Functional Impairment Research Articles

Advances in genetic research on Non-syndromic congenital joint synostosis

Congenital joint synostosis (CJS) is a functional impairment resulting from failure in joint morphogenesis during embryonic development. Clinically, it may be classified as syndromic (sCJS) and non-syndromic (nsCJS) disorders. Common sCJS include chromosomal disorders such as Klinefelter syndrome and single-gene disorders like Apert/Pfeiffer/Crouzon syndromes, Holt-Oram syndrome, Ehlers-Danlos syndrome, and Radial-ulnar synostosis with thrombocytopenia, presenting with multiple system/organ anomalies. By contrast, nsCJS manifest with only joint abnormalities, affecting one or multiple joints. This review has focused on human nsCJS and its genetic etiology. To date, variants in seven genes (NOG, GDF5, FGF9, GDF6, FGF16, SMAD6, and MECOM) have been identified as causative factors for nsCJS. This review has focused on such genes and provided a comprehensive review for the clinical phenotypes, genetic patterns, common variants, and underlying mechanisms associated with nsCJS based on a literature review. In addition, it has also analyzed other candidate genes for nsCJS within the context of relevant signaling pathways involved in joint morphogenesis.

Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms.

The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.

The profile of patients attending to the general emergency department with ocular complaints within the last year: is it a true ocular emergency?

PurposeOcular emergencies require immediate intervention to prevent rapid vision loss or functional impairment. The aim of this study was to determine the proportion of true ocular emergencies among patients who presented to the general emergency department with ocular complaints and were referred to the Eye Clinic.MethodsIn a retrospective cross-sectional study in a tertiary hospital in Istanbul, patients aged 0–100 years who presented to the general emergency department with ocular complaints between January and December 2022 were included. Inconclusive diagnoses and incomplete records were excluded. Patients were divided into three groups: top eye emergencies (TE), relative eye emergencies (REE), and non-emergency eyes (NEE).ResultsAmong the 652,224 individuals seeking care, 9,982 (1.5%) were referred to the Eye Emergency Clinic. Of these, 2,788 (27.9%) were female, and 7,194 (72.1%) were male, with ages ranging from 0 to 98 years. TopEye Emergencies (TEE), Relative Eye Emergencies (REE), and Non-Eye Emergencies (NEE) accounted for 13%, 60%, and 27% of the cases, respectively. Common top-eye emergencies (TEE) include chemical injuries, orbital-preseptal cellulitis, and orbital fractures. Relative eye emergencies (REEs) commonly feature corneal foreign bodies, corneal erosion, and conjunctivitis. Nonemulsion eye (NEE) methods involve simple eye redness, trauma without eye involvement, and subconjunctival haemorrhage.ConclusionsConsistent with the literature, 1.5% of patients presenting to the general emergency department had eye complaints.However, 27% of those referred to the ophthalmological clinic did not have an urgent eye condition. This is partly due to the high proportion of patients presenting to the emergency department with ocular complaints and the lack of knowledge of ophthalmological diseases by emergency physicians, leading to unnecessary referrals to the ophthalmology clinic, resulting in a loss of the workforce and reduced time allocated to patients with true ocular emergencies.

The Association Between Trajectories of Self-reported Psychotic Experiences and Continuity of Mental Health Care in a Longitudinal Cohort of Adolescents and Young Adults.

Young people (YP) with psychotic experiences (PE) have an increased risk of developing a psychiatric disorder. Therefore, knowledge on continuity of care from child and adolescent (CAMHS) to adult mental health services (AMHS) in relation to PE is important. Here, we investigated whether the self-reported trajectories of persistent PE were associated with likelihood of transition to AMHS and mental health outcomes. In this prospective cohort study, interviews and questionnaires were used to assess PE, mental health, and service use in 763 child and adolescent mental health service users reaching their service's upper age limit in 8 European countries. Trajectories of self-reported PE (3 items) from baseline to 24-month follow-up were determined using growth mixture modeling (GMM). Associations were assessed with auxiliary variables and using mixed models. Study results. At baseline, 56.7% of YP reported PE. GMM identified 5 trajectories over 24 months: medium increasing (5.2%), medium stable (11.7%), medium decreasing (6.5%), high decreasing (4.2%), and low stable (72.4%). PE trajectories were not associated with continuity of specialist care or transition to AMHS. Overall, YP with PE reported more mental health problems at baseline. Persistence of PE or an increase was associated with poorer outcomes at follow-up. PE are common among CAMHS users when reaching the upper age limit of CAMHS. Persistence or an increase of PE was associated with poorer mental health outcomes, poorer prognosis, and impaired functioning, but were less discriminative for continuity of care.

