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At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, persons ≥65 years of age and healthcare personnel represented the most vulnerable groups with respect to risk of infection, severe illness, and death. However, as the pandemic progressed, there was an increasingly detrimental effect on young children and adolescents. Severe disease and hospitalization increased over time in pediatric populations, and containment measures created substantial psychosocial, educational, and economic challenges for young people. Vaccination of children against COVID-19 has been shown to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and severe outcomes in pediatric populations and may also help to prevent the spread of variants of concern and improve community immunity. This review discusses the burden of COVID-19 on children throughout the pandemic, the role of children in disease transmission, and the impact of COVID-19 vaccination., Competing Interests: D.J.W. has received consulting fees from Pfizer, Germitac, PDI, and BD in relation to vaccines and disinfection products, was a member of a Data Safety Monitoring Board/Advisory Board at GlaxoSmithKline, and is a member on the board at Society for Healthcare Epidemiology of America (SHEA). K.O.Z. receives salary support from the US National Institutes of Health (NIH) and the US Food and Drug Administration (FDA) through Duke University, has received an honorarium from Pediatric Grand Rounds (Ohio State University) and for an NMA COVID-19 report on provider perspectives, and is on the membership committee for USP. S.Y.T. has received grants from Pfizer Inc., paid directly to the institution, for work unrelated to this manuscript. J.M.M. is an employee and holds stock options at Pfizer Inc. S.P. is an employee of BioNTech SE.

S100A1, a calcium-binding protein, plays a crucial role in regulating Ca 2+ signaling pathways in skeletal and cardiac myocytes via interactions with the ryanodine receptor (RyR) to affect Ca 2+ release and contractile performance. Biophysical studies strongly suggest that S100A1 interacts with RyRs but have been inconclusive about both the nature of this interaction and its competition with another important calcium-binding protein, calmodulin (CaM). Thus, high-resolution cryo-EM studies of RyRs in the presence of S100A1, with or without additional CaM, were needed. The elegant work by Weninger et al. demonstrates the interaction between S100A1 and RyR1 through various experiments and confirms that S100A1 activates RyR1 at sub-micromolar Ca 2+ concentrations, increasing the open probability of RyR1 channels., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Pathogenic Bacillus and clostridial (i.e., Clostridium and Clostridioides ) bacteria express a diverse repertoire of effector proteins to promote disease. This includes production of binary toxins, which enter host epithelial cells and seriously damage the intestinal tracts of insects, animals, and humans. In particular, binary toxins form an AB-type complex composed of a catalytic subunit that is toxic (A) and an oligomeric cell-binding and delivery subunit (B), where upon delivery of A into the cytoplasm of the host cell it catalytically ADP-ribosylates actin and rapidly induces host cell death. In this review, binary toxins expressed by Bacillus thuringiensis , Clostridioides difficile , and Clostridium perfringens will be discussed, with particular focus placed upon the structural elucidations of their respective B subunits and how these findings help to deconvolute how toxic enzyme delivery into target host cells is achieved by these deadly bacteria.

Background: Infection is a serious complication in neurosurgical patients who undergo external ventricular drain (EVD) insertion., Methods: We conducted a quasi-experimental study in patients who underwent EVD insertion to evaluate the impact of a multi-modal strategy to reduce the incidence of external ventricular drain associated infections (EVDAIs). The study was divided into 2 periods; (1) the pre-intervention period when techniques for EVD insertion and maintenance were up to the discretion of the neurosurgeons and (2) the post-intervention after implementation of a multi-modal strategy (cefazolin antibiotic prophylaxis, preoperative chlorhexidine showers, application of postoperative chlorhexidine-impregnated dressing, limited manipulation of the EVD, and meticulous EVD management). The primary outcome was the incidence rate of EVDAIs; secondary outcomes included in-hospital mortality rate, the hospital length of stay., Results: In total, 135 patients were included. The incidence rate of EVDAIs was significantly reduced in the post-intervention period (5.6 cases/1,000 EVD-days) compared with the pre-intervention period (18.2 cases/1,000 EVD-days; P=0.026). There were no differences in all secondary outcomes analyzed. This multi-modal strategy was associated with high satisfaction among health care personnel., Conclusions: Implementation of a multi-modal strategy was associated with a reduction in the incidence of EVDAIs. This was in line with our goal of promoting a new culture of safety despite being in a resource-limited setting., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Throughout the COVID-19 pandemic, many areas in the United States experienced healthcare personnel (HCP) shortages tied to a variety of factors. Infection prevention programs, in particular, faced increasing workload demands with little opportunity to delegate tasks to others without specific infectious diseases or infection control expertise. Shortages of clinicians providing inpatient care to critically ill patients during the early phase of the pandemic were multifactorial, largely attributed to increasing demands on hospitals to provide care to patients hospitalized with COVID-19 and furloughs. 1 HCP shortages and challenges during later surges, including the Omicron variant-associated surges, were largely attributed to HCP infections and associated work restrictions during isolation periods and the need to care for family members, particularly children, with COVID-19. Additionally, the detrimental physical and mental health impact of COVID-19 on HCP has led to attrition, which further exacerbates shortages. 2 Demands increased in post-acute and long-term care (PALTC) settings, which already faced critical staffing challenges difficulty with recruitment, and high rates of turnover. Although individual healthcare organizations and state and federal governments have taken actions to mitigate recurring shortages, additional work and innovation are needed to develop longer-term solutions to improve healthcare workforce resiliency. The critical role of those with specialized training in infection prevention, including healthcare epidemiologists, was well-demonstrated in pandemic preparedness and response. The COVID-19 pandemic underscored the need to support growth in these fields. 3 This commentary outlines the need to develop the US healthcare workforce in preparation for future pandemics.

