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Cytochrome P450 monooxygenases (CYPs) are well known for their ability to catalyze diverse oxidation reactions, playing a significant role in the biosynthesis of various natural products. In the realm of monoterpenoid indole alkaloids (MIAs), one of the largest groups of alkaloids in nature, CYPs are integral to reactions such as hydroxylation, epoxidation, ring opening, ring rearrangement, and aromatization, contributing to the extensive diversification of these compounds. In this study, we investigate the transcriptome, metabolome, and MIA biosynthesis in Tabernaemontana litoralis (milky way tree), a prolific producer of rare pseudoaspidosperma-type MIAs. Alongside known pseudoaspidosperma biosynthetic genes, we identify and characterize three new CYPs that facilitate regio- and stereospecific oxidation of four MIA skeletons: iboga, aspidosperma, pseudoaspidosperma, and quebrachamine. Notably, the tabersonine 14,15-β-epoxidase catalyzes the formation of pachysiphine, the stereoisomer of 14,15-α-epoxytabersonine (lochnericine) found in Catharanthus roseus (Madagascar periwinkle) roots. The pseudovincadifformine 18-hydroxylase is the first CYP identified to modify a pseudoaspidosperma skeleton. Additionally, we demonstrate that the enzyme responsible for C10-hydroxylation of the iboga MIA coronaridine also catalyzes C10-hydroxylation of voaphylline, which bears a quebrachamine skeleton. With the discovery of a new MIA, 11-hydroxypseudovincadifformine, this study provides a comprehensive understanding of MIA biosynthesis and diversification in T. litoralis, highlighting its potential for further exploration., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Monoterpenoid indole alkaloids (MIA) are one of the largest and most complex alkaloid class in nature, boasting many clinically significant drugs such as anticancer vinblastine and antiarrhythmic ajmaline. Many MIAs undergo nitrogen N -methylation, altering their reactivity and affinity to the biological targets through a straightforward reaction. Remarkably, all known MIA N -methyltransferases (NMT) originate from the neofunctionalization of ancestral γ-tocopherol C -methyltransferases (γTMTs), a phenomenon seemingly unique to the Apocynaceae family. In this study, we unveil and characterize a new γTMT-like enzyme from the plant Tabernaemontana elegans (toad tree): perivine N β-methyltransferase (TePeNMT). TePeNMT and other homologs form a distinct clade in our phylogenetic study, setting them apart from other γTMTs and γTMT-like NMTs discovered to date. Enzyme kinetic experiments and enzyme homology modeling studies reveal the significant differences in enzyme active sites between TePeNMT and CrPeNMT, a previously characterized perivine N β-methyltransferase from Catharanthus roseus (Madagascar periwinkle). Collectively, our findings suggest that parallel evolution of ancestral γTMTs may be responsible for the occurrence of perivine N -methylation in T. elegans and C. roseus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Farzana, Richardson, Deschênes, Mai, Njoku, Deslongchamps and Qu.)

Purpose: Black pregnant individuals in Alabama are disproportionately affected by severe maternal morbidity and mortality (SMM). To understand why racial disparities in maternal health outcomes persist and identify potential strategies to reduce these inequities, we sought perspectives from obstetric health care providers, health administrators, and members of local organizations who provide pregnancy, delivery, and postpartum care services in Alabama., Methods: We conducted qualitative in-depth interviews with stakeholders ( n =20), purposively recruited from community-based organizations, clinical settings, government organizations, and academic institutions. Interview guides were based on Howell's conceptual model of pathways to racial disparities in maternal mortality. Data were coded using a modified framework theory approach and analyzed thematically., Results: Racism, unjust laws and policies, and poverty/lack of infrastructure in communities emerged as major themes contributing to racial disparities in maternal health at the community and systems levels. Inadequate health insurance coverage was described as a strong driver of the disparities. Service providers suggested strategies for Alabama should be community focused, evidence based, and culturally sensitive. These should include Medicaid expansion, expanded parental leave, and removal of laws restricting choice. Community- and systems-level interventions should include community infrastructure improvements, choice in maternity services, and provision of digital communication options., Conclusions: Providers shared perspectives on community and structural areas of intervention to reduce racial inequities in SMM. These results can inform discussions with health system and community partners about Alabama and other Deep South initiatives to improve maternal health outcomes in black communities., Competing Interests: No competing financial interests exist., (© Molly B. Richardson et al., 2023; Published by Mary Ann Liebert, Inc.)