Health-related quality of life among inpatients suffering from Traumatic brain injury in an urban setting in Vietnam.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity globally. This study aimed to measure the health-related quality of life (HRQOL) of TBI patients in Vietnam and evaluate the associated factors. A longitudinal study was conducted in Thai Binh, Vietnam, from February to September 2020. The EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) and EQ-Visual Analog Scale (EQ-VAS) were used to measure HRQOL. Socio-demographic characteristics, including age, gender, education level, employment status, marital status, and income, as well as clinical characteristics such as injury severity, cause of injury, comorbidities, and functional status, were collected through patient interviews and medical records. Multivariate Tobit regression analysis was performed to identify variables associated with HRQOL. The study included 212 TBI patients. The mean scores of the VAS and EQ-5D-5L scales were 82.4/100 (SD = 14.49) and 0.9/1.0 (SD = 0.2), respectively, indicating a relatively high HRQOL. However, certain factors significantly impacted HRQOL. Unemployed patients and those with depression or higher injury severity, as measured by the Injury Severity Score (ISS), had notably lower HRQOL scores. Poor sleep quality and severe functional impairments also adversely affected HRQOL, whereas patients discharged for a longer period had slightly better HRQOL scores. This study highlights that while HRQOL is relatively high among TBI patients, mental health disorders, injury severity, and functional impairments are key factors negatively impacting their quality of life. High HRQOL was defined by mean scores on the VAS and EQ-5D-5L scales, with higher scores indicating better quality of life. Home-based interventions addressing these issues could improve HRQOL for TBI patients.

Mentally ill people with means-tested benefits at the job center : Diagnosis spectrum and care-First results from the LIPSY project

Although people receiving means-tested benefits are regularly taken care of at the job center, little is known about their mental health situation and mental health care. The aim of the study was to describe the diagnostic spectrum and the functional status as well as the mental health care utilization of individuals with mental illnesses who are receiving means-tested benefits. Mentally ill people with means-tested benefits were recruited at the job center as part of the "Leipzig Individual Placement and Support for Mentally Ill People" (LIPSY) project, where they were initially diagnosed according to ICD-10 and included in the project if they had amental disorder. Mental healthcare utilization was recorded. In the present study, data from n = 583 consecutively included persons were analyzed descriptively and by multivariate statistics. Of the study participants 60.7% (n = 583; 51.5% female; average age36years; unemployed for an average of 4.8years) suffered from affective disorders, followed by neurotic, stress and somatoform disorders (42.5%). With amean global assessment of functioning (GAF) value of 49.4 (SD 7.7), there was on average aserious impairment. Nearly half of the subjects (48.5%) had never received psychotherapeutic, psychiatric or neurological treatment in the 6 months prior to inclusion in the project. It could be shown that there is abroad spectrum of mental disorders with substantial functional impairment. The data suggest that this group is significantly undertreated and difficult to reach.

Ketone bodies rescue T cell impairments induced by low glucose availability.

Ketogenic diets are proposed as a therapeutic approach for type 1 and type 2 diabetes due to their low glucose intake. However, their potential effects on the immune system need investigation. This study aims to explore how glucose concentration and beta-hydroxybutyrate (BHB) impact T cell phenotype, metabolism, and function, with a focus on systemic inflammatory response (T2D) and autoimmunity (T1D). T cells from healthy donors were cultured in vitro under varying glucose concentrations with or without BHB. Flow cytometry was employed to analyze changes in T cell phenotype, while proliferation was evaluated through a CFSE dilution assay. Additionally, we used a novel flow cytometry method allowing a direct assessment of T cell metabolism. Culturing T cells in low glucose concentrations revealed their dependency on glucose metabolism, leading to reduced proliferation rates, overexpression of exhaustion markers and increased susceptibility to Treg suppression and the influence of immune-modulating drugs such as rapamycin, FK506, and MMF. Notably, T cells cultured in low glucose concentrations increased the expression of BDH1 to utilize BHB as an alternative fuel source. Finally, the addition of BHB to the culture effectively rescued T cell impairments caused by insufficient glucose levels. T cells display limited capacity to adapt to low glucose levels, resulting in profound functional impairment. However, T cell functions can be efficiently recovered by the presence of 2mM BHB.

