Third-generation smallpox vaccines induce low-level cross-protecting neutralizing antibodies against Monkeypox virus in laboratory workers.

Due to the discontinuation of routine smallpox vaccination after its eradication in 1980, a large part of the human population remains naïve against smallpox and other members of the orthopoxvirus genus. As a part of biosafety personnel protection programs, laboratory workers receive prophylactic vaccinations against diverse infectious agents, including smallpox. Here, we studied the levels of cross-protecting neutralizing antibodies as well as total IgG induced by either first- or third-generation smallpox vaccines against Monkeypox virus, using a clinical isolate from the 2022 outbreak. Serum neutralization tests indicated better overall neutralization capacity after vaccination with first-generation smallpox vaccines, compared to an attenuated third-generation vaccine. Results obtained from total IgG ELISA, however, did not show higher induction of orthopoxvirus-specific IgGs in first-generation vaccine recipients. Taken together, our results indicate a lower level of cross-protecting neutralizing antibodies against Monkeypox virus in recipients of third-generation smallpox vaccine compared to first-generation vaccine recipients, although total IgG levels were comparable.

Empowering the Radiation Oncology Triage Nurse Role: A Single-Center Analysis.

BACKGROUND: Triage nurses play a crucial role in addressing patient telephone calls. However, topics that radiation oncology (RO) triage nurses encounter have not been thoroughly investigated. OBJECTIVES: This project established baseline patient issues addressed via telephone by RO triage nurses in a clinically busy academic RO department; identified themes and potential areas for workflow improvement; and evaluated interprofessional perceptions of RO triage from nurses, physicians, and radiation therapists. METHODS: This two-part study was conducted from September through November 2021 using a retrospective chart review that analyzed patient communications to the RO nurse triage line. Physicians, nurses, and radiation therapists completed an online survey about their experiences with nurse triage. FINDINGS: Analysis revealed 13 message themes, with scheduling questions being the most common theme. Survey results indicated that average provider satisfaction with the effectiveness of triage was 3 of 5, perceived triage nurse preparedness to resolve encounters was 3 of 5, and perception of the triage program by physicians was 2.4 of 5.

Virucidal activity of three standard chemical disinfectants against Ebola virus suspended in tripartite soil and whole blood.

Proper disinfection and inactivation of highly pathogenic viruses is an essential component of public health and prevention. Depending on environment, surfaces, and type of contaminant, various methods of disinfection must be both efficient and available. To test both established and novel chemical disinfectants against risk group 4 viruses in our maximum containment facility, we developed a standardized protocol and assessed the chemical inactivation of the two Ebola virus variants Mayinga and Makona suspended in two different biological soil loads. Standard chemical disinfectants ethanol and sodium hypochlorite completely inactivate both Ebola variants after 30 s in suspension at 70% and 0.5% v/v, respectively, concentrations recommended for disinfection by the World Health Organization. Additionally, peracetic acid is also inactivating at 0.2% v/v under the same conditions. Continued vigilance and optimization of current disinfection protocols is extremely important due to the continuous presence of Ebola virus on the African continent and increased zoonotic spillover of novel viral pathogens. Furthermore, to facilitate general pandemic preparedness, the establishment and sharing of standardized protocols is very important as it allows for rapid testing and evaluation of novel pathogens and chemical disinfectants.

[Follow-up Evaluation of a Multimodal Treatment Program for Pregnant Women, Mothers and Fathers who Consume Methamphetamine]. / Verlaufsevaluation eines multimodalen Therapieprogrammes für Methamphetamin-konsumierende Schwangere, Mütter und Väter.

OBJECTIVE: Follow-up evaluation of the addiction therapy part of the multimodal treatment program "Mama Denk an mich" ("Mummy, think of me"), an interdisciplinary cooperation of several departments of the University Hospital Dresden with the local youth welfare offices and addiction counseling centers. METHOD: Description of treatment course and sample of the first 100 patients with a methamphetamine-related disorder and prospective observational study of treatment outcome. RESULTS: Besides a high proportion of first-time treated subjects (51%) and a young mean age (29 years), the sample was notable for precarious socioeconomic conditions and numerous comorbidities. Nevertheless, the comparatively high adherence rate (68%) suggests a good efficacy of the therapeutic methods used. CONCLUSION: Parenthood or pregnancy represent an opportunity to motivate methamphetamine addicts for effective outpatient addiction therapy even in the presence of severe addiction and psychiatric comorbidities.

