Efficiency analysis of rapid antigen test based SARS-CoV-2 in hospital contact tracing and screening regime: test characteristics and cost effectiveness.

In the context of the current SARS-CoV-2 pandemic, reliable and cost-efficient screening and testing strategies are crucial to prevent disease transmission and reduce socioeconomic losses. To assess the efficiency of a rapid antigen test (RAT)-based SARS-CoV-2 contact-tracing and screening regime, we conducted a retrospective analysis of RAT and polymerase chain reaction (PCR) test data over a 1-year period, assessed test characteristics and estimated cost-effectiveness. The RAT had a sensitivity of 70.2% overall and 89.3% for people with a high risk of infectivity. We estimated inpatient treatment and quarantined healthcare worker costs of over € 5860.83, whereas the cost of identifying one SARS-CoV-2 positive person by RAT for our patient cohort was € 1210.75. In contrast, the estimated respective PCR cost was € 5043.32. Therefore, a RAT-based contract tracing and screening regime may be an efficient and cost-effective way to contribute to the early identification and prevention of SARS-CoV-2 transmission.

AMD3100-Mediated CXCR4 Inhibition Impairs Development of Primary Lymphoma of the Central Nervous System.

A hallmark of primary lymphoma of the central nervous system (CNS; PCNSL) is the strong CXCR4 expression of the tumor cells, the function of which is still unknown. In vitro treatment of BAL17CNS lymphoma cells by AMD3100, which inhibits CXCR4-CXCL12 interactions, resulted in the significantly differential expression of 273 genes encoding proteins involved in cell motility, cell-cell signaling and interaction, hematological system development and function, and immunologic disease. Among the genes down-regulated was the one encoding CD200, a regulator of CNS immunologic activity. These data directly translated into the in vivo situation; BAL17CNS CD200 expression was down-regulated by 89% (3% versus 28% CD200+ lymphoma cells) in AMD3100-treated versus untreated mice with BAL17CNS-induced PCNSL. Reduced lymphoma cell CD200 expression may contribute to the markedly increased microglial activation in AMD3100-treated mice. AMD3100 also maintained the structural integrity of blood-brain barrier tight junctions and the outer basal lamina of cerebral blood vessels. Subsequently, lymphoma cell invasion of the brain parenchyma was impaired, and maximal parenchymal tumor size was significantly reduced by 82% in the induction phase. Thus, AMD3100 qualified as a potentially attractive candidate to be included into the therapeutic concept of PCNSL. Beyond therapy, CXCR4-induced suppression of microglial activity is of general neuroimmunologic interest. This study identified CD200 expressed by the lymphoma cells as a novel mechanism of immune escape in PCNSL.

Influence of public health and infection control interventions during the severe acute respiratory syndrome coronavirus 2 pandemic on the in-hospital epidemiology of pathogens: in hospital versus community circulating pathogens.

BACKGROUND: The first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Germany was reported in early February 2020. In addition, extensive control measures on the coronavirus disease 2019 (COVID-19) pandemic have been placed in Germany since March 2020. These include contact and travel restrictions, distance rules, mandatory wearing of face masks and respirators, cancellation of mass events, closures of day-care centers, schools, restaurants and shops, isolation measures, and intensified infection control measures in medical and long-term care facilities. Changes in demand or access to health care services and intensified control measures can lead to changes in transmission dynamics and imply effects on the overall occurrence of infectious diseases in hospitals. METHODS: To analyze the impact of infection control measures implemented in public on infectious diseases in hospitals, surveillance data from Marburg University Hospital were analyzed retrospectively. The analysis was conducted from January 2019 to June 2021, referred to hospital occupancy and mobility data in the county of Marburg-Biedenkopf, and correlated to control measures in hospitals and the general population. RESULTS: The COVID-19 pandemic and associated measures immediately impacted the occurrence of infectious diseases at the Marburg University Hospital. Significant changes were detected for virus-associated respiratory and gastrointestinal diseases. The massive drop in norovirus infections was significantly affected by the onset of the pandemic (P = 0.028). Similar effects were observed for rotavirus (up to - 89%), respiratory syncytial virus (up to - 98%), and adenovirus infections (up to - 90%). The decrease in gastrointestinal and respiratory virus detection rates was significantly affected by the decline in mobility (P < 0.05). Of note, since April 2020, there have been no detected influenza cases. Furthermore, Clostridioides difficile-related infections declined after late 2020 (- 44%). In contrast, no significant changes were detected in the prevalence of susceptible and drug-resistant bacterial pathogens. In particular, the detection rates of methicillin-resistant Staphylococcus aureus isolates or multidrug resistant (MDR) and extended drug resistant (XDR) bacteria remained constant, although the consumption of hand disinfectants and protective equipment increased. CONCLUSIONS: The COVID-19 pandemic and associated public health measures had a significant impact on infectious diseases and the detection of pathogens at the Marburg University Hospital. Significant changes were observed for community transmissible infections, while no such effects on pathogens primarily associated with nosocomial transmission could be detected.