Throughout history, pandemics and their aftereffects have spurred society to make substantial improvements in healthcare. After the Black Death in 14 th century Europe, changes were made to elevate standards of care and nutrition that resulted in improved life expectancy. 1 The 1918 influenza pandemic spurred a movement that emphasized public health surveillance and detection of future outbreaks and eventually led to the creation of the World Health Organization Global Influenza Surveillance Network. 2 In the present, the COVID-19 pandemic exposed many of the pre-existing problems within the US healthcare system, which included (1) a lack of capacity to manage a large influx of contagious patients while simultaneously maintaining routine and emergency care to non-COVID patients; (2) a "just in time" supply network that led to shortages and competition among hospitals, nursing homes, and other care sites for essential supplies; and (3) longstanding inequities in the distribution of healthcare and the healthcare workforce. The decades-long shift from domestic manufacturing to a reliance on global supply chains has compounded ongoing gaps in preparedness for supplies such as personal protective equipment and ventilators. Inequities in racial and socioeconomic outcomes highlighted during the pandemic have accelerated the call to focus on diversity, equity, and inclusion (DEI) within our communities. The pandemic accelerated cooperation between government entities and the healthcare system, resulting in swift implementation of mitigation measures, new therapies and vaccinations at unprecedented speeds, despite our fragmented healthcare delivery system and political divisions. Still, widespread misinformation or disinformation and political divisions contributed to eroded trust in the public health system and prevented an even uptake of mitigation measures, vaccines and therapeutics, impeding our ability to contain the spread of the virus in this country. 3 Ultimately, the lessons of COVID-19 illustrate the need to better prepare for the next pandemic. Rising microbial resistance, emerging and re-emerging pathogens, increased globalization, an aging population, and climate change are all factors that increase the likelihood of another pandemic. 4 .

The Society for Healthcare Epidemiology in America (SHEA) strongly supports modernization of data collection processes and the creation of publicly available data repositories that include a wide variety of data elements and mechanisms for securely storing both cleaned and uncleaned data sets that can be curated as clinical and research needs arise. These elements can be used for clinical research and quality monitoring and to evaluate the impacts of different policies on different outcomes. Achieving these goals will require dedicated, sustained and long-term funding to support data science teams and the creation of central data repositories that include data sets that can be "linked" via a variety of different mechanisms and also data sets that include institutional and state and local policies and procedures. A team-based approach to data science is strongly encouraged and supported to achieve the goal of a sustainable, adaptable national shared data resource.

Deuterium ( 2 H) spin relaxation of 13 CH 2 D methyl groups has been widely applied to investigate picosecond-to-nanosecond conformational dynamics in proteins by solution-state NMR spectroscopy. The B 0 dependence of the 2 H spin relaxation rates is represented by a linear relationship between the spectral density function at three discrete frequencies J(0), J(ω D ) and J(2ω D ). In this study, the linear relation between 2 H relaxation rates at B 0 fields separated by a factor of two and the interpolation of rates at intermediate frequencies are combined for a more robust approach for spectral density mapping. The general usefulness of the approach is demonstrated on a fractionally deuterated (55%) and alternate 13 C- 12 C labeled sample of E. coli RNase H. Deuterium relaxation rate constants (R 1 , R 1ρ , R Q , R AP ) were measured for 57 well-resolved 13 CH 2 D moieties in RNase H at 1 H frequencies of 475 MHz, 500 MHz, 900 MHz, and 950 MHz. The spectral density mapping of the 475/950 MHz data combination was performed independently and jointly to validate the expected relationship between data recorded at B 0 fields separated by a factor of two. The final analysis was performed by jointly analyzing 475/950 MHz rates with 700 MHz rates interpolated from 500/900 MHz data to yield six J(ω D ) values for each methyl peak. The J(ω) profile for each peak was fit to the original (τ M , S f 2 , τ f ) or extended model-free function (τ M , S f 2 , S s 2 , τ f , τ s ) to obtain optimized dynamic parameters., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In this quasi-experimental study, implementing PX-UV to the standard environmental cleaning protocol was associated with a reduction in the overall incidence of multidrug-resistant (MDR) gram-negative organisms ( P = .01) and MDR Acinetobacter baumannii ( P = .001) in intervention intensive care units. However, the intervention did not reduce patient length of stay and 30-day mortality.

We performed a literature review to describe the risk of surgical-site infection (SSI) in minimally invasive surgery (MIS) compared to standard open surgery. Most studies reported decreased SSI rates among patients undergoing MIS compared to open procedures. However, many were observational studies and may have been affected by selection bias. MIS is associated with reduced risk of surgical-site infection compared to standard open surgery and should be considered when feasible.

