A global metagenomic map of urban microbiomes and antimicrobial resistance.

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.

Maternal starvation primes progeny response to nutritional stress.

Organisms adapt to environmental changes in order to survive. Mothers exposed to nutritional stresses can induce an adaptive response in their offspring. However, the molecular mechanisms behind such inheritable links are not clear. Here we report that in Drosophila, starvation of mothers primes the progeny against subsequent nutritional stress. We found that RpL10Ab represses TOR pathway activity by genetically interacting with TOR pathway components TSC2 and Rheb. In addition, starved mothers produce offspring with lower levels of RpL10Ab in the germline, which results in higher TOR pathway activity, conferring greater resistance to starvation-induced oocyte loss. The RpL10Ab locus encodes for the RpL10Ab mRNA and a stable intronic sequence RNA (sisR-8), which collectively repress RpL10Ab pre-mRNA splicing in a negative feedback mechanism. During starvation, an increase in maternally deposited RpL10Ab and sisR-8 transcripts leads to the reduction of RpL10Ab expression in the offspring. Our study suggests that the maternally deposited RpL10Ab and sisR-8 transcripts trigger a negative feedback loop that mediates intergenerational adaptation to nutritional stress as a starvation response.

A window of opportunity: Adverse childhood experiences and time alone with a provider in the United States.

BACKGROUND: To date, there is limited literature on the relationship between Adverse Childhood Experiences (ACEs) and the quality of health care provider encounters. This is key, as people with a history of ACEs have a greater burden of illness. METHODS: This study uses data from the 2020-2021 National Survey of Children's Health to examine relationships between ACEs and (1) spending less than ten minutes with a health care provider, and (2) spending time alone with a health care provider. RESULTS: In general, our results suggested most ACEs were associated with higher odds of a provider spending <10 min with a child during their last preventative care visit, while ACEs were inconsistently related to spending time alone with a provider. Each additional ACE was found to be associated with higher odds of both outcomes. CONCLUSIONS: This work emphasizes the importance of ACEs screening in a health care setting and may set the groundwork for future research investigating mechanisms within these associations. Given the established link between health care quality and patient-provider trust, and health outcomes, intervention work is needed to develop healthcare practices that may encourage the length and quality of health care provider visits.

Decompression alone versus decompression with fusion in patients with lumbar spinal stenosis with degenerative spondylolisthesis: a systematic review and meta-analysis.

INTRODUCTION: Surgical decompression is standard care in the treatment of degenerative spondylolisthesis in patients with symptomatic lumbar spinal stenosis, but there remains controversy over the benefits of adding fusion. The persistent lack of consensus on this matter and the availability of new data warrants a contemporary systematic review and meta-analysis of the literature. METHODS: Multiple online databases were systematically searched up to October 2022 for randomized controlled trials (RCTs) and prospective studies comparing outcomes of decompression alone versus decompression with fusion for lumbar spinal stenosis in patients with degenerative spondylolisthesis. Primary outcome was the Oswestry Disability Index. Secondary outcomes included leg and back pain, surgical outcomes, and radiological outcomes. Pooled effect estimates were calculated and presented as mean differences (MD) with their 95% confidence intervals (CI) at two-year follow-up. RESULTS: Of the identified 2403 studies, eventually five RCTs and two prospective studies were included. Overall, most studies had a low or unclear risk of selection bias and most studies were focused on low grade degenerative spondylolisthesis. All patient-reported outcomes showed low statistical heterogeneity. Overall, there was high-quality evidence suggesting no difference in functionality at two years of follow-up (MD - 0.31, 95% CI - 3.81 to 3.19). Furthermore, there was high-quality evidence of no difference in leg pain (MD - 1.79, 95% CI - 5.08 to 1.50) or back pain (MD - 2.54, 95% CI - 6.76 to 1.67) between patients undergoing decompression vs. decompression with fusion. Pooled surgical outcomes showed less blood loss after decompression only, shorter length of hospital stay, and a similar reoperation rate compared to decompression with fusion. CONCLUSION: Based on the current literature, there is high-quality evidence of no difference in functionality after decompression alone compared to decompression with fusion in patients with degenerative lumbar spondylolisthesis at 2 years of follow-up. Further studies should focus on long-term comparative outcomes, health economic evaluations, and identifying those patients that may benefit more from decompression with fusion instead of decompression alone. This review was registered at Prospero (CRD42021291603).