Bounded integer model-based analysis of psoriasis area and severity index in patients with moderate-to-severe plaque psoriasis receiving BI 730357.

BI 730357 is investigated as an oral treatment of plaque psoriasis. We analyzed the impact of three dosage regimens on the Psoriasis Area and Severity Index (PASI) response with modeling based on phase I and II data from 109 healthy subjects and 274 patients with moderate-to-severe plaque psoriasis. The pharmacokinetics (PK) was characterized by a two-compartment model with dual absorption paths and a first-order elimination. Higher baseline C-reactive protein was associated with lower clearance and patients generally had lower clearance compared with healthy subjects. A bounded integer PK/pharmacodynamic model characterized the effect on the observed PASI. The maximum drug effect was largest for patients with no prior biologic use, smaller for patients with prior use of non-interleukin-17 inhibitors, and smallest for patients with prior interleukin-17 inhibitor use. The models allowed robust simulation of large patient populations, predicting a plateau in PASI outcomes for BI 730357 exposure above 2000 nmol/L.

Palatal brushing for the treatment of denture stomatitis: A multicentre randomized controlled trial.

PURPOSE: To determine the effectiveness of palatal brushing in the treatment of denture-related erythematous stomatitis (DES) in complete denture wearers. METHODS: This two-parallel-arm RCT was conducted in three university clinics in Brazil, Canada, and Chile. Participants (n=77) were randomly allocated to receive (i) instructions for palatal brushing and standard oral/denture hygiene ("intervention"); or (ii) standard oral/denture hygiene instructions only ("control"). Data collection was carried out at the baseline and at 3 and 6 months after intervention. Outcomes included the magnitude of oral Candida carriage and the degree of inflammation of denture-bearing tissues. Groups were compared using generalized estimating equations and chi-square test (α=0.05). RESULTS: Palatal inflammation levels were reduced significantly in the "intervention" compared to "control" group at 6 months (intervention: 70%, control: 40%; chi-square, p=0.04). There was no between-group significant difference in the Candida count from denture and palatal biofilms; however, a subgroup analysis restricted to baseline Candida carriers showed further reduction with the intervention at 6 months. No adversity was observed by trialist or reported by participants. CONCLUSIONS: Including palatal brushing in oral instructions for denture wearers has positive impact on DES-related mucosal inflammation. Thus, our findings endorse the inclusion of palatal brushing in standard oral hygiene instructions to treat DES.

Rapid Onset Chylous Ascites Presenting as the Initial Manifestation of Follicular Lymphoma: A Case Report.

Follicular lymphoma is the most common indolent Non-Hodgkin Lymphoma (NHL) with overall survival measured in years for the majority of patients (NHL carries a somewhat positive prognosis). Baseline clinical genetic characteristics appear to be the best predictors of the clinical course. A few cases appear to be familial; however, no consistent environmental or infectious causation has been identified. Our presenting patient has a case of follicular lymphoma that was initially diagnosed in the setting of rapid onset chylous ascites, a highly atypical and rare presentation. Follicular lymphoma typically presents with painless lymphadenopathy in lymph nodes along the torso. The lymphoma cells divide within the nodes and can be palpated as bumps within the axilla or on the neck above the clavicle. Various prognostic indicators and tumor grading can give providers a sense of survival statistics. Once diagnosed, chemotherapy tends to form the backbone of most treatment regimens with various roles for immunotherapy and radiation.

Exposure to avian coronavirus vaccines is associated with increased levels of SARS-CoV-2-cross-reactive antibodies.

BACKGROUND: Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. METHODS: We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. RESULTS: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared with pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared with pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. CONCLUSION: We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID-19.

