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Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.

Pseudomonas aeruginosa (Pa) is an opportunistic bacterial pathogen responsible for severe hospital acquired infections in immunocompromised and elderly individuals. Emergence of increasingly drug resistant strains and the absence of a broad-spectrum prophylactic vaccine against both T3SA+ (type III secretion apparatus) and ExlA+/T3SA- Pa strains worsen the situation in a post-pandemic world. Thus, we formulated a candidate subunit vaccine (called ExlA/L-PaF/BECC/ME) against both Pa types. This bivalent vaccine was generated by combining the C-terminal active moiety of exolysin A (ExlA) produced by non-T3SA Pa strains with our T3SA-based vaccine platform, L-PaF, in an oil-in-water emulsion. The ExlA/L-PaF in ME (MedImmune emulsion) was then mixed with BECC438b, an engineered lipid A analogue and a TLR4 agonist. This formulation was administered intranasally (IN) to young and elderly mice to determine its potency across a diverse age-range. The elderly mice were used to mimic the infection seen in elderly humans, who are more susceptible to serious Pa disease compared to their young adult counterparts. After Pa infection, mice immunized with ExlA/L-PaF/BECC/ME displayed a T cell-mediated adaptive response while PBS-vaccinated mice experienced a rapid onset inflammatory response. Important genes and pathways were observed, which give rise to an anti-Pa immune response. Thus, this vaccine has the potential to protect aged individuals in our population from serious Pa infection.

Developers are looking for new ways to produce proteins and other substances for food, pharmaceutical and industrial use by genetically engineering food crops to produce the desired substance of interest (i.e., molecular farming). Developers should be aware of the food safety concerns, legality and potential liability, and loss of consumer confidence that could arise if food or other plant materials from these crops were to inadvertently enter the food supply and compromise safety. At the earliest stages of product development, developers should consider whether it is feasible to consistently steward their crops and resulting plant materials from development through disposal to ensure they do not enter the food or feed supply in a way that would be unlawful. Developers should engage FDA’s foods program when considering their stewardship program. While molecular farming holds promise for the economical production of specific proteins and other substances at a large scale, it is important for developers to consider the efforts needed to protect the food supply from the crops used for molecular farming- particularly when the crop chosen for molecular farming is a crop traditionally used for human or animal food.

Shigella spp. are responsible for bacillary dysentery or shigellosis transmitted via the fecal–oral route, causing significant morbidity and mortality, especially among vulnerable populations. There are currently no licensed Shigella vaccines. Shigella spp. use a type III secretion system (T3SS) to invade host cells. We have shown that L-DBF, a recombinant fusion of the T3SS needle tip (IpaD) and translocator (IpaB) proteins with the LTA1 subunit of enterotoxigenic E. coli labile toxin, is broadly protective against Shigella spp. challenge in a mouse lethal pulmonary model. Here, we assessed the effect of LDBF, formulated with a unique TLR4 agonist called BECC470 in an oil-in-water emulsion (ME), on the murine immune response in a high-risk population (young and elderly) in response to Shigella challenge. Dual RNA Sequencing captured the transcriptome during Shigella infection in vaccinated and unvaccinated mice. Both age groups were protected by the L-DBF formulation, while younger vaccinated mice exhibited more adaptive immune response gene patterns. This preliminary study provides a step toward identifying the gene expression patterns and regulatory pathways responsible for a protective immune response against Shigella. Furthermore, this study provides a measure of the challenges that need to be addressed when immunizing an aging population.

