Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

The effect of mindfulness-based intervention on cognitively unimpaired older adults' cognitive function and sleep quality: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to investigate the effect of mindfulness-based intervention (MBI) on cognitively unimpaired older adults' cognitive function and sleep quality.Method: Studies published in English since 2010 were considered for inclusion. Databases searched were PubMed, Embase, Web of Science, and PsycInfo. We included randomized controlled trials (RCTs) with adults over 55 with no known cognitive impairment, that recorded cognitive outcomes and/or sleep quality pre- and post-intervention, and that implemented Mindfulness-Based Stress Reduction (MBSR), or an MBI closely based on MBSR protocol.Results: Seven RCTs fit the inclusion criteria, with 276 participants in MBI groups and 287 in controls. Four studies investigated mindfulness and cognitive function, two investigated mindfulness and sleep quality, and one investigated mindfulness, cognitive function, and sleep quality. Some studies were not reported in sufficient detail to be included in meta-analyses. Results of meta-analyses showed no significant differences between MBI groups vs controls on cognitive measures of executive function, free recall, and delayed recall. Meta-analysis revealed that MBI significantly improved sleep quality compared to controls.Conclusion: Given that poor sleep quality is strongly linked to increased risk of cognitive decline, further research investigating sleep quality's role in the mindfulness-cognitive function relationship in cognitively unimpaired older adults is recommended.

Telephone-based mindfulness intervention positively impacts family communication and stress within rural, African American dementia caregiving teams.

OBJECTIVES: The objective of this paper is to explore how telephone-delivered mindfulness training impacts family conflict and communication within the informal dementia caregiving team, including primary caregivers, their care partner, and the care recipient. METHOD: Primary caregivers and their care partners participated in an eight-week telephone-delivered mindfulness-based intervention (MBI). This study used mixed methods and a pre-post design to evaluate the intervention's effect on family satisfaction, perceived support, and family conflict. RESULTS: Both family satisfaction and perceived informational support increased significantly, and qualitative analysis revealed four key themes illustrating how the mindfulness intervention served to positively impact family conflict and communication among participating caregivers. CONCLUSION: This study provides preliminary evidence for the beneficial effects of an MBI on family functioning among rural African American caregivers of people with Alzheimer's disease and related dementias.

Performance enhancement, bacterial communities optimization and emerging pollutants elimination by microalgal-bacterial consortium for treating aquaculture pond sediments.

Aquaculture pond sediments have a notable influence on the ecosystem balance and farmed animal health. In this study, microalgal-bacterial immobilization (MBI) was designed to improve aquaculture pond sediments via synergistic interactions. The physicochemical characteristics, bacterial communities, and the removal efficiencies of emerging pollutants were systematically investigated. The consortium containing diatom Navicula seminulum and Alcaligenes faecalis was cultivated and established in the free and immobilized forms for evaluating the treatment performance. The results indicated that the immobilized group exhibited superior performance in controlling nutrient pollutants, shaping and optimizing the bacterial community compositions with the enrichment of functional bacteria. Additionally, it showed a stronger positive correlation between the bacterial community shifts and nutrient pollutants removal compared to free cells. Furthermore, the immobilized system maintained the higher removal performance of emerging pollutants (heavy metals, antibiotics, and pathogenic Vibrios) than free group. These findings confirmed that the employment of immobilized N. seminulum and A. faecalis produced more synergistic benefits and exerted more improvements than free cells in ameliorating aquaculture pond sediments, suggesting the potential for engineering application of functional microalgal-bacterial consortium in aquaculture.

The impact of mindfulness on cancer-related cognitive impairment in breast cancer survivors with cognitive complaints.

