Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease

Chagas disease (CD) is a parasitic disease caused by Trypanosoma cruzi protozoa, presenting with cardiomyopathy, megaesophagus, and/or megacolon. To determine the mechanisms of gastrointestinal (GI) CD tissue tropism, we systematically characterized the spatial localization of infection-induced metabolic and microbiome alterations, in a mouse model of CD. Notably, the impact of the transition between acute and persistent infection differed between tissue sites, with sustained large-scale effects of infection in the esophagus and large intestine, providing a potential mechanism for the tropism of CD within the GI tract. Infection affected acylcarnitine metabolism; carnitine supplementation prevented acute-stage CD mortality without affecting parasite burden by mitigating infection-induced metabolic disturbances and reducing cardiac strain. Overall, results identified a previously-unknown mechanism of disease tolerance in CD, with potential for new therapeutic regimen development. More broadly, results highlight the potential of spatially resolved metabolomics to provide insight into disease pathogenesis and infectious disease drug development.Open Access fees paid for in whole or in part by the University of Oklahoma Libraries. This work was supported by start-up funds from the University of Oklahoma to L.-I.M. and the National Institute of Allergy and Infectious Diseases of the NIH under award number R21AI148886 to L.-I.M. Initial tissue collection was supported by a postdoctoral fellowship to L.-I.M. from the Canadian Institutes of Health Research (award number 338511; www.cihr-irsc.gc.ca/). Microbial community analysis was supported, in part, by an NIH grant (award number NIH 2R01-GM089886 to K.S). Immunological characterization was performed on instrumentation from the OU Protein Production and Characterization Core facility, supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the NIH under grant number P20GM103640. Histology samples were processed by the University of Oklahoma Health Sciences Center, Stephenson Cancer Center Tissue Pathology Shared Resource, supported by the National Cancer Institute Cancer Center Support Grant P30CA225520 and COBRE P20GM103639. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.Ye

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Appropriate Reporting of G-Codes & C-Modifiers by Therapists Who Treat Chronic Wounds

Passed in 2012, the Middle Class Tax Relief & Jobs Creation Act requires the Centers for Medicare & Medicaid Services (CMS) to implement a data collection system for outpatient therapy services provided to Medicare beneficiaries. The process is required to collect data on beneficiary function during the course of therapy services in order to provide a better understanding of beneficiary conditions, outcomes, and expenditures. The goal is for this data to be used to develop a new payment system for outpatient therapy services, which includes physical therapy (PT), occupational therapy (OT), and speech-language pathology (SLP). The process that was developed is termed “functional limitation reporting” (FLR) and consists of “G-codes” and severity modifiers (“C-modifiers”), which will be explained in further detail within this article. As of July 1, 2013, any therapy service claims submitted without the applicable G-codes and modifiers are returned as unpaid

Clinical utility of mobile phone-based thermography and low-cost infrared handheld thermometry in high-risk diabetic foot

Literature is replete with robust studies documenting the potential clinical utility and net protective effect of the use of temperature assessment/inflammometry in high-risk diabetic foot. We present a mobile phone-based device (FLIR One Personal Thermal Imager, FLIR, Inc., Wilsonville, OR, USA) and a stand-alone handheld device (Nubee, Duarte California, USA) to provide simple, quantifiable images to assist in rapid clinical visualization. Therefore, the purpose of this manuscript was to highlight the potential day-to-day application of these tools

Prescribing Home Digital Thermometry Coupled with Activity Dosing and Optimized Offloading to Prolong Diabetic Foot Remission: A Case Report

People with a history of diabetic foot ulcers (DFUs) experience diminished health-related quality of life and are at a 40% annual risk of DFU recurrence. Due to a fear of DFU recurrence, people in DFU remission participate less in physical activity and moderate-intensity exercise when compared to people with diabetes who have not had wounds. There is novel evidence to suggest that too little activity during DFU remission contributes to only low magnitudes of repetitive tissue loading creating a higher susceptibility to skin trauma during inadvertent high-activity bouts. Conversely, a hasty return to too much activity could lead to rapid recurrence. There is now high-level evidence from multiple meta-analyses to indicate that home-based foot temperature monitoring, coupled with activity modification and daily inspection of the feet for impending signs of ulceration, could reduce the risk of ulcer recurrence by 50%. There is little evidence, however, to guide the decision-making regarding the appropriate quantity and frequency of physical activity during DFU remission and the acceptability from the patient perspective. This has resulted in limited uptake of this novel intervention in clinical practice. Earlier, we proposed that activity can be dosed for people in foot ulcer remission, just like insulin or medication is dosed. Here, we describe a patient-centered approach to implementing home foot temperature monitoring coupled with daily foot checks and dosage-based return to physical activity in a patient in DFU remission, including his perspective. We believe using such an approach could maximize ulcer-free days in remission, thereby improving quality of life

Dosing activity and return to preulcer function in diabetes-related foot ulcer remission patient recommendations and guidance from the Limb Preservation Consortium at USC and the Rancho Los Amigos National Rehabilitation Center

Diabetes-related foot ulcers are a leading cause of global morbidity, mortality, and health-care costs. People with a history of foot ulcers have a diminished quality of life attributed to limited walking and mobility. One of the largest concerns is ulceration recurrence. Approximately 40% of patients with ulcerations will have a recurrent ulcer in the year after healing, and most occur in the first 3 months after wound healing. Hence, this period after ulceration is called ‘‘remission’’ due to this risk of reulceration. Promoting and fostering mobility is an integral part of everyday life and is important for maintaining good physical health and health-related quality of life for all people living with diabetes. In this short perspective, we provide recommendations on how to safely increase walking activity and facilitate appropriate off-loading and monitoring in people with a recently healed foot ulcer, foot reconstruction, or partial foot amputation. Interventions include monitored activity training, dosed out in steadily increasing increments and coupled with daily skin temperature monitoring, which can identify dangerous ‘‘hotspots’’ prone to recurrence. By understanding areas at risk, patients are empowered to maximize ulcer-free days and to enable an improved quality of life. This perspective outlines a unified strategy to treat patients in the remission period after ulceration and aims to provide clinicians with appropriate patient recommendations based on best available evidence and expert opinion to educate their patients to ensure a safe transition to footwear and return to activity

Decreased Trabecular Bone Mass in Col22a1-Deficient Mice

The bone matrix is constantly remodeled by the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. Whereas type I collagen is the most abundant bone matrix protein, there are several other proteins present, some of them specifically produced by osteoblasts. In a genome-wide expression screening for osteoblast differentiation markers we have previously identified two collagen-encoding genes with unknown function in bone remodeling. Here we show that one of them, Col22a1, is predominantly expressed in bone, cultured osteoblasts, but not in osteoclasts. Based on this specific expression pattern we generated a Col22a1-deficient mouse model, which was analyzed for skeletal defects by mu CT, undecalcified histology and bone-specific histomorphometry. We observed that Col22a1-deficient mice display trabecular osteopenia, accompanied by significantly increased osteoclast numbers per bone surface. In contrast, cortical bone parameters, osteoblastogenesis or bone formation were unaffected by the absence of Col22a1. Likewise, primary osteoblasts from Col22a1-deficient mice did not display a cell-autonomous defect, and they did not show altered expression of Rankl or Opg, two key regulators of osteoclastogenesis. Taken together, we provide the first evidence for a physiological function of Col22a1 in bone remodeling, although the molecular mechanisms explaining the indirect influence of Col22a1 deficiency on osteoclasts remain to be identified