Housing Correlates in Pregnant and Parenting Women Using Methamphetamine and Accessing Psychiatric Care.

Background: Integrated care is a promising model for pregnant and parenting women with problems related to methamphetamine use. Yet more research is imperative to guide services for this vulnerable population as methamphetamine use contributes to housing instability, which is associated with heavier use and overdose death. Method: This prospective observational study analyzed how housing at discharge from psychiatric care was related to patient characteristics, program participation, and aftercare in 102 pregnant and/or parenting women. Results: Twelve of 23 women who were unstably housed at admission (three of six homeless) achieved stable housing by discharge from integrated care. Women were more likely unstably housed at discharge when unstably housed at admission, single, living apart from at least one minor, or when the other parent had a substance use disorder (p < 0.05). Unstably housed women at discharge were also more likely to have used social and inpatient services, and to transition to inpatient rehabilitation (p < 0.05). Among baseline characteristics, logistic regression identified unstable housing at admission (OR = 6.07) and being single (OR = 4.01) as the strongest unique contributors to unstable housing at discharge (p < 0.05). Conclusion: Unstably housed women and single women seem particularly at risk of remaining in precarious living conditions despite accessing integrated care for problems associated with methamphetamine use. Future work should investigate whether stronger partnerships with government and community agencies could be a way forward to help these women attain and maintain stable housing.

Methaemoglobinemia after Liposuction under Tumescent Local Anaesthesia - Diagnostic Value of Pulse Oximetry.

Background: Tumescent local anaesthesia with prilocain can lead to clinically significant methemoglobin levels. New generation multiple wavelength pulse oximeters (e. g. Masimo Radical 7®) can measure methemoglobin levels. Methods: In this prospective observational study we compared the venous methemoglobin levels and the corresponding pulse oximetric values of the Radical 7® in patients undergoing tumescent local anaesthesia for liposuction procedures. The measurements were performed in Hanseklinik, Luebeck, Germany between 2008 and 2011. Results: In 133 patients, we measured a maximum methemoglobin level of 18 per cent. In a Bland-Altman analysis we found a mean bias of +2.2 % (-4.1 to 8.4 limits of agreement) for pulse oximetric values compared to hemoximetry. Conclusion: Pulse oximetric measurement of methemoglobin is an early-warning tool for the detection of clinically significant methaemoglobinemia in patients with tumescent local anaesthesia.

Serological testing for SARS-CoV-2 antibodies in clinical practice: A comparative diagnostic accuracy study.

BACKGROUND: Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies, and the performance in clinical practice is essentially unclear. OBJECTIVES: We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease-2019 (COVID-19) and (b) prediction of neutralizing antibodies against SARS-CoV-2 in real-life clinical settings. METHODS: We prospectively included 2573 consecutive health-care workers and 1085 inpatients with suspected or possible previous COVID-19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme-linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; and lateral flow immunoassay, LFI), epitopes of SARS-CoV-2 (nucleocapsid, N; receptor-binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan-Ig) were conducted. A positive real-time PCR test from a nasopharyngeal swab was defined as previous COVID-19. Neutralization assays with live SARS-CoV-2 were performed in a subgroup of patients to assess neutralization activity (n = 201). RESULTS: The sensitivity to detect patients with previous COVID-19 was ≥85% in anti-N ECLIA (86.8%) and anti-S1 ELISA (86.2%). Sensitivity was 84.7% in anti-S1/S2 CLIA, 84.0% in anti-RBD+LFI, 81.0% in anti-N CLIA, 79.2% in anti-RBD ELISA, and 65.6% in anti-N ELISA. The specificity was 98.4% in anti-N ECLIA, 98.3% in anti-N CLIA, 98.2% in anti-S1 ELISA, 97.7% in anti-N ELISA, 97.6% in anti-S1/S2 CLIA, 97.2% in anti-RBD ELISA, and 96.1% in anti-RBD+LFI. The sensitivity to detect neutralizing antibodies was ≥85% in anti-S1 ELISA (92.7%), anti-N ECLIA (91.7%), anti-S1/S2 CLIA (90.3%), anti-RBD+LFI (87.9%), and anti-RBD ELISA (85.8%). Sensitivity was 84.1% in anti-N CLIA and 66.2% in anti-N ELISA. The specificity was ≥97% in anti-N CLIA (100%), anti-S1/S2 CLIA (97.7%), and anti-RBD+LFI (97.9%). Specificity was 95.9% in anti-RBD ELISA, 93.0% in anti-N ECLIA, 92% in anti-S1 ELISA, and 65.3% in anti-N ELISA. Diagnostic accuracy measures were consistent among subgroups. CONCLUSIONS: The diagnostic accuracy of serological tests for SARS-CoV-2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID-19 deviated substantially from the manufacturer's specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re-infection.

