Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) and Sjögren Tool for Assessing Response (STAR) to B Cell-Targeted Therapy in the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS).

OBJECTIVE: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints. METHODS: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. RESULTS: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG. Furthermore, rituximab significantly down-regulated genes involved in immune-cell recruitment, lymphoid organization alongside antigen presentation, and T cell co-stimulatory pathways. In the peripheral compartment, rituximab down-regulated immunoglobulins  and auto-antibodies together with pro-inflammatory cytokines and chemokines. Interestingly, patients classified as responders  according to STAR displayed significantly higher baseline levels of C-X-C motif chemokine ligand-13 (CXCL13), interleukin (IL)-22, IL-17A, IL-17F, and tumor necrosis factor-α (TNF-α), whereas a longitudinal analysis of serum T cell-related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS-responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ-receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. CONCLUSION: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification.

Ecological habitat partitioning and feeding specialisations of coastal minke whales (Balaenoptera acutorostrata) using a recently designated MPA in northeast Scotland.

In the design of protected areas for cetaceans, spatial maps rarely take account of the life-history and behaviour of protected species relevant to their spatial ambit, which may be important for their management. In this study, we examined the distribution and feeding behaviours of adult versus juvenile minke whales (Balaenoptera acutorostrata) from long-term studies in the Moray Firth in northeast Scotland, where a Marine Protected Area (MPA) has recently been designated. Data were collected during dedicated boat surveys between 2001 and 2022 inclusive, from which 784 encounters with 964 whales of confirmed age-class (471 juveniles and 493 adults) were recorded from 56,263 km of survey effort, resulting in 238 focal follows. Adults and juveniles were occasionally seen together, but their distributions were not statistically correlated, and GIS revealed spatial separation / habitat partitioning by age-class-with juveniles preferring shallower, inshore waters with sandy-gravel sediments, and adults preferring deeper, offshore waters with greater bathymetric slope. GAMs suggested that the partitioning between age-classes was predominantly based on the differing proximity of animals to the shore, with juveniles showing a preference for the gentlest seabed slopes, and both adults and juveniles showing a similar preference for sandy gravel sediment types. However, the GAMs only used sightings data with available survey effort (2008 to 2022) and excluded depth due to collinearity issues. Whilst adult minkes employed a range of "active" prey-entrapment specialisations, showing inter-individual variation and seasonal plasticity in their targeted prey, juveniles almost exclusively used "passive" (low energy) feeding methods targeting low-density patches of inshore prey. These findings corroborate the need to incorporate demographic and behavioural data into spatial models when identifying priority areas for protected cetacean species. Not all areas within an MPA have equal value for a population and a better knowledge of the spatial preferences of these whales within the designated Scottish MPAs, appointed for their protection, is considered vital for their conservation.

Impacts of Austerity on Urogenital Infection Rates in Active Duty Servicewomen.

INTRODUCTION: Female warfighters are at increased risk of urogenital infections (UGIs) when serving in austere environments with varying levels of access to water, sanitation, and hygiene resources. Urogenital infections among servicewomen were among the top five reported medical encounters and one of the top seven reasons for medical evacuation from deployed locations between 2008 and 2013. In this study, we examine the use of water and sanitation resources across three environments (home duty station, field training, and deployment) and analyze associations between water, sanitation, and hygiene resource access and UGIs during training or deployment. The analyses are based on answers from 751 diverse active duty servicewomen (ADSW) at a large military installation in the southeastern USA. MATERIALS AND METHODS: Data for this population-based, prospective, cross-sectional survey design were collected during the administration of the Military Women's Readiness Urogenital Health Questionnaire. This research study was guided by two specific research questions derived from self-reported data in sections 2 and 3 of the questionnaire. RESULTS: The sample consisted of an extremely diverse pool of U.S. Army ADSW attached to highly operational units with robust field training and deployment tempos. Over one-half of the participants reported being diagnosed with one or more UGIs before military service. Of that participant group, more than 76.0% experienced one or more infections since joining the military. We found that the majority of UGIs occurred while U.S. Army ADSW were at their home duty stations rather than during field training or deployment. Of the three types of UGIs, bacterial vaginosis is more often associated with water and sanitation constraints. None of the water factors were significantly associated with UGIs during deployment. Intentional dehydration was not associated with UGIs in either field training or deployment, but intentionally delaying urination was associated with a significant increase in the odds of developing urinary tract infection during deployment. We identified trends in hygiene practices that may put ADSW at a higher risk for UGIs. CONCLUSIONS: Austere conditions, which may exist in any service environment, pose risks to the urogenital health and wellness of a female warfighter. Access to clean water and sanitation resources in military settings is essential for optimal health and operational readiness. It is necessary to identify and investigate critical research and policy gaps in need of investment and support for successful, evidence-based integration of female warfighters into military combat roles and to optimize their performance.