Enhancing Outcomes in Alzheimer's Disease: Exploring the Effects of a Diversified Rehabilitation Program Combined with Donepezil on Apathy, Cognitive Function, and Family Caregiver Burden

Background and objective: Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive decline, behavioral changes, and functional impairments. Apathy, a common symptom in Alzheimer's disease, refers to a lack of motivation, interest, and emotional responsiveness. It can significantly impact patients' quality of life and increase caregiver burden. This study aimed to determine the effects of a diversified rehabilitation program combined with donepezil on apathy, cognitive function, and family caregiver burden of Alzheimer's disease patients. Methods: A total of 105 Alzheimer's disease patients treated at our hospital between January 2020 and January 2023 were selected and analyzed retrospectively. They were assigned to the control group (n = 50) or the observation group (n = 55). The two groups did not differ in terms of general data such as age and sex. All patients were treated with donepezil orally. The control group was given routine nursing, whereas the observation group was given a diversified rehabilitation program intervention, including cognitive training and emotional support. The Hasegawa's dementia scale, mini-mental state examination, and Montreal cognitive assessment scale were adopted to evaluate the cognitive function of the two groups before and after treatment. A caregiver burden scale, the Zarit Burden Interview (ZBI) and the Apathy Evaluation Scale Informant version (AES-I) were used to evaluate the caregiver burden and apathy of the two groups. Results: A significantly higher overall response rate to treatment was found in the observation group (94.55%) than in the control group (80.00%) (p = 0.024). After treatment, scores on the Hasegawa's dementia scale, mini-mental state examination, and Montreal cognitive assessment scale of the two groups increased to varying degrees, with greater increases in the observation group than in the control group (p < 0.05). The ZBI and AES-I scores of the two groups decreased to different degrees after treatment, with greater decreases in the observation group than in the control group (p < 0.05). Conclusion: A diversified rehabilitation program combined with donepezil can substantially alleviate the apathy of Alzheimer's disease patients, improve their cognitive function, and reduce the burden on their families.

Associations between readmission and patient-reported measures in acute psychiatric inpatients: a multicenter prospective longitudinal study.

This study examined whether patient-reported measures (PRMs) addressing quality of life, personal agency, functional impairment, and treatment satisfaction at hospital discharge were associated with future readmission during a 12-month follow-up period. The study also examined whether readmission influenced changes in the same measures. A multicenter prospective cohort study was conducted at 21 psychiatric hospitals in Japan. Participants completed the EuroQol-five-dimensions-five-level (EQ-5D), the Five-item Subjective Personal Agency Scale, and the Sheehan Disability Scale (SDS) at the time of index admission (T1), discharge from index admission (T2), and 6months (T3) and 12months (T4) after discharge. Inpatient treatment satisfaction was assessed at T2. Readmission and variables potentially associated with hospitalization and PRMs were evaluated using mixed-effects logistic regression models and mixed models for repeated measures. A total of 491 participants were followed for 12months (attrition rate: 19.4%), and 480 were included in the EQ-5D analysis. The most common diagnoses were schizophrenia (59%), depression (14%), and bipolar disorder (13%). No patient-reported measures were significantly associated with readmission over the follow-up period. Interaction of readmission and time did not significantly affect changes in EQ-5D. Readmission did significantly influence SDS score changes between T2 and T3 (B = 1.78, 95% CI = 0.30-3.25, p = 0.018) and between T3 and T4 (B = 1.43, 95% CI = 0.14-2.72, p = 0.029).The same influence of readmission on SDS score changes was not observed in the model which adjusted for all potential covariates. Readmission was potentially associated with changes in self-reported functional impairment. Findings highlight the potential role of intensive post-discharge services in preventing readmission, rather than relying on time-of-discharge PRMs in order to predict readmission risk. This study was registered in UMIN Clinical Trials Registry (UMIN000034220).