Telemedical Support Using Smartphones for Spine Surgery in Low- and Middle-Income Countries.

Objective: Low- and middle-income countries (LMICs) face many challenges compared to industrialized nations, most notably in regard to the health care system. Patients often have to travel long distances to receive medical care with few reliable transportation mechanisms. In time-critical emergencies, this is a significant disadvantage. One specialty that is particularly affected by this is spine surgery. Within this field, traumatic injuries and acutely compressive pathologies are often time-critical. Increasing global networking capabilities through internet access offers the possibility for telemedical support in remote regions. Recently, high-performance cameras and processors became available in commercially available smartphones. Due to their wide availability and ease of use, this could provide a unique opportunity to offer telemedical support in LMICs. Methods: We conducted a feasibility study with a neurosurgical institution in east Africa. To ensure telemedical support, a commercially available smartphone was selected as the experimental hardware. Preoperatively, resolution, contrast, brightness, and color reproduction were assessed under theoretical conditions using a test chart. Intraoperatively, the image quality was assessed under different conditions. In the first step, the instrumentation table was displayed, and the mentor surgeon marked an instrument that the mentee surgeon should recognize correctly. In the next evaluation step, the surgical field was shown on film and the mentor surgeon marked an anatomical structure, and in the last evaluation step, the screen of the X-ray machine was captured, and the mentor surgeon again marked an anatomical structure. Subjective image quality was rated by two independent reviewers using the similar modified Likert scale as before on a scale of 1-5, with 1 indicating inadequate quality and 5 indicating excellent quality. Results: The image quality during the video calls was rated as sufficient overall. When evaluating the test charts, a quality of 97% ± 5 on average was found for the chart with the white background and a quality of 84% ± 5 on average for the chart with the black background. The color reproduction, the contrast, and the reproduction of brightness were rated excellent. Intraoperatively, the visualization of the instrument table was also rated excellent. Visualization of the operative site was rated 1.5 ± 0.5 on average and it was not possible to recognize relevant anatomical structures with the required confidence for surgical procedures. Image quality of the X-ray screen was rated 1.5 ± 0.9 on average. Conclusion: Current generation smartphones have high imaging performance, high computing power, and excellent connectivity. However, relevant anatomical structures during spine surgery procedures and on the X-ray screen in the operating room could not be identified with reliability to provide adequate surgical support. Nevertheless, our study showed the potential in smartphones supporting surgical procedures in LMICs, which could be helpful in other surgical fields.

Circular sisRNA identification and characterisation.

Stable Intronic Sequence RNA (sisRNA) is a relatively new class of non-coding RNA. Found in many organisms, these sisRNA produced from their host genes are generally involved in regulatory roles, controlling gene expression at multiple levels through active involvement in regulatory feedback loops. Large scale identification of sisRNA via genome-wide RNA sequencing has been difficult, largely in part due to its low abundance. Done on its own, RNA sequencing often yields a large mass of information that is ironically uninformative; the potential sisRNA reads being masked by other highly abundant RNA species like ribosomal RNA and messenger RNA. In this review, we present a practical workflow for the enrichment of circular sisRNA through the use of transcriptionally quiescent systems, rRNA-depletion, and RNase R treatment prior to deep sequencing. This workflow allows circular sisRNA to be reliably detected. We also present various methods to experimentally validate the circularity and stability of the circular sisRNA identified, as well as a few methods for further functional characterisation.

Feasibility of smart glasses in supporting spinal surgical procedures in low- and middle-income countries: experiences from East Africa.

