Reaching the unreached through building trust: a mixed-method study on COVID-19 vaccination in rural Lao PDR.

INTRODUCTION: The global COVID-19 vaccine rollout has been impacted by socioeconomic disparities and vaccine hesitancy, but few studies examine reasons for changed attitudes. In Lao People's Democratic Republic (Lao PDR), a nationwide government-led initiative was developed in response to COVID-19, focused on community health ownership and trust in primary healthcare. The intervention team including health and governance sectors conducted capacity-building workshops with local staff and community representatives and visited villages for vaccination outreach. This study investigates the impact of this intervention on COVID-19 vaccine acceptance in rural communities. METHODS: Conducted in Xiengkhuang province, Lao PDR, from December 2022 to February 2023, the study employed a sequential mixed-methods research design. Data on vaccinated individuals from 25 villages were collected from 11 primary healthcare units; pre-post analysis was applied. Qualitative data, gathered through interviews and focus group discussions with villagers, village authorities, health staff and local government (n=102) in six villages, underwent inductive thematic analysis. RESULTS: First-dose vaccine uptake after the intervention increased significantly (6.9 times). Qualitative analysis identified key reasons for vaccination hesitancy: (1) mistrust due to rumours and past experiences; (2) poor communication and inconsistent messaging and (3) challenges in access for priority groups. Influencing factors during the intervention included (1) effective local-context communication; (2) leveraging existing community structures and influential individuals in a multisectoral approach and (3) increased community motivation through improved satisfaction, ownership and relationships. CONCLUSION: This study highlights the impact and methods of building trust with unreached populations in health interventions, emphasising locally led solutions. Successful reversal of vaccine hesitancy was achieved by addressing root causes and fostering ownership at community and local government levels through a 'positive approach'. This diverges from conventional supplemental immunisation activities and holds potential for systematically building trust between unreached populations and health systems. Further research could explore the impacts of routine vaccination for sustained improvements in health equity.

Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ.

Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1ß (IL-1ß), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1ß concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.

Pedicle screw pull-out testing in polyurethane foam blocks: Effect of block orientation and density.

Synthetic bone models such as polyurethane (PU) foam are a well-established substitute to cadaveric bone for screw pull-out testing; however, little attention has been given to the effect of PU foam anisotropy on orthopaedic implant testing. Compressive and screw pull-out performance in three PU foam densities; 0.16 g/cm3 (PCF 10), 0.32 g/cm3 (PCF 20) and 0.64 g/cm3 (PCF 40) were performed in each of the X, Y or Z orientations. The maximum compressive force, stiffness in the linear region, maximum stress and modulus were determined for all compression tests. Pedicle screws were inserted and pulled out axially to determine maximum pull-out force, energy to failure and stiffness. One-way ANOVA and post hoc tests were used to compare outcome variables between PU foam densities and orientations, respectively. Compression tests demonstrated the maximum force was significantly different between all orientations for PCF 20 (X, Y and Z) while stiffness and maximum stress were different between X versus Y and X versus Z. Maximum pull-out force was significantly different between all orientations for PCF 10 foam. No significant differences were noted for other foam densities. There is potential for screw pull-out testing results to be significantly affected by orientation in lower density PU foams. It is recommended that a single, known orientation of the PU foam block be used for experimental testing.

Trauma Bay Evaluation and Resuscitative Decision-Making.

The reader of this article will now have the ability to reflect on all aspects of high-quality trauma bay care, from resuscitation to diagnosis and leadership to debriefing. Although there is no replacement for experience, both clinically and in a simulation environment, trauma clinicians are encouraged to make use of this article both as a primer at the beginning of a trauma rotation and a reference text to revisit after difficult cases in the trauma bay. Also, periods of reflection seem appropriate in the busy but, of course, rewarding career in trauma care.

Through the looking glass: empowering youth community advisory boards in Tanzania as a sustainable youth engagement model to inform policy and practice.

