Cenicriviroc prevents dysregulation of astrocyte/endothelial cross talk induced by ischemia and HIV-1 via inhibiting the NLRP3 inflammasome and pyroptosis.

Blood-brain barrier (BBB) breakdown is one of the pathophysiological characteristics of ischemic stroke, which may contribute to the progression of brain tissue damage and subsequent neurological impairment. Human immunodeficiency virus (HIV)-infected individuals are at greater risk for ischemic stroke due to diminished immune function and HIV-associated vasculopathy. Studies have shown that astrocytes are involved in maintaining BBB integrity and facilitating HIV-1 infection in the brain. The present study investigated whether targeting astrocyte-endothelial cell signaling with cenicriviroc (CVC), a dual chemokine receptor (CCR)2 and CCR5 antagonist, may protect against dysregulation of cross talk between these cells after oxygen-glucose deprivation/reoxygenation (OGD/R) combined with HIV-1 infection. Permeability assay with 10 kDa fluorescein isothiocyanate (FITC)-dextran demonstrated that CVC alleviated endothelial barrier disruption in noncontact coculture of human brain microvascular endothelial cells (HBMECs) with HIV-1-infected human astrocytes, and reversed downregulation of tight junction protein claudin-5 induced by OGD/R- and HIV-1. Moreover, CVC attenuated OGD/R- and HIV-1-triggered upregulation of the NOD-like receptor protein-3 (NLRP3) inflammasome and IL-1ß secretion. Treatment with CVC also suppressed astrocyte pyroptosis by attenuating cleaved caspase-1 levels and the formation of cleaved N-terminal GSDMD (N-GSDMD). Secretome profiling revealed that CVC ameliorated secretion levels of chemokine CC chemokine ligand 17 (CCL17), adhesion molecule intercellular adhesion molecule-1 (ICAM-1), and T cell activation modulator T cell immunoglobulin and mucin domain 3 (TIM-3) by astrocytes synergistically induced by OGD/R and HIV-1. Overall, these results suggest that CVC contributes to restoring astrocyte-endothelial cross interactions in an astrocyte-dependent manner via protection against NLRP3 activation and pyroptosis.NEW & NOTEWORTHY The present study reveals the role of astrocytic NOD-like receptor protein-3 (NLRP3) inflammasome in dysfunctional astrocyte-endothelial cross interactions triggered in response to oxygen/glucose deprivation injury associated with human immunodeficiency virus type 1 (HIV-1) infection. Our results suggest that blocking NLRP3 inflammasome activation and pyroptosis-mediated inflammation with cenicriviroc (CVC) may constitute a potentially effective therapeutic strategy for blood-brain barrier (BBB) protection during HIV-1-associated ischemic stroke.

How Does Narcolepsy Impact Health-Related Quality of Life? A Mixed-Methods Study.

Study Objectives: The purpose of this study was to identify patient-centered issues affecting Health-Related Quality of Life (HRQoL) in people with narcolepsy (PWN) and to evaluate patient-reported outcome measures using a mixed-methods approach. Methods: Twenty-nine adults (93% female, mean age = 31 years) with an established diagnosis of narcolepsy (Type I = 58.6%) completed focus group interviews using live videoconferencing. Additionally, participants completed the Patient-Reported Outcomes Measurement Information System (PROMIS) measures along with legacy measures commonly used in narcolepsy research (Epworth Sleepiness Scale, Patient Health Questionnaire, Short-Form 36). Results: Thematic analysis of qualitative data revealed that HRQoL was impacted by the constancy of sleepiness, unpredictability of narcolepsy symptoms, and negative public perception of narcolepsy. Challenges to accessibility and/or quality of care included dissatisfaction with non-sleep specialists' understanding of narcolepsy, the unpredictability of symptoms, and the cost of health care. There was enthusiasm for developing a psychosocial intervention to improve HRQoL using online access, but there were mixed opinions regarding the format, provider background, and content of the intervention. Elevations (T-score > 60) were found on PROMIS measures of depression, anxiety, fatigue, and sleep impairment. These patterns were consistent with the levels reported on legacy measures. PWN Type I reported lower levels of general health relative to Type II (p < .05). Conclusions: These findings lay the groundwork for more targeted efforts to address areas of diminished HRQoL in PWN. Additionally, PROMIS measures appear to be suitable and efficient instruments for assessing HRQoL in PWN.

