SARS-CoV-2 surface and air contamination in an acute healthcare setting during the first and second pandemic waves.

BACKGROUND: Surfaces and air in healthcare facilities can be contaminated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Previously, the authors identified SARS-CoV-2 RNA on surfaces and air in their hospital during the first wave of the coronavirus disease 2019 pandemic (April 2020). AIM: To explore whether the profile of SARS-CoV-2 surface and air contamination had changed between April 2020 and January 2021. METHODS: This was a prospective, cross-sectional, observational study in a multi-site London hospital. In January 2021, surface and air samples were collected from comparable areas to those sampled in April 2020, comprising six clinical areas and a public area. SARS-CoV-2 was detected using reverse transcription polymerase chain reaction and viral culture. Sampling was also undertaken in two wards with natural ventilation alone. The ability of the prevalent variants at the time of the study to survive on dry surfaces was evaluated. FINDINGS: No viable virus was recovered from surfaces or air. Five percent (N=14) of 270 surface samples and 4% (N=1) of 27 air samples were positive for SARS-CoV-2, which was significantly lower than in April 2020 [52% (N=114) of 218 surface samples and 48% (N=13) of 27 air samples (P<0.001, Fisher's exact test)]. There was no clear difference in the proportion of surface and air samples positive for SARS-CoV-2 RNA based on the type of ventilation in the ward. All variants tested survived on dry surfaces for >72 h, with a <3-log10 reduction in viable count. CONCLUSION: This study suggests that enhanced infection prevention measures have reduced the burden of SARS-CoV-2 RNA on surfaces and air in healthcare facilities.

Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets.

COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine.

The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells.

SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide-a well-tolerated drug widely used in advanced prostate cancer-reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.

Population implications of the deployment of novel universal vaccines against epidemic and pandemic influenza.

There is increasing interest in the development of new, 'universal' influenza vaccines (UIVs) that--unlike current vaccines--are effective against a broad range of seasonal influenza strains, as well as against novel pandemic viruses. While the existing literature discusses the potential epidemiological benefits of UIVs, it is also important to anticipate their potential unintended population consequences. Using mathematical modelling, we illustrate two such types of adverse consequences. First, by reducing the amount of infection-induced immunity in a population without fully replacing it, a seasonal UIV programme may permit larger pandemics than in the absence of vaccination. Second, the more successful a future UIV programme is in reducing transmission of seasonal influenza, the more vulnerable the population could become to the emergence of a vaccine escape variant. These risks could be mitigated by optimal deployment of any future UIV vaccine: namely, the use of a combined vaccine formulation (incorporating conventional as well as multiple universal antigenic targets) and achieving sufficient population coverage to compensate for any reductions in infection-induced immunity. In the absence of large-scale trials of UIVs, disease-dynamic models can provide helpful, early insights into their potential impact. In future, data from continuing vaccine development will be invaluable in developing robustly predictive modelling approaches.

The Clinical Use of Monolaurin as a Dietary Supplement: A Review of the Literature.

OBJECTIVE: The purpose of this study was to determine what the peer-reviewed literature says about the clinical applications, therapeutic dosages, bioavailability, efficacy, and safety of monolaurin as a dietary supplement. METHODS: This was a narrative review using the PubMed database and the terms "monolaurin" and its chemical synonyms. Commercial websites that sell monolaurin were also searched for pertinent references. The reference sections of the newer articles were searched for any other relevant articles. Consensus was reached among the authors as to what articles had clinical relevance. RESULTS: Twenty-eight articles were found that appeared to address the clinical use of monolaurin. CONCLUSION: There are many articles that address the antimicrobial effects of monolaurin in vitro. Only 3 peer-reviewed papers that evidence in vivo antimicrobial effects of monolaurin in humans were located, and these were only for intravaginal and intraoral-that is, topical-use. No peer-reviewed evidence was found for the clinical use of monolaurin as a human dietary supplement other than as a nutrient.

Barriers to peer-reviewed journal article publication of abstracts presented at the 2006-2008 Association of Chiropractic Colleges Educational Conference and Research Agenda Conference Meetings.

