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.

Creation and impact of containment units with high-risk zones during the coronavirus disease 2019 (COVID-19) pandemic.

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.

Strategies utilized to prevent and control SARS-CoV-2 transmission in two congregate, psychiatric healthcare settings during the pandemic.

BACKGROUND: The COVID-19 pandemic has had a substantial effect on the delivery of psychiatric health care. Inpatient psychiatric health care facilities have experienced outbreaks of COVID-19, making these areas particularly vulnerable. METHODS: Our facility used a multidisciplinary approach to implement enhanced infection prevention and control (IPC) interventions in our psychiatric health care areas. RESULTS: In a 16-month period during the COVID-19 pandemic, our 2 facilities provided >29,000 patient days of care to 1,807 patients and identified only 47 COVID-19 positive psychiatric health inpatients (47/1,807, or 2.6%). We identified the majority of these cases by testing all patients at admission, preventing subsequent outbreaks. Twenty-one psychiatric health care personnel were identified as COVID+ during the same period, with 90% linked to an exposure other than a known positive case at work. DISCUSSION: The IPC interventions we implemented provided multiple layers of safety for our patients and our staff. Ultimately, this resulted in low SARS-CoV-2 infection rates within our facilities. CONCLUSIONS: Psychiatric health care facilities are uniquely vulnerable to COVID-19 outbreaks because they are congregate units that promote therapeutic interactions in shared spaces. IPC interventions used in acute medical care settings can also work effectively in psychiatric health care, but often require modifications to ensure staff and patient safety.

A Functional Model of [Fe]-Hydrogenase.

[Fe]-Hydrogenase catalyzes the hydrogenation of a biological substrate via the heterolytic splitting of molecular hydrogen. While many synthetic models of [Fe]-hydrogenase have been prepared, none yet are capable of activating H2 on their own. Here, we report the first Fe-based functional mimic of the active site of [Fe]-hydrogenase, which was developed based on a mechanistic understanding. The activity of this iron model complex is enabled by its unique ligand environment, consisting of biomimetic pyridinylacyl and carbonyl ligands, as well as a bioinspired diphosphine ligand with a pendant amine moiety. The model complex activates H2 and mediates hydrogenation of an aldehyde.

Reconstitution of [Fe]-hydrogenase using model complexes.

[Fe]-Hydrogenase catalyses the reversible hydrogenation of a methenyltetrahydromethanopterin substrate, which is an intermediate step during the methanogenesis from CO2 and H2. The active site contains an iron-guanylylpyridinol cofactor, in which Fe(2+) is coordinated by two CO ligands, as well as an acyl carbon atom and a pyridinyl nitrogen atom from a 3,4,5,6-substituted 2-pyridinol ligand. However, the mechanism of H2 activation by [Fe]-hydrogenase is unclear. Here we report the reconstitution of [Fe]-hydrogenase from an apoenzyme using two FeGP cofactor mimics to create semisynthetic enzymes. The small-molecule mimics reproduce the ligand environment of the active site, but are inactive towards H2 binding and activation on their own. We show that reconstituting the enzyme using a mimic that contains a 2-hydroxypyridine group restores activity, whereas an analogous enzyme with a 2-methoxypyridine complex was essentially inactive. These findings, together with density functional theory computations, support a mechanism in which the 2-hydroxy group is deprotonated before it serves as an internal base for heterolytic H2 cleavage.

[Fe]-hydrogenase and models that contain iron-acyl ligation.

[Fe]-hydrogenase is a newly characterized type of hydrogenase. This enzyme heterolytically splits hydrogen in the presence of a natural substrate. The active site of the enzyme contains a mono-iron complex with intriguing iron-acyl ligation. Several groups have recently developed iron-acyl complexes as synthetic models of [Fe]-hydrogenase. This Focus Review summarizes the studies of this enzyme and its model compounds, with an emphasis on our own research in this area.

Dihydrogen complexes of iridium and rhodium.

A series of iridium and rhodium pincer complexes have been synthesized and characterized: [(POCOP)Ir(H)(H(2))] [BAr(f)(4)] (1-H(3)), (POCOP)Rh(H(2)) (2-H(2)), [(PONOP)Ir(C(2)H(4))] [BAr(f)(4)] (3-C(2)H(4)), [(PONOP)Ir(H)(2))] [BAr(f)(4)] (3-H(2)), [(PONOP)Rh(C(2)H(4))] [BAr(f)(4)] (4-C(2)H(4)) and [(PONOP)Rh(H(2))] [BAr(f)(4)] (4-H(2)) (POCOP = κ(3)-C(6)H(3)-2,6-[OP(tBu)(2)](2); PONOP = 2,6-(tBu(2)PO)(2)C(5)H(3)N; BAr(f)(4) = tetrakis(3,5-trifluoromethylphenyl)borate). The nature of the dihydrogen-metal interaction was probed using NMR spectroscopic studies. Complexes 1-H(3), 2-H(2), and 4-H(2) retain the H-H bond and are classified as η(2)-dihydrogen adducts. In contrast, complex 3-H(2) is best described as a classical dihydride system. The presence of bound dihydrogen was determined using both T(1) and (1)J(HD) coupling values: T(1) = 14 ms, (1)J(HD) = 33 Hz for the dihydrogen ligand in 1-H(3), T(1)(min) = 23 ms, (1)J(HD) = 32 Hz for 2-H(2), T(1)(min) = 873 ms for 3-H(2), T(1)(min) = 33 ms, (1)J(HD) = 30.1 Hz for 4-H(2).