BACKGROUND: Interventions that target cancer-related cognitive impairment (CRCI) to improve the quality of life of cancer survivors are needed. In this study, the potential of a mindfulness-based intervention to reduce CRCI in breast cancer survivors, compared with physical training and a wait list control group, was investigated. METHODS: Breast cancer survivors with cognitive complaints (N = 117) were randomly allocated to a mindfulness (n = 43), physical training (n = 36), or wait list control condition (n = 38). Participants completed neuropsychological tests and questionnaires before the intervention, immediately after, and 3 months after intervention. The primary outcome measure was the change in cognitive complaints over time. Secondary outcomes were objective cognitive impairment and psychological well-being. All outcomes were compared between groups over time using linear mixed models, including participants with missing values. RESULTS: Of the 117 included participants, 96 completed the three assessments. Participants in the three groups reported decreased cognitive complaints after intervention, without group differences. There were no between-group differences in objective cognitive impairment after intervention compared with baseline. Compared with the wait list control group, participants reported increased mindfulness skills and reduced emotional distress after mindfulness and reduced emotional distress and fatigue after physical training. CONCLUSION: Contrary to the hypothesis, all groups reported an improvement in cognitive complaints over time. It is suggested that priming and acknowledgment of CRCI might alter the experience of cognitive impairment. Additionally, both mindfulness-based intervention and physical training can improve psychological well-being of breast cancer survivors with cognitive complaints.

Engineering Under-Coordinated Active Sites with Tailored Chemical Microenvironments over Mosaic Bismuth Nanosheets for Selective CO2 Electroreduction to Formate.

Selective electrochemical reduction of CO2 into fuels or chemical feedstocks is a promising avenue to achieve carbon-neutral goal, but its development is severely limited by the lack of highly efficient electrocatalysts. Herein, cation-exchange strategy is combined with electrochemical self-reconstruction strategy to successfully develop diethylenetriamine-functionalized mosaic Bi nanosheets (mBi-DETA NSs) for selective electrocatalytic CO2 reduction to formate, delivering a superior formate Faradaic efficiency of 96.87% at a low potential of -0.8 VRHE . Mosaic nanosheet morphology of Bi can sufficiently expose the under-coordinated Bi active sites and promote the activation of CO2 molecules to form the OCHO- * intermediate. Moreover, in situ attenuated total reflectance infrared spectra further corroborate that surface chemical microenvironment modulation of mosaic Bi nanosheets via DETA functionalization can improve CO2 adsorption on the catalyst surface and stabilize the key intermediate (OCHO- *) due to the presence of amine groups, thus facilitate the CO2 -to-HCOO- reaction kinetics and promote formate formation.

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence.

BACKGROUND: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. METHODS: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. RESULTS: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. CONCLUSIONS: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs.

Cognitive profile of people with mild behavioral impairment in Brain Health Registry participants.

OBJECTIVES: Dementia assessment includes cognitive and behavioral testing with informant verification. Conventional testing is resource-intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. The aim of this study was to assess the relationship between informant-rated behavioral changes and participant-completed neuropsychological test performance in older adults, both measured remotely via an online unsupervised platform, the Brain Health Registry (BHR). DESIGN: Observational cohort study. SETTING: Community-dwelling older adults participating in the online BHR. Informant reports were obtained using the BHR Study Partner Portal. PARTICIPANTS: The final sample included 499 participant-informant dyads. MEASUREMENTS: Participants completed online unsupervised neuropsychological assessment including Forward Memory Span, Reverse Memory Span, Trail Making B, and Go/No-Go tests. Informants completed the Mild Behavioral Impairment Checklist (MBI-C) via the BHR Study Partner portal. Cognitive performance was evaluated in MBI+/- individuals, as was the association between cognitive scores and MBI symptom severity. RESULTS: Mean age of the 499 participants was 67, of which 308/499 were females (61%). MBI + status was associated with significantly lower memory and executive function test scores, measured using Forward and Reverse Memory Span, Trail Making Errors and Trail Making Speed. Further, significant associations were found between poorer objectively measured cognitive performance, in the domains of memory and executive function, and MBI symptom severity. CONCLUSION: These findings support the feasibility of remote, informant-reported behavioral assessment utilizing the MBI-C, supporting its validity by demonstrating a relationship to online unsupervised neuropsychological test performance, using a previously validated platform capable of assessing early dementia risk markers.

