Focal Sites Research Articles

Potential Therapeutic effect of Bee Venom on Cisplatin-Induced Hepatotoxicity

The fact that cisplatin (CIS) can induce hepatotoxicity has limited its therapeutic uses, although it is recognised as a highly potent antineoplastic drug. Bee venom (BV) is an important toxin that exerts a potent anti-inflammatory effect and demonstrates significant pharmacological activities. The aim of this research was to investigate the therapeutic impact of BV administration orally on CIS-induced hepatotoxicity in a rat model when compared with individual drug therapy. Thirty albino male rats were used in this study. The rats were classified into three groups, each with ten rats (n = 10). The control group was group I, while groups II and III got CIS (a single dose of 7.5 mg/kg interperitoneally). After 24 hours, group III received BV (1 mg/kg orally), which was then administered daily for four weeks. The rats’ serum liver functions were estimated. The oxidative stress, antioxidant status, inflammatory mediators and fibrogenic and apoptotic markers were determined in the liver tissues. The results revealed that the administration of CIS induced a significant elevation in the serum aspartate aminotransferase, alanine aminotransferase and bilirubin levels, which was associated with a decrease in the albumin level. Additionally, significant increases in the hepatic tissue malondialdehyde, tumor necrosis factor alpha, interferon gamma, transforming growth factor beta, fibronectin and caspase-3 levels were noted. Moreover, significant decreases in the superoxide dismutase and catalase activities as well as the glutathione level were detected in the hepatic tissues. The administration of BV resulted in the notable amelioration of the aforementioned parameters. Interestingly, these parameters were restored to almost normal levels following administration of CIS and BV. The histopathological investigation revealed multiple focal inflammation sites that appeared to be associated with hepatic necrosis in the hepatic tissues of the CIS-treated rats. The co-administration of BV preserved the normal architecture of the hepatic tissues. These results indicate that the co-administration of BV exerts potent anti-hepatotoxic and cytoprotective effects by combating oxidative stress, inflammation, fibrogenic and apoptotic markers and histopathological changes. Thus, this study provides strong evidence of the superiority of combination drug therapy when compared with individual drug therapy.

Synthesis and biological evaluation of fluorescent hyaluronic acid modified amorphous calcium phosphate drug carriers for tumor-targeting

Cancer is becoming a major threat to national public health security. The integration of disease diagnosis and monitoring with treatment has become a hot spot for researchers. The amorphous calcium phosphate (ACP) nanoparticles prepared by the group in the previous stage could not precisely treat the lesion without tumor targeting and imaging characteristics. In this paper, water-soluble hyaluronic acid fluorescent carbon nanoparticles (HA-FCNs) were prepared and co-interacting with ACP nanoparticles to form hyaluronic acid fluorescent carbon/amorphous calcium phosphate (HA-FCNs/ACP) nanoparticles. The basic characteristics were characterized and the biological characteristics before and after drug loading were evaluated. HA-FCNs/ACP nanoparticles have good hemocompatibility, pH responsiveness, and enzymatic release. HA-FCNs and HA-FCNs/ACP nanoparticles are dispersed in the cytoplasm through the overexpressed CD44 receptors, which are actively targeted into A549 cells. Besides, the migration of A549 cells would be inhibited after cells were treated with drug-loaded nanomaterials. Therefore, the as-prepared nanoparticles can be used to monitor and treat focal sites through tumor-targeting bioimaging, pH-responsive, and enzymatic drug release properties, thus enabling integrated diagnosis and treatment.