Allostery is an essential biological phenomenon in which perturbation at one site in a biomolecule elicits a functional response at a distal location(s). It is integral to biological processes, such as cellular signaling, metabolism, and transcription regulation. Understanding allostery is also crucial for rational drug discovery. In this work, we focus on an allosteric S100B protein that belongs to the S100 class of EF-hand Ca 2+ -binding proteins. The Ca 2+ -binding affinity of S100B is modulated allosterically by TRTK-12 peptide binding 25 Å away from the Ca 2+ -binding site. We investigated S100B allostery by carrying out nuclear magnetic resonance (NMR) measurements along with microsecond-long molecular dynamics (MD) simulations on S100B/Ca 2+ with/without TRTK-12 at different NaCl salt concentrations. NMR HSQC results show that TRTK-12 reorganizes how S100B/Ca 2+ responds to different salt concentrations at both orthosteric and allosteric sites. The MD data suggest that TRTK-12 breaks the dynamic aromatic and hydrogen-bond interactions (not observed in X-ray crystallographic structures) between the hinge/helix and Ca 2+ -binding EF-hand loop of the two subunits in the homodimeric protein. This triggers rearrangement in the protein network architectures and leads to allosteric communication. Finally, computational studies of S100B at distinct ionic strengths suggest that ligand-bound species are more robust to the changing environment relative to the S100B/Ca 2+ complex.

Intravesical Bacillus Calmette-Guérin (BCG) is a standard therapy for non-muscle-invasive bladder cancer used in urology clinics and inpatient settings. We present a review of infection risks to patients receiving intravesical BCG, healthcare personnel who prepare and administer BCG, and other patients treated in facilities where BCG is prepared and administered. Knowledge of these risks and relevant regulations informs appropriate infection prevention measures.

Background: Infection precautions (IP) facilitate standardized and safe patient care. Research has demonstrated several barriers to IP adherence among health care personnel (HCP) but potential exposure risk to SARS-CoV-2 and job role has not been considered., Methods: Researchers used self-reported baseline surveys with 191 HCPs at a university medical center to examine factors that may have affected IP adherence (eg, personal protective equipment [PPE] and hand hygiene errors) over the 2 weeks prior to the survey. Chi-square tests were used to determine if differences existed first, among job role and IP adherence, and second, the potential risk of exposure to SARS-CoV-2 and IP adherence. A binary logistic regression estimated if PPE nonadherence was associated with COVID-19 stress, job role, and potential exposure risk to SARS-CoV-2., Results: PPE nonadherence varied by job role. Those in the Other group (ie, nonphysician/non-nursing HCP) reported significantly fewer errors (9.6%) compared to Physicians (26.5%) and Registered Nurses (33.3%). Hand/glove hygiene errors between COVID-19 patient rooms varied by job role. Respondents who had higher risks of exposure to SARS-CoV-2 were 5.74 times more likely to experience errors., Conclusions: The results provide implications for adopting systems-level approaches to support worker knowledge and engagement across job roles to improve IP adherence., (Published by Elsevier Inc.)

N95 respirator contamination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during clinical care of patients with coronavirus disease 2019 is poorly understood. We performed a prospective observational study on healthcare provider's (HCP's) N95 respirators' and face shields' SARS-CoV-2 contamination during aerosol-generating procedures on SARS-CoV-2-positive patients housed in a COVID-19-specific unit. Medical masks worn on top of HCP's N95 respirators, and under face shields, during study aerosol-generating procedures were used as surrogates to detect contamination to avoid waste. Thirty-three HCPs were studied, and a total of 33 mask and 27 face shields were sampled. Masks were cut into 9 pieces and face shields were sampled twice, front and back, to determine locality of contamination; however, no positive samples were identified using standard polymerase chain reaction techniques with a CT value up to 40. All 9 mask piece samples were then pooled, as were face shield samples, using centrifugal concentration with polyethersulfone membranes. Once pooled and concentrated, overall, 9 (15%) samples were positive via real-time polymerase chain reaction: 5 from masks (15.2%) and 4 from face shields (14.8%)., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Despite the relatively high mortality and the difficulty in diagnosis, nearly one-third of patients hospitalized with a documented diagnosis of encephalitis did not undergo a lumbar puncture (LP). When an LP was performed, pathogen-specific testing was greatly underutilized. Infectious etiologies were most common, but over 40% of cases were idiopathic at discharge. These findings suggest that there is a substantial opportunity to improve the quality of care through more accurate and timely diagnosis., Competing Interests: The authors declare no conflict of interest.

