Spatial proteomics of hippocampal subfield-specific pathology in Alzheimer's disease and primary age-related tauopathy.

INTRODUCTION: Alzheimer's disease (AD) and primary age-related tauopathy (PART) both harbor 3R/4R hyperphosphorylated-tau (p-tau)-positive neurofibrillary tangles (NFTs) but differ in the spatial p-tau development in the hippocampus. METHODS: Using Nanostring GeoMx Digital Spatial Profiling, we compared protein expression within hippocampal subregions in NFT-bearing and non-NFT-bearing neurons in AD (n = 7) and PART (n = 7) subjects. RESULTS: Proteomic measures of synaptic health were inversely correlated with the subregional p-tau burden in AD and PART, and there were numerous differences in proteins involved in proteostasis, amyloid beta (Aß) processing, inflammation, microglia, oxidative stress, and neuronal/synaptic health between AD and PART and between definite PART and possible PART. DISCUSSION: These results suggest subfield-specific proteome differences that may explain some of the differences in Aß and p-tau distribution and apparent pathogenicity. In addition, hippocampal neurons in possible PART may have more in common with AD than with definite PART, highlighting the importance of Aß in the pathologic process. HIGHLIGHTS: Synaptic health is inversely correlated with local p-tau burden. The proteome of NFT- and non-NFT-bearing neurons is influenced by the presence of Aß in the hippocampus. Neurons in possible PART cases share more proteomic similarities with neurons in ADNC than they do with neurons in definite PART cases.

Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a sporadic neurodegenerative tauopathy variably affecting brainstem and cortical structures and characterized by tau inclusions in neurons and glia. The precise mechanism whereby these protein aggregates lead to cell death remains unclear. To investigate the contribution of these different cellular abnormalities to PSP pathogenesis, we performed single-nucleus RNA sequencing and analyzed 45,559 high quality nuclei targeting the subthalamic nucleus and adjacent structures from human post-mortem PSP brains with varying degrees of pathology compared to controls. Cell-type specific differential expression and pathway analysis identified both common and discrete changes in numerous pathways previously implicated in PSP and other neurodegenerative disorders. This included EIF2 signaling, an adaptive pathway activated in response to diverse stressors, which was the top activated pathway in vulnerable cell types. Using immunohistochemistry, we found that activated eIF2α was positively correlated with tau pathology burden in vulnerable brain regions. Multiplex immunofluorescence localized activated eIF2α positivity to hyperphosphorylated tau (p-tau) positive neurons and ALDH1L1-positive astrocytes, supporting the increased transcriptomic EIF2 activation observed in these vulnerable cell types. In conclusion, these data provide insights into cell-type-specific pathological changes in PSP and support the hypothesis that failure of adaptive stress pathways play a mechanistic role in the pathogenesis and progression of PSP.

COVID-19 Vaccination Hesitancies: A Spanish-Language Focus Group Analysis in Texas.

COVID-19 related health disparities are prevalent among higher risk populations like the Hispanic community. Vaccination is one readily available public health tool, yet vaccine uptake is lower among minority populations and hesitations and concerns are high. In the present study, interpersonal and media sources of information about COVID-19 were discussed in a series of six focus groups with Spanish-language dominant and bilingual English-Spanish respondents in a large metropolitan area in Texas. Participants reported using legacy media as a main source of information about COVID-19 vaccines and encountered conspiracy theories and misinformation on social media. Using the Health Belief Model as the theoretical lens, we found individuals' and family members' perceived susceptibility to COVID-19 played a part in participants wanting to find and get the vaccine. Provider recommendations may have served as cues to action. Ease of receiving the vaccines at church and pharmacies may have served to boost participants self-efficacy. Perceived barriers include vaccine specific reasons such as the fast pace of initial authorization, side effects, and long-term effects along with conspiracy theories. Prevailing information gaps regarding the COVID-19 vaccines and the resulting uncertainty are discussed. Understanding information sources and the trust Hispanic communities place in these sources is important in designing effective health messages.

Correction: The physicochemical fingerprint of Necator americanus.

[This corrects the article DOI: 10.1371/journal.pntd.0005971.].

Battlefield acupuncture instead of opioids for abscess drainage in the pediatric emergency department.

Procedural analgesia with opioids is often needed during incision and drainage (I/D) of pilonidal or large abscesses in the pediatric emergency department (PED). In response to the ongoing opioid misuse pandemic, the Joint Commission has mandated that nonpharmacologic therapies be offered to patients for pain first. Battlefield Acupuncture (BFA) is an auricular acupuncture protocol that is drug free, can achieve rapid pain relief, and is used in the United States military. BFA for painful procedures in the PED has not been reported. We describe 4 cases where BFA was utilized in a PED for pain during I/D of abscesses.

The physicochemical fingerprint of Necator americanus.