Patterns in Urogenital Health in Active Duty Servicewomen: A Prospective Cross-Sectional Survey Evaluating Impacts of Water, Sanitation, and Hygiene Resources Across Three Military Environments.

INTRODUCTION: Female warfighters are at risk for sex-specific and frequently unrecognized urogenital health challenges that may impede their ability to serve. The constraints on water, sanitation, and hygiene (WASH) resources by austere environments, whether at home or abroad, require women to practice unhealthy hygiene behaviors that jeopardize their urogenital health. In this manuscript, we examine the use of WASH resources by U.S. Army active duty servicewomen (ADSW) across three settings-home duty, field training, and deployment-to determine how the changing availability of WASH resources alters hygiene and sanitation practices in austere environments. Additionally, we report findings from a previously developed theoretical framework for determining the impacts of austere environments on ADSW's hygiene knowledge, behaviors, and outcomes. MATERIALS AND METHODS: This study used a prospective, cross-sectional survey design with population sampling and generalized ordered logit regression models. We recruited ADSW assigned to a large military installation in the southeastern United States after conducting a structured field hygiene training for female readiness. RESULTS: We surveyed a highly diverse sample of 751 ADSW and found that the use of WASH resources significantly differs between field training and deployment. Clean running water significantly differed among all settings, with nearly 70% reporting clean running water to be rarely or never available during field training. Bathing facility types significantly differed in each setting, with Cadillac bathrooms more often used during deployment than during field training and wipe baths more often used during field training than during deployment. We found that women were significantly less likely to wash their private areas more than 2 days a week during field training, compared to deployment. Women reported changing their underwear ≤2 times per week in field training environments as compared to during deployment. Soap and water were reported as the most common ways of washing in both home duty stations and during deployment, followed by wipes at home duty stations and in deployed settings. Participants reported wipes as their primary bathing method during field training, followed by soap and water. Participants used intentional dehydration or delayed urination more frequently in field training than during deployment. Women reported significant differences in holding their urine between field training and deployment, with principal reasons reported as "dirty facilities" and "distance to the nearest restroom." Significantly, they reported safety concerns when bathing, using the bathroom, or toileting facilities across the three settings. CONCLUSIONS: This is the first study to characterize sex-specific challenges by a large sample of operational ADSW and to explore the use of WASH resources in home duty, field training, and deployment settings. The results show that field training is more austere than deployed settings, indicating that austerity, not deployment, increases the urogenital infection risk for ADSW. With women more integrated into the military strategy than at any time in U.S. history, military leaders can use our results to develop interventions that ameliorate the unique challenges that influence the military readiness and overall health of female warfighters.

Management of Chronic Multisymptom Illness: Synopsis of the 2021 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline.

In 2019, senior leaders within the US Department of Veterans Affairs and the US Department of Defense commissioned the update of a clinical practice guideline for managing chronic multisymptom illness. Clinical experts were assembled across both agencies to systematically review evidence and to develop treatment recommendations based on that evidence. This effort resulted in the development of 29 evidence-based recommendations for providing care for individuals with chronic multisymptom illness.

Operation Allies Refuge and Operation Allies Welcome: Military Perioperative and Perianesthesia Nursing Support to the Afghan Evacuation Mission.