Does Muscle Atrophy and Fatty Infiltration Plateau or Persist in Chronic Spinal Cord Injury?

Atrophy and fatty infiltration of lower extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic syndrome and related diabetes and cardiovascular disease. The objective of this study was to prospectively measure changes in muscle atrophy and fat content of distal lower extremity muscles and explore related factors in a cohort of adults with chronic SCI and diverse impairments. Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf from 70 participants with chronic SCI (50 male, mean age 49 years, C2-T12, American Spinal Injury Association Impairment Scale A-D) at study enrollment and annually for 2 years. Mixed-model repeated measures analysis of variance (rANOVA) examined longitudinal changes in muscle area and density, and regression analyses explored factors related to muscle changes using 16 potential correlates selected a priori. A high degree of individual variation in muscle area and density change was observed over 2 years (range: 8.5 to -22.6 cm2; 6.4 to -8.6 mg/cm3). Repeated measures analysis of variance revealed significant reductions in muscle area (estimated mean difference [95% confidence intervals] -1.76 [-3.29 to -0.23]) cm2, p = 0.025) and density (-1.04 [-1.94 to -0.14] mg/cm3, p < 0.024); however, changes in area were not significant with outliers removed. Regression analyses explained a small proportion of the variability in muscle density change; however, none of the preselected variables were significantly related to changes in muscle density after post hoc sensitivity analyses. Lower extremity muscle size and fat content may not reach a "steady-state" after chronic SCI. Progressive atrophy and fatty infiltration of lower extremity muscle may have adverse implications for metabolic syndrome and cardiovascular disease risk and related mortality after chronic SCI.

Improving reliability of pQCT-derived muscle area and density measures using a watershed algorithm for muscle and fat segmentation.

In peripheral quantitative computed tomography scans of the calf muscles, segmentation of muscles from subcutaneous fat is challenged by muscle fat infiltration. Threshold-based edge detection segmentation by manufacturer software fails when muscle boundaries are not smooth. This study compared the test-retest precision error for muscle-fat segmentation using the threshold-based edge detection method vs manual segmentation guided by the watershed algorithm. Three clinical populations were investigated: younger adults, older adults, and adults with spinal cord injury (SCI). The watershed segmentation method yielded lower precision error (1.18%-2.01%) and higher (p<0.001) muscle density values (70.2±9.2 mg/cm3) compared with threshold-based edge detection segmentation (1.77%-4.06% error, 67.4±10.3 mg/cm3). This was particularly true for adults with SCI (precision error improved by 1.56% and 2.64% for muscle area and density, respectively). However, both methods still provided acceptable precision with error well under 5%. Bland-Altman analyses showed that the major discrepancies between the segmentation methods were found mostly among participants with SCI where more muscle fat infiltration was present. When examining a population where fatty infiltration into muscle is expected, the watershed algorithm is recommended for muscle density and area measurement to enable the detection of smaller change effect sizes.

A 3-fold-symmetric ligand based on 2-hydroxypyridine: regulation of ligand binding by hydrogen bonding.

A tripodal ligand based on 2-hydroxypyridine is presented. Cu-Cl adducts of H3thpa with Cu(I) and Cu(II) provide complexes featuring highly directed, intramolecular hydrogen-bonding interactions. An upper limit for the hydrogen-bonding free energy to Cu(I)-Cl was estimated at ∼18 kcal/mol.

Exploring the safety and quality of mobile X-ray imaging in a new infectious disease biocontainment unit: an in situ simulation and video-reflexive study.