Administration of neutralizing antibodies (nAbs) has proved to be effective by providing immediate protection against SARS-CoV-2. However, dual strategies combining virus neutralization and immune response stimulation to enhance specific cytotoxic T cell responses, such as dendritic cell (DC) cross-priming, represent a promising field but have not yet been explored. Here, a broadly nAb, TN T , are first generated by grafting an anti-RBD biparatopic tandem nanobody onto a trimerbody scaffold. Cryo-EM data show that the TN T structure allows simultaneous binding to all six RBD epitopes, demonstrating a high-avidity neutralizing interaction. Then, by C-terminal fusion of an anti-DNGR-1 scFv to TN T , the bispecific trimerbody TN T DNGR-1 is generated to target neutralized virions to type 1 conventional DCs (cDC1s) and promote T cell cross-priming. Therapeutic administration of TN T DNGR-1, but not TN T , protects K18-hACE2 mice from a lethal SARS-CoV-2 infection, boosting virus-specific humoral responses and CD8 + T cell responses. These results further strengthen the central role of interactions with immune cells in the virus-neutralizing antibody activity and demonstrate the therapeutic potential of the Fc-free strategy that can be used advantageously to provide both immediate and long-term protection against SARS-CoV-2 and other viral infections., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Semicritical medical devices are defined as items that come into contact with mucous membranes or nonintact skin (e.g., gastrointestinal endoscopes, endocavitary probes). Such medical devices require minimally high-level disinfection., Methods: Analyze the methods used to reprocess semicritical medical devices and identify methods and new technologies to reduce the risk of infection., Results: The reprocessing methods for semicritical medical devices is described as well as a shift from high-level disinfection to sterilization for lumened endoscopes., Conclusions: Strict adherence to current guidelines and transition to sterilization for endoscopes is required as more outbreaks have been linked to inadequately disinfected endoscopes and other semicritical items than any other reusable medical devices., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To prevent healthcare-associated infections, it is essential that critical medical devices be sterilized before use. Although there are several sterilization technologies for medical devices, only ethylene oxide (ETO) sterilization has virtually universal material compatibility., Methods: We searched the published English literature (Google, Google scholar and PubMed) for articles on the sterilization of medical devices by ethylene oxide, the consequences of ETO closures, and alternative sterilization technologies/solutions., Results: ETO's compatibility and effectiveness with medical products allows for sterilization of many medical devices that would otherwise be rendered ineffective or unsafe if sterilized with an alternative method., Conclusions: At present, there are no alternatives to ETO that provide the same sterility assurance and result in the same device performance as ETO; therefore, it is likely irreplaceable for years., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the relationship between home disinfectant use and the prevalence of antibiotic resistance among environmental isolates of human pathogens., Methods: Bacteria were cultured from 5 kitchen and 5 bathroom sites using quantitative methods. Antibiotic susceptibility was determined by standard methods. Home disinfectant use was assessed via a questionnaire., Results: The overall total mean log 10 counts (total CFU) for the kitchen and bathroom were 4.31 and 4.88, respectively. Gram-positive bacteria were more common in the bathroom (4.05) than in the kitchen (3.60), while Gram-negative bacilli were more common in the kitchen (4.23) than in the bathroom (3.86). The sink and bath drains were the most contaminated sites with 6.16-log 10 of total CFU and 6.6-log 10 in the kitchen and bathroom, respectively. Households reported cleaning frequency with a variety of commercial products. Most respondents used antibacterial products (eg, soaps, surface disinfectants) in the home. Antibiotic-resistant pathogens were infrequently isolated in the homes evaluated., Conclusions: Compared to pathogens causing community-acquired clinical infections in the ICARE study, pathogens isolated from households are less likely to demonstrate antibiotic resistance. In addition, no relationship between antibacterial use or frequency of cleaning or disinfection and antibiotic resistance was revealed., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Biofilms are surface-attached communities of bacteria embedded in an extracellular matrix. This matrix shields the resident cells from desiccation, chemical perturbation, invasion by other bacteria, and confers reduced susceptibility to antibiotics and disinfectants. There is growing evidence that biofilms on medical instruments (especially endoscopes) and environmental surfaces interfere with cleaning and disinfection., Methods: The English literature on the impact of biofilms in medicine was reviewed with a focus on the impact of biofilms on reusable semicritical medical instruments and hospital environmental surfaces., Results: Biofilms are frequently present on hospital environmental surfaces and reusable medical equipment. Important health care...associated pathogens that readily form biofilms on environmental surfaces include Staphylococcus aureus, Pseudomonas aeruginosa, and Candida auris. Evidence has demonstrated that biofilms interfere with cleaning and disinfection., Discussion: New technologies such as ..úself-disinfecting..Ñ surfaces or continuous room disinfection systems may reduce or disrupt biofilm formation and are under study to reduce the impact of the contaminated surface environment on health care...associated infections., Conclusions: Future research is urgently needed to develop methods to reduce or eliminate biofilms from forming on implantable medical devices, reusable medical equipment, and hospital surfaces., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale: Fever is frequently an early indicator of infection and often requires rigorous diagnostic evaluation., Objectives: This is an update of the 2008 Infectious Diseases Society of America and Society (IDSA) and Society of Critical Care Medicine (SCCM) guideline for the evaluation of new-onset fever in adult ICU patients without severe immunocompromise, now using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology., Panel Design: The SCCM and IDSA convened a taskforce to update the 2008 version of the guideline for the evaluation of new fever in critically ill adult patients, which included expert clinicians as well as methodologists from the Guidelines in Intensive Care, Development and Evaluation Group. The guidelines committee consisted of 12 experts in critical care, infectious diseases, clinical microbiology, organ transplantation, public health, clinical research, and health policy and administration. All task force members followed all conflict-of-interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual and the IDSA. There was no industry input or funding to produce this guideline., Methods: We conducted a systematic review for each population, intervention, comparison, and outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as best-practice statements., Results: The panel issued 12 recommendations and 9 best practice statements. The panel recommended using central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, or esophageal balloon thermistors when these devices are in place or accurate temperature measurements are critical for diagnosis and management. For patients without these devices in place, oral or rectal temperatures over other temperature measurement methods that are less reliable such as axillary or tympanic membrane temperatures, noninvasive temporal artery thermometers, or chemical dot thermometers were recommended. Imaging studies including ultrasonography were recommended in addition to microbiological evaluation using rapid diagnostic testing strategies. Biomarkers were recommended to assist in guiding the discontinuation of antimicrobial therapy. All recommendations issued were weak based on the quality of data., Conclusions: The guidelines panel was able to formulate several recommendations for the evaluation of new fever in a critically ill adult patient, acknowledging that most recommendations were based on weak evidence. This highlights the need for the rapid advancement of research in all aspects of this issue-including better noninvasive methods to measure core body temperature, the use of diagnostic imaging, advances in microbiology including molecular testing, and the use of biomarkers., Competing Interests: Supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH). Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. Van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antibiotic Resistance Leadership Group UM1AI104681), the NIH, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics Limited, Hylomorph, BioFire, Shionogi, IDSA, NBME, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: New and emerging infectious diseases continue to represent a public health threat. Emerging infectious disease threats include pathogens increasing in range (eg, Mpox), zoonotic microbes jumping species lines to cause sustained infections in humans via person-to-person transmission (SARS-CoV-2) and multidrug-resistant pathogens (eg, Candida auris)., Materials and Methods: We searched the published English literature and reviewed the selected articles on SARS-CoV-2, Mpox, and Candida auris with a focus on environmental survival, contamination of the patient's hospital environment, susceptibility of the pathogen to antiseptics and disinfectants and infection prevention recommendations., Results: All three pathogens (ie, SARS-CoV-2, Mpox, and Candida auris) can survive on surfaces for minutes to hours and for Mpox and C auris for days. Currently available antiseptics (eg, 70%-90% alcohol hand hygiene products) are active against SARS-CoV-2, Mpox and C auris. The U.S Environmental Protection Agency provides separate lists of surface disinfectants active against SARS-CoV-2, Mpox, and C auris., Discussion: The risk of environment-to-patient transmission of SARS-CoV-2, Mpox and Candida auris, is very low, low-moderate and high, respectively. In the absence of appropriate patient isolation and use of personal protection equipment, the risk of patient-to-health care provider transmission of SARS-CoV-2, Mpox, and C auris is high, moderate and low, respectively., Conclusions: Appropriate patient isolation, use of personal protective equipment by health care personnel, hand hygiene, and surface disinfection can protect patients and health care personnel from acquiring SARS-CoV-2, Mpox, and C auris from infected patients., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Adherence to professional guidelines and/or manufacturer's instructions for use regarding proper disinfection and sterilization of medical devices is crucial to preventing cross transmission of pathogens between patients. Emerging pathogens (e.g., Candida auris) and complex medical devices provide new challenges., Methods: A search for published English articles on new disinfection and sterilization technologies was conducted by Google, Google scholar and PubMed., Results: Several new disinfection methods or products (e.g., electrostatic spraying, new sporicides, colorized disinfectants, "no touch" room decontamination, continuous room decontamination) and sterilization technologies (e.g., new sterilization technology for endoscopes) were identified., Conclusions: These technologies should reduce patient risk., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hospital patient room surfaces are frequently contaminated with multidrug-resistant organisms. Since studies have demonstrated that inadequate terminal room disinfection commonly occurs, ..