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Rocky Mountain spotted fever (RMSF) is the deadliest tickborne disease in the Western Hemisphere. RMSF is caused by the bacterium Rickettsia rickettsii, which is primarily transmitted to humans by Dermacentor [...]

Native and invasive tick species pose serious public health concerns in the United States, particularly in northeastern states. Recent and rapid expansion of the lone star tick (Amblyomma americanum) into [...]

Rocky Mountain spotted fever (RMSF), a tickbome disease caused by Rickettsia rickettsii, is the leading cause of death from rickettsial infections in the Western Hemisphere (1). The disease can progress [...]

Spotted fever rickettsiosis in solid organ transplant recipients is rarely described, and all reports document disease acquired months to years after the transplant, after recognized tick bites or exposures to [...]

Abstract Amblyomma maculatum sensu lato (s.l.) is an ixodid tick found in the semi-arid southwestern United States and northern Mexico where it is a parasite of medical and veterinary significance, including as a vector for Rickettsia parkeri, a cause of spotted fever rickettsiosis in the Americas. To describe the comprehensive natural history of this tick, monthly small mammal trapping and avian mist netting sessions were conducted at sites in Cochise County Arizona, within the Madrean Archipelago region where human cases of R. parkeri rickettsiosis and adult stages of A. maculatum s.l. were previously documented. A total of 1949 larvae and nymphs were removed from nine taxonomic groups of rodents and ten species of birds and were used in combination with records for adult stages collected both from vegetation and hunter-harvested animals to model seasonal activity patterns. A univoltine phenology was observed, initiated by the onset of the annual North American monsoon and ceasing during the hot, dry conditions preceding the following monsoon season. Cotton rats (Sigmodon spp.) were significantly more likely to be infested than other rodent taxa and carried the highest tick loads, reflecting a mutual affinity of host and ectoparasite for microhabitats dominated by grass.

Rocky Mountain spotted fever (RMSF) is a severe tickborne disease that can reach epidemic proportions in communities with certain social and ecologic risk factors. In some areas, the case-fatality rate of brown dog tick-associated RMSF is up to 50%. Because of the spread of brown dog tick–associated RMSF in the southwestern United States and northern Mexico, the disease has the potential to emerge and become endemic in other communities that have large populations of free-roaming dogs, brown dog ticks, limited resources, and low provider awareness of the disease. By using a One Health approach, interdisciplinary teams can identify communities at risk and prevent severe or fatal RMSF in humans before cases occur. We have developed a conceptual framework for RMSF prevention to enable communities to identify their RMSF risk level and implement prevention and control strategies.

Purpose – Guided by several of the 9 essentials of what it means to be a PDS (NAPDS, 2021), authors share a plea to rethink the teacher burnout-attrition-staffing crisis with a call toward a moral imperative of recentering an ethic of care. Many schools are operating under anti-care practices which directly undermine teacher wellness in part due to secondary traumatic stress, rising workload demands and intensive student needs. Design/methodology/approach – Reflecting a compilation of teacher voices, including participants from three research studies and the collective decades-worth experience of educator scholars, this paper presents a synthesis of educator burnout and the role of educator wellness within trauma-informed social emotional learning initiatives. Findings – The practical model of educator resilience offers a potential solution to burnout and attrition by prioritizing care for teachers individually and collectively prior to addressing care for students. Originality/value – The model articulates educator resilience as the motivational force of life within a school community focused on an ethic of care that drives the collective and individuals within the collective to be their best. This aligns with foundation principles of PDS schools and Goodlad and colleagues’ decades-old call to foreground the moral dimensions of teaching in school reform (1990).

We document a case of Rickettsia parkeri rickettsiosis in a patient in Connecticut, USA, who became ill after a bite from a Gulf Coast tick (Amblyomma maculatum). We used PCR to amplify R. parkeri DNA from the detached tick. The patient showed a 4-fold rise in IgG reactive with R. parkeri antigens.