Sexual function, health functionality, and quality of life in females with pulmonary arterial hypertension: a cross-sectional study.

Pulmonary arterial hypertension (PAH) can have several consequences on sexual function, which can lead to worsened quality of life. The study sought to assess sexual function and its association with health functionality and quality of life in females with PAH. A descriptive cross-sectional study was carried out in pulmonary circulation outpatient clinics from January 2022 to March 2023 in females diagnosed with pulmonary hypertension. Assessment was carried out through the application of the Female Sexual Function Index, the 36-item World Health Organization Disability Assessment Schedule, and the Medical Outcome Study 36-Item Short Form Survey. Data were analyzed using SPSS version 22.0 and JASP, and Spearman's correlation tests were applied between the instruments, with a P value <.05 considered significant. A total of 91 females were assessed. It was identified that 90.1% of females had sexual dysfunction, with worse scores in females with sexual dysfunction in the domains of satisfaction, arousal, and desire, with average health functionality and quality of life. There were significant correlations between the domains of mobility, getting along, life activities, and the overall functionality score with some domains of sexual function, especially arousal and satisfaction. We found significant correlations between some domains of quality-of-life assessment with the domains of desire, arousal, and satisfaction, and with the overall score of sexual function assessment, as well as strong correlations between health functionality and quality of life. The data reinforce the need for rehabilitation programs and social support for this population. This is one of the few studies to evaluate sexual function, quality of life, and health functionality in women with PAH. Due to limitations in data collection, we were unable to assess certain factors such as hormone levels and a history of sexual abuse. We identified a high prevalence of sexual dysfunction in females with PAH with mild functional impairment and a moderate quality-of-life score with correlations between sexual function, health functionality, and quality of life.

Evaluating the Functional Impairment of Assault Victims in a Judicial Context: A Multicentered Retrospective Study in Seven French Forensics Units.

Functional impairment is of major importance in the evaluation of assault victims. French law assesses the seriousness of the violence in terms of the functional impairment experienced by the victims, quantified by the duration of the victims' inability to fulfill their usual daily activities, measured in days of "total incapacity to work" (TIW). Significant variations in the duration of TIW have been reported depending on the examination centers or physician. To date, few studies, all monocentric, have focused on the determinants of this variability. We aimed to study the functional impairment of assault victims by searching for determinants of TIW. We conducted a retrospective multicenter study, including assault victims from seven forensic medicine units. The data were automatically extracted from the medical certificates drawn up and gathered within the ORFéAD database. Thirty-eight variables were studied, relating to the victim's characteristics, the circumstances of the examination and the assault, the physical and psychological symptoms, and the duration of TIW. A total of 5,663 victims were included, including 2,438 (43%) women. The median age was 32 years (min; max [10; 98]). The median duration of TIW was 2 days (min; max [0; 182]). Male gender, age, time to examination, examination center, traumatic injuries (ecchymosis, hematoma, wound, bone fracture), use of a weapon, and functional limitation were associated with the duration of TIW (p < .05). The associations formerly identified in a monocentric setting were confirmed and new determinants were identified. This study has allowed a better understanding of the factors influencing the evaluation of functional impairment and determination of the TIW of assault victims. This first study using ORféAD is intended to be supplemented by the participation of other forensic units, and the inclusion of other variables, such as violence type, victim categories, or the examining physician.

A systematic cognitive behavioral therapy approach for pediatric disorders of gut-brain interaction.