More young people are living in the world than ever before, 90% of whom reside in low and middle income countries (LMICs). To address their needs, it is critical to have sustainable youth engagement when determining policy and to advance effective implementation of youth-focused interventions. Youth Community Advisory Boards (CABs) are a sustainable mechanism to achieve this goal. This paper describes engagement with youth CAB members across four locations in Tanzania. To set youth CAB meeting agendas and priorities, we asked youth CAB members to write (using free text) the top five challenges faced by young people in their communities (highest to lower priority). The Google Forms survey link was presented at the May 2023 youth CAB meeting and disseminated through WhatsApp. The survey was completed by smartphone, tablet, or paper provided to the youth liaison for data entry. Results were translated from Swahili to English and coded using excel. Findings were then presented back to the youth CABs at the September 2023 meeting. At that meeting, youth CAB members were then asked to write (free text) potential solutions to the most commonly described challenges. The surveys had response rates of 90% (84/93) for challenges and 78% (71/93) for solutions. The number one reported challenge was unemployment and financial instability (45%). Gender based violence (13%), sexual reproductive health issues (8%), and alcohol and drug use (8%) were in the top four both by priority and frequency of report. Other important challenges included physical and mental health, malnutrition, relationships, education, and societal and environmental norms, among others. Solutions included job creation, improved education, expanded legal systems, youth-friendly health care services, and increased social support through peer networks and community support. The National Accelerated Action and Investment Agenda for Adolescent Health and Wellbeing (NAIA-AHW) 2021/22-2024/25 includes most, but not all, of these top challenges and solutions. Ensuring young people have a seat at the policy table is critical to effective youth-empowerment in health and other related programs. Including a youth CAB member to represent this collective in youth-related government activities is a sustainable model to achieve this goal.

Association between functional network connectivity, retina structure and microvasculature, and visual performance in patients after thalamic stroke: An exploratory multi-modality study.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmologic symptoms and retinal changes have been increasingly observed following thalamic stroke, and there is mounting evidence indicating distinct alterations occurring in the vision-related functional network. However, the intrinsic correlations between these changes are not yet fully understood. Our objective was to explore the altered patterns of functional network connectivity and retina parameters, and their correlations with visual performance in patients with thalamic stroke. METHODS: We utilized resting-state functional MRI to obtain multi-modular functional connectivity (FC), and optical coherence tomography-angiography to measure various retina parameters, such as the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), superficial vascular complex (SVC), and deep vascular complex. Visual acuity (VA) was used as a metric for visual performance. RESULTS: We included 46 patients with first-ever unilateral thalamic stroke (mean age 59.74 ± 10.02 years, 33 males). Significant associations were found between FC of attention-to-default mode and SVC, RNFL, and GCIPL, as well as between FC of attention-to-visual and RNFL (p < .05). Both RNFL and GCIPL exhibited significant associations with FC of visual-to-visual (p < .05). Only GCIPL showed an association with VA (p = .038). Stratified analysis based on a disease duration of 6 months revealed distinct and significant linking patterns in multi-modular FC and specific retina parameters, with varying correlations with VA in each subgroup. CONCLUSION: These findings provide valuable insight into the neural basis of the associations between brain network dysfunction and impaired visual performance in patients with thalamic stroke. Our novel findings have the potential to inform future targeted and individualized therapies. However, further comprehensive studies are necessary to validate our results.

Correlation between serum biomarkers, brain volume, and retinal neuronal loss in early-onset Alzheimer's disease.

PURPOSE: To compare the peripapillary retinal nerve fiber layer (pRNFL), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) thickness measurement in early-onset Alzheimer's disease (EOAD) and controls using spectral domain optical coherence tomography (SD-OCT). We also assessed the relationship between SD-OCT measurements and cognitive measures, serum biomarkers for Alzheimer's disease (AD), and cerebral microstructural volume. METHODS: pRNFL, RNFL, and GCC thicknesses were measured in 43 EOAD and 42 controls using SD-OCT. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status, magnetic resonance imaging (MRI) tool was used to quantify cerebral microstructural volume, and serum biomarkers were quantified from peripheral blood. RESULTS: EOAD patients had thinner pRNFL (P < 0.001), RNFL (P = 0.008), and GCC (P = 0.018) thicknesses compared to controls after adjusting for multiple factors. pRNFL thickness correlated (P = 0.016) with serum t-tau level. Serum Aß42 (P < 0.05) concentration correlated with RNFL thickness. Importantly, occipital lobe volume (P = 0.010) correlated with GCC thicknesses in EOAD patients. CONCLUSION: Our findings suggest that retinal thickness may be useful markers for assessing neurodegenerative process in EOAD.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

AIMS: Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. METHODS: Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. RESULTS: We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). CONCLUSION: Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

The Association of Retinal Microvasculature With Gray Matter Changes and Structural Covariance Network: A Voxel-Based Morphometry Study.

