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Rocky Mountain spotted fever (RMSF) is an ongoing public health crisis in Mexico, particularly in states bordering the United States. The national highest incidence and mortality of RMSF occur in this region, resulting in a case-fatality rate that ranges annually between 10% and 50%, primarily affecting vulnerable groups such as children, elderly adults, and persons living in poverty. Multiple biological, environmental, and social determinants can explain its growing presence throughout the country and how it challenges the health system and society. It is necessary to integrate resources and capacities from health authorities, research centers, and society to succeed in dealing with this problem. Through a scientific symposium, a group of academicians, U.S. health officials, and Mexican health authorities met on November 8-10, 2023, in Hermosillo, Mexico, to discuss the current situation of RMSF across the country and the challenges associated with its occurrence. An urgent call for action to improve national capacity against RMSF in the aspects of epidemiological and acarological surveillance, diagnosis, medical care, case and outbreak prevention, health promotion, and research was urged by the experts. The One Health approach is a proven multidisciplinary strategy to integrate policies and interventions to mitigate and prevent the burden of cases, deaths, and suffering caused by RMSF in Mexico.

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.

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.

BACKGROUND: Benign prostatic hyperplasia, lower urinary tract symptoms, and prostate cancer often co-occur. Their effect on urinary function is an important consideration regarding prostate cancer treatment choices. While prostate volume (PV) and urinary symptoms are commonly used in treatment choice decision making, their association with post-treatment urinary function is unknown. We evaluated the associations between PV and baseline urinary function with treatment choice and post-treatment urinary function among men with localized prostate cancer. METHODS: We identified 1647 patients from CEASAR, a multicenter population-based, prospective cohort study of men with localized prostate cancer, for analysis. Primary outcomes were treatment choice and health-related quality of life (HRQOL) assessed by the 26-item Expanded Prostate Index Composite (EPIC-26) at pre-specified intervals up to 5 years. Multivariable analysis was performed, controlling for demographic and clinicopathologic features. RESULTS: Median baseline PV was 36 mL (IQR 27-48), and baseline urinary irritative/obstructive domain score was 87 (IQR 75-100). There was no observed clinically meaningful association between PV and treatment choice or post-treatment urinary function. Among patients with poor baseline urinary function, treatment with radiation or surgery was associated with statistically and clinically significant improvement in urinary function at 6 months which was durable through 5 years (improvement from baseline at 5 years: radiation 20.4 points, surgery 24.5 points). CONCLUSIONS: PV was not found to be associated with treatment modality or post-treatment urinary irritative/obstructive function among men treated for localized prostate cancer. Men with poor baseline urinary irritative/obstructive function improve after treatment with surgery or radiation therapy.

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.

BackgroundWomen with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC.MethodsWe performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves.ResultsOf the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of the 659 patients with International Federation of Obstetrics and Gynecology stage data, 156 (23.7%) had stage I disease, 64 (9.7%) had stage II, 395 (59.9%) had stage III, and 44 (6.7%) had stage IV. Of the 377 patients with surgical data, 200 (53.0%) had no visible residual disease. Of the 361 patients with chemotherapy data, 330 (91.4%) received first-line platinum-based chemotherapy. The median follow-up duration was 5.0 years. The median progression-free survival and overall survival were 43.2 months and 110.4 months, respectively. Multivariate analysis indicated a statistically significant impact of stage and residual disease on progression-free survival and overall survival. Platinum-based chemotherapy was not associated with a survival advantage.ConclusionThis multicentre analysis indicates that complete surgical cytoreduction to no visible residual disease has the most impact on improved survival in LGSC. This finding could immediately inform and change practice.

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.