS score was 7.0 (range: 5.0 to 9.0) before treatment, 0.0 (range: 0.0 to 0.3) at week 1, and 2.0 (range: 0.0 to 0.3) at week 4 (p = 0.000). There were significant distinctions between the groups in terms of both the monthly count of migraine days and the severity of headaches (p = 0.000). The combination of repeated MTrPIs and ONB proves more effective than ONB alone in managing patients with CM and cervical MTrP. In patients with CM, performing TrPs examination and adding treatments for this may contribute to the treatment. In cases where patients endure prolonged episodes of headache associated with chronic migraine, the inclusion of trigger point injections alongside peripheral nerve blocks may offer enhanced therapeutic benefits.

Dorsal hippocampal astrocytes mediate the development of heroin withdrawal-enhanced fear learning

There is a significant co-occurrence of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms linking chronic opioid use, withdrawal, and the development of PTSD are poorly understood. Our previous research has shown that proinflammatory cytokines, expressed primarily by astrocytes in the dorsal hippocampus (DH), play a role in the development of heroin withdrawal-enhanced fear learning (HW-EFL), an animal model of PTSD-OUD comorbidity. Given the role of astrocytes in memory, fear learning, and opioid use, our experiments aimed to investigate their involvement in HW-EFL. Experiment 1 examined the effect of withdrawal from chronic heroin administration on GFAP surface area and volume, and identified increased surface area and volume of GFAP immunoreactivity in the dentate gyrus (DG) following 24-hour heroin withdrawal. Experiment 2 examined astrocyte morphology and synaptic interactions at the 24-hour withdrawal timepoint using an astroglial membrane-bound GFP (AAV5-GfaABC1D-lck-GFP). Although we did not detect significant changes in surface area and volume of GfaABC1D-Lck-GFP labelled astrocytes, we did observe a significant increase in the colocalization of astrocyte membranes with PSD-95 (postsynaptic density protein 95) in the DG. Experiment 3 tested if stimulating astroglial Gi signaling in the DH alters HW-EFL, and our results demonstrate this manipulation attenuates HW-EFL. Collectively, these findings contribute to our current understanding of the effects of heroin withdrawal on astrocytes and support the involvement of astrocytes in the comorbid relationship between opioid use and anxiety disorders.

Shared genetic architecture between hypothyroidism and rheumatoid arthritis: A large-scale cross-trait analysis

BackgroundIn recent years, mounting evidence has indicated a co-morbid relationship between hypothyroidism and rheumatoid arthritis (RA), however, the shared genetic factors underlying this association remain unclear. This study aims to investigate the common genetic architecture between hypothyroidism and RA. MethodsGenome-wide association study (GWAS) summary statistics from recently published studies were utilized to examine the genetic correlation, shared genetic loci, and potential causal relationship between hypothyroidism and RA. Statistical methods included linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), cross-trait meta-analyses, colocalization analysis, multi-marker analysis of genomic annotation (MAGMA), tissue-specific enrichment analysis (TSEA), functional enrichment analysis, and latent causal variable method (LCV). ResultsOur study demonstrated a significant genetic correlation between hypothyroidism and RA(LDSC:rg=0.3803,p=7.23e-11;HDL:rg=0.3849,p=1.02e-21). Through cross-trait meta-analysis, we identified 1035 loci, including 43 novel genetic loci. By integrating colocalization analysis and the MAGMA algorithm, we found a substantial number of genes, such as PTPN22, TYK2, and CTLA-4, shared between the two diseases, which showed significant enrichment across 14 tissues. These genes were primarily associated with the regulation of alpha-beta T cell proliferation, positive regulation of T cell activation, positive regulation of leukocyte cell-cell adhesion, T cell receptor signaling pathway, and JAK-STAT signaling pathway. However, our study did not reveal a significant causal association between the two diseases using the LCV approach. ConclusionBased on these findings, there is a significant genetic correlation between hypothyroidism and RA, suggesting a shared genetic basis for these conditions.

Alterations of amygdala volume and functional connectivity in migraine patients comorbid with and without depression.