Biological and synthetic molecular motors, fueled by various physical and chemical means, can perform asymmetric linear and rotary motions that are inherently related to their asymmetric shapes. Here, we describe silver-organic micro-complexes of random shapes that exhibit macroscopic unidirectional rotation on water surface through the asymmetric release of cinchonine or cinchonidine chiral molecules from their crystallites asymmetrically adsorbed on the complex surfaces. Computational modeling indicates that the motor rotation is driven by a pH-controlled asymmetric jet-like Coulombic ejection of chiral molecules upon their protonation in water. The motor is capable of towing very large cargo, and its rotation can be accelerated by adding reducing agents to the water., (© 2023. The Author(s).)

Lung cancer is the leading cause of cancer mortality in the USA. In the rural Black Belt region of Alabama, high rates of lung cancer incidence and mortality coupled with disproportionate lack of access to health services stresses the need for navigating high risk and disproportionately affected groups towards successfully obtaining lung cancer screenings. We utilized our well-accepted Community Health Advisor (CHA) model for education and awareness. This study seeks to evaluate the results of the Alabama Lung Cancer Awareness, Screening, and Education (ALCASE) training on CHAs, program evaluation, and lessons learned. A total of 202 participants were eligible and enrolled for CHA training. One hundred thirty CHAs were included for the final analyses. Descriptive statistics were computed; differences in pre-test and post-test scores were compared across demographic characteristics of the participants using paired t-test/one-way ANOVA. Of the 130 CHAs, 46% were 65 years or older; 98% were African Americans, and 87% were female; 17% of participants were cancer survivors. The mean post-test scores were 2.2 points greater than mean pre-test scores, and the difference was significant (mean (SD): pre-test = 20.8 (2.8) versus post-test = 23 (2.2); p = 0.001). No notable difference in pre-test and post-test scores were observed by CHA's demographic characteristics except by their county of residence or work (p = 0.0019). We demonstrate the capability and value of successfully recruiting and training motivated community members to be able to serve educators to better reach medically underserved and historically excluded communities., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

At Advocate Aurora Health, the board of directors established parameters for effectively executing the governance (G) function related to ESG activities while adopting a comprehensive approach to ESG that includes the corporate commitment to health equity. Establishing a board diversity, equity, and inclusion (DEI) committee with external experts served to integrate these efforts with the ESG strategy. This approach will continue to guide the board of directors of Advocate Health, formed in December 2022, by the combination of Advocate Aurora Health and Atrium Health. Our experience has demonstrated that empowering individual board committee members of not-for-profit healthcare organizations to embrace their unique responsibility for driving ESG requires collective efforts in the boardroom as well as a commitment to board refreshment and diversity., Competing Interests: The author declares no conflicts of interest., (Copyright © 2023 Foundation of the American College of Healthcare Executives.)

Antimicrobial resistance (AMR) is threatening modern medicine. While the primary cost of AMR is paid in the healthcare domain, the agricultural and environmental domains are also reservoirs of resistant microorganisms and hence perpetual sources of AMR infections in humans. Consequently, the World Health Organisation and other international agencies are calling for surveillance of AMR in all three domains to guide intervention and risk reduction strategies. Technologies for detecting AMR that have been developed for healthcare settings are not immediately transferable to environmental and agricultural settings, and limited dialogue between the domains has hampered opportunities for cross-fertilisation to develop modified or new technologies. In this feature, we discuss the limitations of currently available AMR sensing technologies used in the clinic for sensing in other environments, and what is required to overcome these limitations.

Background: Focus groups and workshops can be used to gain insights into the persistence of and potential solutions for environmental health priorities in underserved areas. The objective of this study was to characterize focus group and workshop outcomes of a community-academic partnership focused on addressing environmental health priorities in an urban and a rural location in Alabama between 2012 and 2019., Methods: Six focus groups were conducted in 2016 with 60 participants from the City of Birmingham (urban) and 51 participants from Wilcox County (rural), Alabama to discuss solutions for identified environmental health priorities based on previous focus group results in 2012. Recorded focus groups were transcribed and analyzed using the grounded theory approach. Four follow-up workshops that included written survey instruments were conducted to further explore identified priorities and determine whether the priorities change over time in the same urban (68 participants) and rural (72 participants) locations in 2018 and 2019., Results: Consistent with focus groups in 2012, all six focus groups in 2016 in Birmingham identified abandoned houses as the primary environmental priority. Four groups listed attending city council meetings, contacting government agencies and reporting issues as individual-level solutions. Identified city-level solutions included city-led confiscation, tearing down and transferring of abandoned property ownership. In Wilcox County, all six groups agreed the top priority was drinking water quality, consistent with results in 2012. While the priority was different in Birmingham versus Wilcox County, the top identified reason for problem persistence was similar, namely unresponsive authorities. Additionally, individual-level solutions identified by Wilcox County focus groups were similar to Birmingham, including contacting and pressuring agencies and developing petitions and protesting to raise awareness, while local policy-level solutions identified in Wilcox County included government-led provision of grants to improve septic systems, and transparency in allocation of funds. Workshops in 2018 and 2019 further emphasized water quality as the top priority in Wilcox County, while participants in Birmingham transitioned from abandoned houses as a top priority in 2018 to drinking water quality as a new priority in 2019., Conclusions: Applying a community-engaged approach in both urban and rural locations provided better understanding of the unique opportunities and challenges for identifying potential interventions for environmental health priorities in both locations. Results can help inform future efforts to address locally defined environmental health issues and solutions., (© 2021. The Author(s).)