Purpose: Increasing evidence suggests that retinal microvasculature may reflect global cerebral atrophy. However, little is known about the relation of retinal microvasculature with specific brain regions and brain networks. Therefore, we aimed to unravel the association of retinal microvasculature with gray matter changes and structural covariance network using a voxel-based morphometry (VBM) analysis. Methods: One hundred and forty-four volunteers without previously known neurological diseases were recruited from West China Hospital, Sichuan University between April 1, 2021, and December 31, 2021. Retinal microvasculature of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were measured by optical coherence tomography angiography using an automatic segmentation. The VBM and structural covariance network analyses were applied to process brain magnetic resonance imaging (MRI) images. The associations of retinal microvasculature with voxel-wise gray matter volumes and structural covariance network were assessed by linear regression models. Results: In the study, 137 participants (mean age = 59.72 years, 37.2% men) were included for the final analysis. Reduced perfusion in SVP was significantly associated with reduced voxel-wise gray matter volumes of the brain regions including the insula, putamen, occipital, frontal, and temporal lobes, all of which were located in the anterior part of the brain supplied by internal carotid artery, except the occipital lobe. In addition, these regions were also involved in visual processing and cognitive impairment (such as left inferior occipital gyrus, left lingual gyrus, and right parahippocampal gyrus). In regard to the structural covariance, the perfusions in SVP were positively related to the structural covariance of the left lingual gyrus seed with the left middle occipital gyrus, the right middle occipital gyrus, and the left middle frontal gyrus. Conclusions: Poor perfusion in SVP was correlated with reduced voxel-wise gray matter volumes and structural covariance networks in regions related to visual processing and cognitive impairment. It suggests that retinal microvasculature may offer a window to identify aging related cerebral alterations.

Characterization of retinal microvasculature and structure in atrial fibrillation.

Background and objective: Quantitative changes in retinal microvasculature are associated with subclinical cardiac alterations and clinical cardiovascular diseases (i.e., heart failure and coronary artery disease). Nonetheless, very little is known about the retinal vascular and structural changes in patients with atrial fibrillation (AF). Our study aims to characterize the microvasculature and structure of the retina in AF patients and explore their differences in different types of AF (paroxysmal and sustained AF). Methods: This cross-sectional study was conducted at the Departments of Neurology and Cardiology in West China Hospital, Chengdu, China. Individuals aged 40 years or older with a diagnosis of AF were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 40 years or older and without a history of AF, ocular abnormalities/disease, or any significant systemic illness were recruited. The retinal vascular and structural parameters were assessed using swept-source optical coherence tomography (SS-OCT)/SS-OCT angiography. Echocardiographic data of left atrium (LA) diameter were collected in patients with AF at the time of inclusion. Results: A total of 242 eyes of 125 participants [71 men (56.8%); mean (SD) age, 61.98 (8.73) years] with AF and 219 eyes of 111 control participants [53 men (47.7%); mean (SD) age, 62.31 (6.47) years] were analyzed. In our AF cohort, 71 patients with paroxysmal AF and 54 patients with sustained AF (i.e., persistent/permanent AF) were included. Decreased retinal microvascular perfusion (ß coefficient = -0.08; 95% CI, -0.14 to -0.03) and densities (ß coefficient = -1.86; 95% CI, -3.11 to -0.60) in superficial vascular plexus (SVC) were found in the eyes of the participants with AF. In regard to retinal structures, thinner ganglion cell-inner plexiform layer (GCIPL; ß coefficient = -2.34; 95% CI, -4.32 to -0.36) and retinal nerve fiber layer (RNFL) thicknesses (ß coefficient = -0.63; 95% CI, -2.09 to -0.18) were observed in the eyes of the participants with AF. The retinal parameters did not significantly differ between paroxysmal and sustained AF (all P > 0.05). However, significant interactions were observed between LA diameter and AF subtypes with the perfusion and densities in SVC (P < 0.05). Conclusion: This study found that individuals with AF had decreased retinal vascular densities and perfusion in SVC, as well as thinner GCIPL and RNFL thickness compared with age- and sex-matched control participants. The differences of the retinal microvasculature in SVC between paroxysmal and sustained AF depend on the LA diameter. Given our findings, further longitudinal studies with our participants are of interest to investigate the natural history of retinal microvascular and structural changes in individuals across the clinical process of AF and AF subtypes.

Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults.

Purpose: We explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort. Methods: This observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (µm) were measured on the OCT tool. Results: Older adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p < 0.05) between GCIPL and PWMH and total WMH was observed in our older adults. Conclusion: Both GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline.

Automated evaluation of retinal hyperreflective foci changes in diabetic macular edema patients before and after intravitreal injection.

Purpose: Fast and automated reconstruction of retinal hyperreflective foci (HRF) is of great importance for many eye-related disease understanding. In this paper, we introduced a new automated framework, driven by recent advances in deep learning to automatically extract 12 three-dimensional parameters from the segmented hyperreflective foci in optical coherence tomography (OCT). Methods: Unlike traditional convolutional neural networks, which struggle with long-range feature correlations, we introduce a spatial and channel attention module within the bottleneck layer, integrated into the nnU-Net architecture. Spatial Attention Block aggregates features across spatial locations to capture related features, while Channel Attention Block heightens channel feature contrasts. The proposed model was trained and tested on 162 retinal OCT volumes of patients with diabetic macular edema (DME), yielding robust segmentation outcomes. We further investigate HRF's potential as a biomarker of DME. Results: Results unveil notable discrepancies in the amount and volume of HRF subtypes. In the whole retinal layer (WR), the mean distance from HRF to the retinal pigmented epithelium was significantly reduced after treatment. In WR, the improvement in central macular thickness resulting from intravitreal injection treatment was positively correlated with the mean distance from HRF subtypes to the fovea. Conclusion: Our study demonstrates the applicability of OCT for automated quantification of retinal HRF in DME patients, offering an objective, quantitative approach for clinical and research applications.

Optic Nerve Head Changes Measured by Swept Source Optical Coherence Tomography and Angiography in Patients with Intracranial Hypertension.

INTRODUCTION: This study explored the structural and microvascular changes in the optic nerve head (ONH) of patients with intracranial hypertension (IH) by using swept-source optical coherence tomography (SS-OCT)/OCT angiography (OCTA) and evaluated their association with clinical features. METHODS: The optic disc morphology, peripapillary retinal nerve fiber layer (pRNFL), ganglion cell-inner plexiform layer (GCIPL), and microvascular densities of the nerve fiber layer plexus (NFLP), superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were measured by the SS-OCT/OCTA tool. Frisen score, visual acuity, and intracranial pressure were assessed and recorded in patients with IH. RESULTS: Sixty-one patients with IH and 65 controls were included in this study. Patients with IH showed thicker pRNFL and GCIPL thickness with larger ONH rim area when compared to controls (P < 0.001). Microvascular densities were increased in NFLP while densities were reduced in SVP, ICP, and DCP when compared to controls (P < 0.001). Structural thickness and microvascular densities were significantly correlated with Frisen scores (P < 0.05) and intracranial pressure (P < 0.05) in patients with IH. CONCLUSION: Structural and microvasculature variations of the ONH were found in patients with IH compared to controls. Importantly, we showed that structural and microvascular changes in the ONH were correlated with their Frisen score and intracranial pressure in patients with IH.

Length of Carotid Plaque Impacts Retinal Microvascular Densities of Carotid Artery Stenosis Patients.