OBJECTIVE: We investigated the self-reported barriers to publication for authors of abstracts presented at the most recent chiropractic scientific meetings for which publication rates are known, that is the 2006 to 2008 Association of Chiropractic Colleges Educational Conference and Research Agenda Conference (ACC/RAC) meetings. METHODS: A 4-question electronic survey was sent via email to 1 of the listed authors for each abstract not published as a full paper within 4 years of the 2006 to 2008 ACC/RAC meetings. Each author was asked to complete the survey for only 1 abstract. Taking into account authors who appeared on more than 1 abstract, a link to the electronic survey was emailed to 111 potential participants. RESULTS: Of 111 participants, 67 completed a survey for a return rate of 60%. Over 80% (55/67) of the respondents were chiropractors who were faculty members at educational institutions. Of the subjects, 30% (20/67) indicated that the meeting abstract had either been published after 2012 or still was in the publishing process. For those who had not submitted a manuscript for publication, the most frequently cited barriers to publishing were pursuit of publishing as a low priority followed by a lack of time to prepare a manuscript. CONCLUSION: The main barriers to publishing in this sample were that publishing had a low priority compared to other possible uses of the abstract author's time and a perceived lack of time to pursue the publication process.

The Hangover: The Early and Lasting Effects of the Controversial Incorporation of X-Ray Technology into Chiropractic.

Chiropractic first adopted the X-ray in 1910 for the purpose of demonstrating tiny misalignments of spinal bones, theorised to cause all disease, which they called chiropractic subluxations. This paper explores the apparent contradiction and resultant controversy of a system of natural healing adopting a medical technology. It centres on the actions of B.J. Palmer, the first chiropractor to use X-rays. It also clarifies details of Palmer's decision to incorporate the technology and interprets the change in the sociological context of boundary work. The continuing use of the subluxation paradigm for radiography by chiropractors has had a lingering effect on the profession, a metaphorical hangover of vitalism that is not consistent with modern healthcare practice. As a result of this conflict, arguments within the profession on the use of X-rays contribute to the continuing schism between evidence-based and subluxation-based chiropractors.

Publication Rates of Abstracts Presented at the 2006 Meeting of the American Academy of Optometry.

PURPOSE: The purposes of this study were to investigate the publication rates of presentations at the 2006 meeting of the American Academy of Optometry (AAO), differences in the publication rates of platform versus poster presentations, consistency of the meeting abstract compared with the full-length journal article, whether abstracts were clinical or basic science, and when and in which journals articles appeared. METHODS: Abstracts were obtained directly from the AAO. Literature searches using PubMed and VisionCite were performed to locate peer-reviewed journal articles based on those abstracts. Whether the article was based on a poster or platform presentation, congruence of the information in the abstract and the article (i.e., authorship, title, methods, and conclusions), type of study (clinical or basic science), subject category, and journal and year in which the article appeared were recorded. RESULTS: We identified 518 proceeding abstracts, 108 of which ultimately were published between 2006 and 2013, giving an overall publication rate of 21%. Thirty-three percent of platform presentations eventually were published versus 18% of posters. Congruency showed that 17% of articles had the same title as the meeting abstract, 36% had the same authorship, and 53% had the same methods. Eighty-one percent of articles were clinical in nature, whereas 19% of them were basic science. Thirty-seven percent of articles dealt with the subjects of cornea and contact lenses. Articles were found in 39 different journals, with 34% of them appearing in Optometry and Vision Science. Eighty-eight percent of articles were published within 4 years after the meeting. CONCLUSIONS: The publication rate from the 2006 AAO meeting was 21%. Platform presentations were more likely to be published than posters. Congruency rates of abstracts to articles are lower than national meetings in other fields. The vast majority of articles were published within 4 years after the meeting.

Harnessing alveolar macrophages for sustained mucosal T-cell recall confers long-term protection to mice against lethal influenza challenge without clinical disease.

