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The filovirus Taï Forest virus (TAFV) caused a single human case of infection originating from a chimpanzee outbreak, demonstrating that humans are susceptible to TAFV infection. Existing animal disease models use intramuscular (IM) infection; however, natural filovirus infection likely occurs mucosal. We aimed to develop a ferret disease model by inoculation of TAFV by the IM, intranasal (IN), or aerosol routes. The IM group showed minimal signs of disease while IN and aerosol inoculations resulted in moderate to severe disease and partial lethality. The surviving IN or IM TAFV-infected ferrets were rechallenged IM or IN with Ebola virus (EBOV) as a pilot study assessing the cross-protection potential between these closely related viruses. Only ferrets IN-inoculated with TAFV and IN-inoculated with EBOV were protected from disease, all others succumbed to disease after EBOV infection. This data shows that ferrets are a feasible model to assess TAFV pathogenicity by mucosal exposure routes and that possible cross-protection between TAFV and EBOV may be achieved upon mucosal exposure.

The first isolate of the emerging filovirus Lloviu virus (LLOV) was obtained in 2022. No animal disease models have been established. We assessed the pathogenic potential of LLOV in ferrets after intranasal, intramuscular, or aerosol exposure. The lack of disease development shows ferrets are not a disease model for LLOV.

The recent outbreaks of Marburg virus disease (MVD) in Guinea, Ghana, Equatorial Guinea, and Tanzania, none of which had reported previous outbreaks, imply increasing risks of spillover of the causative viruses, Marburg virus (MARV) and Ravn virus (RAVV), from their natural host animals. These outbreaks have emphasized the need for the development of rapid diagnostic tests for this disease. Using monoclonal antibodies specific to the viral nucleoprotein, we developed an immunochromatography (IC) assay for the rapid diagnosis of MVD. The IC assay was found to be capable of detecting approximately 102−4 50% tissue culture infectious dose (TCID50)/test of MARV and RAVV in the infected culture supernatants. We further confirmed that the IC assay could detect the MARV and RAVV antigens in the serum samples from experimentally infected nonhuman primates. These results indicate that the IC assay to detect MARV can be a useful tool for the rapid point-of-care diagnosis of MVD.

Marburg virus (MARV), a filovirus, was first identified in 1967 in Marburg, Germany, and Belgrade, former Yugoslavia. Since then, MARV has caused sporadic outbreaks of human disease with high case fatality rates in parts of Africa, with the largest outbreak occurring in 2004/05 in Angola. From 2021 to 2023, MARV outbreaks occurred in Guinea, Ghana, New Guinea, and Tanzania, emphasizing the expansion of its endemic area into new geographical regions. There are currently no approved vaccines or therapeutics targeting MARV, but several vaccine candidates have shown promise in preclinical studies. We compared three vaccine platforms simultaneously by vaccinating hamsters with either a single dose of an adenovirus-based (ChAdOx-1 MARV) vaccine, an alphavirus replicon-based RNA (LION-MARV) vaccine, or a recombinant vesicular stomatitis virus-based (VSV-MARV) vaccine, all expressing the MARV glycoprotein as the antigen. Lethal challenge with hamster-adapted MARV 4 weeks after vaccination resulted in uniform protection of the VSV-MARV and LION-MARV groups and 83% of the ChAdOx-1 MARV group. Assessment of the antigen-specific humoral response and its functionality revealed vaccine-platform-dependent differences, particularly in the Fc effector functions.

NVX-CoV2373 is a vaccine containing a full-length stabilized recombinant spike protein trimer that is administered in two doses 3 weeks apart along with a saponin-based adjuvant. In a randomized trial, approximately 20,000 participants received the vaccine and 10,000 a placebo. Vaccine efficacy against infection was 90%, and reactogenicity was similar to that of other Covid-19 vaccines.

SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI.