Purpose: We explored the retinal microvascular changes in carotid artery stenosis (CAS) and their relationship with carotid plaque morphology. Methods: All participants were diagnosed with carotid artery stenosis by a neurologist. Participants underwent digital subtraction angiography (DSA) and optical coherence tomography angiography (OCTA) imaging. The degree and length of carotid plaque were obtained from the DSA tool. OCTA tool measured the densities in the superficial vascular complex (SVC) and deep vascular complex (DVC). Results: One hundred seventeen patients with CAS patients were included in our data analysis. Eyes with ipsilateral stenosis had reduced retinal microvascular densities when compared to contralateral eyes in patients with CAS (P = 0.016 for SVC, and P = 0.004 for DVC). Microvascular densities correlated with the length of carotid plaque (P = 0.015 for SVC, and P = 0.022 for DVC) in our CAS cohort, although they did not correlate with the degree of carotid plaque (P = 0.264 for SVC, and P = 0.298 for DVC). However, when stratified into moderate and severe subgroups, the degree of carotid plaque correlated with microvascular densities in patients with severe stenosis (P = 0.045 for SVC, and P = 0.038 for DVC). Conclusions: Our study suggests that OCTA can noninvasively detect retinal microvascular changes in patients with CAS and that these changes correlated with the length of the stenosis, but future studies are required to confirm these findings. Translational Relevance: Noninvasive and rapid acquisition of the OCTA image might have the potential to be used as a screening tool to detect microvascular changes in carotid artery stenosis.

APOE ε4 Gene Carriers Demonstrate Reduced Retinal Capillary Densities in Asymptomatic Older Adults.

Early identification of Apolipoprotein E (APOE)-related microvascular pathology will help to study the microangiopathic contribution to Alzheimer's disease and provide a therapeutic target for early intervention. To evaluate the differences in retinal microvasculature parameters between APOE ε4 carriers and non-carriers, asymptomatic older adults aged ≥ 55 years underwent APOE ε4 genotype analysis, neuropsychological examination, and optical coherence tomography angiography (OCTA) imaging. One hundred sixty-three older adults were included in the data analysis. Participants were also defined as cognitively impaired (CI) and non-cognitively impaired (NCI) according to their MoCA scores and educational years. APOE ε4 carriers demonstrated reduced SVC (p = 0.023) compared to APOE ε4 non-carriers. Compared to NCI, CI participants showed reduced SVC density (p = 0.006). In the NCI group, no significant differences (p > 0.05) were observed in the microvascular densities between APOE ε4 carriers and non-carriers. In the CI group, APOE ε4 carriers displayed reduced microvascular densities compared to non-carriers (SVC, p = 0.006; DVC, p = 0.048). We showed that CI and APOE ε4 affect retinal microvasculature in older adults. Quantitative measures of the retinal microvasculature could serve as surrogates for brain microcirculation, providing an opportunity to study microvascular contributions to AD.

Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method.

BACKGROUND: In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not been defined. This randomized prospective clinical 3-phases trial initially tested eight clinically relevant combinations of intramuscular administration in 50 dogs (phase 1). The quality of each combination was rated using a purposefully developed negative score (NS; 0-21.5, the lower the NS the better the quality of sedation) to judge the quality of sedation, the occurrence of side effects, and the need for additional anaesthetics. Based on the results of the NS, the eight combinations were divided into "promising" and "unsatisfactory" subgroups. In phase 2, a new combination (N) was calculated and tested in six dogs replacing the worst of the eight initial combinations. This procedure was repeated until the NS could not be improved any further. In phase 3, the best combination was tested in 100 adult dogs undergoing diagnostic or therapeutic procedures. RESULTS: The optimal combination established was dexmedetomidine 0.005 mg/kg, ketamine 1 mg/kg, and butorphanol 0.3 mg/kg with a median NS of 1.5 (interquartile range 1.5-2.4). In all 112 dogs receiving this combination, the quality of sedation was satisfactory and no severe side effects were detected. CONCLUSIONS: The application of this optimization method allowed the calculation of an optimal drug combination to sedate cardiovascularly healthy dogs. After having being tested in 112 animals, this combination can consequently be considered safe. Therefore, this combination can now be used in daily clinical practice for cardiovascularly healthy adult dogs undergoing minor procedures.

Interplay between nutrient transporters ensures fertility in the malaria mosquito Anopheles gambiae.