Vaccines that induce T cells, which recognize conserved viral proteins, could confer universal protection against seasonal and pandemic influenza strains. An effective vaccine should generate sufficient mucosal T cells to ensure rapid viral control before clinical disease. However, T cells may also cause lung injury in influenza, so this approach carries inherent risks. Here we describe intranasal immunization of mice with a lentiviral vector expressing influenza nucleoprotein (NP), together with an NFκB activator, which transduces over 75% of alveolar macrophages (AM). This strategy recalls and expands NP-specific CD8+ T cells in the lung and airway of mice that have been immunized subcutaneously, or previously exposed to influenza. Granzyme B-high, lung-resident T-cell populations persist for at least 4 months and can control a lethal influenza challenge without harmful cytokine responses, weight loss, or lung injury. These data demonstrate that AM can be harnessed as effective antigen-presenting cells for influenza vaccination.

Publication rates of abstracts presented at the Association of Chiropractic Colleges Educational Conference/Research Agenda Conference from 2002 to 2008.

Objective : The purposes of this study were to investigate the overall publication rates of presentations at the Association of Chiropractic Colleges Educational Conference/Research Agenda Conference (ACC/RAC) meetings (2002-2008), differences in the publication rates of platform vs poster presentations, and the consistency of the meeting abstract compared to the full-length journal article. Methods : Abstracts were obtained from proceedings published in the Journal of Chiropractic Education. Literature searches using PubMed and the Index to the Chiropractic Literature (ICL) were performed to locate peer-reviewed journal articles based upon those abstracts. Whether the article was based upon a poster or platform presentation, and the congruence of the information in the abstract and article were recorded. Results : We identified 776 proceeding abstracts, 249 of which eventually were published between 2002 and 2012. The overall publication rate was 32.2%. A total of 42.7% of platform presentations eventually were published vs 20.3% of posters. Congruency showed that 43.2% had the same title as the meeting abstract, 59.7% had the same authorship, and 88.8% had the same methods. Conclusion : Publication rates of abstracts from spine and orthopedic surgery national meetings range from 34% to 59%. The ACC/RAC meetings have similar publication rates. More platform than poster presentations reach full publication. The congruency of ACC/RAC abstracts to published articles is higher than national meetings in other fields.

Chiropractic management of a US Army veteran with low back pain and piriformis syndrome complicated by an anatomical anomaly of the piriformis muscle: a case study.

OBJECTIVE: The purpose of this article is to present the case of a patient with an anatomical anomaly of the piriformis muscle who had a piriformis syndrome and was managed with chiropractic care. CASE REPORT: A 32-year-old male patient presented to a chiropractic clinic with a chief complaint of low back pain that radiated into his right buttock, right posterior thigh, and right posterior calf. The complaint began 5 years prior as a result of injuries during Airborne School in the US Army resulting in a 60% disability rating from the Veterans Administration. Magnetic resonance imaging demonstrated a mildly decreased intradiscal T2 signal with shallow central subligamentous disk displacement and low-grade facet arthropathy at L5/S1, a hypolordotic lumbar curvature, and accessory superior bundles of the right piriformis muscle without morphologic magnetic resonance imaging evidence of piriformis syndrome. INTERVENTION AND OUTCOME: Chiropractic treatment included lumbar and sacral spinal manipulation with soft tissue massage to associated musculature and home exercise recommendations. Variations from routine care included proprioceptive neuromuscular facilitation stretches, electric muscle stimulation, acupressure point stimulation, Sacro Occipital Technique pelvic blocking, CranioSacral therapy, and an ergonomic evaluation. CONCLUSION: A patient with a piriformis anomaly with symptoms of low back pain and piriformis syndrome responded positively to conservative chiropractic care, although the underlying cause of the piriformis syndrome remained.

Hetereogeneity of dose and time effects of estrogen on neuron-specific neuronal protein and phosphorylated cyclic AMP response element-binding protein in the hippocampus of ovariectomized rats.

