Estimation of Ambulation and Survival in Neurodegeneration with Brain Iron Accumulation Disorders.

BACKGROUND: Neurodegeneration with Brain Iron Accumulation (NBIA) disorder is a group of ultra-orphan hereditary diseases with very limited data on its course. OBJECTIVES: To estimate the probability of preserving ambulatory ability and survival in NBIA. METHODS: In this study, the electronic records of the demographic data and clinical assessments of NBIA patients from 2012 to 2023 were reviewed. The objectives of the study and factors impacting them were investigated by Kaplan-Meier and Cox regression methods. RESULTS: One hundred and twenty-two genetically-confirmed NBIA patients consisting of nine subtypes were enrolled. Twenty-four and twenty-five cases were deceased and wheelchair-bound, with a mean disease duration of 11 ± 6.65 and 9.32 ± 5 years. The probability of preserving ambulation and survival was 42.9% in 9 years and 28.2% in 15 years for classical Pantothenate Kinase-Associated Neurodegeneration (PKAN, n = 18), 89.4% in 7 years and 84.7% in 9 years for atypical PKAN (n = 39), 23% in 18 years and 67.8% in 14 years for Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN, n = 23), 75% in 20 years and 36.5% in 33 years for Kufor Rakeb Syndrome (KRS, n = 17), respectively. The frequencies of rigidity, spasticity, and female gender were significantly higher in deceased cases compared to surviving patients. Spasticity was the only factor associated with death (P value = 0.03). CONCLUSIONS: KRS had the best survival with the most extended ambulation period. The classical PKAN and MPAN cases had similar progression patterns to loss of ambulation ability, while MPAN patients had a slower progression to death. Spasticity was revealed to be the most determining factor for death.

Neurodegeneration with Brain Iron Accumulation Disorders and Retinal Neurovascular Structure.

BACKGROUND: The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking. OBJECTIVES: To investigate NBIA's neurological and ophthalmological manifestations. METHODS: This cross-sectional study was conducted on genetically confirmed NBIA patients and an age-gender-matched control group. The thickness of retinal layers, central choroidal thickness (CCT), and capillary plexus densities were measured by spectral domain-optical coherence tomography (SD-OCT) and OCT angiography, respectively. The patients also underwent funduscopy, electroretinography (ERG), visual evoked potential (VEP), and neurological examination (Pantothenate-Kinase Associated Neurodegeneration-Disease Rating Scale [PKAN-DRS]). The generalized estimating equation model was used to consider inter-eye correlations. RESULTS: Seventy-four patients' and 80 controls' eyes were analyzed. Patients had significantly decreased visual acuity, reduced inner or outer sectors of almost all evaluated layers, increased CCT, and decreased vessel densities, with abnormal VEP and ERG in 32.4% and 45.9%, respectively. There were correlations between visual acuity and temporal peripapillary nerve fiber layer (positive) and between PKAN-DRS score and disease duration (negative), and scotopic b-wave amplitudes (positive). When considering only the PKAN eyes, ONL was among the significantly decreased retinal layers, with no differences in retinal vessel densities. Evidence of pachychoroid was only seen in patients with Kufor Rakeb syndrome. CONCLUSION: Observing pathologic structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes in further investigations. © 2023 International Parkinson and Movement Disorder Society.

Olfactory status in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders. METHODS: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set. RESULTS: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients. CONCLUSION: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies.

Transcranial sonography in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Transcranial Sonography is a non-invasive technique that has been used as a diagnostic tool for a variety of neurodegenerative disorders. However, the utility and potential application of this technique in NBIA disorders is scarce and inconclusive. METHODS: In this cross-sectional retrospective case-control study, the echogenicity of Substantia Nigra (SN), Lentiform Nucleus (LN), and Diameter of the Third Ventricle (DTV) were assessed by TCS in genetically confirmed NBIA patients referring to the movement disorder clinic. The normal echogenicity area of SN was defined based on the 90th percentile of an age-and-gender-matched control group. NBIA patients underwent neurologic examination at each visit, but their brain magnetic resonance imaging and demographics were extracted from electronic records. RESULTS: Thirty-five NBIA patients of four subtypes with a mean disease duration of 10.54 years and 35 controls were enrolled. The normally defined SN echogenicity in controls was 0.23 cm2. DTV and SN echogenicity areas were significantly higher in patients compared to the controls (P = 0.002 and < 0.001, respectively). Around 85% and 63% of the patients showed LN and SN hyperechogenicity at least on one side, respectively. Disease duration was positively correlated with DTV (r = 0.422, p = 0.015). Cases with Pantothenate Kinase Associated Neurodegeneration (n = 23) also had significantly higher DTV and SN echogenicity area compared to the controls. CONCLUSION: Despite most NBIA patients displayed increased DVT and higher SN and LN hyperechogenicity than healthy controls, the discriminatory role of TCS on different NBIA subtypes remains to be determined.