ABSTRACT Shigellosis (bacillary dysentery) is a severe diarrheal disease caused by members of the genus Shigella, which results in 90 million cases annually around the world. The Shigella type III secretion system (T3SS) is a specialized secretion system that is the primary virulence factor it uses to infect the colonic mucosa. The type III secretion apparatus (T3SA) proteins IpaB and IpaD, as well as the genetic fusion, DBF, have been demonstrated to protect mice from Shigella spp. infection in a lethal pulmonary model. In a previous study, we fused LTA1, the active moiety of lethal toxin from enterotoxigenic Escherichia coli to DBF to produce a self-adjuvanting vaccine candidate L-DBF, which cross-protected mice against four serotypes of Shigella flexneri and Shigella sonnei. Here, we exposed mice with one or two sublethal doses of S. flexneri 2a to identify whether the immune response induced by L-DBF in the host would be affected by prior infection by homologous or heterologous Shigella serotypes. We demonstrate that pre-infection with two sublethal doses of S. flexneri 2a did not elicit cross-protection against S. sonnei, while vaccination with L-DBF did. Our results indicate that L-DBF is a feasible vaccine candidate that offers cross-protection against Shigella’s different serotypes even after prior exposure to the pathogen. This work provides a proof of concept that a novel subunit vaccine can not only protect a naïve host from Shigella challenge, but also can protect against challenge after prior infection by the same or different Shigella serotypes. IMPORTANCE Shigellosis is endemic to low- and middle-income regions of the world where children are especially vulnerable. In many cases, there are pre-existing antibodies in the local population and the effect of prior exposure should be considered in the development and testing of vaccines against Shigella infection. Our study shows that L-DBF-induced immune responses are not adversely affected by prior exposure to this pathogen. Moreover, somewhat different cytokine profiles were observed in the lungs of vaccinated mice not having been exposed to Shigella, suggesting that the immune responses elicited by Shigella infection and L-DBF vaccination follow different pathways.

We engineer an artificial optical clock transition in 40Ca+ with a continuous dynamical decoupling scheme. It suppresses inhomogeneous tensor shifts as well as the linear Zeeman shift, making it suitable for multi-ion operation. Coherence times approaching the natural lifetime limit ensure low statistical uncertainties on the optical transition. We continuously apply the dressing fields, making the tailored transition robust against magnetic field fluctuations during the entire clock probe time.

Shigellosis (bacillary dysentery) is a severe gastrointestinal infection with a global incidence of 90 million cases annually. Despite the severity of this disease, there is currently no licensed vaccine against shigellosis. Shigella’s primary virulence factor is its type III secretion system (T3SS), which is a specialized nanomachine used to manipulate host cells. A fusion of T3SS injectisome needle tip protein IpaD and translocator protein IpaB, termed DBF, when admixed with the mucosal adjuvant double-mutant labile toxin (dmLT) from enterotoxigenic E. coli was protective using a murine pulmonary model. To facilitate the production of this platform, a recombinant protein that consisted of LTA-1, the active moiety of dmLT, and DBF were genetically fused, resulting in L-DBF, which showed improved protection against Shigella challenge. To extrapolate this protection from mice to humans, we modified the formulation to provide for a multivalent presentation with the addition of an adjuvant approved for use in human vaccines. Here, we show that L-DBF formulated (admix) with a newly developed TLR4 agonist called BECC438 (a detoxified lipid A analog identified as Bacterial Enzymatic Combinatorial Chemistry candidate #438), formulated as an oil-in-water emulsion, has a very high protective efficacy at low antigen doses against lethal Shigella challenge in our mouse model. Optimal protection was observed when this formulation was introduced at a mucosal site (intranasally). When the formulation was then evaluated for the immune response it elicits, protection appeared to correlate with high IFN-γ and IL-17 secretion from mucosal site lymphocytes.

Salmonella enterica, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, S. enterica causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the Salmonella pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic E. coli to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined via challenging the mice with S. enterica serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from S. enterica challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against S. enterica.