Previous studies have shown changes in the cyclic AMP response element-binding protein (CREB) signaling pathway in CA1 and CA3 regions of the rostral hippocampus with 10 µg estrogen treatment for 14 days. It appears that estrogen's action on CREB phosphorylation in brain structures depends on other estrogen doses and lengths of treatment. We therefore examined the effects of moderate regimens [2.5 µg estradiol benzoate (EB) for 4 or 14 days] on mean numbers of neuron-specific neuronal protein (NeuN)-positive cells and phosphorylated CREB (pCREB)-positive cells and subregion volume defined by NeuN and pCREB immunolabeling and compared those results with results from the high regimen (10 µg EB for 14 days) in CA1, CA2, and CA3 regions and dorsal (DDG) and ventral (VDG) dentate gyrus and hilus of the hippocampus of ovariectomized rats by stereology. For whole hippocampus, all regimens increased mean neuronal (NeuN) numbers and pCREB-positive cell and volume compared with sesame oil (SO) in CA1, CA2, and CA3 regions, DDG and VDG, and hilus. In rostral hippocampus, however, some hippocampal subregions were not responsive to the high regimen, and the moderate regimens appear to be more effective for increasing mean number of NeuN-positive neurons and pCREB-positive cells and subregion volume. Heterogeneity in responsiveness to estrogen was mainly seen within rostral, but not whole, hippocampal subregions. Our results indicate that responsiveness of cells expressing NeuN and pCREB to different EB regimens may vary depending on the specific region of the hippocampus.

A historical lesson from Franciscus Sylvius and Jacobus Sylvius.

OBJECTIVES: One of the most commonly used eponymous terms in neuroscience and gross anatomy is Sylvius. The 2 most recognized uses of this term today are the sylvian fissure for the lateral cerebral sulcus and the sylvian aqueduct for the cerebral aqueduct. There is some controversy surrounding these terms because there were 2 famous anatomists named Sylvius after whom these structures could easily have been named. The purpose of this article is to provide a brief historical review of these 2 scientists and offer an observation on the historical use of the name Sylvius as an anatomical term. DISCUSSION: Franciscus Sylvius was a popular teacher at the University of Leiden. One of his most famous students, Thomas Bartholinus, published F Sylvius' neuroanatomical work on the lateral cerebral sulcus. Although this structure had been known from antiquity, Bartholinus' description linked F Sylvius' name to the structure. As well, the description of the cerebral aqueduct was also published in other influential anatomy texts as an attempt by students to honor F Sylvius' name, despite the fact that this structure had been described more than a century before. Jacobus Sylvius was a successful but reportedly disliked anatomist at the University of Paris. Although he urged his students to learn from dissection rather than lectures or books, he had an unyielding devotion to Galen's teachings. His most famous student, Vesalius, went on to refute many of Galen's ideas as documented in his later publications. The rift between teacher (J Sylvius) and student (Vesalius) may have resulted in the marginalization of J Sylvius as a figure immortalized in anatomical texts. This may be the probable reason that J Sylvius' name is not associated with anatomical terms. CONCLUSION: The lesson from this brief review of the 2 Dr Sylviuses may be that a teacher's historical legacy being preserved as an eponym may have more to do with his or her likability than productivity during his or her lifetime.

Rapid generation of a well-matched vaccine seed from a modern influenza A virus primary isolate without recourse to eggs.

Most influenza vaccines are produced in chicken eggs but recent human influenza strains often do not grow well in this substrate. The PER.C6 cell line is an alternative platform for vaccine production. Here we demonstrate that PER.C6 cells faithfully propagate recent clinical isolates, without selecting for mutations in the HA gene. PER.C6 cells support the rescue of recombinant influenza viruses from cDNA. We used sequence data from a surveillance programme to generate a PR8-based seed virus with the HA and NA of a contemporary circulating H3N2 human strain, A/England/611/07 (E611) that did not itself grow in eggs. We engineered mutations that affected receptor-binding, G186V or L194P, into the E611 HA gene. Whilst the L194P mutation conferred efficient growth in eggs, G186V did not. The L194P mutation was also spontaneously selected during egg propagation of E611/PR8 7:1 recombinant virus. This suggests generation of a single recombinant vaccine seed might satisfy manufacturers that utilize either eggs or cells for vaccine production.