High Level Bioaerosol Protection against Infective Aerosols: How Medical Face Masks Compare against Respirators.

Face masks and respirators are commonly used to prevent the transmission of infectious diseases that spread by respiratory droplets and aerosols. However, there is still uncertainty about the protective effect of the different types of masks against virus containing aerosols. To determine the as-worn bioaerosol protection efficacy of different face coverings and estimate the possible protective function against airborne diseases, we challenged different respirators and medical masks on a standardized dummy head with a bioaerosol containing MS2 bacteriophages as virus surrogates. In our experiments, FFP2 respirators showed the highest filtration efficacy 94 ± 4 (SD) % followed by medical masks 93 ± 3 (SD) % and KN95 respirators 90 ± 7 (SD) %. Nevertheless, we found no statistically significant difference between respirators and medical masks in terms of provided protection against infective aerosols. Our findings indicate that both respirators and medical masks provide a high as-worn bioaerosol protection efficacy against virus containing aerosols, and therefore, a very high protection against airborne diseases. Considering the higher comfort, better availability, and lower price of medical masks in contrast to respirators, it is recommendable to use medical face masks especially in low risk situations and in general public.

Expression of Cas9 in a Syngeneic Model of Primary Central Nervous System Lymphoma Induces Intracerebral NK and CD8 T Cell-Mediated Lymphoma Cell Lysis Via Perforin.

The development of clustered regulatory interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR-Cas9)-mediated gene modification has opened an exciting avenue of targeting genes to study the pathogenesis of diseases and to develop novel therapeutic concepts. However, as the effector protein Cas9 is of bacterial origin, unwanted side effects due to a host immune response against Cas9 need to be considered. Here, we used the syngeneic model of BAL17CNS-induced primary lymphoma of the central nervous system (PCNSL, CNS) in BALB/c mice to address this issue. Surprisingly, stable expression of Cas9 in BAL17CNS (BAL17CNS/Cas9) cells rendered them unable to establish PCNSL on intracerebral transplantation. Instead, they induced a prominent intracerebral immune response mediated by CD8 T cells, which lysed BAL17CNS/Cas9 cells via perforin. In addition, B cells contributed to the immune response as evidenced by serum anti-Cas9 antibodies in BALB/c mice as early as day 8 after transplantation of BAL17CNS/Cas9 cells. In athymic BALB/cnu/nu mice, NK cells mounted a vigorous intracerebral immune response with perforin-mediated destruction of BAL17CNS/Cas9 cells. Thus, in the CNS, perforin produced by NK and CD8 T cells was identified as a mediator of cytotoxicity against BAL17CNS/Cas9 cells. These observations should be taken into account when considering therapeutic CRISPR-Cas9-mediated tumor cell manipulation for PCNSL.

Development of a web-based contact tracing and point-of-care-testing workflow for SARS-CoV-2 at a German University Hospital.

INTRODUCTION: In late 2019, a novel coronavirus was detected in China. Supported by its respiratory transmissibility, even by people infected without symptomatic disease, this coronavirus soon began to rapidly spread worldwide. BACKGROUND: Many countries have implemented different infection control and containment strategies due to ongoing community transmission. In this context, contact tracing as well as adequate testing and consequent quarantining of high-risk contacts play leading roles in containing the virus by interrupting infection chains. This approach is especially important in the hospital setting where contacts often cannot be avoided and physical distance is usually not possible. Furthermore, health care workers (HCWs) usually have contact with a variety of vulnerable people, making it essential to identify infections among hospital employees as soon as possible to interrupt the rapid spread of SARS-CoV-2 in the facility. Several electronic tools for contact tracing, such as specific software or mobile phone apps, are available for the public health sector. In contrast, contact tracing in hospitals often has to be carried out without helpful electronic tools, and an enormous amount of human resources is typically required. AIM: For rapid contact tracing and effective infection control and management measures for HCWs in hospitals, adapted technical solutions are needed. METHODS: In this study, we report the development of our containment strategy to a web-based contact tracing and rapid point-of-care-testing workflow. RESULTS/CONCLUSION: Our workflow yielded efficient control of the rapidly evolving situation during the SARS-CoV-2 pandemic from May 2020 until January 2021 at a German University Hospital.

Medical face masks offer self-protection against aerosols: An evaluation using a practical in vitro approach on a dummy head.