OBJECTIVE: Telemedicine technology has been developed to allow surgeons in countries with limited resources to access expert technical guidance during surgical procedures. The authors report their initial experience using state-of-the-art wearable smart glasses with wireless capability to transmit intraoperative video content during spine surgery from sub-Saharan Africa to experts in the US. METHODS: A novel smart glasses system with integrated camera and microphone was worn by a spine surgeon in Dar es Salaam, Tanzania, during 3 scoliosis correction surgeries. The images were transmitted wirelessly through a compatible software system to a computer viewed by a group of fellowship-trained spine surgeons in New York City. Visual clarity was determined using a modified Snellen chart, and a percentage score was determined on the smallest line that could be read from the 8-line chart on white and black backgrounds. A 1- to 5-point scale (from 1 = unrecognizable to 5 = optimal clarity) was used to score other visual metrics assessed using a color test card including hue, contrast, and brightness. The same scoring system was used by the group to reach a consensus on visual quality of 3 intraoperative points including instruments, radiographs (ability to see pedicle screws relative to bony anatomy), and intraoperative surgical field (ability to identify bony landmarks such as transverse processes, pedicle screw starting point, laminar edge). RESULTS: All surgeries accomplished the defined goals safely with no intraoperative complications. The average download and upload connection speeds achieved in Dar es Salaam were 45.21 and 58.89 Mbps, respectively. Visual clarity with the modified white and black Snellen chart was 70.8% and 62.5%, respectively. The average scores for hue, contrast, and brightness were 2.67, 3.33, and 2.67, respectively. Visualization quality of instruments, radiographs, and intraoperative surgical field were 3.67, 1, and 1, respectively. CONCLUSIONS: Application of smart glasses for telemedicine offers a promising tool for surgical education and remote training, especially in low- and middle-income countries. However, this study highlights some limitations of this technology, including optical resolution, intraoperative lighting, and internet connection challenges. With continued collaboration between clinicians and industry, future iterations of smart glasses technology will need to address these issues to stimulate robust clinical utilization.

Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity.

BACKGROUND: Atopic dermatitis (AD) is a common skin disease affecting up to 20% of the global population, with significant clinical heterogeneity and limited information about molecular subtypes and actionable biomarkers. Although alterations in the skin microbiome have been described in subjects with AD during progression to flare state, the prognostic value of baseline microbiome configurations has not been explored. OBJECTIVE: Our aim was to identify microbial signatures on AD skin that are predictive of disease fate. METHODS: Nonlesional skin of patients with AD and healthy control subjects were sampled at 2 time points separated by at least 4 weeks. Using whole metagenome analysis of skin microbiomes of patients with AD and control subjects (n = 49 and 189 samples), we identified distinct microbiome configurations (dermotypes A and B). Blood was collected for immunophenotyping, and skin surface samples were analyzed for correlations with natural moisturizing factors and antimicrobial peptides. RESULTS: Dermotypes were robust and validated across 2 additional cohorts (63 individuals), with strong enrichment of subjects with AD in dermotype B. Dermotype B was characterized by reduced microbial richness, depletion of Cutibacterium acnes, Dermacoccus and Methylobacterium species, individual-specific outlier abundance of Staphylococcus species (eg, S epidermidis, S capitis, S aureus), and enrichment in metabolic pathways (eg, branched chain amino acids and arginine biosynthesis) and virulence genes (eg, ß-toxin, δ-toxin) that defined a pathogenic ecology. Skin surface and circulating host biomarkers exhibited a distinct microbial-associated signature that was further reflected in more severe itching, frequent flares, and increased disease severity in patients harboring the dermotype B microbiome. CONCLUSION: We report distinct clusters of microbial profiles that delineate the role of microbiome configurations in AD heterogeneity, highlight a mechanism for ongoing inflammation, and provide prognostic utility toward microbiome-based disease stratification.

The liver-gut microbiota axis modulates hepatotoxicity of tacrine in the rat.

The gut microbiota possesses diverse metabolic activities, but its contribution toward heterogeneous toxicological responses is poorly understood. In this study, we investigated the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics, and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variations in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g., Lactobacillus, Bacteroides, and Enterobacteriaceae) and approximately 9% higher ß-glucuronidase gene abundance compared with nonresponders. In the validation study, coadministration with oral ß-glucuronidase derived from Escherichia coli and pretreatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. CONCLUSION: This study establishes pertinent gut microbial influences in modifying the hepatotoxicity of tacrine, providing insights for personalized medicine initiatives. (Hepatology 2018;67:282-295).

Validity and reliability of the ten-item Connor-Davidson Resilience Scale (CD-RISC10) instrument in patients with axial spondyloarthritis (axSpA) in Singapore.