úno touch..Ñ methods of terminal room disinfection have been developed such as ultraviolet light (UV) devices and hydrogen peroxide (HP) systems., Methods: This paper reviews published clinical trials of ..úno touch..Ñ methods and ..úself-disinfecting..Ñ surfaces., Results: Multiple papers were identified including clinical trials of UV room disinfection devices (N.ß=.ß20), HP room disinfection systems (N.ß=.ß8), handheld UV devices (N.ß=.ß1), and copper-impregnated or coated surfaces (N.ß=.ß5). Most but not all clinical trials of UV devices and HP systems for terminal disinfection demonstrated a reduction of colonization/infection in patients subsequently housed in the room. Copper-coated surfaces were the only ..úself-disinfecting..Ñ technology evaluated by clinical trials. Results of these clinical trials were mixed., Discussion: Almost all clinical trials reviewed used a ..úweak..Ñ design (eg, before-after) and failed to assess potential confounders (eg, compliance with hand hygiene and environmental cleaning)., Conclusions: The evidence is strong enough to recommend the use of a ..úno-touch..Ñ method as an adjunct for outbreak control, mitigation strategy for high-consequence pathogens (eg, Candida auris or Ebola), or when there are an excessive endemic rates of multidrug-resistant organisms., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: With aging of the population in the United States, there are more people in long-term care facilities than in hospitals. Nursing home residents have a high prevalence of colonization with multidrug-resistant organisms (MDROs). A shared environment with vulnerable patients can facilitate intra- and inter-facility transmission of MDROs. The aim of this paper is to examine the role of the nursing home environment in MDRO transmission and provide infection prevention strategies., Methods: We searched the published literature and reviewed selected articles on contamination, transmission, and infection associated with the nursing home environment., Results: Nursing home residents were frequently colonized with MDROs, leading to contamination of the surrounding environment with the same pathogen. Surface contamination with MDROs was common in nursing home patient rooms, and to a substantial but lesser frequency in common rooms. Shared rooms were a risk factor for MDRO transmission between patients., Conclusions: Since outbreaks and infections via the environmental contamination cause substantial burden of morbidity and mortality in the nursing home residents, it is essential for healthcare personnel to recognize the role of the nursing home environment in infection transmission and adhere to the current infection prevention guidelines for cleaning and disinfection of environmental surfaces., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antimicrobial Resistance Leadership Group UM1AI104681), the National Institutes of Health, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics, Hylomorph, BioFire, Shionogi, Infectious Diseases Society of America, National Board of Medical Examiners, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST Diagnostics, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: There are several sources of pathogens that cause surgical site infections (SSI) to include the patients endogenous microflora and exogenous sources (e.g., air, surfaces, staff, surgical equipment)., Methods: We searched the published English literature (Google, Google Scholar, PubMed) for articles on reprocessing surgical instruments, effectiveness of sterilization methods, microbial load on surgical instruments, frequency of "contaminated" instruments, and the infection risk associated with "contaminated" surgical instruments and immediate use steam sterilization., Results: There is substantial redundancy in instrument reprocessing to include: even if a patient was exposed to a "contaminated" instrument, the decontamination and sterilization process would have removed and/or inactivated the contaminating pathogens due to the exceptional effectiveness of the manual and mechanical cleaning (i.e., washer-disinfector) and the remarkable robustness of sterilization technology; and the low-level of microorganisms on surgical instruments after use and before cleaning., Conclusions: A critical review of the literature suggests that the risk of acquiring an SSI from instruments used in surgery is essentially zero if the sterilization cycle is validated., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Each year in the United States there are approximately 100,000,000 outpatient/inpatient surgical procedures. Each of these procedures involves contact by a medical device or surgical instrument with a patient's sterile tissue and/or mucous membrane. A major risk of all such procedures is the introduction of infection., Methods: We searched published literature for articles on the use and effectiveness of disinfectants, sterilization methods and antiseptics., Results: The level of disinfection is dependent on the intended use of the object: critical (items that contact sterile tissue such as surgical instruments), semicritical (items that contact mucous membrane such as endoscopes), and noncritical (devices that contact only intact skin such as stethoscopes) items require sterilization, high-level disinfection and low-level disinfection, respectively. Cleaning must always precede high-level disinfection and sterilization. Antiseptics are essential to infection prevention as part of a hand hygiene program as well as other uses such as surgical hand antisepsis and pre-operative patient skin preparation., Conclusions: When properly used, disinfection and sterilization can ensure the safe use of invasive and non-invasive medical devices. Cleaning should always precede high-level disinfection and sterilization. Strict adherence to current disinfection and sterilization guidelines is essential to prevent patient infections and exposures to infectious agents., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Galeterone, 3β-(hydroxy)-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (Gal, 1) and VNPP433-3β, 3β-(1H-imidazole-1-yl-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (2) are potent molecular glue degrader modulators of AR/AR-V7 and Mnk1/2-eIF4E signaling pathways, and are promising Phase 3 and Phase 1 drug candidates, respectively. Because appropriate salts can be utilized to create new chemical entities with enhanced aqueous solubility, in vivo pharmacokinetics, and enhanced in vitro and in vivo efficacies, the monohydrochloride salt of Gal (3) and the mono- and di-hydrochlorides salts of compound 2, compounds 4 and 5, respectively, were synthesized. The salts were characterized using 1 H NMR, 13 C NMR and HRMS analyses. Compound 3 displayed enhanced in vitro antiproliferative activity (7.4-fold) against three prostate cancer cell lines but surprisingly decreased plasma exposure in the pharmacokinetics study. The antiproliferative activities of the compound 2 salts (4 and 5) were equivalent to that of compound 2, but their oral pharmacokinetic profiles were significantly enhanced. Finally, and most importantly, oral administration of the parent compounds (1 and 2) and their corresponding salts (3, 4 and 5) caused dose-dependent potent inhibition/regression of aggressive and difficult-to-treat CWR22Rv1 tumor xenografts growth, with no apparent host toxicities and were highly more efficacious than the blockbuster FDA-approved prostate cancer drugs, Enzalutamide (Xtandi) and Docetaxel (Taxotere). Thus, the HCl salts of Gal (3) and VNPP433-3β (4 and 5) are excellent orally bioavailable candidates for clinical development., Competing Interests: Declaration of Competing Interest Vincent C. O. Njar is the lead inventor of Gal (1) and VNPP433-3β (2), the patents and technologies thereof are owned by the University of Maryland, Baltimore. Puranik Purushottamachar is a co-inventor of VNPP433-3β (2). Vincent C. O. Njar, Puranik Purushottamachar, Elizabeth Thomas, and Retheesh S. Thankan are co-inventors of the Gal (1) and VNPP433-3β (2) hydrochloride salts. David J. Weber declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Immune mediated graft loss still represents a major risk to transplant recipients. Creative approaches to immunosuppression that exploit the recipient's own alloregulatory mechanisms could reduce the need for pharmacologic immunosuppression and potentially induce immune tolerance. In the process of studying recipient derived myeloid derived suppressor cells (MDSCs), we identified key alloregulatory MDSC mechanisms, mediated by isolatable proteins IL-4, IL-34, and IL-10. We sought to purify these proteins and fuse them for subsequent infusion into transplant recipients as a means of inducing an alloregulatory response. In this introductory investigation, we leveraged molecular engineering technology to create a fusion protein (FP) of three cytokine coding sequences of IL-4, IL-34, and IL-10 and demonstrated their expressions by Western Blot analysis. Following purification, we tested whether FP IL-4/IL-34/IL-10 (FP1) can protect heart transplant allografts. Injection of FP1 significantly prolonged allogeneic cardiac graft survival in a dose-dependent fashion and the increase of graft survival time exceeded survival attributable to IL-34 alone. In vitro, MDSCs cells were expanded by FP1 treatment. However, FP1 did not directly inhibit T cell proliferation in vitro. In conclusion, newly developed FP1 improves the graft survival in cardiac transplantation mouse model. Significant additional work to optimize FP1 or include other novel proteins could supplement current treatment options for transplant patients., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Determine the food(s) most likely contaminated by Salmonella Javiana associated with a salmonellosis outbreak involving 2 hospitals in North Carolina that were within 50 miles of each other in November 2021., Methods: A 2:1 matched case-control study was conducted. Food histories were obtained from hospital food orders and potential confounder covariates were collected from patient medical records. Attack rates and conditional logistic regression odds ratios (OR) were estimated at the 80% confidence interval (CI) for each food exposure and salmonellosis., Results: There were 21 cases and 42 controls included. Fruit cups had the strongest association with salmonellosis (matched and adjusted OR = 7.9 80% CI: 2.7, 23.6). Hospital-specific ORs varied for several food items, but attack rates analyses provided additional evidence that fruit cups were a likely common source., Conclusion: Our analyses implicated fruit cups in an outbreak of salmonellosis in 2 hospitals. Other methodologic challenges included selection of controls among sick patients, heterogeneity of food exposures, reliance on food orders rather than foods consumed, and retention of food history records. Understanding and anticipating these challenges through changes to policies and operational procedures is critical for conducting efficient and effective case-control studies in the hospital setting., (Copyright © 2023. Published by Elsevier Inc.)