The U.S. Ocean Biocode

Abstract Biodiversity is the engine of ocean ecosystems and economies. Efficiently characterizing it, rapidly at high resolution, is the frontier for understanding global change and management. The biggest impediment to breaching that frontier is inadequate DNA reference libraries, which can currently identify <25% of animal species in environmental profiles. Over the course of the decade, we will build from our existing global network of museums, universities, federal agencies, and the private sector in a broad collaboration to produce the Ocean Biocode, a well-sampled, voucher-based, open-access reference library of U.S. marine species that will eliminate “dark taxa” (no name or phylogenetic position) from U.S. waters and support a new era in high-resolution oceanography and environmental science founded on accurate environmental DNA sampling. We need not sequence every species; a strategic, empirically guided inventory will fill key gaps by focusing BioBlitz efforts at one focal site in each marine ecoregion of the U.S. EEZ, targeting taxa missing from regional libraries, coupled with genome skimming, to create reference libraries of whole mtDNA and nuclear ribosomal cluster. This Ocean Biocode moves beyond the barcode to allow design of targeted probes for non-amplicon species detection, yielding species-level information to stakeholders and enabling future technologies.

Melioidosis in Critical Care: A Review.

Key Points(1) Diabetes, hazardous alcohol use, and/or significant heart disease are more likely to develop a critical illness with melioidosis. (2) Pneumonia is the most common presentation. Those with pneumonia or bacteremia are most likely to require intensive care unit admissions. (3) Culture is the mainstay for the diagnosis. However, it is noted that Burkholderia pseudomallei is often wrongly identified as Pseudomonas or other Burkholderia species by commonly available commercial techniques. (4) Therapy consists of an intensive phase with intravenous antibiotics to prevent mortality followed by an eradication phase with oral antibiotics to prevent relapse. (5) Meropenem is the drug of choice for those with septic shock or neurological involvement. For patients with nonpulmonary organ focal sites of infection (neurologic, prostatic, bone, joint, cutaneous, and soft tissue melioidosis), the addition of trimethoprim-sulfamethoxazole (TMP-SMX) to ceftazidime/carbapenem during intensive therapy is recommended. TMP-SMX is the drug of choice for oral antibiotic therapy during the eradication phase. (6) Adequate source control is essential for successful treatment and to prevent relapse. (7) The use of granulocyte-colony stimulating factor (G-CSF) those with septic shock is controversial.How to cite this articleSridharan S, B Princess I, Ramakrishnan N. Melioidosis in Critical Care: A Review. Indian J Crit Care Med 2021; 25(Suppl 2):S161–S165.

Population responses of pest birds across a forest cover gradient in the Chaco ecosystem

Industrial agriculture can trigger an increase in abundance of some bird species, promoting the emergence of pests, causing damage to crops and economic loss for farmers. Even though there are different strategies to control pest birds (chemicals, hunting, repellents, etc), in general they are inefficient. Moreover, these strategies can threaten non-target species, and toxic substances can be bioaccumulated in the food chain of wildlife animals. An alternative strategy (or at least complementary) could be the design of agricultural landscapes that balance natural habitats and crop production areas in a way that would not trigger the abundance increases of potential pest birds. We assessed population trends of four bird species (potentially agricultural pests) across a forest cover gradient, and consequently, a gradient of agricultural cover expansion, at a landscape level. The study was conducted in the Chaco forest, one of the most threatened ecosystems worldwide due to agricultural expansion. Studied species were Eared Dove (Zenaida auriculata), Spot-winged Pigeon (Patagioenas maculosa), Picazuro Pigeon (Patagioenas picazuro) and Monk Parakeet (Myiopsitta monachus), and their populations are often considered as the major pest birds for agriculture in several areas of Argentina and in other countries of South America. Abundances of birds species were measured in focal sites (forest patches) and the percentage of forest cover was estimated within buffers of 2000 m radius surrounding each site. A total of 12 local landscapes were surveyed. Results show that population responses (i.e. changes in abundance) to the gradient of forest cover were idiosyncratic. The main result shows that relative abundance of Eared Dove, the most abundant species, was triggered when landscapes had less than 16% of forest cover: landscapes with low forest cover (less than 10%) contained six times the relative abundance of Eared Dove than landscapes with a high percentage of forest cover (close to 100%). We propose that as pest birds in agroecosystems are a problem at the landscape or regional scale, solutions should be thought at such scale. In this context, landscapes in the region should conserve more than 16% of forest cover to attempt to control one of the most abundant pest bird species of South America.