Co-adoption pathways toward a low-carbon energy system.

Low-carbon technology adoption is an essential element of energy transitions toward net-zero emissions around the world. To exploit the full potential of low-carbon technologies, households should ideally co-adopt multiple low-carbon technologies. Whereas previous research primarily investigated predictors of single-technology adoption in isolation, here we focus on the co-adoption of multiple low-carbon technologies, including solar photovoltaics, stationary batteries, heat pumps, and electric vehicles, to examine the interconnections between adoption decisions and the potential of certain technologies to serve as "entry points" for the co-adoption of multiple low-carbon technologies. Based on a sample of 1967 homeowners, we identified unique demographic and psychological variables associated with co-adoption. We moreover observed specific co-adoption patterns across time in that the adoption of one technology increased the likelihood of adopting another technology. This effect, however, was primarily driven by co-adoption in close temporal proximity, pointing to opportunities for targeted policies that support technology bundles.

Self-Awareness and Stereotypes: Accurate Prediction of Implicit Gender Stereotyping.

Research showing that people can predict the patterns of their implicit evaluations toward social groups has raised questions concerning how widely these findings extend to other domains, such as semantic implicit stereotyping. In a preregistered laboratory study, participants were asked to predict their scores on five implicit gender stereotyping Implicit Associations Tests (IATs). Within-subjects correlations between IAT score predictions and IAT scores showed high levels of accuracy. Although part of the IAT score patterns could be predicted from shared knowledge, own predictions significantly outperformed predictions of random others and normative patterns, suggesting self-awareness beyond reliance on shared knowledge. In line with dual-process models emphasizing that different information is captured by implicit as opposed to explicit measures, predictions explained correlations between implicit and traditional explicit stereotyping measures, and led to acknowledgment of bias. Discussion focuses on understanding conscious awareness of semantic automatic processes and conceptualizations of the cognitions underlying implicit measures.

Supporting families to achieve a healthy weight development for their child with overweight/obesity using the STARKIDS intervention: study protocol for a cluster-randomized controlled trial.

BACKGROUND: Childhood and adolescent overweight and obesity are among the most serious health challenges today. Structured weight reduction programs can be helpful to reduce severe health consequences but evidence is partly scarce. The STARKIDS program aims to improve on some of these limitations and is designed to be a structured, stepwise, digitally supported intervention program for the whole family. It is divided into two intervention steps spanning over 1.5 years and aims at promoting a healthy weight development of children/adolescents with overweight/obesity and an increase in quality of life. METHODS: The STARKIDS intervention is evaluated in a cluster-randomized study design by comparing it with a control group receiving a one-time structured counselling in the pediatric practice. The study aims to include 1000 families with children/adolescents with overweight/obesity from 100 pediatric practices. The main outcomes are reduction in body mass index percentiles and improvements in children's/adolescent's quality of life, secondary outcomes refer to the contents of the intervention such as diet, physical activity, stress, and media habits. All outcomes are measured on three measurement time points: (T0) at baseline/inclusion in the study, (T1) baseline + 12 months which is the end of step 1 of the STARKIDS intervention, and (T2) baseline + 18 months which is the end of step 2 of the STARKIDS intervention. DISCUSSION: The stepwise, e-health-supported STARKIDS program is a low-threshold intervention program for families with children/adolescents with overweight/obesity. With the proof of concept, STARKIDS provides the potential to be implemented as a standard care tool for the prevention and intervention of childhood/adolescence obesity in the German health system. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00022813  (acknowledged primary register of the World Health Organization). Registered on 27 November 2020 (Universal Trial Number U1111-1254-9536).

Huntington's disease and neurovascular structure of retina.

BACKGROUND: Retinal biomarkers in neurodegenerative disorders have attracted much attention in recent years. Recent studies have reported visual dysfunction in Huntington's disease (HD). However, little is known about retinal structural changes in HD. METHODS: A total of 50 subjects, including 25 motor-manifest HD patients and 25 gender- and age-matched controls, were enrolled. Unified Huntington's Disease Rating Score-Motor part was assessed in HD patients. Spectral-domain Optical Coherence Tomography (SD-OCT) was used to evaluate the macular thickness and peripapillary retinal nerve fiber layer (pRNFL). Superficial and deep capillary plexus densities were measured using OCT angiography (OCTA). To account for inter-eye correlation, generalized estimating equation (GEE) model was used. RESULTS: HD patients had a significant reduction in macular thickness in both inner and outer superior sectors and the inferior outer sector. Inferior pRNFLs were significantly decreased in thickness. There was no significant difference in retinal capillary plexus density between the two groups. Age and disease duration were negatively correlated with macular thickness in HD patients. However, the severity of motor involvement was not correlated with SD-OCT or OCTA parameters. CONCLUSIONS: We observed attenuated pRNFL and macular retinal thickness in patients with HD, independent of macular capillary plexus parameters. It can support the hypothesis that the retina may be a potential biomarker for monitoring the neurodegenerative process in HD.