Triple-negative breast cancer (TNBC) and its recently identified subtype, quadruple negative breast cancer (QNBC), collectively account for approximately 13% of reported breast cancer cases in the United States. These aggressive forms of breast cancer are associated with poor prognoses, limited treatment options, and lower overall survival rates. In previous studies, our research demonstrated that VNLG-152R exhibits inhibitory effects on TNBC cells both in vitro and in vivo and the deuterated analogs were more potent inhibitors of TNBC cells in vitro. Building upon these findings, our current study delves into the molecular mechanisms underlying this inhibitory action. Through transcriptome and proteome analyses, we discovered that VNLG-152R upregulates the expression of E3 ligase Synoviolin 1 (SYVN1), also called 3-hydroxy-3-methylglutaryl reductase degradation (HRD1) in TNBC cells. Moreover, we provide genetic and pharmacological evidence to demonstrate that SYVN1 mediates the ubiquitination and subsequent proteasomal degradation of MNK1/2, the only known kinases responsible for phosphorylating eIF4E. Phosphorylation of eIF4E being a rate-limiting step in the formation of the eIF4F translation initiation complex, the degradation of MNK1/2 by VNLG-152R and its analogs impedes dysregulated translation in TNBC cells, resulting in the inhibition of tumor growth. Importantly, our findings were validated in vivo using TNBC xenograft models derived from MDA-MB-231, MDA-MB-468, and MDA-MB-453 cell lines, representing different racial origins and genetic backgrounds. These xenograft models, which encompass TNBCs with varying androgen receptor (AR) expression levels, were effectively inhibited by oral administration of VNLG-152R and its deuterated analogs in NRG mice. Importantly, in direct comparison, our compounds are more effective than enzalutamide and docetaxel in achieving tumor growth inhibition/repression in the AR+ MDA-MD-453 xenograft model in mice. Collectively, our study sheds light on the involvement of SYVN1 E3 ligase in the VNLG-152R-induced degradation of MNK1/2 and the therapeutic potential of VNLG-152R and its more potent deuterated analogs as promising agents for the treatment of TNBC across diverse patient populations., Competing Interests: VN is the lead inventor of VNLG-152R and its deuterated analogs, the patents and technologies thereof are owned by the University of Maryland, Baltimore. PP, RT, ET are co-inventors of the deuterated analogs of VNLG-152R. Authors RT, VR and VN were employed by the company Isoprene Pharmaceuticals, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Thankan, Thomas, Purushottamachar, Weber, Ramamurthy, Huang, Kane and Njar.)