Background. Sexual and gender minority youth (SGMY) experience health inequities compared with cisgender heterosexuals, and these inequities are heightened in areas with high structural stigma. Quantitative research shows school assets (e.g., adult support) are associated with better health for SGMY. Though some qualitative studies elucidated how school staff support SGMY, none have triangulated such strategies in a geographically and sociodemographically diverse sample of school staff and SGMY. This paper describes a multi-perspective qualitative study design and offers lessons learned from conducting such a study. Methods. Using a novel stratified sampling frame, we interviewed 60 SGMY and 29 school staff who attended/worked at high schools in U.S. states with low, medium, and high structural stigma. To ensure sociodemographic diversity, we constructed sampling quotas, and recruited SGMY using social media and staff using a multi-pronged approach. Results. The stratified sampling strategy met our goal of enrolling diverse SGMY and staff participants. SGMY participants attended schools in low (n = 20), medium (n = 22), and high (n = 18) structural stigma states. We enrolled 18 cisgender girls, 18 cisgender boys, and 24 gender minority youth. Fifty-three percent of SGMY were youth of color, and 45% attended schools in rural areas. School staff participants worked at schools in low (n = 11), medium (n = 11), and high (n = 7) structural stigma states. School staff participants were 55% heterosexual, 91% cisgender, and had diverse roles (e.g., teacher, principal, librarian, and nurse). Conclusions. This paper describes new methods for collecting qualitative data from diverse SGMY and school staff. Some lessons learned from this study include the importance of using trauma-informed interviewing methods, having a suicidality safety protocol, establishing a priori sampling quotas, and creating tailored social media advertisements. With these data we will explore the heterogeneity of SGMY and school staff experiences across varying structural stigma levels, yielding foundational information for future school-based interventions.

Background. Most West Nile virus (WNV) infections in humans are asymptomatic; severe disease occurs in relatively few patients and typically manifests as encephalitis, meningitis, or acute flaccid paralysis. A few cases of life-threatening disease with diffuse hemorrhagic manifestations have been reported in Africa; however, this clinical presentation has not been documented for any of the >16,700 cases of WNV disease reported in the United States during 1999–2004. We describe a case of fulminant WNV infection in a 59-year-old Florida man who died following a brief illness that resembled hemorrhagic disease caused by Rickettsia rickettsii, dengue virus or yellow fever virus. Methods. Traditional and contemporary diagnostic assays, including culture isolation, electron microscopic examination, reverse-transcriptase polymerase chain reaction amplification, and immunohistochemical stains, were used to confirm systemic WNV infection in the patient. Results. WNV was isolated in a cell culture from a skin biopsy specimen obtained from the patient shortly prior to death. Electron microscopic examination identified the isolate as a flavivirus, and reverse-transcriptase polymerase chain reaction amplified specific WNV sequences from the isolate and patient tissue. Quantitative polymerase chain reaction identified approximately 1 × 107 viral copies/mL in the patient's serum. WNV antigens were detected by immunohistochemical stains in intravascular mononuclear cells and endothelium in skin, lung, liver, kidney, spleen, bone marrow, and central nervous system; no viral antigens were identified in neurons or glial cells of the central nervous system. Conclusions. Although hemorrhagic disease is a rare manifestation of WNV infection, the findings provided by this report may offer new insights regarding the clinical spectrum and pathogenesis of WNV disease in humans.

High-resolution X-ray imaging techniques using optical elements such as zone plates are widely used for viewing the internal structure of samples in exquisite detail. The resolution attainable is ultimately limited by the manufacturing tolerances for the optics. Combining ideas from crystallography and holography, this limit may be surpassed by the method of coherent diffractive imaging (CDI) 1 . Although CDI shows particular promise in applications involving X-ray free-electron lasers 2 , it is also emerging as an important new technique for imaging at third-generation synchrotrons. The limited coherent output of these sources, however, is a significant barrier to obtaining shorter exposure times. A fundamental assumption of coherent diffractive imaging is that the incident light is well-approximated by a single optical frequency. In this Letter, we demonstrate the first experimental realization of ‘polyCDI’, using a broadband source to achieve a factor of 60 reduction in the exposure time over quasi-monochromatic coherent diffractive imaging. Poor coherence resulting from long exposure times is a problem for many coherent diffractive X-ray imaging schemes. Here, researchers show that coherent diffractive imaging using a broadband source can achieve a 60-fold reduction in exposure time.

To the Editor: The elderly patients studied by Weinberger and colleagues (May 30 issue) 1 may have had additional access to physicians and nurses during the six-month period after their discharge from the hospital, but the question remains: Did they receive primary care? Too often, what is called primary care lacks the critical component of continuity of care by a physician who is specifically trained and skilled in the comprehensive first contact with and ongoing care of a population. 2 Table 1 of Weinberger et al. shows that members of the study group were assigned to “primary care physicians,” whom they did . . .