Gal - T Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.

BACKGROUND: Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout (GalT-KO) pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. In this study, we compare outcomes between autografts and cold preserved xenografts in a rat sciatic model of nerve gap repair. METHODS: Fifty male Lewis rats had a 1 cm sciatic nerve defect repaired using either: autograft and suture (n=10); 1-week or 4-week cold preserved xenograft and suture (n=10 per group); 1-week or 4-week cold preserved xenograft and photochemical tissue bonding using a human amnion wrap (PTB/HAM) (n=10 per group). Rats with xenografts were given tacrolimus until 4 months post-operatively. At 4 and 7 months, rats were euthanized and nerve sections harvested. Monthly sciatic functional index (SFI) scores were calculated. RESULTS: All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the 1-week cold preserved PTB/HAM group. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold preserved groups had significantly lower scores than the 4-week cold preserved suture group. CONCLUSIONS: Our results in the rat sciatic model suggest that GalT-KO nerve xenografts may be viable alternatives to autografts and demonstrate the need for further studies of long-gap repair and comparison with acellular nerve allografts. CLINICAL RELEVANCE: This proof-of-concept study in the rat sciatic model demonstrates that cold preserved GalT-KO porcine xenografts support axonal regeneration, as well as axonal viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.

Differences in social media use by COVID-19 vaccination status.

The near-ubiquitous use of social media in the United States (U.S.) highlights the utility of social media for encouraging vaccination. Vaccination campaigns have used social media to reach audiences, yet research linking the use of specific social media platforms and vaccination uptake is nascent. This descriptive study assesses differences in social media use by COVID-19 vaccination status among adults overall and those who reported baseline vaccine hesitancy. We used data from a nationally representative longitudinal survey of U.S. adults administered between January 2021-August 2022 (n = 2,908). Results indicated a positive association between frequent Instagram and/or Twitter use and vaccination status (p <.05). Among baseline vaccine hesitant adults, results indicated a positive association between frequent TikTok, Instagram, and/or Twitter use and vaccination status (p <.05). Findings have implications for research that examines the content of social media platforms and their environment on vaccine attitudes and uptake.

Association Between the "We Can Do This" Campaign and COVID-19 Booster Uptake, U.S., 2021-2022.

Introduction: Monovalent COVID-19 boosters lower the risk of COVID-19 disease, infection, hospitalization, and death. This study examined associations between exposure to a booster public education campaign (the booster campaign) and the increases in booster uptake and reduced length of time until booster uptake among U.S. adults. Methods: Data included a national survey panel of U.S. adults and booster campaign paid media (i.e., digital impressions and TV gross rating points) from September 2021 to May 2022. Multilevel logistic regression models examined the association between exposure to the booster campaign and the likelihood of booster uptake. A Cox proportional hazard model evaluated the association between the booster campaign and booster uptake timing. Interaction terms between the booster campaign media variables and first-dose COVID-19 vaccine date examined differential effects of the booster campaign based on when individuals received their first dose. Results: Interactions between first-dose vaccination date and the booster campaign were statistically significant for cumulative digital impressions (ß=4.75e-08; 95% CIs=5.93e-09, 8.90e-08) and TV gross rating points (ß = 4.62e-05; 95% CIs=5.09e-06, 8.73e-05), suggesting that booster uptake was strongest among those who received their first-dose COVID-19 vaccine later. Booster campaign cumulative digital impressions and TV gross rating points were associated with accelerated booster uptake among those with later first-dose vaccination dates (digital: ß=9.98e-08; 95% CIs=2.70e-08, 1.73e-07; TV: ß=0.0001; 95% CIs=2.80e-05, 0.0002), relative to those with earlier first-dose vaccination dates. Conclusions: The booster campaign may have increased monovalent booster uptake and reduced how long individuals waited until getting their booster. Public education campaigns show promise in stemming the tide of pandemic fatigue and increasing booster confidence.

Racial and ethnic differences in COVID-19 vaccine readiness among adults in the United States, January 2021-April 2023.