OBJECTIVES: During a precommissioning inspection of a new biocontainment centre, radiographers noted structural features of quarantine rooms that could compromise staff and patient safety and the X-ray image quality, even after significant modifications had been made to an earlier radiography protocol. The aim of this study was to explore the safety and effectiveness of the modified protocol, in the new space, and identify improvements, if required. DESIGN: A qualitative study using in situ simulation and video-reflexive methods. SETTING: A newly built biocontainment centre, prior to its commissioning in 2021, in a large, tertiary hospital in Sydney, Australia. PARTICIPANTS: Five radiographers, and a nurse and a physician from the biocontainment centre, consented to participate. All completed the study. INTERVENTIONS: Two simulated mobile X-ray examinations were conducted in the unit prior to its commissioning; simulations were videoed. Participants and other stakeholders analysed video footage, collaboratively, and sessions were audio recorded, transcribed and analysed thematically. Problems and potential solutions identified were collated and communicated to the hospital executive, for endorsement and actioning, if possible. RESULTS: Four themes were identified from the data: infection exposure risks, occupational health and exposure risks, communication and X-ray image quality. Facilitated group reviews of video footage identified several important issues, across these four areas of risk, which had not been identified previously. CONCLUSIONS: In situ simulation is used, increasingly, to evaluate and improve healthcare practices. This study confirmed the added value of video-reflexive methods, which provided experienced participants with a richer view of a familiar protocol, in a new setting. Video footage can be examined immediately, or later if required, by a broader group of stakeholders, with diverse experience or expertise. Using video reflexivity, clinicians identified potential safety risks, which were collated and reported to the hospital executive, who agreed to implement modifications.

Rigid Plate Fixation for Closure of Emergent Sternotomies for Trauma.

BACKGROUND: No studies to date have evaluated the use of rigid plate fixation for emergent sternotomy in trauma patients. We evaluated our use of rigid plate fixation vs wire cerclage in patients requiring emergent sternotomy. We hypothesized there would be no difference in complications related to sternal closure between the two groups. METHODS: We performed a retrospective cohort study to include all patients who underwent emergent sternotomy from 1/1/2018 to 1/31/2021 and survived to have their sternum closed. Outcomes in patients closed with wire cerclage group (WC) were compared to patients who underwent rigid plate fixation (RPF). RESULTS: Twenty-two patients underwent emergent sternotomy. There were 11 patients in each group. There was no significant difference in admission demographics, ISS, or admission characteristics between the two groups. Complication rates related to closure (wound infection and hardware removal) were not significantly different (WC 27% vs RPF 9%, P = .58). Neither hospital length of stay (WC: 29 days vs RPF: 13 days, P = .13), ICU length of stay (WC: 6 days vs RPF: 7 days, P = .62), nor the number of ventilator days (WC: 3 days vs RPF: 1 day, P .11) were statistically different. All patients survived to discharge. DISCUSSION: This is the first study comparing RPF and WC for sternotomy closure in the setting of trauma. We found no difference in the rate of wound related complications. This study demonstrates the feasibility of rigid plate fixation for trauma sternotomy closure and lays the foundation for future prospective studies.

Underdiagnosis of Hyperparathyroidism in Patients With Nephrolithiasis in a Community Setting.

Objective Untreated primary hyperparathyroidism (PHPT) has wide-ranging multisystemic effects. Recent studies based in the US have shown a less than 25% screening rate for PHPT. Our study aims to detect whether similar deficiencies exist in our community healthcare system while quantifying the prevalence of PHPT underdiagnosis and inadequate surgical referrals. Study design This retrospective quantitative study enrolled patients aged ≥18 years with imaged-confirmed nephrolithiasis at our healthcare facilities from 2017 to the present (n=2021). Patients with documented calcium levels and kidney/ureter stones were included. Descriptive and univariate analyses were performed. Results A total of 2021 subjects met the criteria to be enrolled in the study. 26.6% (n=537) of patients with nephrolithiasis had elevated calcium levels on record. 13.6% (n=73) of hypercalcemic patients were screened for PHPT with an intact parathyroid hormone (PTH). A majority (63%, n=46) of patients with intact PTH had PHPT defined as PTH levels >55 pg/mL. Ultimately, only 19.6% (n=9) of patients with PHPT were referred for surgical intervention, and there was no significant difference in referral rate between patients with PHPT and those without (p=0.913). Conclusions PHPT is underdiagnosed in our community, leading to a significantly low rate of surgical referral and delay in management. Implementation of hospital protocols to aid in improving diagnosis and interventions could improve outcomes for PHPT patients.

Test-retest reliability of pulse wave velocity in individuals with chronic spinal cord injury.