Hyperspectral image-based analysis of thermal damage for ex-vivo bovine liver utilizing radiofrequency ablation

Background & objectiveThermal ablation is the predominant methodology to treat liver tumors for segregating patients who are not permitted to have surgical intervention. However, noticing or predicting the size of the thermal strategies is a challenging endeavor. We aim to analyze the effects of ablation district volume following radiofrequency ablation (RFA) of ex-vivo liver exploiting a custom Hyperspectral Imaging (HSI) system. Materials and methodsRFA was conducted on the ex-vivo bovine liver at focal and peripheral blood vessel sites and observed by Custom HSI system, which has been designed to assess the exactness and proficiency using visible and near-infrared wavelengths region for tissue thermal effect. The experiment comprised up to ten trials with RFA. The experiment was carried out in two stages to assess the percentage of the thermal effect on the investigated sample superficially and for the side penetration effect. Measuring the diffuse reflectance (Ŗd) of the sample to identify the spectral reflectance shift which could differentiate between normal and ablated tissue exploiting the designed cross-correlation algorithm for monitoring of thermal ablation. ResultsDetermination of the diffuse reflection (Ŗd) spectral signature responses from normal, thermal effected, and thermal ablation regions of the investigated liver sample. Where the ideal wavelength range at (600–640 nm) could discriminate between these different regions. Then, exploited the converted RGB image of the HS liver tissue after RFA for more validations which shows that the optimum wavelength for differentiation at (530–560 nm and 600–640 nm). Finally, applying statistical analysis to validate our results presenting that wavelength 600 nm had the highest standard deviation (δ) to differentiate between various thermally affected regions regarding the normal tissue and wavelength 640 nm shows the highest (δ) to differentiate between the ablated and normal regions. ConclusionThe designed and implemented medical imaging system incorporated the hyperspectral camera capabilities with the associate cross-correlation algorithm that could successfully distinguish between the ablated and thermally affected regions to assist the surgery during the tumor therapy.

Progression to Symptomatic Multiple Myeloma Predicted by Texture Analysis-Derived Parameters in Patients Without Focal Disease at 18F-FDG PET/CT

This retrospective study is focused on the possible clinical implications of texture analysis-derived PET parameters in patients with smoldering multiple myeloma. Several texture features are significantly associated with progression to symptomatic multiple myeloma and with a shorter time to progression. The results of this study may lead to early identification of patients who could benefit from specific therapies.Background: The aim of the study was to determine whether positron emission tomography parameters derived from texture analysis of axial and peripheral skeleton predict progression to symptomatic multiple myeloma (MM) in patients undergoing 18F-​fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) without evidence of focal sites of 18F-FDG uptake. Patients and Methods: Patients with smoldering MM who underwent 18F-FDG PET/CT from May 2014 to June 2018 were retrospectively reviewed. Volumes of interest (VOIs) were placed on T5-T7 and L2-L4, iliac crests, and femoral diaphyses. Dedicated software (LIFEx) allowed us to obtain PET-derived first-, second-, and higher order texture features. Possible associations between PET parameters and progression to symptomatic MM were determined. Kaplan–Meier curves allowed to assess time to progression (TTP) based on the PET parameters. Results: Forty-five patients were included: 26 patients (58%) did not meet the criteria for symptomatic MM, but 19 patients (42%) progressed to symptomatic MM. Several texture features extracted from VOIs placed on iliac crests and femoral diaphyses were significantly associated with progression to symptomatic MM and with a shorter TTP (P < .05); conversely, the above-mentioned parameters extracted from VOIs placed on T5-T7 and L2-L4 did not significantly differ among the patients with regard to their progression to symptomatic MM and length of TTP, except for the gray-level zone length matrix–short-zone low-gray-level emphasis and gray-level zone length matrix–low gray-level zone emphasis. Particularly, second- and higher order texture features showed a significant association with the above-mentioned outcomes. Conclusion: Texture features derived from PET may be an expression of subtle disease distribution in the axial and peripheral bone marrow.