With health equity growing as a priority within health care, health systems must transform that calling into action within their social, economic, and political environments. The current literature has not compared how different organizations manage the same health disparities intervention. This qualitative study aims to illustrate how different organizations navigated the implementation and sustainability of a hypertension disparities intervention by comparing experiences across Federally Qualified Health Centers (FQHCs), a private health system, and other non-clinical partnering organizations. As a study within a randomized controlled trial designed to reduce disparities in hypertension care, we conducted interviews with health care leaders before and after participation in the trial's multi-level intervention. Before participation, we interviewed five health care leaders representing five health systems. Following the intervention, we interviewed 14 leaders representing the five health systems and two partnering organizations. Discussions focused on intervention implementation and plans for sustainability. The primary considerations in implementation were appropriate staffing and multi-level organizational buy-in. When discussing long-term planning, health systems prioritized the structure of a stepped-care protocol incorporating community health workers (CHWs) and case managers. The sustainability of the CHW intervention at FQHCs was dependent on funding, whereas a private, non-FQHC physician practice network focused on expanding current resources for more patients. These findings serve as anticipatory guidance for organizations aiming to reduce hypertension disparities and provide support for policies that financially assist these interventions. Further investigation is warranted on the organizational factors that may influence the degree of success in eliminating health care disparities., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Personal characteristics may be associated with believing misinformation and not believing in best practices to protect oneself from COVID-19., Objective: To examine the associations of a person's age, race/ethnicity, education, residence, health literacy, medical mistrust level, and sources of health-related information with their COVID-19 health and conspiracy myth beliefs., Design: We surveyed adults with hypertension in Maryland and Pennsylvania between August 2020 and March 2021. Incorrect responses were summed for eight health (mean = 0.68; range 0-5) and two conspiracy (mean = 0.92; range 0-2) COVID-19 questions. Higher scores indicated more incorrect responses. Statistical analyses included two-sample t-tests, Spearman's correlation, and log binomial regression., Participants: In total, 561 primary care patients (mean age = 62.3 years, 60.2% female, 46.0% Black, 10.2% Hispanic, 28.2% with a Bachelor's degree or higher, 42.8% with annual household income less than $60,000) with a diagnosis of hypertension and at least one of five commonly associated conditions., Main Measures: Sociodemographic characteristics, health literacy, medical mistrust level, source of health-related information, and COVID-19 conspiracy and health myth beliefs., Key Results: In multivariable analyses, participants who did not get information from medical professional sources (prevalence ratio (PR) = 1.28; 95% CI = 1.06-1.55), had less than a bachelor's degree (PR = 1.49; 95% CI = 1.12-1.99), were less confident filling out medical forms (PR = 1.24; 95% CI = 1.02-1.50), and had higher medical mistrust (PR = 1.34; 95% CI = 1.05-1.69) were more likely to believe any health myths. Participants who had less than a bachelor's degree (PR = 1.22; 95% CI = 1.02-1.45), were less confident filling out medical forms (PR = 1.21; 95% CI = 1.09-1.34), and had higher medical mistrust (PR = 1.72; 95% CI = 1.43-2.06) were more likely to believe any conspiracy myths., Conclusions: Lower educational attainment and health literacy, greater medical mistrust, and certain sources of health information are associated with misinformed COVID-19 beliefs. Programs addressing misinformation should focus on groups affected by these social determinants of health by encouraging reliance on scientific sources., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Sickle cell disease (SCD) is a painful chronic blood disorder that causes serious complications and comorbidities, often leading to premature death. SCD impacts millions of people worldwide, including an estimated 100 000 in the United States, most of whom are Black or Latino. We analyzed Medicaid enrollment, claims, and encounter data via the Transformed Medicaid Statistical Information System (T-MSIS) to examine the 2021 health care utilization and spending of Medicaid enrollees with SCD. Our analysis found that Medicaid enrollees with SCD have high annual medical and pharmacy expenditures that are not evenly distributed across the population. Among the most severe enrollees with genotypes eligible for clinical trials, those in the top 5% of health care spending incurred, on average, nearly $200 000 per year for this chronic condition., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

The existence of coastal ecosystems depends on their ability to gain sediment and keep pace with sea level rise. Similar to other coastal areas, Northeast Florida (United States) is experiencing rapid population growth, climate change, and shifting wetland communities. Rising seas and more severe storms, coupled with the intensification of human activities, can modify the biophysical environment, thereby increasing coastal exposure to storm-induced erosion and inundation. Using the Guana Tolomato Matanzas National Estuarine Research Reserve as a case study, we analyzed the distribution of coastal protection services-expressly, wave attenuation and sediment control-provided by estuarine habitats inside a dynamic Intracoastal waterway. We explored six coastal variables that contribute to coastal flooding and erosion-(a) relief, (b) geomorphology, (c) estuarine habitats, (d) wind exposure, (e) boat wake energy, and (f) storm surge potential-to assess physical exposure to coastal hazards. The highest levels of coastal exposure were found in the north and south sections of the Reserve (9% and 14%, respectively) compared to only 4% in the central, with exposure in the south driven by low wetland elevation, high surge potential, and shorelines composed of less stable sandy and muddy substrate. The most vulnerable areas of the central Reserve and main channel of the Intracoastal waterway were exposed to boat wakes from larger vessels frequently traveling at medium speeds (10-20 knots) and had shoreline segments oriented towards the prevailing winds (north-northeast). To guide management for the recently expanded Reserve into vulnerable areas near the City of Saint Augustine, we evaluated six sites of concern where the current distribution of estuarine habitats (mangroves, salt marshes, and oyster beds) likely play the greatest role in natural protection. Spatially explicit outputs also identified potential elevation maintenance strategies such as living shorelines, landform modification, and mangrove establishment for providing coastal risk-reduction and other ecosystem-service co-benefits. Salt marshes and mangroves in two sites of the central section (N-312 and S-312) were found to protect more than a one-quarter of their cross-shore length (27% and 73%, respectively) from transitioning to the highest exposure category. Proposed interventions for mangrove establishment and living shorelines could help maintain elevation in these sites of concern. This work sets the stage for additional research, education, and outreach about where mangroves, salt marshes, and oyster beds are most likely to reduce risk to wetland communities in the region., Competing Interests: Gregory M. Verutes is an Academic Editor for PeerJ and employed by Blue Forest Conservation., (© 2024 Verutes et al.)