BACKGROUND: Pulse wave velocity (PWV), which reflects arterial stiffness, is an important predictor of future coronary artery disease. The test-retest reliability of PWV has not been investigated in people with spinal cord injury (SCI). PURPOSE: To report the test-retest (day-to-day) reliability of PWV measurements among people with SCI, and to determine the smallest real difference (SRD) of PWV values. PARTICIPANTS: Twenty men (n = 19) and a woman (n = 1) with SCI (C4-T10; AIS A-D; ≥ 1-year post-injury; 10 with paraplegia and 10 with tetraplegia; time post-injury: 11.8 ± 8.7 years; age: 43.0 ± 12.6 years). METHODS: On two occasions within a 2-week period, aortic PWV (between the common carotid and femoral artery), arm PWV (between the brachial and radial artery), and leg PWV (between femoral and posterior tibial artery) were assessed at the same time of day using Doppler flowmeters. RESULTS: No statistically significant differences were found between days 1 and 2 in aortic PWV (day 1: 941 ± 185 cm/seconds, day 2: 917 ± 160 cm/seconds, P = 0.257), leg PWV (day 1: 1088 ± 141 cm/seconds, day 2: 1122 ± 165 cm/seconds, P = 0.099) and arm PWV (day 1: 1283 ± 185 cm/seconds, day 2: 1358 ± 256 cm/seconds, P = 0.180). The aortic and leg PWVs had high test-retest reliability (intraclass correlation coefficient: ICC = 0.920 and 0.913, respectively; P < 0.001 for both) and arm PWV had moderate test-retest reliability (ICC = 0.598, P = 0.03). SRDs for each PWV were 104 cm/seconds (aortic PWV), 97 cm/seconds (leg PWV) and 143 cm/seconds (arm PWV). CONCLUSION: The test-retest reliability of PWV assessment is high among patients with chronic SCI. Changes in aortic PWV values above 104 cm/seconds with repeated testing like represent true changes in health status.

A Surface Exposed, Two-Domain Lipoprotein Cargo of a Type XI Secretion System Promotes Colonization of Host Intestinal Epithelia Expressing Glycans.

The only known required component of the newly described Type XI secretion system (TXISS) is an outer membrane protein (OMP) of the DUF560 family. TXISSOMPs are broadly distributed across proteobacteria, but properties of the cargo proteins they secrete are largely unexplored. We report biophysical, histochemical, and phenotypic evidence that Xenorhabdus nematophila NilC is surface exposed. Biophysical data and structure predictions indicate that NilC is a two-domain protein with a C-terminal, 8-stranded ß-barrel. This structure has been noted as a common feature of TXISS effectors and may be important for interactions with the TXISSOMP. The NilC N-terminal domain is more enigmatic, but our results indicate it is ordered and forms a ß-sheet structure, and bioinformatics suggest structural similarities to carbohydrate-binding proteins. X. nematophila NilC and its presumptive TXISSOMP partner NilB are required for colonizing the anterior intestine of Steinernema carpocapsae nematodes: the receptacle of free-living, infective juveniles and the anterior intestinal cecum (AIC) in juveniles and adults. We show that, in adult nematodes, the AIC expresses a Wheat Germ Agglutinin (WGA)-reactive material, indicating the presence of N-acetylglucosamine or N-acetylneuraminic acid sugars on the AIC surface. A role for this material in colonization is supported by the fact that exogenous addition of WGA can inhibit AIC colonization by X. nematophila. Conversely, the addition of exogenous purified NilC increases the frequency with which X. nematophila is observed at the AIC, demonstrating that abundant extracellular NilC can enhance colonization. NilC may facilitate X. nematophila adherence to the nematode intestinal surface by binding to host glycans, it might support X. nematophila nutrition by cleaving sugars from the host surface, or it might help protect X. nematophila from nematode host immunity. Proteomic and metabolomic analyses of wild type X. nematophila compared to those lacking nilB and nilC revealed differences in cell wall and secreted polysaccharide metabolic pathways. Additionally, purified NilC is capable of binding peptidoglycan, suggesting that periplasmic NilC may interact with the bacterial cell wall. Overall, these findings support a model that NilB-regulated surface exposure of NilC mediates interactions between X. nematophila and host surface glycans during colonization. This is a previously unknown function for a TXISS.

Anticoagulation and bone marrow biopsy: is it safe to proceed?