Siland a R package for estimating the spatial influence of landscape

The spatial distributions of populations are both influenced by local variables and by characteristics of surrounding landscapes. Understanding how landscape features spatially structure the frequency of a trait in a population, the abundance of a species or the species’ richness remains difficult specially because the spatial scale effects of the landscape variables are unknown. Various methods have been proposed but their results are not easily comparable. Here, we introduce “siland”, a general method for analyzing the effect of landscape features. Based on a sequential procedure of maximum likelihood estimation, it simultaneously estimates the spatial scales and intensities of landscape variable effects. It does not require any information about the scale of effect. It integrates two landscape effects models: one is based on focal sample site (Bsiland, b for buffer) and one is distance weighted using Spatial Influence Function (Fsiland, f for function). We implemented “siland” in the adaptable and user-friendly R eponym package. It performs landscape analysis on georeferenced point observations (described in a Geographic Information System shapefile format) and allows for effects tests, effects maps and models comparison. We illustrated its use on a real dataset by the study of a crop pest (codling moth densities).

Factors confounding koala habitat mapping at multiple decision‐making scales

SummaryThe Koala (Phascolarctos cinereus) is an arboreal marsupial found throughout southeastern Australia. A high risk of extinction in some areas requires adherence to legislation mandating protection of high‐quality habitat. The Koala primarily eats leaves of the Eucalyptus genus and wildlife managers are, in most cases, currently dependent on habitat maps depicting food resource availability derived from low‐resolution regional‐extent (~100,000 hectares) vegetation maps. These maps might not capture resource variability at planning extents (0.1–300 ha), or at resolutions where Koala ecology processes operate (5–50 ha). Consequently, potentially high‐quality habitat may not be considered in planning decisions. Whether low‐resolution habitat mapping adequately captures food resource variability is therefore relevant to map users at non‐regional extents. We examined four different broad‐scale low‐resolution habitat maps within a small area (150 ha) in southeast Queensland and compared the classifications of each. Map units were generally ranked in the same hierarchical order; however, differences in methodologies meant that, between maps, some units varied widely in assigned habitat quality. Two maps were assessed using quantitative Queensland Herbarium data, and field data we collected. Assessment using overstorey species emphasised habitat quality differences between habitat map units better than the alternative whole‐of‐canopy method. Maps relying on interpretation of vegetation descriptions for habitat class definition sometimes overestimated food tree cover proportions and stakeholders need to be cognisant of these limitations. One method assigned Very Low Suitability to a 60‐ha focal study site containing evidence of Koala use, and we strongly recommend that field validation should be an integral part of habitat management at these scales. We conclude that, rather than mapping approaches encompassing several habitat attributes within a single map, layered datasets, each with specific attributes, would provide greater utility for stakeholders by allowing them to use layers individually or in combination as required.

Leaf turgor loss point shapes local and regional distributions of evergreen but not deciduous tropical trees.

Summary The effects of climate change on tropical forests will depend on how diverse tropical tree species respond to drought. Current distributions of evergreen and deciduous tree species across local and regional moisture gradients reflect their ability to tolerate drought stress, and might be explained by functional traits.We measured leaf water potential at turgor loss (i.e. ‘wilting point’; πtlp), wood density (WD) and leaf mass per area (LMA) on 50 of the most abundant tree species in central Panama. We then tested their ability to explain distributions of evergreen and deciduous species within a 50 ha plot on Barro Colorado Island and across a 70 km rainfall gradient spanning the Isthmus of Panama.Among evergreen trees, species with lower πtlp were associated with drier habitats, with πtlp explaining 28% and 32% of habitat association on local and regional scales, respectively, greatly exceeding the predictive power of WD and LMA. In contrast, πtlp did not predict habitat associations among deciduous species.Across spatial scales, πtlp is a useful indicator of habitat preference for tropical tree species that retain their leaves during periods of water stress, and holds the potential to predict vegetation responses to climate change.

Fewer-Angle SPECT/CT Blood Pool Imaging for Infection and Inflammation.