Since the appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the question regarding the efficacy of various hygiene measures and the use of personal protective equipment (PPE) has become the focus of scientific and above all public discussion. To compare respirators, medical face masks, and cloth masks and determine if it is recommendable to wear face masks to protect the individual wearer of the mask from inhaling airborne particles, we challenged 29 different masks with aerosols and tested the pressure drop as a surrogate for breathing resistance owing to the mask material. We found that Type II medical face masks showed the lowest pressure drop (12.9±6.8 Pa/cm2) and therefore additional breathing resistance, whereas respirators such as the KN95 (32.3±7.0 Pa/cm2) and FFP2 (26.8±7.4 Pa/cm2) showed the highest pressure drops among the tested masks. The filtration efficacy of the mask material was the lowest for cloth masks (28±25%) followed by non-certified face masks (63±19%) and certified medical face masks (70±10%). The materials of the different respirators showed very high aerosol retentions (KN95 [94±4%] and FFP2 [98±1%]). For evaluating the as-worn filtration performance simulating real live conditions each mask type was also tested on a standardized dummy head. Cloth masks and non-EN-certified face masks had the worst as-worn filtration efficacies among the tested masks, filtering less than 20% of the test aerosol. Remarkably, certified type II medical face masks showed similar (p>0.5) as-worn filtration results (47±20%) than KN95 masks (41±4%) and FFP2 masks (65±27%), despite having a lower pressure drop. Face shields did not show any significant retention function against aerosols in our experiment. Our results indicate that it seems recommendable to wear face masks for providing base protection and risk reduction against inhaling airborne particles, in low-risk situations. In our study, especially EN 14683 type II certified medical face masks showed protective effectiveness against aerosols accompanied by minimal additional breathing resistance. FFP2 Respirators, on the other hand, could be useful in high-risk situations but require greater breathing effort and therefore physical stress for users.

Direct Costs of a Contact Isolation Day: A Prospective Cost Analysis at a Swiss University Hospital.

We prospectively evaluated direct costs of contact precautions using on-site observation. Additional mean costs per patient day were calculated for extra materials used, increased workload, and one-off isolation activities. The cost of contact precautions was $158.90 (95% confidence interval, $124.90‒$192.80) per patient day. Infect Control Hosp Epidemiol 2018;39:101-103.

Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines.

Trefoil factor family (TFF) peptides have been shown to effect cell proliferation, apoptosis, migration and invasion of normal cells and various cancer cell lines. In the literature TFF peptides are controversially discussed as tumor suppressors and potential tumor progression factors. In the study presented, we investigated the effect of TFF3 overexpression on growth, viability, migration and tumorigenicity of the human retinoblastoma cell lines Y-79, WERI-Rb1, RBL-13 and RBL-15. As revealed by WST-1 and TUNEL assays as well as DAPI and BrdU cell counts, recombinant human TFF3 significantly lowers retinoblastoma cell viability and increases apoptosis levels. Transient TFF3 overexpression likewise significantly increases RB cell apoptosis. Stable, lentiviral TFF3 overexpression lowers retinoblastoma cell viability, proliferation and growth and significantly increases cell death in retinoblastoma cells. Blockage experiments using a broad-spectrum caspase inhibitor and capase-3 immunocytochemistry revealed the involvement of caspases in general and of caspase-3 in particular in TFF3 induced apoptosis in retinoblastoma cell lines. Soft agarose and in ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF3 overexpression influences anchorage independent growth and significantly decreases the size of tumors forming from retinoblastoma cells. Our study demonstrates that forced TFF3 expression exerts a significant pro-apoptotic, anti-proliferative, and tumor suppressive effect in retinoblastoma cells, setting a starting point for new additive chemotherapeutic approaches in the treatment of retinoblastoma.

Cadherin-11 localizes to focal adhesions and promotes cell-substrate adhesion.

Cadherin receptors have a well-established role in cell-cell adhesion, cell polarization and differentiation. However, some cadherins also promote cell and tissue movement during embryonic development and tumour progression. In particular, cadherin-11 is upregulated during tumour and inflammatory cell invasion, but the mechanisms underlying cadherin-11 stimulated cell migration are still incompletely understood. Here, we show that cadherin-11 localizes to focal adhesions and promotes adhesion to fibronectin in Xenopus neural crest, a highly migratory embryonic cell population. Transfected cadherin-11 also localizes to focal adhesions in different mammalian cell lines, while endogenous cadherin-11 shows focal adhesion localization in primary human fibroblasts. In focal adhesions, cadherin-11 co-localizes with ß1-integrin and paxillin and physically interacts with the fibronectin-binding proteoglycan syndecan-4. Adhesion to fibronectin mediated by cadherin-11/syndecan-4 complexes requires both the extracellular domain of syndecan-4, and the transmembrane and cytoplasmic domains of cadherin-11. These results reveal an unexpected role of a classical cadherin in cell-matrix adhesion during cell migration.