We aimed to assess the validity and reliability of the ten-item Connor-Davidson Resilience Scale (CD-RISC10) in patients with axial spondyloarthritis (axSpA) in Singapore. We used cross-sectional data from 108 patients with axSpA recruited from a dedicated axSpA clinic in a Singapore tertiary referral hospital from 2017 to 2018. Analyses were guided by the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework. Face validity was assessed through cognitive debriefing interviews (CDIs). Internal consistency was assessed through Cronbach's alpha. Test-retest reliability was assessed through intraclass correlation (ICC). Measurement error was assessed through smallest detectable change (SDC). Construct validity was assessed through six a priori hypotheses through correlation of the CD-RISC10 score with other patient-reported outcome measures. Structural validity was assessed using confirmatory factor analysis (CFA). Fit indices evaluated were root-mean-square error of approximation (RMSEA), comparative fit index (CFI), Tucker-Lewis index (TFI), and standardized root-mean-squared residual (SRMR). Ten patients completed the CDIs and face validity was supported. Among 108 patients (median age: 37(21-77), 81.5% males, 93.5% Chinese), the CD-RISC10 demonstrated good internal consistency (Cronbach's alpha = 0.94), and excellent test-retest reliability [ICC = 0.964 (95% CI 0.937-0.980)]. SDC was calculated as 1.88. Construct validity was established by meeting five out of the six a priori hypotheses. Structural validity was supported as CFA confirmed a one-factor model, with adequate fit statistics after adding three covariances (RMSEA = 0.077; CFI = 0.975; TLI = 0.964; SRMR = 0.036). This study supports the CD-RISC10 as a valid and reliable measure of resilience for use in patients with axSpA.

Intrafractional motion management in external beam radiotherapy.

The recent advancements in radiotherapy technologies have made delivery of the highly conformal dose to the target volume possible. With the increasing popularity of delivering high dose per fraction in modern radiotherapy schemes such as in stereotactic body radiotherapy and stereotactic body ablative therapy, high degree of treatment precision is essential. In order to achieve this, we have to overcome the potential difficulties caused by patient instability due to immobilization problems; patient anxiety and random motion due to prolonged treatment time; tumor deformation and baseline shift during a treatment course. This is even challenging for patients receiving radiotherapy in the chest and abdominal regions because it is affected by the patient's respiration which inevitably leads to tumor motion. Therefore, monitoring of intrafractional motion has become increasingly important in modern radiotherapy. Major intrafractional motion management strategies including integration of respiratory motion in treatment planning; breath-hold technique; forced shallow breathing with abdominal compression; respiratory gating and dynamic real-time tumor tracking have been developed. Successful intrafractional motion management is able to reduce the planning target margin and ensures planned dose delivery to the target and organs at risk. Meanwhile, the emergency of MRI-linear accelerator has facilitated radiation-free real-time monitoring of soft tissue during treatment and could be the future modality in motion management. This review article summarizes the various approaches that deal with intrafractional target, organs or patient motion with discussion of their advantages and limitations. In addition, the potential future advancements including MRI-based tumor tracking are also discussed.

Combining images and anatomical knowledge to improve automated vein segmentation in MRI.

PURPOSE: To improve the accuracy of automated vein segmentation by combining susceptibility-weighted images (SWI), quantitative susceptibility maps (QSM), and a vein atlas to produce a resultant image called a composite vein image (CV image). METHOD: An atlas was constructed in common space from manually traced MRI images from ten volunteers. The composite vein image was derived for each subject as a weighted sum of three inputs; an SWI image, a QSM image and the vein atlas. The weights for each input and each anatomical location, called template priors, were derived by assessing the accuracy of each input over an independent data set. The accuracy of vein segmentations derived automatically from each of the CV image, SWI, and QSM image sets was assessed by comparison with manual tracings. Three different automated vein segmentation techniques were used, and ten performance metrics evaluated. RESULTS: Vein segmentations using the CV image were comprehensively better than those derived from SWI or QSM images (mean Cohen's d = 1.1). Sixty permutations of performance metric, benchmark image, and automated segmentation technique were evaluated. Vein identification improvements that were both large and significant (Cohen's d > 0.80, p < 0.05) were found in 77% of the permutations, compared to no improvement in 5%. CONCLUSION: The accuracy of automated vein segmentations derived from the composite vein image was overwhelmingly superior to segmentations derived from SWI or QSM alone.