Nursing has a long and celebrated history of providing life-saving care during crises and periods of great need. Following the government collapse in Afghanistan and the withdrawal of US troops, a severe humanitarian and human rights crisis emerged. The US military participated in one of the largest and most complex humanitarian missions in history to aid Afghan relief efforts. US and coalition forces evacuated more than 130,000 people in the chaotic Allied airlift from the Kabul Airport. The overarching missions, Operation Allies Refuge and Operation Allies Welcome, provided humanitarian support to at-risk Afghan nationals who contributed to the Global War on Terrorism efforts, as well as US citizens living in Afghanistan. Landstuhl Regional Medical Center (LRMC), an overseas military treatment facility located in Germany, supported the healthcare needs of Afghan evacuees and injured US service members during the humanitarian crisis. LRMC clinicians provided emergent, urgent, and specialty care while advocating for evacuee health, wellness, and living conditions. Perioperative and perianesthesia nurses were essential to the humanitarian response, as many evacuees and injured US service members arrived in Germany requiring immediate surgical interventions. In this article, we describe the vital contributions of military perioperative and perianesthesia nurses to the Operation Allies Refuge and Operation Allies Welcome missions, and share our experiences providing humanitarian relief. Military and civilian healthcare planners can learn from our humanitarian relief contributions, experiences, and lessons to strategically prepare their health systems to respond to future crises.

The Military Treatment Facility COVID-19 Response in an Isolated Rural Environment: Challenges and Lessons Learned.

The coronavirus disease-2019 (COVID-19) pandemic remains an extraordinary event that continues to strain healthcare systems worldwide. Unlike the military treatment facilities (MTFs) in the USA, which have ready access to tertiary care facilities, those MTFs in foreign countries confront a host of challenges in meeting mission requirements. In this article, we discuss the MTFs' COVID-19 response in the rural environment of Bavaria, Germany. Relevant factors including regional and clinic response, force health protection, and contingency planning, which influenced the MTFs response, are identified. These factors are further analyzed from a "lessons learned" perspective, and recommendations to shape the future response to a pandemic are provided. This current crisis portends a future where pandemics may remain an omnipresent threat.

A Novel Stress Fracture Rehabilitation Program: A Pilot Study.

INTRODUCTION: Stress fractures (SFx) of the tibia are common and limit military readiness, but there is presently no scientifically validated program that objectively fosters tibia SFx rehabilitation. Therefore, this pilot study evaluated the feasibility of a Graduated Exercise Program (GEP) based on the theory that programmed rest between exercise bouts improves the osteogenic response, which may enhance rehabilitation and military readiness. METHODS: Participants were randomly assigned to the GEP or standard-of-care exercise program. Both programs use a walk-jog-run progression, but the GEP splits daily exercise into morning and evening episodes and provides 5 days of programmed rest after each stage is completed. The GEP included autonomy support to foster program adherence. Outcome measures included adherence, subjective and ActiGraph-validated objective assessments of exercise duration and intensity, pain assessments, and autonomy support assessments. Participants offered suggestions for program improvement. RESULTS: Quantitative findings were mixed, but more importantly, this pilot study showed that the measurement, support, and self-reporting parameters were feasible, with high compliance by participants. Barriers to recruitment and retention were identified, along with solutions to overcome these barriers, starting with obtaining unit support for GEP participation. CONCLUSION: This pilot study demonstrated the feasibility of a GEP with autonomy support, along with challenges and their solutions, providing the foundation for a formal large-sample study.

COVID 19: An unprecedented opportunity for nurse practitioners to reform healthcare and advocate for permanent full practice authority.

The coronavirus disease 2019 (COVID-19) pandemic ushered in a new era for advanced practice registered nurses, as emergency regulatory and policy changes expanded the nurse practitioner (NP) scope of practice. The legislative changes enabled NPs to bolster the national pandemic response by working to the full extent of their education and training. The changes are only temporary, and many have contemplated the permanent impact of COVID-19 when healthcare transitions to a postpandemic normal. NPs now have a unique opportunity to educate others about the merit of their role and advocate for permanent legislative changes. In this creative controversy manuscript, we build a case that national NP full practice authority increases access to care and is vital for a sustainable and resilient healthcare system that can react to future pandemic crises.