Cognitive Behavioral Therapy (CBT) for youth with Disorders of Gut-Brain Interaction (DGBIs) is effective; however, there are calls in the field to strengthen the evidence base and identify specific mechanisms of treatment that yield the most benefit for this patient population. A unique, systematic treatment approach of CBT with initial evidence for success for pediatric patients with DGBIs was evaluated to further demonstrate its clinical utility in this population. This was a retrospective study of 42 pediatric patients aged 11-17 years with DGBIs, who were diagnosed and referred for CBT by pediatric gastroenterology providers. Providers also completed a survey rating acceptability and effectiveness of CBT. The systematic CBT approach included 10 sessions delivered by a psychologist at an integrated Pediatric GI Clinic. Review of 42 pediatric charts showed significant decreases in self-reported functional disability, abdominal pain, as well as depression and anxiety symptoms pre- to post-CBT completion. A moderation effect was observed where patients reporting higher levels of depressive symptoms and primary symptom of abdominal pain reported smaller reductions in functional impairment compared to those with lower levels of depression and primary symptom of nausea or vomiting. Pediatric Gastroenterology providers were satisfied with this psychological treatment approach. This study provides evidence for acceptability and effectiveness of implementation of a systematic CBT approach for pediatric DGBIs in an integrated GI clinic, as well as areas worthy of future research, including identifying the most important mechanisms of treatment and factors that influence treatment response.

Calcium Deregulation in Neurodegeneration and Neuroinflammation in Parkinson's Disease: Role of Calcium-Storing Organelles and Sodium-Calcium Exchanger.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that lacks effective treatment strategies to halt or delay its progression. The homeostasis of Ca2+ ions is crucial for ensuring optimal cellular functions and survival, especially for neuronal cells. In the context of PD, the systems regulating cellular Ca2+ are compromised, leading to Ca2+-dependent synaptic dysfunction, impaired neuronal plasticity, and ultimately, neuronal loss. Recent research efforts directed toward understanding the pathology of PD have yielded significant insights, particularly highlighting the close relationship between Ca2+ dysregulation, neuroinflammation, and neurodegeneration. However, the precise mechanisms driving the selective loss of dopaminergic neurons in PD remain elusive. The disruption of Ca2+ homeostasis is a key factor, engaging various neurodegenerative and neuroinflammatory pathways and affecting intracellular organelles that store Ca2+. Specifically, impaired functioning of mitochondria, lysosomes, and the endoplasmic reticulum (ER) in Ca2+ metabolism is believed to contribute to the disease's pathophysiology. The Na+-Ca2+ exchanger (NCX) is considered an important key regulator of Ca2+ homeostasis in various cell types, including neurons, astrocytes, and microglia. Alterations in NCX activity are associated with neurodegenerative processes in different models of PD. In this review, we will explore the role of Ca2+ dysregulation and neuroinflammation as primary drivers of PD-related neurodegeneration, with an emphasis on the pivotal role of NCX in the pathology of PD. Consequently, NCXs and their interplay with intracellular organelles may emerge as potentially pivotal players in the mechanisms underlying PD neurodegeneration, providing a promising avenue for therapeutic intervention aimed at halting neurodegeneration.

Concurrent Validity of the Anxiety Disorders Section of the Anxiety Disorder Interview Schedule- Autism Spectrum Addendum (ADIS-ASA) in Autistic Youth.

Examine the concurrent validity of specific Anxiety Disorders Section of the Anxiety Disorder Interview Schedule for DSM-IV-Autism Spectrum Addendum (ADIS-ASA)-Parent Interview in a sample of 167 autistic youth who met diagnostic criteria for an anxiety-related disorder (Mage = 9.91; 78.4% male; 82% non-Hispanic; 77.67% White). Concurrent validity of Diagnostic and Statistical Manual (DSM)-defined ADIS-ASA anxiety disorder diagnostic caseness was examined via relations with (a) parent-reported dimensions of youth anxiety symptomology and (b) dimensional measures of youth anxiety-related functional impairment, respectively, using logistic regression models and point-biserial correlations. Significant relations were found between separation anxiety disorder and social anxiety disorder (but not generalized anxiety disorder nor obsessive-compulsive disorder) caseness, respectively, and theoretically consistent facets of dimensional youth anxiety symptomology. Relations between ADIS-ASA diagnostic caseness and youth functional impairment-related variables revealed that only separation anxiety disorder demonstrated robust evidence of convergent validity. Despite mixed findings concerning relations between ADIS-ASA anxiety disorder diagnostic caseness and dimensional measures of anxiety severity and anxiety-related impairment, the present findings provide further support for the status of the ADIS-ASA as a gold standard for assessment of anxiety in autistic youth. This work also highlights the importance of continuing to improve precision in measurement of anxiety symptomology in autistic youth, with implications for clinical assessment.