Necator americanus, a haematophagous hookworm parasite, infects ~10% of the world's population and is considered to be a significant public health risk. Its lifecycle has distinct stages, permitting its successful transit from the skin via the lungs (L3) to the intestinal tract (L4 maturing to adult). It has been hypothesised that the L3 larval sheath, which is shed during percutaneous infection (exsheathment), diverts the immune system to allow successful infection and reinfection in endemic areas. However, the physicochemical properties of the L3 larval cuticle and sheath, which are in direct contact with the skin and its immune defences, are unknown. In the present study, we controlled exsheathment, to characterise the sheath and underlying cuticle surfaces in situ, using atomic force microscopy (AFM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). AFM revealed previously unseen surface area enhancing nano-annuli exclusive to the sheath surface and confirmed greater adhesion forces exist between cationic surfaces and the sheath, when compared to the emergent L3 cuticle. Furthermore, ToF-SIMS elucidated different chemistries between the surfaces of the cuticle and sheath which could be of biological significance. For example, the phosphatidylglycerol rich cuticle surface may support the onward migration of a lubricated infective stage, while the anionic and potentially immunologically active heparan sulphate rich deposited sheath could result in the diversion of immune defences to an inanimate antigenic nidus. We propose that our initial studies into the surface analysis of this hookworm provides a timely insight into the physicochemical properties of a globally important human pathogen at its infective stage and anticipate that the development and application of this analytical methodology will support translation of these findings into a biological context.

'Bubble-free' electrochemical delamination of CVD graphene films.

The production of large amounts of hydrogen bubbles, typical of electrochemical delamination methods based on the electrolysis of water, results in mechanical damage to graphene during the delamination, transfer, and drying steps. Here a novel 'bubble-free' delamination method is introduced which exploits the electrochemical dissolution of native copper oxide at a potential lower than that required for the formation of hydrogen bubbles, enabling the production of defect-free graphene stack.

Morphologically robust NiFe2O4 nanofibers as high capacity Li-ion battery anode material.

In this work, the electrochemical performance of NiFe2O4 nanofibers synthesized by an electrospinning approach have been discussed in detail. Lithium storage properties of nanofibers are evaluated and compared with NiFe2O4 nanoparticles by galvanostatic cycling and cyclic voltammetry studies, both in half-cell configurations. Nanofibers exhibit a higher charge-storage capacity of 1000 mAh g(-1) even after 100 cycles with high Coulmbic efficiency of 100% between 10 and 100 cycles. Ex situ microscopy studies confirmed that cycled nanofiber electrodes maintained the morphology and remained intact even after 100 charge-discharge cycles. The NiFe2O4 nanofiber electrode does not experience any structural stress and eventual pulverisation during lithium cycling and hence provides an efficient electron conducting pathway. The excellent electrochemical performance of NiFe2O4 nanofibers is due to the unique porous morphology of continuous nanofibers.

Perceived Breastfeeding Support Assessment Tool (PBSAT): development and testing of psychometric properties with Pakistani urban working mothers.

INTRODUCTION: breast feeding is an essential source of nutrition among young babies; however, in Pakistan a gradual decline in prevalence of breast feeding, especially among urban working mothers, has been reported. Previous studies among Pakistani urban working mothers have revealed that ensuring exclusivity and continuation of breast feeding is challenging if social and/or workplace environmental support is minimal or absent. This problem indicated a crucial need to assess availability of breast-feeding support for Pakistani urban working mothers by using a comprehensive, reliable, and validated tool in their national language (Urdu). PURPOSE: to develop and test the psychometric properties of the 'Perceived Breastfeeding Support Assessment Tool' (PBSAT) that can gauge Pakistani urban working mothers' perceptions about breast-feeding support. METHODOLOGY: this methodological research was undertaken in five phases. During phase I, a preliminary draft of the PBSAT was developed by using the Socio-ecological model, reviewing literature, and referring to two United States based tools. In Phase II, the instrument was evaluated by seven different experts, and, in Phase III, the instrument was revised, translated, and back translated. In Phase IV, the tool was pilot tested among 20 participants and then modified on the basis of statistical analysis. In Phase V, the refined instrument was tested on 200 breast-feeding working mothers recruited through purposive sampling from the government and private health-care settings in Karachi, Pakistan. Approvals were received from the Ethical Review Committees of the identified settings. FINDINGS: the 29-item based PBSAT revealed an acceptable inter-rater reliability of 0.95, and an internal consistency reliability coefficient (Cronbach's alpha) of 0.85. A construct validity assessment through Exploratory Factor Analysis revealed that the PBSAT has two dimensions, 'workplace environmental support' (12 items; α=0.86) and 'social environmental support' (17 items; α=0.77). CONCLUSION: the study developed a 29-item based two-dimensional tool (in Urdu) that has acceptable psychometric properties. The PBSAT is context specific, comprehensive, and user-friendly, so it can be administered by health-care workers, employers, policy makers, and researchers to improve the quality of services of breast-feeding urban working mothers, and could ultimately improve child health in Pakistan.