The comorbid relationship between migraine and depression has been well recognized, but its underlying pathophysiology is unclear. Here, we aimed to explore the structural changes of the amygdala and the abnormal functional connectivity of the centromedial amygdala (CMA) in migraineurs with depression. High-resolution T1-weighted and functional magnetic resonance images were acquired from 22 episodic migraineurs with comorbid depression (EMwD), 21 episodic migraineurs without depression (EM), and 17 healthy controls (HC). Voxel-based morphometry and resting-state functional connectivity (rsFC) were applied to examine the intergroup differences in amygdala volume. The bilateral amygdala volume was increased in the EMwD and EM groups compared with the HC group, but there were no differences between the EMwD and EM groups. The right CMA exhibited decreased rsFC in the left dorsolateral prefrontal cortex (DLPFC) in the EMwD group compared with the EM group, while rsFC increased between the CMA and the contralateral DLPFC in the EM group compared with the HC group. In addition, the EM group showed decreased rsFC between the left CMA and the left pallidum compared with the HC group. Enlarged amygdala is an imaging feature of EM and EMwD. The inconsistency of rsFC between CMA and DLPFC between migraineurs with and without depression might indicate that decreased rsFC between CMA and DLPFC is a neuropathologic marker for the comorbidity of migraine and depression. The core regions might be a potential intervention target for the treatment of EMwD in the future.

Relationship between periodontal disease and obstructive sleep apnea in adults: A systematic review

The purpose of this systematic review was to evaluate whether there are scientific evidence regarding the association between periodontitis and obstructive sleep apnea (OSA) in adults. An electronic search was performed on MEDLINE/PubMed for prospective and retrospective longitudinal studies, cohort studies, and case–control studies conducted in human adults affected by both OSA and periodontitis. Two reviewers extracted the data using a custom Excel spreadsheet. A methodological assessment of the quality of the studies was performed using the Newcastle–Ottawa Scale. Fourteen studies were included. All studies evaluated the association between periodontitis and OSA. None of the studies evaluated the cause–effect relationship. Eleven studies found a significant positive relationship between periodontitis and OSA, whereas three found no statistically significant association. Several study limitations were observed, such as lack of standardization of study groups, diagnosis of periodontitis and OSA, and differences in study design. Evidence of a plausible association between periodontitis and OSA was found. The possible relationship could be explained by systemic inflammation, oral breathing, and the comorbid relationship attributable to common risk factors. Observational and randomized controlled studies are needed to clarify the mechanism of interaction between the two conditions.

Exploring the Relationship of Comorbidities, Smoking Status, HRCT Findings With COVID-19 Disease Severity and Outcomes.

Coronavirus disease 2019 (COVID-19) is a serious illness that can affect multiple organs including the lungs. The COVID-mortality risk is attributed to the quick transmission of the virus, the severity of disease, and preclinical risk factors, such as the presence of comorbidities. High-resolution computed tomography (HRCT) can predict disease severity in COVID-19 patients. This was a retrospective cohort study in which data were obtained from COVID centers at tertiary care hospitals in Azad Jammu and Kashmir. Details of clinical characteristics and HRCT findings along with details of smoking and comorbid history were obtained. Fever at hospital admission, HRCT findings, and having a partner predicted disease severity showed a significant p-value of <0.05. Old age and living in a combined household were associated with severe outcomes (p<0.05). Symptoms of shortness of breath (SOB) on hospital admission could predict the need for ICU admission in COVID-19 patients. HRCT has a good predictive value for disease severity in patients with COVID-19, and old age is a risk factor. Although, limited associations were established in the analysis, in this study hyperlipidemia and hypertension significantly affected the course of disease. Further studies should be done to explore the relationship.

Relationships of Psychiatric Comorbidities with the Risk of Hospitalization for Motor Vehicle Crash Injury in Young‐Onset Dementia: A Nationwide Population‐Based Study in Taiwan

AbstractBackgroundAlthough the association between young‐onset dementia and hospitalization for motor vehicle crash injury (MVCI) has been shown, little is known about the relationship between the risk of MVCI and psychiatric comorbidities in young‐onset dementia. This study investigates the which psychiatric comorbidities in young‐onset dementia increases the risk of MVCI.MethodIn this retrospective population‐based cohort study, we identified 39,344 dementia aged 40‐64 years from the Taiwan National Health Insurance Research Database (NHIRD) entries between 2006 and 2012. MVCI‐related hospitalization was determined using linked data from the Police‐reported Traffic Accident Registry and the NHIRD between 2006 and 2015. We performed the Cox regression model to estimate the association of the risk of hospitalization for MVCI with young‐onset dementia comorbid with specific psychiatric disorders, including anxiety disorders, depressive disorders, bipolar disorders, alcohol‐related disorders, other substance‐related disorders, and insomnia.ResultOf the 39,344 participants included in the study, all participants encountered 1,013 hospitalizations for MVCI in the 222,239.8 person‐years observed, representing incidence densities of hospitalization for MVCI of 45.58 (95% CI 42.77‐48.39) per 10,000 person‐years. The incidence densities of hospitalization for MVCI increased when young‐onset dementia comorbid with anxiety disorders (56.17 per 10,000 person‐years), depressive disorders (58.61 per 10,000 person‐years), bipolar disorders (83.55 per 10,000 person‐years), alcohol‐related disorders (85.64 per 10,000 person‐years), other substance‐related disorders (84.79 per 10,000 person‐years), and insomnia (59.80 per 10,000 person‐years). However, the risk of hospitalization for MVCI was only significantly increased when young‐onset dementia comorbid with bipolar disorders (HR, 1.60; 95% CI: 1.21‐2.13), alcohol‐related disorders (HR, 1.55; 95% CI: 1.27‐1.90) and insomnia (HR, 1.26; 95% CI: 1.07‐1.47).ConclusionYounger adults with dementia comorbid with specific psychiatric disorders rise the risk of hospitalization for MVCI, which suggests the reinforcement transport safety in those population is needed.