7T-fMRI: Faster temporal resolution yields optimal BOLD sensitivity for functional network imaging specifically at high spatial resolution.

Recent developments in accelerated imaging methods allow faster acquisition of high spatial resolution images. This could improve the applications of functional magnetic resonance imaging at 7 Tesla (7T-fMRI), such as neurosurgical planning and Brain Computer Interfaces (BCIs). However, increasing the spatial and temporal resolution will both lead to signal-to-noise ratio (SNR) losses due to decreased net magnetization per voxel and T1-relaxation effect, respectively. This could potentially offset the SNR efficiency gains made with increasing temporal resolution. We investigated the effects of varying spatial and temporal resolution on fMRI sensitivity measures and their implications on fMRI-based BCI simulations. We compared temporal signal-to-noise ratio (tSNR), observed percent signal change (%∆S), volumes of significant activation, Z-scores and decoding performance of linear classifiers commonly used in BCIs across a range of spatial and temporal resolution images acquired during an ankle-tapping task. Our results revealed an average increase of 22% in %∆S (p=0.006) and 9% in decoding performance (p=0.015) with temporal resolution only at the highest spatial resolution of 1.5×1.5×1.5mm3, despite a 29% decrease in tSNR (p<0.001) and plateaued Z-scores. Further, the volume of significant activation was indifferent (p>0.05) across spatial resolution specifically at the highest temporal resolution of 500ms. These results demonstrate that the overall BOLD sensitivity can be increased significantly with temporal resolution, granted an adequately high spatial resolution with minimal physiological noise level. This shows the feasibility of diffuse motor-network imaging at high spatial and temporal resolution with robust BOLD sensitivity with 7T-fMRI. Importantly, we show that this sensitivity improvement could be extended to an fMRI application such as BCIs.

Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study.

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a "research priorities" consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and ClavisporaAspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.

Cerebral quantitative susceptibility mapping predicts amyloid-ß-related cognitive decline.

See Derry and Kent (doi:10.1093/awx167) for a scientific commentary on this article.The large variance in cognitive deterioration in subjects who test positive for amyloid-ß by positron emission tomography indicates that convergent pathologies, such as iron accumulation, might combine with amyloid-ß to accelerate Alzheimer's disease progression. Here, we applied quantitative susceptibility mapping, a relatively new magnetic resonance imaging method sensitive to tissue iron, to assess the relationship between iron, amyloid-ß load, and cognitive decline in 117 subjects who underwent baseline magnetic resonance imaging and amyloid-ß positron emission tomography from the Australian Imaging, Biomarkers and Lifestyle study (AIBL). Cognitive function data were collected every 18 months for up to 6 years from 100 volunteers who were either cognitively normal (n = 64) or diagnosed with mild cognitive impairment (n = 17) or Alzheimer's disease (n = 19). Among participants with amyloid pathology (n = 45), higher hippocampal quantitative susceptibility mapping levels predicted accelerated deterioration in composite cognition tests for episodic memory [ß(standard error) = -0.169 (0.034), P = 9.2 × 10-7], executive function [ß(standard error) = -0.139 (0.048), P = 0.004), and attention [ß(standard error) = -0.074 (0.029), P = 0.012]. Deteriorating performance in a composite of language tests was predicted by higher quantitative susceptibility mapping levels in temporal lobe [ß(standard error) = -0.104 (0.05), P = 0.036] and frontal lobe [ß(standard error) = -0.154 (0.055), P = 0.006]. These findings indicate that brain iron might combine with amyloid-ß to accelerate clinical progression and that quantitative susceptibility mapping could be used in combination with amyloid-ß positron emission tomography to stratify individuals at risk of decline.

Iron accumulation in the basal ganglia in Huntington's disease: cross-sectional data from the IMAGE-HD study.