Optic nerve elongation during fronto-facial surgery for Crouzon syndrome: 3D quantification and clinical implications.

Fronto-facial monobloc advancement with internal distraction (FFMBA) is a key procedure in the management of syndromic craniosynostoses. FFMBA involves circumferential dissection and linear enlargement of the orbit, potentially leading to mechanical stress on the optic nerve (ON). Several reports of transient vision loss during the distraction process led us to investigate ON shape modifications during facial advancement, with the aim to potentially refine current clinical guidelines on postoperative management and the distraction schedule. Twenty-six patients with Crouzon syndrome were included in this study. ONs were segmented on pre- and postoperative CT scans. Distraction amplitudes, linear and curved lengths, and cross-section diameters of the ON were assessed along the main axis of the nerve. A two-level hierarchical multivariate linear model was used to screen for factors associated with ON morphology. The mean age at FFMBA was 4.4 ± 3.8 years. Two patients presented with transient impaired vision during distraction. The final mean fronto-orbital and temporo-zygomatic distraction amplitudes were 18 ± 4 mm and 18 ± 6 mm, respectively. At the end of distraction, ONs were elongated (+1.8 mm for curved lengths, p = 0.013), and their mean cross-section was reduced (-1.9 mm2, p < 0.001) in the proximal intraorbital portion (first 15 mm). In the 2 patients with visual symptoms, functional impairment was associated with ON area reduction (OR 0.487, p < 0.001) and increased temporo-zygomatic distraction amplitude (OR 2.240, p < 0.001). ON was elongated during FFMBA, with proximal diameter reduction. Transient visual impairment with normal fundus examination during distraction seemed to have a morphological basis, based on 2 cases. These results suggest the importance of vision monitoring associated with fundus examination during distraction, and advocate for early extubation after FFMBA to allow clinical follow-up.

The mortality burden of cachexia or weight loss in patients with colorectal or pancreatic cancer: A systematic literature review.

Cancer-associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer in recent literature. The SLR was conducted following PRISMA guidelines. Embase® and PubMed were searched to identify articles published in English between 1 January 2016 and 10 October 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by international consensus (IC) diagnostic criteria or a broader definition of any weight loss. Included publications were studies in ≥100 patients with colorectal or pancreatic cancer. Thirteen publications in patients with colorectal cancer and 13 with pancreatic cancer met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 (58%) reported any weight loss. An association between survival and cachexia or weight loss was assessed across studies using multivariate (n=23) or univariate (n=3) analyses and within each study across multiple weight loss categories. Cachexia/weight loss was associated with a statistically significantly poorer survival in at least one weight loss category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Cachexia or weight loss was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two-thirds of the studies. The classification of weight loss varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could help inform prognosis and influence early disease management strategies.

Mitochondrial dysfunction and NDUFS3: Insights from a PINK1B9 Drosophila model in Parkinson’s disease pathogenesis

PTEN-induced kinase1 (PINK1) mutation is the main cause of autosomal recessive inheritance and early-onset Parkinson’s disease. Mitochondrial respiratory chain complex I (CI) functional impairment has been considered to be an important factor in the pathogenesis of PD in recent years. In addition, NDUFS3 (nicotinamide adenine dinucleotide deoxylase iron-thionein 3) is one of the core subunits of mitochondrial CI. Therefore, this study explored the role of NDUFS3 gene in PINK1B9 transgenic Drosophila and its possible related mechanisms. In this study, the PD transgenic Drosophila model of MHC-Gal4/UAS system was selected to specifically activate the expression of PINK1B9 gene in the chest muscle tissue of Drosophila melanogaster. NDUFS3 RNAi interference was used to interfere with PINK1B9 transgenic Drosophila melanogaster and its effect on PD transgenic flies was studied. The results suggest that down-regulation of NDUFS3 gene expression may have a protective effect on PINK1B9 transgenic Drosophila melanogaster, and we speculate that down-regulation of NDUFS3 gene expression to reduce oxidative stress and restore mitochondrial function may be related to mitochondrial stress response.

An evaluation of the associations among posttraumatic stress disorder, depression, and complicated grief in active duty military personnel with traumatic loss.