Racial and ethnic minority groups have been disproportionately affected by COVID-19 and have experienced systemic, attitudinal, and access-related barriers to COVID-19 vaccination. We examined differences in COVID-19 vaccine readiness-a composite measure of vaccination intention and behavior-between non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic Asian American/Pacific Islander, and American Indian/Alaska Native U.S. adults. Using data from a cross-sectional survey administered to nationally representative samples of âˆ¼ 5,000 U.S. adults each month from January 2021 to April 2023 (n = 135,989), we conducted weighted ttests comparing the monthly percentage of participants from racial/ethnic groups who were "Vaccine Ready." Initial racial/ethnic disparities in vaccine readiness were attenuated within a 7-month period, after which adults from most minority racial/ethnic groups became equally or more vaccine ready compared to non-Hispanic White adults (p < 0.05). Findings suggest that barriers to vaccine readiness that were more prevalent in non-White racial/ethnic groups may have largely been addressed.

Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology.

We present open-source tools for 3D analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (i) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (ii) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable financial resources. We tested our tools on synthetic and real data from two NIH Alzheimer's Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected differences between post mortem confirmed Alzheimer's disease cases and controls. The tools are available in our widespread neuroimaging suite "FreeSurfer" ( https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools ).

Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients.

The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue. This tumour-specific shift in FLT can be used to distinguish tumours from normal tissue with an accuracy of over 97% across tumour types, and can be visualized at the cellular level using microscopy and in larger specimens through wide-field imaging. Unlike fluorescence intensity, which depends on imaging-system parameters, tissue depth and the amount of dye taken up by tumours, FLT is a photophysical property that is largely independent of these factors. FLT imaging with indocyanine green may improve the accuracy of cancer surgeries.

Bedside Clinician's Guide to Pulmonary Artery Catheters.

BACKGROUND: Pulmonary artery catheters provide important information about cardiac function, mixed venous oxygenation, and right-sided pressures and potentially provide temporary pacing ability. OBJECTIVE: To provide bedside clinicians with guidance for techniques to insert right heart monitors and devices, describe risk factors for difficult insertion and contraindications to placement, and provide updates on new technologies that may be encountered in the intensive care unit. METHODS: An extensive literature review was performed. Experienced clinicians were asked to identify topics not addressed in the literature. RESULTS: Advanced imaging techniques such as transesophageal echocardiography or fluoroscopy can supplement traditional pressure waveform-guided insertion when needed, and several other techniques can be used to facilitate passage into the pulmonary artery. Caution is warranted when attempting insertion in patients with right-sided masses or preexisting conduction abnormalities. New technologies include a pacing catheter that anchors to the right ventricle and a remote monitoring device that is implanted in the pulmonary artery. DISCUSSION: Bedside clinicians should be aware of risk factors such as atrial fibrillation with dilated atria, decreased ventricular function, pulmonary hypertension, and right-sided structural abnormalities that can make pulmonary artery catheter insertion challenging. Clinicians should be familiar with advanced techniques and imaging options to facilitate placement. CONCLUSION: The overall risk of serious complications with right heart catheter placement and manipulation is low and often outweighed by its benefits, specifically pressure monitoring and pacing.

Does covid-19 affect pregnancies?

The coronavirus has been linked to adverse pregnancy outcomes, but vaccines help to keep mothers and babies safe, reports Michael Marshall.

Cry1 expression during postnatal development is critical for the establishment of normal circadian period.

The mammalian circadian system generates an approximate 24-h rhythm through a complex autoregulatory feedback loop. Four genes, Period1 (Per1), Period2 (Per2), Cryptochrome1 (Cry1), and Cryptochrome2 (Cry2), regulate the negative feedback within this loop. Although these proteins have distinct roles within the core circadian mechanism, their individual functions are poorly understood. Here, we used a tetracycline trans-activator system (tTA) to examine the role of transcriptional oscillations in Cry1 and Cry2 in the persistence of circadian activity rhythms. We demonstrate that rhythmic Cry1 expression is an important regulator of circadian period. We then define a critical period from birth to postnatal day 45 (PN45) where the level of Cry1 expression is critical for setting the endogenous free running period in the adult animal. Moreover, we show that, although rhythmic Cry1 expression is important, in animals with disrupted circadian rhythms overexpression of Cry1 is sufficient to restore normal behavioral periodicity. These findings provide new insights into the roles of the Cryptochrome proteins in circadian rhythmicity and further our understanding of the mammalian circadian clock.

Covid-19's impact on the gut.

The coronavirus is increasingly being linked to gastrointestinal symptoms, but how the infection affects the gut - or how to treat it - is unclear, reports Michael Marshall.

TDP-43 and tau concurrence in the entorhinal subfields in primary age-related tauopathy and preclinical Alzheimer's disease.