We compared the effectiveness of 4 sampling methods to recover Staphylococcus aureus , Klebsiella pneumoniae and Clostridioides difficile from contaminated environmental surfaces: cotton swabs, RODAC culture plates, sponge sticks with manual agitation, and sponge sticks with a stomacher. Organism type was the most important factor in bacterial recovery.

Transglutaminase 2 (TG2) is a key cancer cell survival protein in many cancer types. As such, efforts are underway to characterize the mechanism of TG2 action. In this study, we report that TG2 stimulates CD44v6 activity to enhance cancer cell survival via a mechanism that involves formation of a TG2/CD44v6/ERK1/2 complex that activates ERK1/2 signaling to drive an aggressive cancer phenotype. TG2 and ERK1/2 bind to the CD44v6 C-terminal intracellular cytoplasmic domain to activate ERK1/2 and stimulate cell proliferation and invasion. This is the same region that binds to ERM proteins and ankyrin to activate CD44v6-dependent cell proliferation, invasion, and migration. We further show that treatment with hyaluronan (HA), the physiologic CD44v6 ligand, stimulates CD44v6 activity, as measured by ERK1/2 activation, but that this response is severely attenuated in TG2 or CD44v6 knockdown or knockout cells. Moreover, treatment with TG2 inhibitor reduces tumor growth and that is associated with reduced CD44v6 level and ERK1/2 activity, and reduced stemness and epithelial-mesenchymal transition (EMT). These changes are replicated in CD44v6 knockout cells. These findings suggest that a unique TG2/CD44v6/ERK1/2 complex leads to increased ERK1/2 activity to stimulate an aggressive cancer phenotype and stimulate tumor growth. These findings have important implications for cancer stem cell maintenance and suggest that cotargeting of TG2 and CD44v6 with specific inhibitors may be an effective anticancer treatment strategy., Implications: TG2 and CD44v6 are important procancer proteins. TG2 and ERK1/2 bind to the CD44v6 C-terminal domain to form a TG2/CD44v6/ERK1/2 complex that activates ERK1/2 to stimulate the cancer phenotype., (©2023 American Association for Cancer Research.)

Despite recent guidance from the Centers for Disease Control and Prevention (CDC) allowing institutions to relax in-facility masking strategies and due to our evolving understanding of respiratory pathogen transmission during the coronavirus disease 2019 (COVID-19) pandemic, we propose an updated standard for universal precautions in healthcare settings: permanently including universal masking in routine patient-care interactions. Such a practice prioritizes safety for patients, healthcare providers (HCPs), and visitors.