Medical Therapy Versus Balloon Sinus Dilation in Adults With Chronic Rhinosinusitis (MERLOT): 12-Month Follow-up.

Background Chronic rhinosinusitis (CRS) is a devastating disease affecting nearly 30 million people in the United States. An interim analysis of data from the present study suggested that, in patients who had previously failed medical therapy, balloon sinus dilation (BSD) plus medical management (MM) provides a significant improvement in the quality of life (QOL) at 24 weeks postprocedure compared to MM alone. Objective The primary objective of this final analysis was to evaluate the durability of treatment effects through the 52-week follow-up. Methods Adults aged 19 and older with CRS who had failed MM elected either BSD plus MM or continued MM. Patients were evaluated at 2 (BSD arm only), 12, 24, and 52 weeks posttreatment. Balloon dilations were performed either as an office-based procedure under local anesthesia or in the operating room per physicians' and patients' discretion. The primary end point was change in patient-reported QOL as measured by Chronic Sinusitis Survey (CSS) total score from baseline to the 24-week follow-up. Secondary outcomes including changes in CSS, Rhinosinusitis Disability Index (RSDI), and Sino-Nasal Outcome Test (SNOT) total and subscores, sinus medication usage, missed days of work/school, number of medical care visits, and sinus infections from baseline to the 52-week follow-up are reported here within. Results BSD led to sustained greater improvements in self-reported QOL using the CSS and RSDI total scores with a trend toward improvement in the SNOT-20 total score from baseline to the 52-week follow-up compared to continued MM. There were no changes in medication usage apart from nasal steroid usage for which the MM cohort had an increase in usage. There were no device-related serious adverse events. Conclusion The current analysis highlights the safety, effectiveness, and durability of BSD in CRS patients aged 19 and older who had previously failed MM.

Design and implementation of a low-cost, portable OCT system.

Optical coherence tomography (OCT) is a widely used biomedical imaging tool, primarily in ophthalmology to diagnose and stage retinal diseases. In order to increase access for a wider range of applications and in low resource settings, we developed a portable, low-cost OCT system that has comparable imaging performance to commercially available systems. Here, we present the system design and characterization and compare the system performance to other commercially available OCT systems. In addition, future cost reductions and potential additional applications of the low-cost OCT system are discussed.

Opportunities and Benefits for Powerchair Users Through Power Soccer.

Power soccer (or powerchair football), the first competitive team sport for users of motorized wheelchairs, is receiving increased attention among people with disabilities, healthcare professionals, and academics. The present study provides a qualitative analysis of the experiences of 34 American power soccer athletes. Participant observation and in-depth interviews with 11 female and 23 male athletes were conducted between 2007 and 2013. Results indicate that involvement in power soccer provides participants with an increased sense of empowerment, acquisition of social capital, and psychosocial benefits, including a deep satisfaction of the desire to participate in competitive sports and an opportunity to be independent. Implications of these findings for improving the quality of life of people with physical disabilities and for future research are discussed.

Global Reprogramming of Host Kinase Signaling in Response to Fungal Infection.

Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular lifestyle is important for virulence. Host mechanisms controlling fungal phagocytosis and replication remain obscure. Here, we perform a global phosphoproteomic analysis of the host response to Cryptococcus infection. Our analysis reveals numerous and diverse host proteins that are differentially phosphorylated following fungal ingestion by macrophages, thereby indicating global reprogramming of host kinase signaling. Notably, phagocytosis of the pathogen activates the host autophagy initiation complex (AIC) and the upstream regulatory components LKB1 and AMPKα, which regulate autophagy induction through their kinase activities. Deletion of Prkaa1, the gene encoding AMPKα1, in monocytes results in resistance to fungal colonization of mice. Finally, the recruitment of AIC components to nascent Cryptococcus-containing vacuoles (CnCVs) regulates the intracellular trafficking and replication of the pathogen. These findings demonstrate that host AIC regulatory networks confer susceptibility to infection and establish a proteomic resource for elucidating host mechanisms that regulate fungal intracellular parasitism.