Abstract Hard ticks (Acari: Ixodidae) have been historically identified by morphological methods which require highly specialized expertise and more recently by DNA-based molecular assays that involve high costs. Although both approaches provide complementary data for tick identification, each method has limitations which restrict their use on large-scale settings such as regional or national tick surveillance programs. To overcome those obstacles, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been introduced as a cost-efficient method for the identification of various organisms, as it balances performance, speed, and high data output. Here we describe the use of this technology to validate the distinction of two closely related Dermacentor tick species based on the development of the first nationwide MALDI-TOF MS reference database described to date. The dataset obtained from this protein-based approach confirms that tick specimens collected from United States regions west of the Rocky Mountains and identified previously as Dermacentor variabilis are the recently described species, Dermacentor similis. Therefore, we propose that this integrative taxonomic tool can facilitate vector and vector-borne pathogen surveillance programs in the United States and elsewhere.

Abstract PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4CRBN, and mediate potent PTPN2/N1 degradation in cells and mice. To provide mechanistic insights into the cooperative complex formation introduced by degraders, we employed a combination of structural approaches. Our crystal structure reveals how PTPN2 is recognized by the tri-substituted thiophene moiety of the degrader. We further determined a high-resolution structure of DDB1-CRBN/Cmpd-1/PTPN2 using single-particle cryo-electron microscopy (cryo-EM). This structure reveals that the degrader induces proximity between CRBN and PTPN2, albeit the large conformational heterogeneity of this ternary complex. The molecular dynamic (MD)-simulations constructed based on the cryo-EM structure exhibited a large rigid body movement of PTPN2 and illustrated the dynamic interactions between PTPN2 and CRBN. Together, our study demonstrates the development of PTPN2/N1 heterobifunctional degraders with potential applications in cancer immunotherapy. Furthermore, the developed structural workflow could help to understand the dynamic nature of degrader-induced cooperative ternary complexes.

Spotted fever rickettsiosis is rarely observed in solid organ transplant recipients, and all previously reported cases have been associated with tick bite months to years after transplantation. We describe a kidney transplant recipient in North Carolina, USA, who had a moderately severe Rickettsia parkeri infection develop during the immediate posttransplant period.

We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.

Objectives This study aimed to generate new qualitative insights to understand the rehabilitation needs of people living with a confirmed or presumed diagnosis of ischaemia with no obstructive coronary arteries (INOCA), explore which aspects of current cardiovascular prevention and rehabilitation programmes could meet the needs of people with INOCA and where adjustments (if any) may be appropriate.Design Semistructured qualitative interview study.Participants Interviews were undertaken (n=17; 88% female, age range 31–69 years) with people with a confirmed or presumed diagnosis of INOCA.Results Findings highlighted concerns around a lack of evidence-based guidance for cardiovascular prevention and rehabilitation programmes for patients with INOCA. Participants expressed a desire for modular cardiovascular prevention and rehabilitation programmes that could be accessed flexibly to accommodate episodic fluctuations in symptoms. Participants suggested that existing cardiovascular prevention and rehabilitation programme content needed adjustment including enhanced psychosocial support, supervised low-impact physical activity and specialist dietary advice and medication reviews. Additional elements specific to INOCA should be made available as appropriate including acute care planning and a module to provide information and support for female-specific issues. The importance of involving INOCA patients in the codesign of future programmes and associated training was emphasised.Conclusions People with INOCA are willing to engage with cardiovascular prevention and rehabilitation programmes and express a desire for more support. This patient group shares some barriers to rehabilitation programme attendance with other cardiac patient groups, but they also have specific concerns about the need for improved professional knowledge and evidence-based guidance regarding the management of INOCA. Cardiovascular rehabilitation programmes need to be delivered flexibly and individually tailored to ensure the relapsing and remitting nature of INOCA and associated support needs are addressed.

Abstract The commissioning of multi-petawatt class laser facilities around the world is gathering pace. One of the primary motivations for these investments is the acceleration of high-quality, low-emittance electron bunches. Here we explore the interaction of a high-intensity femtosecond laser pulse with a mass-limited dense target to produce MeV attosecond electron bunches in transmission and confirm with three-dimensional simulation that such bunches have low emittance and nano-Coulomb charge. We then perform a large parameter scan from non-relativistic laser intensities to the laser-QED regime and from the critical plasma density to beyond solid density to demonstrate that the electron bunch energies and the laser pulse energy absorption into the plasma can be quantitatively described via the Zero Vector Potential mechanism. These results have wide-ranging implications for future particle accelerator science and associated technologies.