Females from many mosquito species feed on blood to acquire nutrients for egg development. The oogenetic cycle has been characterized in the arboviral vector Aedes aegypti, where after a bloodmeal, the lipid transporter lipophorin (Lp) shuttles lipids from the midgut and fat body to the ovaries, and a yolk precursor protein, vitellogenin (Vg), is deposited into the oocyte by receptor-mediated endocytosis. Our understanding of how the roles of these two nutrient transporters are mutually coordinated is however limited in this and other mosquito species. Here, we demonstrate that in the malaria mosquito Anopheles gambiae, Lp and Vg are reciprocally regulated in a timely manner to optimize egg development and ensure fertility. Defective lipid transport via Lp silencing triggers abortive ovarian follicle development, leading to misregulation of Vg and aberrant yolk granules. Conversely, depletion of Vg causes an upregulation of Lp in the fat body in a manner that appears to be at least partially dependent on target of rapamycin (TOR) signaling, resulting in excess lipid accumulation in the developing follicles. Embryos deposited by Vg-depleted mothers are completely infertile, and are arrested early during development, likely due to severely reduced amino acid levels and protein synthesis. Our findings demonstrate that the mutual regulation of these two nutrient transporters is essential to safeguard fertility by ensuring correct nutrient balance in the developing oocyte, and validate Vg and Lp as two potential candidates for mosquito control.

Retinal microvascular and structural changes in intracranial hypertension patients correlate with intracranial pressure.

AIMS: We aimed to evaluate the retinal microvascular and structural changes in intracranial hypertension (IH) patients compared with an age- and sex-matched control group. We also investigated the association between clinical parameters and retinal changes in IH patients. METHODS: Intracranial hypertension patients were divided into eyes with papilledema (IH-P) and eyes without papilledema (IH-WP). IH patients underwent lumbar puncture to measure intracranial pressure (ICP); visual acuity was performed using the Snellen chart. Optical coherence tomography (OCT) was used to image and measure the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) while OCT angiography was used to image and measure the superficial vascular complex (SVC) and deep vascular complex (DVC). RESULTS: Intracranial hypertension patients showed reduced microvascular densities and thinner retinal thicknesses compared with the control group (all p < 0.001). Compared with the control group, IH-P showed reduced microvascular densities and thinner retinal thicknesses (all p < 0.001). IH-P showed reduced SVC density and thinner retinal thicknesses when compared with IH-WP (p = 0.008 for SVC, p = 0.025 for RNFL, and p = 0.018 for GCIPL). ICP correlated with the microvascular densities and GCIPL thickness in IH patients (p = 0.025 for GCIPL, p = 0.004 for SVC, and p = 0.002 for DVC). A significant association of ICP with SVC (p = 0.010) and DVC (p = 0.005) densities were also found in IH-P. CONCLUSIONS: Given the observed differences in these noninvasive retinal imaging markers, further research into their clinical utility in IH is needed.

Pelagic calcium carbonate production and shallow dissolution in the North Pacific Ocean.

Planktonic calcifying organisms play a key role in regulating ocean carbonate chemistry and atmospheric CO2. Surprisingly, references to the absolute and relative contribution of these organisms to calcium carbonate production are lacking. Here we report quantification of pelagic calcium carbonate production in the North Pacific, providing new insights on the contribution of the three main planktonic calcifying groups. Our results show that coccolithophores dominate the living calcium carbonate (CaCO3) standing stock, with coccolithophore calcite comprising ~90% of total CaCO3 production, and pteropods and foraminifera playing a secondary role. We show that pelagic CaCO3 production is higher than the sinking flux of CaCO3 at 150 and 200 m at ocean stations ALOHA and PAPA, implying that a large portion of pelagic calcium carbonate is remineralised within the photic zone; this extensive shallow dissolution explains the apparent discrepancy between previous estimates of CaCO3 production derived from satellite observations/biogeochemical modeling versus estimates from shallow sediment traps. We suggest future changes in the CaCO3 cycle and its impact on atmospheric CO2 will largely depend on how the poorly-understood processes that determine whether CaCO3 is remineralised in the photic zone or exported to depth respond to anthropogenic warming and acidification.