Avaliação da implementação das boas práticas de manipulação em unidade de acolhimento institucional por meio de um Programa de Incentivo fiscal e capacitação / Evaluation of the implementation of good handling practices in an institutional inclusion unit through a tax incentive Program and training

O objetivo deste estudo foi de avaliar a implementação das Boas Práticas de Manipulação em Unidade de Acolhimento Institucional de Santa Maria/RS, por meio de um programa de incentivo fiscal e capacitação, e o efeito do investimento realizado. No primeiro mês, aplicou-se uma lista de verificação para avaliar as Boas Práticas de Manipulação. Posteriormente elaborou-se um plano de ação para ajustar as não conformidades, levantar os custos e encaminhar o projeto para aprovação. Após aprovação, realizou-se a capacitação e estipulou-se o prazo de oito meses para efetuar adequação dos itens. No último mês aplicou-se novamente a lista de verificação. Na primeira aplicação, a Unidade apresentou 38 % de adequação; e após os investimentos a conformidade foi de 93 %. Nesta primeira aplicação, os itens controle integrado de pragas, documentação e registro, e responsabilidade não apresentaram adequação. Após os investimentos, estes itens e o abastecimento de água, manejo de resíduos, matéria-prima, ingredientes, embalagem, armazenamento e transporte do alimento preparado obtiveram 100 % de adequação; e o item com maior investimento foi de edificações, instalações, móveis e utensílios. Após a execução de investimento e capacitação houve aumento no percentual de adequação, em relação às Boas Práticas de Manipulação...

Loss of Xenopus cadherin-11 leads to increased Wnt/ß-catenin signaling and up-regulation of target genes c-myc and cyclin D1 in neural crest.

Xenopus cadherin-11 (Xcadherin-11) is an exceptional cadherin family member, which is predominantly expressed in cranial neural crest cells (NCCs). Apart from mediating cell-cell adhesion it promotes cranial NCC migration by initiating filopodia and lamellipodia formation. Here, we demonstrate an unexpected function of Xcadherin-11 in NCC specification by interfering with canonical Wnt/ß-catenin signaling. Loss-of-function experiments, using a specific antisense morpholino oligonucleotide against Xcadherin-11, display a nuclear ß-catenin localization in cranial NCCs and a broader expression domain of the proto-oncogene cyclin D1 which proceeds c-myc up-regulation. Additionally, we observe an enhanced NCC proliferation and an expansion of specific NCC genes like AP2 and Sox10. Thereby, we could allocate NCC proliferation and specification to different gene functions. To clarify which domain in Xcadherin-11 is required for early NCC development we tested different deletion mutants for their rescue ability in Xcadherin-11 morphants. We identified the cytoplasmic tail, specifically the ß-catenin binding domain, to be necessary for proper NCC development. We propose that Xcadherin-11 is necessary for controlled NCC proliferation and early NCC specification in tuning the expression of the canonical Wnt/ß-catenin target genes cyclin D1 and c-myc by regulating the concentration of the nuclear pool of ß-catenin.

Effectiveness of pulmonary rehabilitation in exercise capacity and quality of life in chronic obstructive pulmonary disease patients with and without global fat-free mass depletion.

OBJECTIVE: To investigate the effectiveness of pulmonary rehabilitation (PR) in exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD) with and without global fat-free mass (FFM) depletion. DESIGN: Retrospective case-control. SETTING: Outpatient clinic, university center. PARTICIPANTS: COPD patients (N=102) that completed PR were initially evaluated. INTERVENTION: PR including whole-body and weight training for 12 weeks, 3 times per week. MAIN OUTCOME MEASURES: St. George Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and FFM evaluation applied before and after PR. RESULTS: Patients were stratified according to their FFM status measured by bioelectric impedance. They were considered depleted if the FFM index was ≤ 15 kg/m(2) in women and ≤ 16 kg/m(2) in men. From the initial sample, all depleted patients (n=31) composed the FFM depleted group. It was composed predominantly by women (68%) with a mean age ± SD of 64.4 ± 7.3 years and a forced expiratory volume in 1 second of 33.6%=-13.2% predicted. Paired for sex and age, 31 nondepleted patients were selected from the initial sample to compose the nondepleted group. Improvement in the 6MWD was similar in these 2 groups after PR. Both groups improved SGRQ scores, although the observed power was small and did not allow adequate comparison between depleted and nondepleted patients. There was no difference between groups in weight change, whereas FFM tended to be greater in depleted patients. This increase had no correlation with the 6MWD or the SGRQ. CONCLUSIONS: Benefits of PR to exercise capacity were similar comparing FFM depleted and nondepleted COPD patients. Although FFM change tended to be greater in depleted patients, this increase had no definite relation with clinical outcomes.