Multiband Photogrammetry and Hybrid Image Analysis for the Investigation of a Wall Painting by Paolo de San Leocadio and Francesco Pagano in the Cathedral of Valencia.

A workflow for the photogrammetric combination of non-invasive multispectral imaging techniques ranging from ultraviolet (UV) and visible (VIS) to near infrared (NIR) for the investigation of wall paintings is presented. Hereby, different methods for image analysis and visualisation techniques are discussed. This includes the combination of spectral bands in hybrid false-colour images and image analysis by applying NDVI/NDPI and PCA. The aim of the research is to generate a high-resolution photogrammetric image set, providing information on underdrawings, material differences, damages, painting techniques and conservation measures. The image data are superimposed with pixel accuracy in a geographic information system (GIS) for further analysis, tracing of observations and findings and the annotation of further information. The research is carried out on the 'Adoration of the Shepherds', an early Spanish Renaissance wall painting created in 1472 by Paolo de San Leocadio and Francesco Pagano in the Cathedral of Valencia. The wall painting is preserved in an unfinished condition, and half of it is represented by the initial plaster and preparation layers. This gives the possibility to compare and evaluate the observations of the finished areas as well as carry out an in-depth study of the working techniques.

Risk of burnout and depression: A survey of veterinary anaesthesia specialists in-training during COVID-19.

OBJECTIVE: To investigate risk, risk factors and effects on adherence to adequate clinical standards, of burnout and depression in veterinary anaesthesia residents. STUDY DESIGN: Closed online cross-sectional survey study. STUDY POPULATION: A sample of 89 residents registered to the European and/or the American Colleges of Veterinary An (ae)sthesia and Analgesia out of a total of 185. METHODS: A link to access an online questionnaire, which included the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), the Harvard National Depression Screening Day Scale (HANDS) and 28 questions developed to assess adherence to adequate clinical standards, was sent by email to 185 residents. The three components of the MBI-HSS namely emotional exhaustion (EE), depersonalization and reduced personal accomplishment were analysed separately. Analysis of proportions and two-step regression statistical modelling were used for data analysis, and p values < 0.05 were considered statistically significant. RESULTS: The response rate was 48%. Based on HANDS and MBI-HSS scores, 49% of the residents were at high risk of both depression and burnout. These residents expressed greater concern of delivering inadequate animal care (p < 0.001), of decreased quality of supervision during COVID-19 (p = 0.038) and of negative impact of the pandemic on their training programme (p = 0.002) than residents at low-to-moderate risk. Working in a clinical environment for ≥ 60 hours/week was a risk factor for both depression (p = 0.016) and EE (p = 0.022), while female sex was a risk factor for EE only (p = 0.018). CONCLUSIONS AND CLINICAL RELEVANCE: A large proportion of residents is at high risk of depression and burnout, a scenario likely worsened by the pandemic. The findings of this study suggest that reducing the clinical workload and increasing the level of support and supervision may help to improve residents' mental health.

The variables in the rationing of nursing care in cardiology departments.

BACKGROUND: The rationing of nursing care is a complex process that affects the quality of medical services. PURPOSE: An assessment of the impact of nursing care rationing on burnout and life satisfaction in cardiology departments. METHODS: The study included 217 nurses working in the cardiology department. The Perceived Implicit Rationing of Nursing Care, the Maslach Burnout Inventory, and the Satisfaction with Life Scale were used. RESULTS: A greater emotional exhaustion, the more frequently the rationing of nursing care (r = 0.309, p < 0.061) and the lower the job satisfaction (r=-0.128, p = 0.061). Higher life satisfaction was associated with less frequent rationing of nursing care (r=-0.177, p = 0.01), better quality of care provided (r = 0.285, p < 0.001), and higher job satisfaction (r = 0.348, p < 0.01). CONCLUSION: Higher levels of burnout contribute to more frequent rationing of nursing care, poorer evaluation of the quality of care provided, and lower job satisfaction. Life satisfaction is associated with less frequent rationing of care, better evaluation of the quality of care provided, and greater job satisfaction.