OBJECTIVES: To measure iron accumulation in the basal ganglia in Huntington's disease (HD) using quantitative susceptibility mapping (QSM), and to ascertain its relevance in terms of clinical and disease severity. METHODS: In this cross-sectional investigation, T2* weighted imaging was undertaken on 31 premanifest HD, 32 symptomatic HD and 30 control participants as part of the observational IMAGE-HD study. Group differences in iron accumulation were ascertained with QSM. Associations between susceptibility values and disease severity were also investigated. RESULTS: Compared with controls, both premanifest and symptomatic HD groups showed significantly greater iron content in pallidum, putamen and caudate. Additionally, iron accumulation in both putamen and caudate was significantly associated with disease severity. CONCLUSIONS: These findings provide the first evidence that QSM is sensitive to iron deposition in subcortical target areas across premanifest and symptomatic stages of HD. Such findings could open up new avenues for biomarker development and therapeutic intervention.

MRI-based glomerular morphology and pathology in whole human kidneys.

Nephron number (N(glom)) and size (V(glom)) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess N(glom) and V(glom) in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure N(glom) and V(glom) in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an ~6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.

Event-based prospective memory is independently associated with self-report of medication management in older adults.

BACKGROUND: Identifying potentially modifiable risk factors for medication non-adherence in older adults is important in order to enhance screening and intervention efforts designed to improve medication-taking behavior and health outcomes. The current study sought to determine the unique contribution of prospective memory (PM) (i.e. 'remembering to remember') to successful self-reported medication management in older adults. METHODS: Sixty-five older adults with current medication prescriptions completed a comprehensive research evaluation of sociodemographic, psychiatric, and neurocognitive functioning, which included the memory for adherence to medication scale (MAMS), prospective and retrospective memory questionnaire (PRMQ), and a performance-based measure of PM that measured both semantically related and semantically unrelated cue-intention (i.e. when-what) pairings. RESULTS: A series of hierarchical regressions controlling for biopsychosocial, other neurocognitive, and medication-related factors showed that elevated complaints on the PM scale of the PRMQ and worse performance on an objective semantically unrelated event-based PM task were independent predictors of poorer medication adherence as measured by the MAMS. CONCLUSIONS: PM plays an important role in self-report of successful medication management among older adults. Findings may have implications for screening for older individuals 'at risk' of non-adherence, as well as the development of PM-based interventions to improve medication adherence and, ultimately, long-term health outcomes in older adults.

Carotid stenosis: a risk factor for cerebral white-matter disease.

BACKGROUND: We sought to study the association between carotid stenosis and white-matter hyperintensity (WMH) among patients without intracranial large-vessel stenosis. METHODS: This was a prospective study of patients with acute lacunar infarcts without concomitant intracranial large-vessel stenosis having undergone carotid ultrasonography. WMH was quantified using the modified Fazekas scale. Patients were grouped into quartiles based on the degree of carotid stenosis. The association among carotid stenosis, vascular risk factors, and WMH were modeled using logistic regression analysis. RESULTS: In all, 100 patients with a mean age of 56.2 ± 11.7 years were studied. The quartile with the greatest carotid stenosis had a mean internal/common carotid artery peak systolic velocity ratio of 2.36. Total WMH was 4.64 in the highest quartile and 2.52 in the lowest quartile of carotid stenosis. Periventricular (pv)-WMH was significantly greater between the highest and lowest quartiles (2.80 versus 1.28, P = .025). No significant difference was observed for deep subcortical WMH (1.84 versus 1.24, P = .281). With increasing carotid stenosis, increase in both ipsilateral and contralateral pv-WMH was observed. When patients with significant carotid stenosis were compared to those without significant carotid stenosis, pv-WMH was significantly higher in the group with significant stenosis even after correcting for age and comorbid vascular risk factors (odds ratio 1.24; confidence interval 1.0-1.54). CONCLUSIONS: Carotid stenosis is an important risk factor for WMH. Volumes of pv-WMH significantly increase with higher grades of carotid stenosis.

Q&A with Jun Wei Pek and Amanda Yunn Ee Ng.

Investigator Jun Wei Pek (J.P.) and graduate student Amanda Yunn Ee Ng (A.Y.) spoke to Cell Reports about their scientific journeys and love of science, their work on gene expression regulation during reproductive development, and challenges encountered during the pandemic.