BACKGROUND: Bone marrow (BM) biopsy is the most common diagnostic procedure in hematology. Bleeding is an expected complication, and its risk is assumed to be increased in patients on anticoagulants. However, the effect of anticoagulation on BM biopsy safety is unclear and guidelines are lacking robust data in this regard. As such, physicians use their clinical judgement to guide periprocedural management of anticoagulation. OBJECTIVE: To provide the best available evidence regarding management of anticoagulation in patients who need BM biopsy. METHODS: We reviewed and summarized available guidelines directing management of periprocedural anticoagulation for BM biopsy, and share our experience and practices with BM biopsy at our institution. RESULTS: The incidence of significant hemorrhage after BM biopsy is very low (0.007-1.1%). BM biopsy is classified as having a low to moderate bleeding risk. Interrupting anticoagulation is not consistently recommended. Strategies exist to minimize bleeding risk for anticoagulated patients. Patients with myeloproliferative neoplasms can develop an acquired von Willebrand syndrome which increases their risk for bleeding and therefore require extra vigilance to ensure appropriate hemostasis. CONCLUSION: Withholding anticoagulation prior to BM biopsy is not routinely recommended. Instead, assessment and optimization of bleeding risk factors should be done on a patient by patient basis.

What do we really know about mindfulness and sleep health?

Over the past decade, the emergence of mindfulness meditation as a self-regulation practice has led to a substantial body of evidence on the use of mindfulness-based interventions (MBIs) for insomnia and sleep disturbances. This literature has matured with several randomized controlled trials now published and a number of systematic reviews and meta-analyses are recently available. Collectively, there is a general support for the effectiveness of MBIs on self-reported patient outcomes although the quality of studies varies and the findings on objective measures are equivocal. Building upon this literature, further research is needed to examine biological correlates associated with mindfulness practice, whether the timing of meditation practice is related to sleep outcomes, who is likely to succeed with MBI, and the use of technology in the delivery of MBIs.

Developing a cognitive behavioral therapy for hypersomnia using telehealth: a feasibility study.

STUDY OBJECTIVES: The purpose of this study was to evaluate the feasibility and acceptability of a novel cognitive behavioral therapy for hypersomnia (CBT-H) in people with central disorders of hypersomnolence and co-occurring depressive symptoms using a telehealth model for delivery and assessment. METHODS: Thirty-five adults with narcolepsy or idiopathic hypersomnia received a 6-session CBT-H delivered individually or in small groups using videoconferencing. The clinical impact of CBT-H was evaluated using the Patient Health Questionnaire, Patient-Reported Outcomes Measurement Information System measures, Epworth Sleepiness Scale, and other patient-reported outcomes collected online at baseline and posttreatment. Feasibility and acceptability of the intervention and telehealth model was also evaluated using qualitative data collected from exit interviews conducted through videoconferencing. RESULTS: Forty percent of the sample achieved a clinically significant baseline to posttreatment change in depressive symptoms (decrease in Patient Health Questionnaire ≥ 5), which is below the prespecified efficacy benchmark (50% of the sample). The prespecified benchmark for a minimal clinically important difference (Cohen's d > 0.5) on other psychosocial measures was met only on the Patient-Reported Outcomes Measurement Information System global self-efficacy (d = 0.62) in the total sample. Qualitative data revealed enthusiasm for the accessibility of telehealth delivery and the usefulness of several cognitive and behavioral modules but also revealed opportunities to refine the CBT-H program. CONCLUSIONS: These findings indicate that this new CBT-H program can potentially reduce depressive symptoms and improve self-efficacy in people with central disorders of hypersomnolence. Furthermore, telehealth is a promising model for remote delivery and data collection to enhance participant accessibility and engagement. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Psychosocial Adjunctive Treatment for Hypersomnia (PATH); URL: https://clinicaltrials.gov/ct2/show/NCT03904238; Identifier: NCT03904238.

Association between abnormal arterial stiffness and cardiovascular risk factors in people with chronic spinal cord injury.