Leveraging Interprofessional Education to Improve Physician/Laboratory Cooperation and Patient Outcomes.

Pathology and laboratory medicine are integral parts of the healthcare team. While this fact is uncontested, efforts to integrate medical laboratory science (MLS) students into interprofessional education (IPE) activities with medical students have been scarce. We contend here that now is the optimal time to explore IPE with medical and MLS students and that doing so will provide significant benefits to students as well as their future patients. Neglecting to capitalize on this opportunity will result in continued interprofessional barriers.

Clinical evaluation of single 4-mm implants in the posterior mandible: A 3-year follow-up pilot study.

STATEMENT OF PROBLEM: Extra-short implants in the posterior mandible can increase the functional surface area and reduce the risk of implant overload. However, reports of treatment using single extra-short implants in the posterior mandible with a midterm follow-up are lacking. PURPOSE: The purpose of this prospective pilot study was to evaluate the clinical behavior of single extra-short 4-mm implants placed in the posterior mandible during a follow-up of 3 years from implant restoration. MATERIAL AND METHODS: A total of 18 participants with a single extra-short 4-mm-long implant placed in the area of the mandibular first molars participated in this pilot study. The survival and success rates of implants, as well as biologic and prosthetic variables, were evaluated during a follow-up of 3 years from implant restoration. RESULTS: The survival rate of the implants was 100%, with no implant or biologic complications recorded. One prosthetic complication (loosening of 1 screw) was observed. CONCLUSIONS: Single extra-short (4 mm) implants in the posterior mandible showed favorable clinical behavior during the first 3-years of follow-up.

Ultra-Thin Veneers: A Current State-of-the-Art

ABSTRACT: Currently, the aesthetic requirements of patients are increasing and they have begun to request more conservative treatments. One alternative to achieve harmonious results is through the indication of ultra-thin veneers. This is considered a conservative technique but the evidence basis for it seems to be limited. The following review attempts to summarize the relevant literature to establish guidelines for clinicians based on scientific evidence regarding the use of ultra-thin veneers. Ultra-thin veneers seem to be a reliable alternative to achieve aesthetic and harmonious results; however, many factors must be considered to ensure correct diagnosis and treatment plan. In addition, the literature is scarce in relation to a consensus on tooth preparation and long-term studies evaluating the success of this type of treatment over time do not exist.

RESUMEN: Actualmente, los requisitos estéticos de los pacientes han aumentando y solicitan tratamientos más conservadores. Una alternativa para lograr resultados armónicos es mediante la indicación de carillas o laminados ultrafinos. Esta se considera una técnica conservadora, pero la base teórica parece ser limitada. La siguiente revisión intenta resumir la literatura relevante para establecer pautas para clínicas basadas en evidencia científica sobre el uso de carillas ultrafinas. Las carillas ultrafinas parecen ser una alternativa confiable para lograr resultados estéticos y armónicos; sin embargo, se deben considerar muchos factores para asegurar un diagnóstico y plan de tratamiento correcto. Además, la literatura es escasa en relación a un consenso sobre la preparación dental y no existen estudios a largo plazo que evalúen el éxito de este tipo de tratamiento a lo largo del tiempo.

Fournier's gangrene mimicking an acute epididymitis.

