Deciphering S100B Allosteric Signaling: The Role of a Peptide Target, TRTK-12, as an Ensemble Modulator.

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 Ca2+-binding proteins. The Ca2+-binding affinity of S100B is modulated allosterically by TRTK-12 peptide binding 25 Å away from the Ca2+-binding site. We investigated S100B allostery by carrying out nuclear magnetic resonance (NMR) measurements along with microsecond-long molecular dynamics (MD) simulations on S100B/Ca2+ with/without TRTK-12 at different NaCl salt concentrations. NMR HSQC results show that TRTK-12 reorganizes how S100B/Ca2+ 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 Ca2+-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/Ca2+ complex.

Healthcare Provider N95 Respirator Contamination Worn Behind Face Shields With SARS-CoV-2 During Routine Clinical Care of Patients With COVID-19.

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%).

Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel.

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.

The impact of minimally invasive surgical approaches on surgical-site infections.

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.

Bacille Calmette-Guérin preparation and intravesical administration to patients with bladder cancer: Risks to healthcare personnel and patients, and mitigation strategies.

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.

Infection precaution adherence varies by potential exposure risks to SARS-CoV-2 and job role: Findings from a US medical center.

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.

The impact of environmental cleaning protocol featuring PX-UV in reducing the incidence of multidrug-resistant gram-negative healthcare-associated infection and colonization in intensive care units in Thailand.

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.

The clinical epidemiology, management, and outcomes of patients diagnosed with encephalitis in North Carolina, 2015-2020.

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.

Society of Critical Care Medicine and the Infectious Diseases Society of America Guidelines for Evaluating New Fever in Adult Patients in the ICU.

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.

Biofilms on medical instruments and surfaces: Do they interfere with instrument reprocessing and surface disinfection.

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.

Disinfection and sterilization: New technologies.

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.

..úNo touch..Ñ methods for health care room disinfection: Focus on clinical trials.

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.

Role of the contaminated environment in transmission of multidrug-resistant organisms in nursing homes and infection prevention.

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.

Evaluation of antibiotic-resistant bacteria in home kitchens and bathrooms: Is there a link between home disinfectant use and antibiotic resistance?

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 log10 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-log10 of total CFU and 6.6-log10 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.

Emerging infectious diseases, focus on infection prevention, environmental survival and germicide susceptibility: SARS-CoV-2, Mpox, and Candida auris.

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.