Feasibility, psychological outcomes and practical use of a stress-preventive leadership intervention in the workplace hospital: the results of a mixed-method phase-II study.

OBJECTIVES: Hospitals are psychologically demanding workplaces with a need for context-specific stress-preventive leadership interventions. A stress-preventive interprofessional leadership intervention for middle management has been developed. This phase-II study investigates its feasibility and outcomes, including work-related stress, well-being and transformational leadership. DESIGN: This is a mixed-methods study with three measure points (T0: baseline, T1: after the last training session, T2: 3-month follow-up). Additionally, focus groups were conducted to assess participants' change in everyday work. SETTING: A tertiary hospital in Germany. PARTICIPANTS: N=93 leaders of different professions. INTERVENTION: An interactive group setting intervention divided in five separate sessions ((1) self-care as a leader, (2) leadership attitudes and behaviour, (3) motives, needs and stressors of employees, (4) strengthen the resource 'team', (5) reflection and focus groups). The intervention was conducted between June 2018 and March 2020 in k=5 runs of the intervention. OUTCOME MEASURES: Feasibility and acceptance were measured with a self-developed intervention specific questionnaire. Psychological outcomes were assessed with the following scales: work-related strain with the Irritation Scale, well-being with the WHO-5 Well-being Index and transformational leadership with the Questionnaire of Integrative Leadership. RESULTS: After the intervention at T2, over 90% of participants reported that they would recommend the intervention to another coworker (92.1%, n=59) and all participants (n=64) were satisfied with the intervention and rated the intervention as practical relevant for their everyday work. Participants' self-rated cognitive irritation was reduced, whereas their well-being and transformational leadership behaviour were improved over time. Focus group discussions revealed that participants implemented intervention contents successfully in their everyday work. CONCLUSIONS: This intervention was feasible and showed first promising intraindividual changes in psychological outcomes. Participants confirmed its practical relevance. As a next step, the intervention will be evaluated as part of a multicentre-randomised controlled trial within the project SEEGEN (SEElische GEsundheit am Arbeitsplatz KrankeNhaus).

Empirical audit and review and an assessment of evidentiary value in research on the psychological consequences of scarcity.

Empirical audit and review is an approach to assessing the evidentiary value of a research area. It involves identifying a topic and selecting a cross-section of studies for replication. We apply the method to research on the psychological consequences of scarcity. Starting with the papers citing a seminal publication in the field, we conducted replications of 20 studies that evaluate the role of scarcity priming in pain sensitivity, resource allocation, materialism, and many other domains. There was considerable variability in the replicability, with some strong successes and other undeniable failures. Empirical audit and review does not attempt to assign an overall replication rate for a heterogeneous field, but rather facilitates researchers seeking to incorporate strength of evidence as they refine theories and plan new investigations in the research area. This method allows for an integration of qualitative and quantitative approaches to review and enables the growth of a cumulative science.

Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19.

BACKGROUND: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. OBJECTIVE: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. METHODS: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. RESULTS: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). CONCLUSIONS: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.

Budget Impact Analysis of Rotavirus Vaccine Adoption in the Childhood Immunization Schedule of Iran.

OBJECTIVES: To examine the budget impact of introducing the RotaTeq® vaccine (Merck and Co Inc, West Point, PA) to the national immunization program in Iran. METHODS: The pre- and postvaccine introduction costs were compared. The total annual costs included the vaccination and diarrhea treatment costs. The health outcome was the estimated annual cases of the disease. To evaluate the net budget impact, the annual prevaccine introduction cost was reduced from the postvaccine introduction cost. The sensitivity analysis was done to reduce the uncertainties. RESULTS: The total cost of vaccination for 5 years would be more than $184 million. Nevertheless, the financial savings would be about $45 million and $7.5 million because of the reduction in the number of patients after vaccination in inpatient and outpatient sectors, respectively. So the incremental cost would be $131 450 210 during 5 years of immunization. CONCLUSIONS: The results show that the inclusion of rotavirus vaccine in the national vaccination program would have a significant effect on health budgets and would raise government expenditure.