Fournier's gangrene is a urologic emergency secondary to a necrotizing soft tissue infection. Fournier's gangrene is characterized by severe pain and features of Fournier's gangrene may include edema, blisters and bullae, crepitus, subcutaneous gas, and systemic symptoms. Risk factors include male gender, alcohol abuse, immunocompromised state, uncontrolled diabetes mellitus, obesity, and malignancy. The diagnosis is made clinically but is often supported by radiography, ultrasound, computed tomography, and magnetic resonance imaging. Treatment consists of emergent hospitalization and surgery to debride the necrotic tissues. Morbidity and mortality for Fournier's gangrene are very high if left untreated. Early surgical intervention is key to the successful treatment of Fournier's gangrene. This case report presents a case of Fournier's gangrene mimicking acute epididymitis and highlights the importance of a thorough physical examination with high clinical suspicion for Fournier's gangrene.

Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(II) complexes.

Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release. In this study, light-sensitive polypyridyl-ruthenium(II) complexes were combined with polypept(o)ides for photocleavable core cross-linked polymeric micelles. Block copolymers of polysarcosine-block-poly(glutamic acid) were synthesized by ring-opening N-carboxyanhydride polymerization and modified with aromatic nitrile-groups on the glutamic acid side chain. The modified copolymers self-assembled into micelles and were cross-linked by cis-diaquabis(2,2'-bipyridine)-ruthenium(II) ([Ru(bpy)2(H2O)2]2+) or cis-diaquabis(2,2'-biquinoline)-ruthenium(II) ([Ru(biq)2(H2O)2]2+). Depending on the flexibility and hydrophobicity of the nitrile linker, either small spherical structures (Dh 45 nm, PDI 0.11) or worm-like micelles were obtained. The cross-linking reaction did not affect the overall size distribution but induced a change in the metal-to-ligand charge transfer peak from 482 to 420 nm and 592 to 548 nm. The cross-linked micelles displayed colloidal stability after incubation with human blood plasma and during gel permeation chromatography in hexafluoroisopropanol. Light-induced cleavage of [Ru(bpy)2(H2O)2]2+ was accomplished within 300 s, while [Ru(biq)2(H2O)2]2+ could not be completely released. Analysis in HuH-7 cells revealed increased cytotoxicity via micellar delivery of [Ru(bpy)2(H2O)2]2+ but mostly irradiation damage for [Ru(biq)2(H2O)2]2+. Further evaluation in ovo confirmed stable circulation pointing towards the future development of quick-release complexes.

Exposure-safety analyses of nintedanib in patients with chronic fibrosing interstitial lung disease.

BACKGROUND: Nintedanib reduces the rate of decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). The recommended dose of nintedanib is 150 mg twice daily (BID). METHODS: Data from Phase II and III trials in IPF and Phase III trials in SSc-ILD and progressive fibrosing ILDs other than IPF were analyzed to investigate the relationship between nintedanib plasma concentrations (exposure) and safety (liver enzyme elevations [defined as transaminase elevations equal or greater than 3 times the upper limit of normal] and diarrhea). RESULTS: Using data from 1403 subjects with IPF treated with 50-150 mg nintedanib BID, a parametric time-to-first-event model for liver enzyme elevations was established. Besides exposure, gender was a significant covariate, with a three-fourfold higher exposure-adjusted risk in females than males. Subsequent analysis of combined data from IPF, SSc-ILD (n = 576) and progressive fibrosing ILD (n = 663) studies suggested a consistent exposure-liver enzyme elevation relationship across studies. No exposure-diarrhea relationship was found using data from the various fibrosing ILDs, but diarrhea risk was dependent on dose administered. CONCLUSIONS: The positive correlation between exposure and risk of liver enzyme elevations was consistent across nintedanib studies in IPF, SSc-ILD and progressing fibrosing ILDs other than IPF. The effect size does not warrant a priori dose adjustment in patients with altered plasma exposure (excluding hepatic impairment patients, where there are specific labelling recommendations). For diarrhea, dose administered was a better predictor than exposure.