A new protocol for rapid SPECT/CT blood pool imaging consisting of fewer image-angle acquisitions (fewer-angle SPECT/CT, or FASpecT/CT) was evaluated for localization of focal sites of soft-tissue inflammation, infection, and osteomyelitis. Methods: Immediately after dynamic flow and standard planar blood pool imaging with 99mTc-methylene diphosphonate, FASpecT/CT was performed with a dual-head γ-camera consisting of 6 steps over 360°, 12 total images with 30° of separation between angles, and 30 s per image, requiring a total imaging time of approximately 3 min. Images were reconstructed using iterative ordered-subset expectation maximization. Before use in a patient-care setting, various FASpecT/CT acquisition protocols were modeled using a phantom to determine the minimum number of stops and the stop duration required to produce a reliable image. Results: FASpecT/CT images provided excellent 3-dimensional localization of spine osteomyelitis, soft-tissue infection of the foot, and tendonitis of the hand and foot using a 3-min image acquisition time. The FASpecT/CT acquisition protocol required 1.3-3.5 min, including camera movement time. This was a reduction of 72%-90% from the time required for the standard 60-angle, 20-s SPECT/CT acquisition. Conclusion: The ability of FASpecT/CT blood pool images to help localize focal sites of hyperemia and inflammation can increase exam sensitivity and specificity. Additionally, using a FASpecT/CT protocol decreases imaging time by up to 90%.

Rhetorics of the Cognitive Vernacular: Blame Amid the Opioid Crisis

ABSTRACT In public discourse, lay cognitive precepts are invoked at every turn. People regularly speak of believing, thinking, knowing, and so forth, ascribing those states to themselves and others alike. This essay identifies the cognitive vernacular as a discernible dimension of public discourse, one that includes such regularly deployed lay precepts as well as popularized psychological and neuroscientific ideas. The cognitive vernacular may find expression in focal texts (e.g., a self-help book on positive thinking), but also pervasively, and somewhat elusively, takes shape in discussions that are otherwise overtly concerned. This essay takes the public discussion regarding the discovery of a teenage heroin ring in Centreville, Virginia, in 2008, a single episode within the large-scale and enduring American opioid crisis, as a focal site to investigate the cognitive vernacular. In doing so, it discerns how lay precepts concerning choice and knowledge are wielded as rhetorical resources to both cast and mitigate blame.

Aboveground biomass corresponds strongly with drone-derived canopy height but weakly with greenness (NDVI) in a shrub tundra landscape

Arctic landscapes are changing rapidly in response to warming, but future predictions are hindered by difficulties in scaling ecological relationships from plots to biomes. Unmanned aerial systems (hereafter ‘drones’) are increasingly used to observe Arctic ecosystems over broader extents than can be measured using ground-based approaches and are facilitating the interpretation of coarse-grained remotely sensed data. However, more information is needed about how drone-acquired remote sensing observations correspond with ecosystem attributes such as aboveground biomass. Working across a willow shrub-dominated alluvial fan at a focal study site in the Canadian Arctic, we conducted peak growing season drone surveys with an RGB camera and a multispectral multi-camera array. We derived photogrammetric reconstructions of canopy height and normalised difference vegetation index (NDVI) maps along with in situ point-intercept measurements and aboveground vascular biomass harvests from 36, 0.25 m2 plots. We found high correspondence between canopy height measured using in situ point-intercept methods compared to drone-photogrammetry (concordance correlation coefficient = 0.808), although the photogrammetry heights were positively biased by 0.14 m relative to point-intercept heights. Canopy height was strongly and linearly related to aboveground biomass, with similar coefficients of determination for point-intercept (R2 = 0.92) and drone-based methods (R2 = 0.90). NDVI was positively related to aboveground biomass, phytomass and leaf biomass. However, NDVI only explained a small proportion of the variance in biomass (R2 between 0.14 and 0.23 for logged total biomass) and we found moss cover influenced the NDVI-phytomass relationship. Vascular plant biomass is challenging to infer from drone-derived NDVI, particularly in ecosystems where bryophytes cover a large proportion of the land surface. Our findings suggest caution with broadly attributing change in fine-grained NDVI to biomass differences across biologically and topographically complex tundra landscapes. By comparing structural, spectral and on-the-ground ecological measurements, we can improve understanding of tundra vegetation change as inferred from remote sensing.