Network based approach to identify interactions between Type 2 diabetes and cancer comorbidities

High blood sugar and insulin insensitivity causes the lifelong chronic metabolic disease called Type 2 diabetes (T2D) which has a higher chance of developing different malignancies. T2D with comorbidities like Cancers can make normal medications for those disorders more difficult. There may be a significant correlation between comorbidities and have an impact on one another's health. These associations may be due to a number of direct and indirect mechanisms. Such molecular mechanisms that underpin T2D and cancer are yet unknown. However, the large volumes of data available on these diseases allowed us to use analytical tools for uncovering their interrelated pathways. Here, we tried to present a system for investigating potential comorbidity relationships between T2D and Cancer disease by looking at the molecular processes involved, analyzing a huge number of freely accessible transcriptomic datasets of various disorders using bioinformatics. Using semantic similarity and gene set enrichment analysis, we created an informatics pipeline that evaluates and integrates Gene Ontology (GO), expression of genes, and biological process data. We discovered genes that are common in T2D and Cancer along with molecular pathways and GOs. We compared the top 200 Differentially Expressed Genes (DEGs) from each selected T2D and cancer dataset and found the most significant common genes. Among all the common genes 13 genes were found most frequent. We also found 4 common GO terms: GO:0000003, GO:0000122, GO:0000165, and GO:0000278 among all the common GO terms between T2d and different cancers. Using these genes and GO term semantic similarity, we calculated the distance between these two diseases. The semantic similarity results of our study showed a higher association of Liver Cancer (LiC), Breast Cancer (BreC), Colorectal Cancer (CC), and Bladder Cancer (BlaC) with T2D. Furthermore we found KIF4A, NUSAP1, CENPF, CCNB1, TOP2A, CCNB2, RRM2, HMMR, NDC80, NCAPG, and IGFBP5 common hub proteins among different cancers correlated to T2D. AGE-RAGE signaling pathway in diabetic complications, Osteoclast differentiation, TNF signaling pathway, IL-17 signaling pathway, p53 signaling pathway, MAPK signaling pathway, Human T-cell leukemia virus 1 infection, and Non-alcoholic fatty liver disease are the 8 most significant pathways found among 18 common pathways between T2D and selected cancers. As a result of our technique, we now know more about disease pathways that are critical between T2D and cancer.

Relationship of comorbidity and platelet function in patients with unstable angina

Background. Platelets play a key role in the pathogenesis of acute coronary syndrome (ACS). In recent years, the amount of data on the advisability of using the platelet function test (PFT) in the appointment of antithrombotic therapy has been growing.Objective. To access PFT in patients with unstable angina and various comorbidities.Design and methods. The study involved 74 patients with the diagnosis of unstable angina. All patients underwent standard clinical examination, PFT (impedance aggregometry with ADP and collagen), assessment of Charlson comorbidity index.Results. The most frequent comorbidities were: hypertension (95 %), type 2 diabetes mellitus (30 %), excessive body weight (35 %), multifocal atherosclerosis (22 %), smoking (24 %). Half of the patients (n = 36) had high level of comorbidity. Patients with a comorbidity index of 5 or more had high platelet aggregation on the 3rd day of hospitalization. Elderly patients, smokers, as well as patients with diabetes mellitus type 2 and multifocal atherosclerosis also had higher values of platelet activity, which may be associated with unfavorable prognosis and risk of recurrent events.Conclusion. We revealed association between PFT and comorbidities both with risk factors or diseases alone and in its integral assessment using the Charlson comorbidity index. Among the individual risk factors, smoking, diabetes mellitus and multifocal atherosclerosis were the most important, which confirms their direct role in the pathogenesis of thrombotic complications.