Towards a mechanistic understanding of mindfulness-based stress reduction (MBSR) using an RCT neuroimaging approach: Effects on regulating own stress in social and non-social situations.

Although much research has shown that mindfulness-based interventions (MBIs) can reduce psychological stress, it is less clear if effects generalize to everyday social situations, which range among the largest stress triggers. Furthermore, mechanisms of MBIs have not been fully established. Emotion regulation (ER) has been suggested as one key mechanism, yet the role of cognitive reappraisal and acceptance strategies is still under debate. To address these questions, a neuroimaging-based randomized controlled trial (RCT) was performed (n=68), comparing mindfulness-based stress reduction (MBSR) with a reading/listening intervention (READ), using a novel dyadic paradigm for self and other emotion regulation under stress as primary outcome on behavior and brain levels and established empathy measures (clinicatrials.gov NCT03035669). Compared to READ, MBSR led to self-reported stress reduction through both cognitive reappraisal and acceptance only when regulating self and not when regulating others' distress. In addition, MBSR led to increased brain activation over time for regulating own (parietal cortex) and others' (precuneus, TPJ) emotions through cognitive reappraisal and acceptance, albeit this effect was also seen for the reading intervention for regulating own stress via reappraisal. Brain changes did not scale with subjective stress reduction and amount of meditation practice. More distant generalization effects of MBSR on socio-emotional functioning (cognitive empathy and compassion) could also not be shown. This study identified both cognitive reappraisal and acceptance as two ER mechanisms of MBSR, but indicates that effects do not extend to social settings.

Modification of the Langendorff system of the isolated beating heart for experimental radiotherapy at a synchrotron: 4000†Gy in a heart beat.

Microbeam radiotherapy could help to cure malignant tumours which are currently still considered therapy-resistant. With an irradiation target in the thoracic cavity, the heart would be one of the most important organs at risk. To assess the acute adverse effects of microbeam irradiation in the heart, a powerful ex vivo tool was created by combining the Langendorff model of the isolated beating mammalian heart with X-Tream dosimetry. In a first pilot experiment conducted at the Biomedical and Imaging Beamline of the Australian Synchrotron, the system was tested at a microbeam peak dose approximately ten times higher than the anticipated future microbeam irradiation treatment doses. The entire heart was irradiated with a dose of 4000 Gy at a dose rate of >6000 Gy s-1, using an array of 50 µm-wide microbeams spaced at a centre-to-centre distance of 400 µm. Although temporary arrhythmias were seen, they reverted spontaneously to a stable rhythm and no cardiac arrest occurred. This amazing preservation of cardiac function is promising for future therapeutic approaches.

RETRACTED - Risk factors for mild behavioral impairment in non-demented geriatrics: a population-based survey in Taiwan.

OBJECTIVES: To investigate potential risk factors for mild behavioral impairment (MBI) among non-demented geriatrics. DESIGN: Population-based, cross-sectional survey. SETTING: Taiwan Alzheimer Disease Association (TADA) Database. PARTICIPANTS: Participants were selected by multistage random sampling of all Taiwan counties. They received in-person interviews between December 2011 and March 2013. MEASUREMENTS: Demographic data, lifestyle and habits, medical comorbidities, cognitive status measured by the Taiwanese Mini-Mental Status Examination (TMSE) and presence of MCI of the participants were collected. Subjects were distributed to the MBI and non-MBI groups. These factors had been evaluated for their effects on MBI in the univariate and multivariable logistic regression models. RESULTS: In total, 6,196 non-demented participants aged 65 years or older, including 409 MBI and 5,787 non-MBI participants, were recruited. After adjustment for age, sex, education, body mass index, lifestyle and habits, medical comorbidities, and MCI, good sleep was associated with lower risk of MBI (OR 0.09, 95% CI 0.07 - 0.12). Low body weight (OR 2.01, 95% CI 1.21-3.33), low-to-medium education (OR 1.40, 95%CI 1.06-1.85; OR 2.32, 95% CI 1.67-3.21), medical comorbidities of hypertension (OR 1.56, 95% CI 1.25-1.95), hyperlipidemia (OR 1.29, 95% CI 1.00-1.67), cancer (OR 2.05, 95% CI 1.37-3.06) were significantly associated with increased MBI risk. MCI neither increased nor decreased risk of MBI (OR 1.00, 95% CI 0.76-1.32). CONCLUSIONS: Good sleep was associated with lower MBI risk. Underweight, lower education, medical comorbidities of cancer, hypertension, hyperlipidemia were predictive of MBI.