Focal and pseudo/rotational activations in human atrial fibrillation defined with automated periodicity mapping.

Defining atrial fibrillation (AF) wave propagation is challenging unless local signal features are discrete or periodic. Periodic focal or rotational activity may identify AF drivers. Our objective was to characterize AF propagation at sites with periodic activation to evaluate the prevalence and relationship between focal and rotational activation. We included 80 patients (61 ± 10 years, persistent AF 49%) from the FaST randomized trial that compared the efficacy of adjunctive focal site ablation versus pulmonary vein isolation. Patients underwent left atrial (LA) activation mapping with a 20-pole circular catheter during spontaneous or induced AF. Five-second bipolar and unipolar electrograms in AF were analyzed. Periodic sites were identified by spectral analysis of the bipolar electrogram. Activation maps of periodic sites were constructed using an automated, validated tracking algorithm, and classified into three patterns: focal sites (FS), rotation (RO), or pseudo-rotation (pRO). The most common propagation pattern at periodic sites was FS for 5-s in all patients (4.9 ± 1.9 per patient). RO and pRO were observed in two and seven patients, respectively, but were all transient (3-5 cycles). Activation from a FS evolved into transient RO/pRO in five patients. No patient had autonomous RO/pRO activations. Patients with RO/pRO had greater LA surface area with periodicity (78 ± 7 vs. 63 ± 16%, p = .0002) and shorter LA periodicity CL (166 ± 10 vs. 190±28 ms, p = .0001) than the rest. Using automated, regional AF periodicity mapping, FS is more prevalent and temporally stable than RO/pRO. Most RO/pRO evolve from neighboring FS. These findings and their implications for AF maintenance require verification with global, panoramic mapping.

Abstract 14910: Role of 3.3fr Mapping Catheters in Defining and Ablating Mechanisms of Ventricular Arrhythmias: A Multicenter Experience

Introduction: Ventricular arrhythmia (VA) mechanisms arising from the crux, summit, and epicardium are often not accessible from the endocardium. The 3.3Fr multipolar mapping catheters (3FMC) (Map-iT, Access Point Technologies, Rogers, MN) can be used to map deep within the coronary sinus (CS) branches and other locations difficult to access with standard catheters. Objective: We present a case series of and techniques for VA ablations guided by the 3FMC. Methods: We retrospectively reviewed VA ablations at 3 centers to describe the utility of the 3FMC in diagnosis and ablation of the arrhythmia. Results: We reviewed 33 patients who underwent VA ablations guided by the 3FMC. Patients (age 59.0 ± 15.4 years, 72% male, LVEF 41.5 ± 10.3%, 93% non-ischemic) had ventricular tachycardia (32%) or high-burden PVCs (68%). The 3FMC was used to interrogate the epicardium via the coronary sinus branches allowing interrogation of the LV crux (Fig. A) and LV summit (Fig. B). Early potentials in the poster-septal branch of CS guided alcohol ablation to focal site in septum not reachable by traditional catheters. Continuous signal on the 3FMC in the posterolateral branch of CS elucidated microreentry and guided more extensive epicardial ablation. Overall, the 3FMC measured signals 18.7 ± 11.3ms early and diagnosed 75% focal, 10% micro-reentrant, and 15% macro-reentrant VAs. Ablation was successful in 76% of cases. Conclusions: High definition mapping with the 3FMC allows diagnosis of VA mechanisms in locations not easily reachable by traditional catheters. Improved mapping of the CS branches enables interrogation and ablation planning of epicardial, summit, and crux VAs and may increase the likelihood of successful VA ablation.

Sequential ultrahigh-density contact mapping of persistent atrial fibrillation: An efficient technique for driver identification.