Purpose: Infants with perceived feeding problems are frequently referred for assessment of their feeding abilities. However, little is known regarding how healthy nondysphagic infants perform on commonly used assessments, making determination of impairment difficult. The aim of this investigation was to elucidate the characteristics of healthy term infant feeding performance using three commonly employed clinical assessments: Neonatal Eating Assessment Tool-Mixed (NeoEat-Mixed), Oral Feeding Scale, and Early Feeding Skills (EFS)., Method: In this prospective case-control study, we recruited 30 infants without feeding impairments to undergo video-monitored bottle feeds under their normal feeding conditions. Caregiver perception of infant feeding was evaluated using the NeoEat-Mixed. Milk ingestion was monitored real time using the Oral Feeding Scale for rate of milk transfer and modified proficiency as characterized by the total volume consumed out of the total volume the caregiver provided. Videos were analyzed by two speech pathologists using the EFS assessment. Descriptive statistics were used to characterize performance., Results: Participants underwent feeding monitoring at an average chronological age of 4 ± 2 months. Caregivers primarily reported normal, nonconcerning feeding patterns across all of the NeoEAT-Mixed outcomes. Infants consumed milk at an average rate of transfer of 7 ± 3 ml/min, a modified proficiency of 50 ± 21%, and achieved the highest OFS score of 4 (93%, n = 28). The majority of infants scored the best EFS score (mature-3) as it related to the absence of color changes during the feed (97%, n = 29), although commonly scored in the worst EFS score (immature-1) in their presentation of one or more compelling stress cues (63%, n = 19)., Conclusion: Establishing healthy term infant normative values for commonly used feeding assessments is critical in accurately distinguishing infants with feeding impairments from those with normal developmental variants.

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a common tumor of elderly Caucasian patients., Methods: Competing multivariable risk models to analyze different types of cSCC associated death (local infiltration [LI], locoregional [LR], and distant metastases [DM]) in terms of prognostic factors., Results and Discussion: 1400 patients were analyzed. In the adjusted multivariable subdistribution hazard approach for tumor volume, the best model for death of cSCC overall revealed the presence of desmoplasia (HR 4.52; p < 0.001), bone invasion (HR 10.06; p < 0.01), and immunosuppression (HR 3.19; p = 0.003) as significant factors. Death due to LI indicated desmoplasia (HR 15.39; p < 0.01) and bone invasion (HR 16.9; p < 0.001) as significant factors. For death by LM, immunosuppression with a HR of 3.27; p = 0.004 was the only significant prognostic factors as well as in death by DM with a HR of 4.54; p = 0.02., Conclusions: The three types of death caused by cSCC can be distinguished based on risk factors with different weights. Patients with these factors should be monitored closely., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The use of nurse care managers (CMs) and community health workers (CHWs) has demonstrated effectiveness in supporting improved blood pressure management among racially, ethnically, and socioeconomically minoritized populations. We partnered with a community advisory board (CAB) to develop a CM and CHW training curriculum and team-based collaborative care intervention to address uncontrolled hypertension. The objective of this study was to train CMs and CHWs to implement patient-centered techniques and address social determinants of health related to hypertension control. In partnership with a CAB, we developed and implemented a training curriculum for the CM/CHW collaborative care team. The training improved CM and CHW confidence in their ability to address medical and nonmedical issues that contribute to uncontrolled hypertension in their patients; however, preexisting norms and beliefs among CMs and CHWs created challenges with teamwork. The training curriculum was feasible and well-received. Additionally, the CMs' and CHWs' reactions provided insights to improve future collaborative care training and teamwork., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We examined measles mortality in the European past in an outbreak in an isolated German village, Hagelloch, in 1861., Methods: Pfeilsticker's contemporary thesis was used to describe the measles case fatality ratio (CFR) and complications. Data on onset of prodromes and rash was used to determine index cases and secondary cases of measles within the household. The church register provided information on survival in 1862., Results: The epidemic affected nearly all children under 14 years of age. The overall CFR was 6.4%(12/187), and 10%(7/70) for children under five years of age; 44% of children were secondary cases (82/187). Secondary cases had higher CFR than index cases (RR = 3.03 (95% CI: 0.91-10.07). Boys had higher CFR than girls (RR = 4.46 (1.03-19.22)). Boys infected by a girl had higher CFR than boys infected by other boys (RR = 6.30 (1.18-85.64)). Children who survived measles virus infection in 1861, did not have higher mortality in the following year compared with those who had not had measles in 1861 (RR = 0.24 (0.07-0.82))., Conclusions: Severe measles in the European past had determinants similar to those observed more recently in low-income countries., Brief Summary: The measles case fatality was 6% in rural Germany in 1861. Mortality was highest for boys infected in the household by a girl. There was no excess mortality after the acute phase of measles infection., Competing Interests: Declaration of Competing Interest Nothing to declare, (Copyright © 2022. Published by Elsevier Ltd.)