Rocky Mountain spotted fever (RMSF), a severe and extraordinarily lethal infectious disease, has emerged as a widespread public health crisis among predominantly vulnerable populations in several countries of Latin America, particularly evident in northern Mexico. Historically, RMSF has gained less attention than many other tropical infectious diseases, resulting in insufficient allocations of resources and development of capabilities for its prevention and control in endemic regions. We argue that RMSF fulfills accepted criteria for a neglected tropical disease (NTD). The relative neglect of RMSF in most Latin American countries contributes to disparities in morbidity and mortality witnessed in this region. By recognizing RMSF as an NTD, an increased public policy interest, equitable and more appropriate allocation of resources, scientific interest, and social participation can ameliorate the impact of this potentially treatable disease, particularly in vulnerable populations.

The brown dog tick, Rhipicephalus sanguineus sensu lato (s.l.), is an important vector for Rickettsia rickettsii, causative agent of Rocky Mountain spotted fever. Current public health prevention and control efforts to protect people involve preventing tick infestations on domestic animals and in and around houses. Primary prevention tools rely on acaricides, often synthetic pyrethroids (SPs); resistance to this chemical class is widespread in ticks and other arthropods. Rhipicephalus sanguineus s.l. is a complex that likely contains multiple unique species and although the distribution of this complex is global, there are differences in morphology, ecology, and perhaps vector competence among these major lineages. Two major lineages within Rh. sanguineus s.l., commonly referred to as temperate and tropical, have been documented from multiple locations in North America, but are thought to occupy different ecological niches. To evaluate potential acaricide resistance and better define the distributions of the tropical and temperate lineages throughout the US and in northern Mexico, we employed a highly multiplexed amplicon sequencing approach to characterize sequence diversity at: 1) three loci within the voltage-gated sodium channel (VGSC) gene, which contains numerous genetic mutations associated with resistance to SPs; 2) a region of the gamma-aminobutyric acid-gated chloride channel gene (GABA-Cl) containing several mutations associated with dieldrin/fipronil resistance in other species; and 3) three mitochondrial genes (COI, 12S, and 16S). We utilized a geographically diverse set of Rh sanguineus s.l. collected from domestic pets in the US in 2013 and a smaller set of ticks collected from canines in Baja California, Mexico in 2021. We determined that a single nucleotide polymorphism (T2134C) in domain III segment 6 of the VGSC, which has previously been associated with SP resistance in Rh. sanguineus s.l., was widespread and abundant in tropical lineage ticks (>50 %) but absent from the temperate lineage, suggesting that resistance to SPs may be common in the tropical lineage. We found evidence of multiple copies of GABA-Cl in ticks from both lineages, with some copies containing mutations associated with fipronil resistance in other species, but the effects of these patterns on fipronil resistance in Rh. sanguineus s.l. are currently unknown. The tropical lineage was abundant and geographically widespread, accounting for 79 % of analyzed ticks and present at 13/14 collection sites. The temperate and tropical lineages co-occurred in four US states, and as far north as New York. None of the ticks we examined were positive for Rickettsia rickettsii or Rickettsia massiliae.

Extraskeletal myxoid chondrosarcoma (EMC) is a malignant cartilage neoplasm usually encountered in the proximal extremities. We report the case of a 58-year-old male who presented initially with a 3-month history of cough. Initial staging demonstrated a right upper lobe mass with bilateral pulmonary nodules and moderate tracer uptake in the right lung mass and right groin on positron emission tomography imaging. Endobronchial ultrasound biopsy confirmed a histological diagnosis of EMC for which the patient underwent right upper lobe wedge resection. Pelvic MRI revealed a peripherally enhancing juxta-articular lesion within the region of the right obturator externus bursa, which was thought initially to represent either a ganglion or paralabral cyst. However, ultrasound-guided biopsy yielded identical histology to the resected lung mass leading to the diagnosis of primary EMC in the right groin with pulmonary metastases. The patient underwent surgical excision of the right groin mass with no local recurrence on the surveillance computed tomography at 5, 12, and 18 months but eventual disease recurrence in the right groin and further progression of the pulmonary metastases at 29 months. We emphasize that the contrast enhancement pattern of EMC can mimic a benign cystic lesion, in particular, when in a juxta-articular location, which has the potential to mislead radiologists and delay diagnosis and definitive treatment.

We present the case of periaortitis which presented initially with left flank pain. A diagnosis of IgG4-related disease (IgG4-RD) was subsequently made and managed as such. IgG4-RD is rare, can be difficult to diagnose, and requires clinical, serological, radiological and pathological correlation, particularly given that serum IgG4 levels may be normal. Immunosuppression is the mainstay treatment for this chronic condition alongside regular rheumatology input.