Aims To describe the association between cardiovascular risk factors and abnormal arterial stiffness, defined by a carotid-femoral pulse wave velocity ≥ 10 m/s, in patients with chronic spinal cord injury (SCI). Methods Ninety consenting adults with chronic SCI (C1-T10 ASIA Impairment Scale A-D) participated in this cross-sectional study. The cardiovascular risk factors considered included age, sex, duration of injury, neurological level of injury (C1-T1, tetraplegia; T2-T12, paraplegia), age at injury, impairment scale category, supine resting systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, leisure time physical activity, treated hypertension, treated hyperlipidemia, diabetes, lipid profiles, fasting blood glucose, glycated hemoglobin, and C reactive protein. Logistic regression analysis was used to determine the association between abnormal arterial stiffness and dichotomized cardiovascular risk factors. Results Dichotomized variables significantly associated with increased arterial stiffness were: age ≥ 52 years (OR 22.1, CI 4.28-113.99); systolic blood pressure ≥ 130 mmHg (OR 11.76, CI 2.89-47.88); heart rate ≥ 62 bpm (OR 6.62, CI 1.33-33.03); and paraplegia (OR 4.26, CI 1.00-18.33). The area under the receiver operating characteristic curve for probability of arterial stiffness was 0.920 (95% CI 0.861-0.978, p < 0.001). Conclusions Age, resting systolic blood pressure, resting heart rate, and neurological level of injury can identify patients at high risk of elevated arterial stiffness in the population with chronic SCI.

Synthesis of Acetone-Derived C6 , C9 , and C12 Carbon Scaffolds for Chemical and Fuel Applications.

A simple, inexpensive catalyst system (Amberlyst 15 and Ni/SiO2 -Al2 O3 ) is described for the upgrading of acetone to a range of chemicals and potential fuels. Stepwise hydrodeoxygenation of the produced ketones can yield branched alcohols, alkenes, and alkanes. An analysis of these products is provided, which demonstrates that this approach can provide a product profile of valuable bioproducts and potential biofuels.

The Effect of Functional Groups in Bio-Derived Fuel Candidates.

Interest in developing renewable fuels is continuing to grow and biomass represents a viable source of renewable carbon with which to replace fossil-based components in transportation fuels. During our own work, we noticed that chemists think in terms of functional groups whereas fuel engineers think in terms of physical fuel properties. In this Concept article, we discuss the effect of carbon and oxygen functional groups on potential fuel properties. This serves as a way of informing our own thinking and provides us with a basis with which to design and synthesize molecules from biomass that could provide useful transportation fuels.

Redox-induced fluoride ligand dissociation stabilized by intramolecular hydrogen bonding.

Chemical reduction of a tripodal Cu(II)-F complex containing pendent hydroxyl groups results in the partial dissociation of a F(-) ligand from Cu. The resulting Cu(I) complex is characterized as containing an outer sphere F(-) anion 'captured' by hydrogen bonds. The pendent hydroxyl groups were found to be crucial for reductive stability.

Nitrite reduction by copper through ligand-mediated proton and electron transfer.

Nitrite reduction by a copper complex featuring a proton-responsive tripodal ligand is demonstrated. Gaseous nitric oxide was confirmed as the sole NO X by-product in quantitative yield. DFT calculations predict that nitrite reduction occurs via a proton and electron transfer process mediated by the ligand. The reported mechanism parallels nitrite reduction by copper nitrite reductase.

Physical activity as medicine among family health teams: an environmental scan of physical activity services in an interdisciplinary primary care setting.

A Family Health Team (FHT) is a multi-disciplinary primary healthcare model that may be an ideal setting to engage patients in physical activity. An environmental scan was conducted to determine the prevalence and characteristics of physical activity services offered by FHTs in Ontario. Of the 186 FHTs, 102 (55%) completed the survey. Almost 60% of responding FHTs offered a physical activity service; however, the availability, duration, size, and target population of the services varied depending on the individual FHT.

Beyond H2: exploiting 2-hydroxypyridine as a design element from [Fe]-hydrogenase for energy-relevant catalysis.

The unique primary and secondary coordination environments surrounding the active site of hydrogenase enzymes play a crucial role in H2 activation and transfer reactions. [Fe]-hydrogenase contains a 2-hydroxypyridine ligand motif, and many researchers have incorporated this design element into synthetic catalysts. Transition metal complexes supported by 2-hydroxypyridine scaffolds are catalysts for chemical conversion schemes relevant to alternative energy applications and, in addition to hydrogenase-type reactivity, find new uses in other chemical domains. In this review, the current status of 2-hydroxypyridine-derived catalysts is described with an emphasis on design features that lead to lower energy catalytic pathways.