Literature supports the existence of drivers as maintainers of atrial fibrillation (AF). Whether ultrahigh density (UHD) contact mapping may detect them is unknown. We sequentially mapped the left atrial (LA) activation during spontaneous persistent AF and performed circumferential pulmonary vein isolation (CPVI), followed by remapping and ablation of potential drivers (rotational and focal propagation sites) with Rhythmia™ in 90 patients. The time reference was an LA appendage (LAA) electrogram (EGM). Regions with uniform color were defined as "organized." Only patients (51) with no previous ablation were considered for acute results and follow-up reporting. LA maps (175 ± 28 ml, 43578 ± 18013 EGM) were acquired in 23 ± 7 min. In all post-CPVI maps potential drivers (7.3 ± 3.2/patient) were visualized: 85% with rotational propagation and continuous low voltage in the center; the remaining with focal propagation and an organized EGM at the site of earliest activation. The RF delivery time for extra-PV driver ablation was 12.2 ± 7.9 min. There was a progressive increase of AF organization: the LAA cycle length prolonged, the number of potential drivers decreased, and the organized LA surface in AF increased from 14 ± 6% to 28 ± 16% (p = .0007). Termination of AF without cardioversion was obtained in 67%. AF recurrence rate at 15 ± 7.3 months was 17.6% after the first procedure. Sequential UHD contact activation mapping of persistent AF allows visualization of potential drivers. A sequential strategy of CPVI followed by ablation of potential drivers with limited RF time resulted in an increasing organization of AF and good acute and long-term results.

Intrathecal Inflammation in Progressive Multiple Sclerosis

Progressive forms of multiple sclerosis (MS) are associated with chronic demyelination, axonal loss, neurodegeneration, cortical and deep gray matter damage, and atrophy. These changes are strictly associated with compartmentalized sustained inflammation within the brain parenchyma, the leptomeninges, and the cerebrospinal fluid. In progressive MS, molecular mechanisms underlying active demyelination differ from processes that drive neurodegeneration at cortical and subcortical locations. The widespread pattern of neurodegeneration is consistent with mechanisms associated with the inflammatory molecular load of the cerebrospinal fluid. This is at variance with gray matter demyelination that typically occurs at focal subpial sites, in the proximity of ectopic meningeal lymphoid follicles. Accordingly, it is possible that variations in the extent and location of neurodegeneration may be accounted for by individual differences in CSF flow, and by the composition of soluble inflammatory factors and their clearance. In addition, “double hit” damage may occur at sites allowing a bidirectional exchange between interstitial fluid and CSF, such as the Virchow–Robin spaces and the periventricular ependymal barrier. An important aspect of CSF inflammation and deep gray matter damage in MS involves dysfunction of the blood–cerebrospinal fluid barrier and inflammation in the choroid plexus. Here, we provide a comprehensive review on the role of intrathecal inflammation compartmentalized to CNS and non-neural tissues in progressive MS.

Observer retention, site selection and population dynamics interact to bias abundance trends in bats

Abstract Many long‐term wildlife population monitoring programmes rely on citizen scientists for data collection. This can offer several benefits over traditional monitoring practices as it is a cost‐effective, large‐scale approach capable of providing long time series data and raising public environmental awareness. Whilst there is a debate about the quality of citizen science data, a standardised sampling design can allow citizen science data to be of a similar quality to those collected by professionals. However, many programmes use subjective, opportunistic selection of monitoring sites and this introduces several types of bias, which are not well understood. Using bat roost counts as a case study, we took a ‘virtual ecologist’ approach to simulate the effect of opportunistic site selection and uneven observer retention on our ability to accurately detect abundance trends. We simulated populations with different levels of temporal variability and site fidelity. Our simulations reveal that opportunistic site selection and low observer retention can result in biased trends and that these biases are magnified when monitored populations exhibit high levels of inter‐annual variation and low site fidelity. These results show that the synergistic effects of observer behaviour, site selection, and population dynamics lead to biased abundance trends in monitoring programmes. This study highlights the value of engaging and retaining citizen science observers, a standardised sampling design, and the collection of metadata. We conclude that monitoring programmes need to be aware of their focal species' temporal variability and site fidelity to adequately assess the potential bias caused by opportunistic site selection and low observer retention. Synthesis and applications. Accurate data on population changes are key for conservation success. Therefore, it is important that citizen science monitoring programmes assess and potentially quantify the biases present in their data. We demonstrate the applicability of an established simulation framework to assess the effect of biases on our ability to correctly detect abundance trends. Our findings highlight that monitoring programmes need to be aware of their study species’ temporal variability and site fidelity to assess and account for the effects of biased site selection and observer retention.