In order to contribute to research into youth crime prevention, the current study aimed to explore the experiences of children in conflict with the law prior to receiving their first caution or conviction. Participants were recruited at a Youth Justice Service and included five children working with the service, their five case managers, and two of their parents/guardians. Data was collected using semi-structured interviews and timelines were used to support the children in sharing their experiences. Data was analysed using Interpretative Phenomenological Analysis, which focuses on understanding how individuals experience the world and how they make sense of those experiences. Six group experiential themes were identified within the analysis. These consider the events leading up to offending and whether it could have been predicted, the extent to which the children felt supported, the effect of school practices, the impact of peer influences, difficulties with managing emotions, and the children’s readiness for change. Each theme is discussed and recommendations for practice and future research are considered. The importance of placing children’s experiences at the forefront of research is highlighted throughout.

Objective To explore the lived experience of people with myocardial ischaemia with no obstructive arteries.Design Qualitative study using semistructured interviews.Setting Telephone interviews with 17 participants living in the UK.Participants 17 people (2 males, 15 females; aged 31–69 years) with a presumed or confirmed diagnosis of myocardial ischaemia with no obstructive arteries, recruited via social media and online patient-led support forums.Results Five themes were generated. Theme 1 describes the wide range of experiences that participants described, particularly the frequency and intensity of symptoms, and the uncertainty and fear that symptoms commonly provoked. Theme 2 describes the major impact on social relationships, employment and other aspects of everyday life. Theme 3 illustrates challenging and traumatising experiences participants described around pathways to diagnosis and accessing medical support. Theme 4 highlights the lack of consensus and clarity that participants had been confronted with around treatment and management. Theme 5 describes coping and supportive strategies valued by participants.Conclusions This study provides insight into the challenges of living with myocardial ischaemia with no obstructive arteries. Findings highlight the significant psychological impact on people living with these conditions and the need for improvements in diagnosis, support and long-term management.

The genus Anaplasma includes several species of tickborne, zoonotic pathogens of global importance. Three recognized species (Anaplasma phagocytophilum, Anaplasma ovis, and Anaplasma bovis) and one provisionally named species (Anaplasma capra) [...]

In humans, microbial organisms known as the microbiota, normally colonize airway passages, skin, the oral cavity, the gastrointestinal tract, and the vagina. There is a growing body of evidence linking the gut microbiota with the overall health of its host. Normally, the microbes that make up the microbiota coexist with a human or animal host without any noticeable difficulty. However, if the symbiotic balance is altered as a result of illness, stress, dietary changes, antibiotic treatment, or other disturbances, the result may be a disruption of normal interactions known as dysbiosis. As a result, the body may become more susceptible to disease. This article examines the most common means by which the microbiota are identified, the process by which the microbiome is acquired, fecal microbial transplantation, and the association of the gut microbiome with specific illnesses such as diabetes and autism. The utility of these applications in developing a teaching module that incorporates the microbiome into courses in physiology or pathophysiology is also reviewed.

Abstract Space-based biomanufacturing has the potential to improve the sustainability of deep space exploration. To advance biomanufacturing, bioprocessing systems need to be developed for space applications. Here, commercial technologies were assessed to design space bioprocessing systems to supply a liquid amine carbon dioxide scrubber with active carbonic anhydrase produced recombinantly. Design workflows encompassed biomass dewatering of 1 L Escherichia coli cultures through to recombinant protein purification. Non-crew time equivalent system mass (ESM) analyses had limited utility for selecting specific technologies. Instead, bioprocessing system designs focused on minimizing complexity and enabling system versatility. Three designs that differed in biomass dewatering and protein purification approaches had nearly equivalent ESM of 357–522 kg eq. Values from the system complexity metric (SCM), technology readiness level (TRL), integration readiness level (IRL), and degree of crew assistance metric identified a simpler, less costly, and easier to operate design for automated biomass dewatering, cell lysis, and protein affinity purification.

We detected the DNA of an Anaplasma bovis–like bacterium in blood specimens from 4 patients from the United States with suspected tickborne illnesses. Initial molecular characterization of this novel agent reveals identity to A. bovis–like bacteria detected in Dermacentor variabilis ticks collected from multiple US states.