The Fountain Head Chiropractic Hospital: the dream that almost came true.

OBJECTIVE: The purpose of this article is to relate information about the life of Dr William Ivens and describe the worldwide effort led by him to establish a chiropractic hospital at the Palmer School of Chiropractic. DISCUSSION: Dr William Ivens, a colorful politician and chiropractor from Winnipeg, Canada, was the driving force behind the idea of establishing a chiropractic hospital at the Palmer School of Chiropractic in Davenport, IA, during the late 1930s. With the blessings of Dr BJ Palmer, president of the Palmer School of Chiropractic, Dr Ivens led an aggressive, worldwide campaign to raise the funds necessary to establish what was to be called the Fountain Head Chiropractic Hospital. During the tumultuous years of 1937-1942, this campaign successfully raised the target sum of $50 000, thought necessary to create the hospital, but the idea never became a reality. These funds were eventually used to purchase the Clear View Sanitarium, a chiropractic psychiatric facility, in Davenport, IA, in 1952. CONCLUSION: Dr William Ivens stands as a prime example of a relatively small, but dedicated, number of chiropractors during the mid-20th century who not only believed in, but toiled for, the idea of chiropractic care being given in an in-patient setting.

Suitability of PER.C6 cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics.

Reverse genetics, the generation of influenza viruses from cDNA, presents a rapid method for creating vaccine strains. The technique necessitates the use of cultured cells. Due to technical and regulatory requirements, the choice of cell lines for production of human influenza vaccines is limited. PER.C6 cells, among the most extensively characterized and documented cells, support growth of all influenza viruses tested to date, and can be grown to high densities in large bioreactors in the absence of serum or micro carriers. Here, the suitability of these cells for the generation of influenza viruses by reverse genetics was investigated. A range of viruses reflective of vaccine strains was rescued exclusively using PER.C6 cells by various transfection methods, including an animal component-free procedure. Furthermore, a whole inactivated vaccine carrying the HA and NA segments of A/HK/156/97 (H5N1) that was both rescued from and propagated on PER.C6 cells, conferred protection in a mouse model. Thus PER.C6 cells provide an attractive platform for generation of influenza vaccine strains via reverse genetics.

Preliminary morphological evidence that vertebral hypomobility induces synaptic plasticity in the spinal cord.

OBJECTIVE: A widely accepted theoretical model suggests that vertebral hypomobility can cause pain and abnormal spinal mechanics because of changes in sensory input from spinal and paraspinal tissues. The purpose of this pilot study was 3-fold: (1) to make a preliminary determination if chronic vertebral hypomobility at L4 through L6 in the rat would affect synaptic density and/or morphology in the superficial dorsal horn of the L2 spinal cord level, (2) to identify relevant outcome variables for future studies, and (3) to obtain preliminary data that would permit estimating an appropriate sample size for future studies. METHODS: Using an established rat model, we fixed 3 contiguous lumbar segments (L4-L6) for 8 weeks with a specially engineered vertebral fixation device. Electron micrographs were obtained from 2 animals from the experimental (fixed) group and each of 3 control groups (no surgery, surgery but no devices implanted, and devices implanted but not fixed). Synapses were randomly selected using a stereological approach and were analyzed for symmetry, curvature, type of postsynaptic profile, and perforations. The synaptic density was also estimated. RESULTS: There was increased synaptic density and percentage of positively curved synapses in the dorsal horn of experimental animals as compared with controls. Experimental animals had a lower percentage of axospinous synapses, with a concomitant increase in the percentage of synapses on dendritic shafts. CONCLUSIONS: These preliminary data suggest for the first time that chronic vertebral hypomobility at L4 through L6 in the rat affects synaptic density and morphology in the superficial dorsal horn of the L2 spinal cord level. More definitive studies are warranted, and the biologic significance of these finding should be investigated.

NS1 proteins of avian influenza A viruses can act as antagonists of the human alpha/beta interferon response.

Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-beta promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-beta induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-beta induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.