Objectives: Quantify the relationship between district policy permitting in-person instruction and educational outcomes during the 2020 to 2021 academic year for kindergarten through eighth grade students., Methods: An ecological, repeated cross-sectional analysis of grade-level proficiency of students enrolled in public school districts in North Carolina (n = 115 school districts) was conducted. Univariate and multivariate analyses were performed to evaluate the association between the proportion of the school year a district spent in-person and 2020 to 2021 end-of-year student proficiency in the district. We then fit a multivariable linear regression model, weighted by district size, and adjusted for district-level 2018 to 2019 proficiency and district-level factors (rural or urban, area deprivation)., Results: Compared to 2018 to 2019, there was a 12.1% decrease (95% confidence interval [CI]: 16.8-19.3) in mathematics and an 18.1% decrease (95% CI: 10.8-13.4) in reading proficiency across the state at the end of 2020 to 2021. Compared to a district that remained entirely remote for the 2020 to 2021 school year, a district offering full in-person instruction had 12% (95% CI: 11%-12.9%) and 4.1% (95% CI: 3.5%-4.8%) more students achieve grade-level proficiency in mathematics and reading, respectively. In-person instruction was associated with greater increases in mathematics proficiency than reading, and greater increases in elementary-level students' proficiency than middle school-level., Conclusions: The proportion of students achieving grade-level proficiency in 2020 to 2021 fell below prepandemic levels at each evaluated time point in the academic year. Increased time spent in-person by a school district was associated with an increased proportion of students achieving grade-level end-of-grade proficiency in both mathematics and reading., (Copyright © 2023 by the American Academy of Pediatrics.)

In this quasi-experimental study, implementing a procalcitonin and Clinical Pulmonary Infection Score (CPIS) successfully reduced inappropriate antibiotic use among severely-to-critically ill COVID-19 patients, multidrug-resistant organisms, and invasive fungal infections during the intervention period in 2 medical centers. However, this strategy did not improve inappropriate antibiotic use among mildly-to-moderately ill COVID-19 patients.

After implementing a coronavirus disease 2019 (COVID-19) infection prevention bundle, the incidence rate ratio (IRR) of non-severe acute respiratory coronavirus virus 2 (non-SARS-CoV-2) hospital-acquired respiratory viral infection (HA-RVI) was significantly lower than the IRR from the pre-COVID-19 period (IRR, 0.322; 95% CI, 0.266-0.393; P < .01). However, HA-RVIs incidence rates mirrored community RVI trends, suggesting that hospital interventions alone did not significantly affect HA-RVI incidence.

Heterogeneous ribonuclear protein A18 (hnRNP A18) is an RNA binding protein (RBP) involved in the hypoxic cellular stress response and regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in melanoma, breast cancer, prostate cancer, and colon cancer solid tumors. hnRNP A18 is comprised of an N-terminal structured RNA recognition motif (RMM) and a C-terminal intrinsically disordered domain (IDD). Upon cellar stressors, such as UV and hypoxia, hnRNP A18 is phosphorylated by casein kinase 2 (CK2) and glycogen synthase kinase 3β (GSK-3β). After phosphorylation, hnRNP A18 translocates from the nucleus to the cytosol where it interacts with pro-survival mRNA transcripts for proteins such as hypoxia inducible factor 1α and CTLA-4. Both the hypoxic cellular response and modulation of immune checkpoints by cancer cells promote chemoradiation resistance and metastasis. In this study, the 1  H, 13  C, and 15  N backbone and sidechain resonances of the 172 amino acid hnRNP A18 were assigned sequence-specifically and provide a framework for future NMR-based drug discovery studies toward targeting hnRNP A18. These data will also enable the investigation of the dynamic structural changes within the IDD of hnRNP A18 upon phosphorylation by CK2 and GSK-3β to provide critical insight into the structure and function of IDDs., (© 2022. The Author(s).)

Background: The rapid spread of coronavirus disease 2019 (COVID-19) required swift preparation to protect healthcare personnel (HCP) and patients, especially considering shortages of personal protective equipment (PPE). Due to the lack of a pre-existing biocontainment unit, we needed to develop a novel approach to placing patients in isolation cohorts while working with the pre-existing physical space., Objectives: To prevent disease transmission to non-COVID-19 patients and HCP caring for COVID-19 patients, to optimize PPE usage, and to provide a comfortable and safe working environment., Methods: An interdisciplinary workgroup developed a combination of approaches to convert existing spaces into COVID-19 containment units with high-risk zones (HRZs). We developed standard workflow and visual management in conjunction with updated staff training and workflows. The infection prevention team created PPE standard practices for ease of use, conservation, and staff safety., Results: The interventions resulted in 1 possible case of patient-to-HCP transmission and zero cases of patient-to-patient transmission. PPE usage decreased with the HRZ model while maintaining a safe environment of care. Staff on the COVID-19 units were extremely satisfied with PPE availability (76.7%) and efforts to protect them from COVID-19 (72.7%). Moreover, 54.8% of HCP working in the COVID-19 unit agreed that PPE monitors played an essential role in staff safety., Conclusions: The HRZ model of containment unit is an effective method to prevent the spread of COVID-19 with several benefits. It is easily implemented and scaled to accommodate census changes. Our experience suggests that other institutions do not need to modify existing physical structures to create similarly protective spaces.