Background: As healthcare systems strive for efficiency, hospital "length of stay outliers" have the potential to significantly impact a hospital's overall utilization. There is a tendency to exclude such "outlier" stays in local quality improvement and data reporting due to their assumed rare occurrence and disproportionate ability to skew mean and other summary data. This study sought to assess the influence of length of stay (LOS) outliers on inpatient length of stay and hospital capacity over a 5-year period at a large urban academic medical center., Methods: From January 2014 through December 2019, 169,645 consecutive inpatient cases were analyzed and assigned an expected LOS based on national academic center benchmarks. Cases in the top 1% of national sample LOS by diagnosis were flagged as length of stay outliers., Results: From 2014 to 2019, mean outlier LOS increased (40.98 to 45.11 days), as did inpatient LOS with outliers excluded (5.63 to 6.19 days). Outlier cases increased both in number (from 297 to 412) and as a percent of total discharges (0.98 to 1.56%), and outlier patient days increased from 6.7 to 9.8% of total inpatient plus observation days over the study period., Conclusions: Outlier cases utilize a disproportionate and increasing share of hospital resources and available beds. The current tendency to exclude such outlier stays in data reporting due to assumed rare occurrence may need to be revisited. Outlier stays require distinct and targeted interventions to appropriately reduce length of stay to both improve patient care and maintain hospital capacity., (© 2021. The Author(s).)

Heatwave warning systems rely on forecasts made for fixed-point weather stations (WS), which do not reflect variation in temperature and humidity experienced by individuals moving through indoor and outdoor locations. We examined whether neighborhood measurement improved the prediction of individually experienced heat index in addition to nearest WS in an urban and rural location. Participants (residents of Birmingham, Alabama [N = 89] and Wilcox County, Alabama [N = 88]) wore thermometers clipped to their shoe for 7 days. Shielded thermometers/hygrometers were placed outdoors within participant's neighborhoods (N = 43). Nearest WS and neighborhood thermometers were matched to participant's home address. Heat index (HI) was estimated from participant thermometer temperature and WS humidity per person-hour (HI[individual]), or WS temperature and humidity, or neighborhood temperature and humidity. We found that neighborhood HI improved the prediction of individually experienced HI in addition to WS HI in the rural location, and neighborhood heat index alone served as a better predictor in the urban location, after accounting for individual-level factors. Overall, a 1 °C increase in HI[neighborhood] was associated with 0.20 °C [95% CI (0.19, 0.21)] increase in HI[individual]. After adjusting for ambient condition differences, we found higher HI[individual] in the rural location, and increased HI[individual] during non-rest time (5 a.m. to midnight) and on weekdays.

Spending time outdoors is associated with increased physical activity; however, high ambient temperature/humidity, together with built environment features in urban versus rural environments, may influence physical activity. We conducted an intervention trial with 89 urban and 88 rural participants performing normal activities on Days 1-2 (baseline) and spending an additional 30 min outdoors on Days 3-7 (intervention) in the summer. Participants wore a pedometer with real-time visual feedback to track daily steps taken and a thermometer clipped to their shoe to track temperatures experienced individually. Hygrometer-thermometers were deployed in participants' neighborhoods to collect finer resolution ambient heat indexes in addition to regional weather station measurements. Using linear mixed effects models and adjusting for ambient conditions and individual-level factors, participants on average walked 637 (95%CI (83, 1192)) more steps and had a 0.59 °C (95%CI (0.30, 0.88)) lower daily mean individually experienced heat index during intervention days compared to baseline days. The intervention benefit of increased physical activity was greater in rural residents who were less active at baseline, compared to urban residents. Our results suggest adding a small amount of additional time outdoors may improve physical activity without increasing participants' heat exposure, even during summer in a humid subtropical climate.