Between 44% and 87% of active duty service members and veterans who deployed following the September 11, 2001, terrorist attacks know someone who was killed or seriously injured in combat. Considering the high frequency and known impact of traumatic loss, it is important to understand if and how traumatic loss may impede posttraumatic stress disorder (PTSD) treatment progress in military personnel. Additionally, experiencing a traumatic loss elevates the risk of developing prolonged grief disorder (PGD), which is associated with higher levels of PTSD symptoms, more functional impairment, and more lifetime suicide attempts among military personnel. Given what is known about the association between PGD and PTSD in treatment-seeking service members and veterans, it is also important to understand whether grief-related symptom severity negatively impacts PTSD treatment response. The current study examined associations among traumatic loss, complicated grief, depressive symptoms, and PTSD treatment response among military personnel (N = 127) who participated in variable-length cognitive processing therapy (CPT). There was no direct, F(2, 125) = 0.77, p =.465, or indirect, β =.02, p =.677, association between a traumatic loss index event and PTSD treatment response compared with other trauma types. Prior assessments of depressive symptom severity were directly related to PTSD at later assessments across two models, ps <.001-p =.021 Participants with a traumatic loss index trauma demonstrated significant reductions in complicated grief, depressive symptoms, and PTSD following CPT, ps <.001, ds = -0.61--0.83. Implications, study limitations, and suggestions for future research are presented.

The Gaming Disorder Identification Test (GADIT) - A screening tool for Gaming Disorder based on ICD-11.

Gaming Disorder was included as an addictive disorder in the latest version of the International Classification of Diseases (ICD-11), published in 2022. The present study aimed to develop a screening tool for Gaming Disorder, the Gaming Disorder Identification Test (GADIT), based on the four ICD-11 diagnostic criteria: impaired control, increasing priority, continued gaming despite harm, and functional impairment. We reviewed 297 questionnaire items from 48existing gaming addiction scales and selected 68 items based on content validity. Two datasets were collected: 1)an online panel (N = 803) from Australia, United States, United Kingdom andCanada, split into a development set (N = 589) and a validation dataset (N = 214); and 2) a university sample (N = 408) from Australia. Item response theory and confirmatory factor analyses were conducted to select eight items to form the GADIT. Validity was established by regressing theGADIT against known correlates of Gaming Disorder. Confirmatory factor analyses ofthe GADIT showed good model fit (RMSEA=<0.001-0.108; CFI = 0.98-1.00), and internal consistency was excellent (Cronbach's alphas = 0.77-0.92). GADIT scores were strongly associated with the Internet Gaming Disorder Test (IGDT-10), and significantly associated with gaming intensity, eye fatigue, hand pain, wrist pain, back or neck pain, and excessive in-game purchases, inboth the validation and the university sample datasets. The GADIT has strong psychometric properties in two independent samples from four English-speaking countries collected through different channels, and shown validity against existing scales and variables that are associated with Gaming Disorder. A cut-off of 5 is tentatively recommended for screening for Gaming Disorder.

A Network Approach to Understanding the Role of Executive Functioning and Alpha Oscillations in Inattention and Hyperactivity-Impulsivity Symptoms of ADHD.

ADHD is a prevalent neurodevelopmental disorder characterized by symptoms of inattention and hyperactivity-impulsivity. Impairments in executive functioning (EF) are central to models of ADHD, while alpha-band spectral power event-related decreases (ERD) have emerged as a putative electroencephalography (EEG) biomarker of EF in ADHD. Little is known about the roles of EF and alpha ERD and their interactions with symptoms of ADHD. We estimated network models of ADHD symptoms and integrated alpha ERD measures into the symptom network. EF emerges as a bridge network node connecting alpha ERD and the hyperactivity/impulsivity and inattention symptoms. We found that EF most closely relates to a subset of symptoms, namely the motoric symptoms, "seat" (difficulty staying seated), and "runs" (running or climbing excessively). EF functions as a bridge node connecting alpha ERD and the ADHD symptom network. Motoric-type symptoms and EF deficits may constitute important nodes in the interplay between behavior/symptoms, cognition, and neurophysiological markers of ADHD.