Pre-Exposure Prophylaxis Integration Into Family Planning Services at Title X Clinics in the Southeastern United States: Protocol for a Mixed Methods Hybrid Type I Effectiveness Implementation Study (Phase 2 ATN 155).

BackgroundAdolescent and young adult women (AYAW), particularly racial and ethnic minorities, in the Southern United States are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) is an effective, scalable, individual-controlled HIV prevention strategy that is grossly underutilized among women of all ages and requires innovative delivery approaches to optimize its benefit. Anchoring PrEP delivery to family planning (FP) services that AYAW already trust, access routinely, and deem useful for their sexual health may offer an ideal opportunity to reach women at risk for HIV and to enhance their PrEP uptake and adherence. However, PrEP has not been widely integrated into FP services, including Title X–funded FP clinics that provide safety net sources of care for AYAW. To overcome potential implementation challenges for AYAW, Title X clinics in the Southern United States are uniquely positioned to be focal sites for conceptually informed and thoroughly evaluated PrEP implementation science studies.ObjectiveThe objective of this study is two-fold: to evaluate multilevel factors associated with the level of PrEP adoption and implementation (eg, PrEP screening, counseling, and prescription) within and across 3 FP clinics and to evaluate PrEP uptake, persistence, and adherence among female patients in these clinics over a 6-month follow-up period.MethodsPhase 2 of Planning4PrEP (Adolescent Medicine Trials Network for HIV/AIDS Interventions 155) is a mixed methods hybrid type 1 effectiveness implementation study to be conducted in three clinics in Metro Atlanta, Georgia, United States. Guided by the Exploration, Preparation, Implementation, and Sustainment framework, this study will prepare clinics for PrEP integration via clinic-wide trainings and technical assistance and will develop clinic-specific PrEP implementation plans. We will monitor and evaluate PrEP implementation as well as female patient PrEP uptake, persistence, and adherence over a 6-month follow-up period.ResultsPhase 2 of Planning4PrEP research activities began in February 2018 and are ongoing. Qualitative data analysis is scheduled to begin in Fall 2020.ConclusionsThis study seeks to evaluate factors associated with the level of PrEP adoption and implementation (eg, PrEP screening, counseling, and prescription) within and across 3 FP clinics following training and implementation planning and to evaluate PrEP uptake, persistence, and adherence among female patients over a 6-month follow-up period. This will guide future strategies to support PrEP integration in Title X–funded clinics across the Southern United States.Trial RegistrationClinicalTrials.gov NCT04097834; https://clinicaltrials.gov/ct2/show/NCT04097834International Registered Report Identifier (IRRID)DERR1-10.2196/18784

Mapping cellular-scale internal mechanics in 3D tissues with thermally responsive hydrogel probes

Local tissue mechanics play a critical role in cell function, but measuring these properties at cellular length scales in living 3D tissues can present considerable challenges. Here we present thermoresponsive, smart material microgels that can be dispersed or injected into tissues and optically assayed to measure residual tissue elasticity after creep over several weeks. We first develop and characterize the sensors, and demonstrate that internal mechanical profiles of live multicellular spheroids can be mapped at high resolutions to reveal broad ranges of rigidity within the tissues, which vary with subtle differences in spheroid aggregation method. We then show that small sites of unexpectedly high rigidity develop in invasive breast cancer spheroids, and in an in vivo mouse model of breast cancer progression. These focal sites of increased intratumoral rigidity suggest new possibilities for how early mechanical cues that drive cancer cells towards invasion might arise within the evolving tumor microenvironment.