Burnout Syndrome among Otorhinolaryngologists during the COVID-19 Pandemic.

Background and Objectives: To determine the prevalence of burnout syndrome among otorhinolaryngologists in Lithuania and investigate associations with sociodemographic and professional factors during the COVID-19 pandemic. Materials and Methods: Burnout was measured using the validated Lithuanian version of the Maslach Burnout Inventory. Demographic characteristics and professional characteristics were collected utilizing an anonymous questionnaire. Results: Eighty otorhinolaryngologists (ORL group) and 30 information technology professionals (the control group) were enrolled in this study. A high level of professional burnout in at least one of the subscales was observed in 82.5% of the ORL group subjects. Depersonalization and burnout syndrome were more frequently detected with increasing age in the ORL group (r = 0.2, p < 0.04). Greater satisfaction with salary and working environment resulted in a lower burnout incidence (r = 0.31, p = 0.001). Conclusions: During the COVID-19 pandemic, the incidence of burnout syndrome has been high among Lithuanian otorhinolaryngologists. Demographic and professional characteristics are significantly related to burnout syndrome among Lithuanian otorhinolaryngologists.

Neuropsychiatric symptoms and cerebrovascular risk in non-demented elders: cross-sectional study using the mild behavioural impairment checklist (MBI-C).

BACKGROUND: Neuropsychiatric symptoms (NPS) may represent early clinical manifestations of evolving brain diseases. Studies underpin the occurrence of NPS in the context of mild cognitive impairment (MCI) and prodromal Alzheimer's disease, where symptoms referred to as 'mild behavioural impairment' (MBI) have been shown to predict conversion to dementia and to hasten cognitive/functional decline. However, the association between NPS and cerebrovascular risk factors has been poorly investigated, despite the high prevalence of the latter among individuals with MCI. The aim of the present study was to investigate the association between MBI and cerebrovascular risk in a clinical sample of non-demented elders. METHODS: Sixty-five MCI and 15 cognitively unimpaired older adults were cross-sectionally assessed with the Mild Behavioural Impairment Checklist (MBI-C), using the cut-off score > 6.5 to define positive screening. Participants were submitted to the Hachinski Ischaemic Score (HIS) to account for cerebrovascular symptoms, vascular risk, and related comorbidities. Neuroimaging scans (magnetic resonance imaging and/or 18F-fluorodeoxyglucose-positron emission tomography) and apolipoprotein E genotype were obtained. RESULTS: Positive associations were found between total MBI-C scores and increasing number of comorbidities present (0-2 comorbidities), but not with three comorbidities. Two domains of the MBI-C-impulse dyscontrol and social inappropriateness-followed the same trend of the MBI-C total score, with higher scores with the increasing numbers of comorbidities. No significant associations were found between MBI symptoms and HIS or cerebrovascular burden in neuroimaging assessment. CONCLUSION: We found weak associations between MBI-C total score and the presence of comorbidities with cerebrovascular risk, but not with structural or functional neuroimaging abnormalities or HIS. This finding may represent that the presence of comorbidities adds limited risk to the occurrence of MBI in this sample of non-demented elders.

Prevalence of mild behavioural impairment domains: a meta-analysis.

BACKGROUND: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta-analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. METHODS: A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta-analysis using a random effects model and meta-regression was performed. RESULTS: Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta-analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44-42.5%), 26.67% (95% CI 18.24-37.23%), 12.58% (95% CI 6.93-21.75%), 6.05% (95% CI 3.44-10.42%), and 2.81% (95% CI 1.67-4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta-regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. CONCLUSIONS: AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.