Reconstitution of Phospholipase A2-Dependent Golgi Membrane Tubules.

The Golgi complex is the Grand Central Station of intracellular membrane trafficking in the secretory and endocytic pathways. Anterograde and retrograde export of cargo from the Golgi complex involves a complex interplay between the formation of coated vesicles and membrane tubules, although much less is known about tubule-mediated trafficking. Recent advances using in vitro assays have identified several cytoplasmic phospholipase A2 (PLA2) enzymes that are required for the biogenesis of membrane tubules and their roles in the functional organization of the Golgi complex. In this chapter we describe methods for the cell-free reconstitution of PLA2-dependent Golgi membrane tubule formation. These methods should facilitate the identification of other proteins that regulate this process.

Nursing in the 8th Evacuation Hospital, 1942-1945.

This article describes the experiences of Army nurses in the University of Virginia sponsored 8th Evacuation Hospital during World War II. In addition, it examines gender and role differences within the Army Medical Department, and how nurses' contributions helped shape the profession. This research used traditional historical methods of inquiry to include both primary and secondary sources of information. Primary sources include newspaper clippings, letters, citations, and photographs from the archival collections of the 8th Evacuation Hospital located in the University of Virginia Historical Collections and Services, Charlottesville, VA, and journal articles from that period. Secondary sources consisted of bibliographical and historical texts. Evidence suggests that advances in the chain-of-evacuation, antibiotics, dissemination of blood products, and nurses' expanded roles all contributed to increased survival of the wounded. Nurses' performance garnered an enduring respect from combatants who received care, as well as the medical officers and enlisted personnel with whom they worked on a daily basis. Collaboration, mutual respect, and coordinated teamwork were critical for mission success. Army nurses demonstrated that they had the mettle to go into a war zone and perform in an exemplary manner.

Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin.

Mutations in the progranulin (PGRN) gene have been linked to two distinct neurodegenerative diseases, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests a critical role of PGRN in lysosomes. However, how PGRN is trafficked to lysosomes is still not clear. Here we report a novel pathway for lysosomal delivery of PGRN. We found that prosaposin (PSAP) interacts with PGRN and facilitates its lysosomal targeting in both biosynthetic and endocytic pathways via the cation-independent mannose 6-phosphate receptor and low density lipoprotein receptor-related protein 1. PSAP deficiency in mice leads to severe PGRN trafficking defects and a drastic increase in serum PGRN levels. We further showed that this PSAP pathway is independent of, but complementary to, the previously identified PGRN lysosomal trafficking mediated by sortilin. Collectively, our results provide new understanding on PGRN trafficking and shed light on the molecular mechanisms behind FTLD and NCL caused by PGRN mutations.

Methods for analyzing the role of phospholipase A2 enzymes in endosome membrane tubule formation.

Cargo export from mammalian endosomal compartments often involves membrane tubules, into which soluble and membrane-bound cargos are segregated for subsequent intracellular transport. These membrane tubules are highly dynamic and their formation is mediated by a variety of endosome-associated proteins. However, little is known about how these membrane tubules are temporally or spatially regulated, so other tubule-associated proteins are likely to be discovered and analyzed. Therefore, methods to examine the biogenesis and regulation of endosome membrane tubules will prove to be valuable for cell biologists. In this chapter, we describe methods for studying this process using both cell-free, in vitro reconstitution assays, and in vivo image analysis tools.

In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography.

Spectroscopic analysis of biological tissues can provide insight into changes in structure and function due to disease or injury. Depth-resolved spectroscopic measurements can be implemented for tissue imaging using optical coherence tomography (OCT). Here, spectroscopic OCT is applied to in vivo measurement of burn injury in a mouse model. Data processing and analysis methods are compared for their accuracy. Overall accuracy in classifying burned tissue was found to be as high as 91%, producing an area under the curve of a receiver operating characteristic curve of 0.97. The origins of the spectral changes are identified by correlation with histopathology.