Phosphorylated tau (p-tau) pathology correlates strongly with cognitive decline and is a pathological hallmark of Alzheimer's Disease (AD). In recent years, phosphorylated transactive response DNA-binding protein (pTDP-43) has emerged as a common comorbidity, found in up to 70% of all AD cases (Josephs et al., Acta Neuropathol, 131(4), 571-585; Josephs, Whitwell, et al., Acta Neuropathol, 127(6), 811-824). Current staging schemes for pTDP-43 in AD and primary age-related tauopathy (PART) track its progression throughout the brain, but the distribution of pTDP-43 within the entorhinal cortex (EC) at the earliest stages has not been studied. Moreover, the exact nature of p-tau and pTDP-43 co-localization is debated. We investigated the selective vulnerability of the entorhinal subfields to phosphorylated pTDP-43 pathology in preclinical AD and PART postmortem tissue. Within the EC, posterior-lateral subfields showed the highest semi-quantitative pTDP-43 density scores, while the anterior-medial subfields had the lowest. On the rostrocaudal axis, pTDP-43 scores were higher posteriorly than anteriorly (p < 0.010), peaking at the posterior-most level (p < 0.050). Further, we showed the relationship between pTDP-43 and p-tau in these regions at pathology-positive but clinically silent stages. P-tau and pTDP-43 presented a similar pattern of affected subregions (p < 0.0001) but differed in density magnitude (p < 0.0001). P-tau burden was consistently higher than pTDP-43 at every anterior-posterior level and in most EC subfields. These findings highlight pTDP-43 burden heterogeneity within the EC and the posterior-lateral subfields as the most vulnerable regions within stage II of the current pTDP-43 staging schemes for AD and PART. The EC is a point of convergence for p-tau and pTDP-43 and identifying its most vulnerable neuronal populations will prove key for early diagnosis and disease intervention.

Development of C1q Affinity Chromatography for the Study of C1q-IgG Interactions.

The classical complement system represents a central effector mechanism of Abs initiated by the binding of C1q to target bound IgG. Human C1q contains six heterotrimeric globular head groups that mediate IgG interaction, resulting in an avidity-driven binding event involving multiple IgG molecules binding a single C1q. Accordingly, surface bound IgG molecules are thought to assemble into noncovalent hexameric rings for optimal binding to the six-headed C1q. To study the C1q-Fc interaction of various Abs and screen for altered C1q binding mutants, we developed, to our knowledge, a novel HPLC-based method. Employing a single-chain form of C1q representing one C1q head group, our HPLC methodology was able to detect the interaction between the single-chain monomeric form of C1q and various ligands. We show that, despite a narrow window of specific binding owing to the low affinity of the monomeric C1q-IgG interaction, this approach clearly distinguished between IgG subclasses with established C1q binding properties. IgG3 displayed the strongest binding, followed by IgG1, with IgG2 and IgG4 showing the weakest binding. Fc mutants known to have increased C1q binding through oligomerization or enhanced C1q interaction showed greatly increased column retention, and IgG glycovariants displayed a consistent trend of increasing retention upon increasing galactosylation and sialylation. Furthermore, the column retention of IgG isotypes and glycovariants matches both the cell surface recruitment of C1q and complement-mediated cytotoxicity induced by each variant on an anti-CD20 Ab backbone. This methodology therefore provides a valuable tool for testing IgG Ab (glyco)variants for C1q binding, with clear relevance for therapeutic Ab development.

How covid-19 affects the brain.

The coronavirus can cause neurological symptoms. Research is starting to reveal how they occur and if they are treatable, reports Michael Marshall.

Successful Treatment of Delayed Localized Necrotizing Inflammatory Myositis After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA-1273 Vaccine: A Case Report.

Reported adverse reactions to the mRNA-1273 vaccine (Spikevax, Moderna Inc) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) range from mild, local delayed cutaneous reactions to rarer, more serious reactions such as myocarditis. Here, we describe the presentation and successful treatment of delayed, localized necrotizing inflammatory myositis following a third dose of the mRNA-1273 SARS-CoV-2 vaccine. To our knowledge, this is the first report of biopsy-confirmed, delayed inflammatory myositis after administration of an mRNA-1273 SARS-CoV-2 vaccine booster.

Ortner's syndrome: A rare case of hoarseness secondary to chronic aortic dissection.

Ortner's syndrome, also known as cardiovocal syndrome, is a rare presentation of aortic dissection. Symptoms occur as a result of recurrent laryngeal nerve compression. Our report describes a case of a patient who complained of hoarseness for a few months and was eventually diagnosed with chronic aortic dissection.