Background: Inserting a chest drain for a left-sided neonatal pneumothorax carries a risk of penetrating the pericardium. We identified reference ranges for the chest wall thickness (CWT) and distance between the pericardium and parietal pleura to improve safety of chest tube insertion., Method: We prospectively measured the CWT using ultrasound in 20 neonates (body weight [BW] 640-2,700 g, age <10 days) at the usual site of puncture in the 4th and 5th intercostal space (ICS). Furthermore, we measured the minimal distance between the parietal pleura and the cardiac silhouette in 131 neonatal chest X-rays (birth weight, 420-4,930 g [divided into 11 weight groups]; age <10 days). Both data sets were transformed into weight-dependent percentiles (Ps). We considered the difference between the sum of P 2.5 for the CWT plus P 2.5 for pleura-heart distance minus P 97.5 for the CWT as a safe corridor for placing the tip of the needle., Results: At both ICSs, curves for the above metrics did not cross, indicating a narrow but safe corridor for each BW with at least 97.5% probability. This safety corridor was 4.6-5.2 mm wide for the 4th and 2.8-3.4 mm for the 5th ICS., Conclusion: These data offer a reference for left-sided chest drain insertion for BW <2,700 g, which may help to improve safety of the procedure., (© 2021 S. Karger AG, Basel.)

Formed at the confluence of marine and fresh waters, estuaries experience both the seaside pressures of rising sea levels and increasing storm severity, and watershed and precipitation changes that are shifting the quality and quantity of freshwater and sediments delivered from upstream sources. Boating, shoreline hardening, harvesting pressure, and other signatures of human activity are also increasing as populations swell in coastal regions. Given this shifting landscape of pressures, the factors most threatening to estuary health and stability are often uncertain. To identify the greatest contemporary threats to coastal wetlands and oyster reefs across the southeastern United States (Mississippi to North Carolina), we summarized recent population growth and land-cover change and surveyed estuarine management and science experts. From 1996 to 2019, human population growth in the region varied from a 17% decrease to a 171% increase (mean = +43%) with only 5 of the 72 SE US counties losing population, and nearly half growing by more than 40%. Individual counties experienced between 999 and 19,253 km 2 of new development (mean: 5725 km 2 ), with 1-5% (mean: 2.6%) of undeveloped lands undergoing development over this period across the region. Correspondingly, our survey of 169 coastal experts highlighted development, shoreline hardening, and upstream modifications to freshwater flow as the most important local threats facing coastal wetlands. Similarly, experts identified development, upstream modifications to freshwater flow, and overharvesting as the most important local threats to oyster reefs. With regards to global threats, experts categorized sea level rise as the most pressing to wetlands, and acidification and precipitation changes as the most pressing to oyster reefs. Survey respondents further identified that more research, driven by collaboration among scientists, engineers, industry professionals, and managers, is needed to assess how precipitation changes, shoreline hardening, and sea level rise are affecting coastal ecosystem stability and function. Due to the profound role of humans in shaping estuarine health, this work highlights that engaging property owners, recreators, and municipalities to implement strategies to improve estuarine health will be vital for sustaining coastal systems in the face of global change., (Copyright © 2021 Elsevier Ltd. All rights reserved.)