Assessment of the in vitro cytochrome P450 (CYP) inhibition potential of nafithromycin, a next generation lactone ketolide antibiotic.

Nafithromycin is a next generation lactone ketolide antibiotic slated to enter phase III clinical development in India for the treatment of CABP as a shorter 800 mg-OD X3 day therapeutic regimen. Nafithromycin exhibits potent activity against MDR Streptococcus pneumoniae including erythromycin and telithromycin-resistant resistant strains. Older macrolides/ketolides are reported to be potent inhibitors of CYP3A4/5. To facilitate comparative assessment of drug-drug interaction potential, CYP inhibitory activities of nafithromycin was evaluated in comparison with clarithromycin, telithromycin, cethromycin and solithromycin. CYP inhibitory activities were assessed against key CYP isoforms (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and CYP3A4/5) using human liver microsomes. Additionally, time-dependent inhibition (TDI), metabolism-based inhibition (MBI) and k inact /K I activities were also investigated for CYP3A4/5. Nafithromycin did not inhibit key CYP enzymes and was found to be a weak inhibitor of CYP3A4/5. Comparator antibiotics were found to be potent inhibitors with 2- to 50-fold leftward shifts in CYP3A4/5 IC50 values, while such shift was not noted for nafithromycin. k inact /K I ratio of nafithromycin was 3- to 153-fold lower than comparator drugs, further substantiating its lower affinity for CYP3A4/5. In sum, weaker inhibition and lower k inact /K I ratio for CYP3A4/5, points towards nafithromycin's lower propensities towards clinical drug-drug interactions as compared to other macrolides/ketolides antibiotics.

Molecular Breast Imaging in Clinical Practice.

OBJECTIVE. The purpose of this article is to review clinical uses and image interpretation of molecular breast imaging (MBI) and clarify radiation risks. CONCLUSION. MBI detects additional cancers compared with conventional imaging in women with dense breasts and those with elevated risk of breast cancer. Its role as an imaging biomarker of cancer risk and in assessing neoadjuvant chemotherapy response is growing. Radiation risk is minimal; benefit-to-risk ratio is similar to that of mammography. MBI is low cost, well tolerated, and easily adapted into clinical practice.

Profile of mild behavioral impairment and factor structure of the Mild Behavioral Impairment Checklist in cognitively normal older adults.

OBJECTIVES: In this large population study, we set out to examine the profile of mild behavioral impairment (MBI) by using the Mild Behavioral Impairment Checklist (MBI-C) and to explore its factor structure when employed as a self-reported and informant-rated tool. DESIGN: This was a population-based cohort study. SETTING: Participants were recruited from the Platform for Research Online to Investigate Genetics and Cognition in Aging study (https://www.protect-exeter.org.uk). PARTICIPANTS: A total of 5,742 participant-informant dyads participated in the study. MEASUREMENTS: Both participants and informants completed the MBI-C. The factor structure of the MBI-C was evaluated by exploratory factor analysis. RESULTS: The most common MBI-C items, as rated by self-reported and informants, related to affective dysregulation (mood/anxiety symptoms), being present in 34% and 38% of the sample, respectively. The least common items were those relating to abnormal thoughts and perception (psychotic symptoms) (present in 3% and 6% of the sample, respectively). Only weak correlations were observed between self-reported and informant-reported MBI-C responses. Exploratory factor analysis for both sets of respondent answers indicated that a five-factor solution for the MBI-C was appropriate, reflecting the hypothesized structure of the MBI-C. CONCLUSION: This is the largest and most detailed report on the frequency of MBI symptoms in a nondementia sample. The full spectrum of MBI symptoms was present in our sample, whether rated by self-reported or informant report. However, we show that the MBI-C performs differently in self-reported versus informant-reported situations, which may have important implications for the use of the questionnaire in clinic and research.