This study investigated changes in glycemic control following a small increase in time spent outdoors. Women participants with type 2 diabetes (N = 46) wore an iBUTTON temperature monitor and a pedometer for 1 week and recorded their morning fasting blood glucose (FBG) daily. They went about their normal activities for 2 days (baseline) and were asked to add 30 min of time outdoors during Days 3-7 (intervention). Linear mixed effects models were used to test whether morning FBG values were different on days following intervention versus baseline days, and whether steps and/or heat exposure changed. Results were stratified by indicators of good versus poor glycemic control prior to initiation of the study. On average, blood glucose was reduced by 6.1 mg/dL (95% CI - 11.5, - 0.6) on mornings after intervention days after adjusting for age, BMI, and ambient weather conditions. Participants in the poor glycemic control group (n = 16) experienced a 15.8 mg/dL decrease (95% CI - 27.1, - 4.5) in morning FBG on days following the intervention compared to a 1.6 mg/dL decrease (95%CI - 7.7, 4.5) for participants in the good glycemic control group (n = 30). Including daily steps or heat exposure did not attenuate the association between intervention and morning FBG. The present study suggests spending an additional 30 min outdoors may improve glycemic control; however, further examination with a larger sample over a longer duration and determination of mediators of this relationship is warranted.

Context: An accurate assessment of lumbar spine active range of motion (AROM) is clinically important. Dual inclinometry is recommended as the optimal technique for measuring lumbar flexion AROM; however, the procedures differ in the literature., Objective: To compare 2 different handheld digital dual inclinometry (HDDI) techniques for evaluating lumbar flexion AROM., Design: The study was a repeated-measures design consisting of 2 trials., Setting: Laboratory., Participants: A sample of 69 adult volunteers (28 men and 41 women; mean age 23.8 [2.4] y) without pain or injury to their back, hips, or abdomen for at least 3 months participated in the study., Intervention: Using standardized methods, 1 trained tester performed 2 different HDDI measurements of standing lumbar flexion AROM on each subject. Each subject performed one repetition of AROM lumbar flexion per HDDI measurement. The HDDI measures differed in the process for placing the upper inclinometer, with one technique identifying the upper landmark by skilled palpation of the T12 spinous process and the other technique by measuring 15-cm cephalad to the S2 region landmark to approximate the location of the T12 spinous process., Main Outcome Measures: A dependent t test, Pearson correlation coefficient (r), the 95% limits of agreement, and Bland-Altman plots were used to examine agreement between the techniques., Results: Dependent t testing showed no significant differences between the techniques (mean difference = 1.2°, P = .11). A strong correlation existed between the 2 HDDI techniques (r = .80, P < .001). The Bland-Altman plot illustrated that 64 of the 69 data points were within the 95% limits of agreement for the 2 techniques., Conclusions: The findings suggest that HDDI measurements of lumbar flexion AROM are comparable when using either of the 2 HDDI techniques described. Clinicians can make an evidence-based choice for using either method of measuring lumbar flexion AROM.

Heat stress is a significant health concern that can lead to illness, injury, and mortality. The wet bulb globe temperature (WBGT) index is one method for monitoring environmental heat risk. Generally, WBGT is estimated using a heat stress monitor that includes sensors capable of measuring ambient, wet bulb, and black globe temperature, and these measurements are combined to calculate WBGT. However, this method can be expensive, time consuming, and requires careful attention to ensure accurate and repeatable data. Therefore, researchers have attempted to use standard meteorological measurements, using single data sources as an input (e.g., weather stations) to calculate WBGT. Building on these efforts, we apply data from a variety of sources to calculate WBGT, understand the accuracy of our estimated equation, and compare the performance of different sources of input data. To do this, WBGT measurements were collected from Kestrel 5400 Heat Stress Trackers installed in three locations in Alabama. Data were also drawn from local weather stations, North American Land Data Assimilation System (NLDAS), and low cost iButton hygrometers. We applied previously published equations for estimating natural wet bulb temperature, globe temperature, and WBGT to these diverse data sources. Correlation results showed that WBGT estimates derived from all proxy data sources-weather station, weather station/iButton, NLDAS, NLDAS/iButton-were statistically indistinguishable from each other, or from the Kestrel measurements, at two of the three sites. However, at the same two sites, the addition of iButtons significantly reduced root mean square error and bias compared to other methods., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2020. The Authors.)

Advances in bioconjugation, the ability to link biomolecules to each other, small molecules, surfaces, and more, can spur the development of advanced materials and therapeutics. We have discovered that pyrocinchonimide, the dimethylated analogue of maleimide, undergoes a surprising transformation with biomolecules. The reaction targets amines and involves an imide transfer, which has not been previously reported for bioconjugation purposes. Despite their similarity to maleimides, pyrocinchonimides do not react with free thiols. Though both lysine residues and the N -termini of proteins can receive the transferred imide, the reaction also exhibits a marked preference for certain amines that cannot solely be ascribed to solvent accessibility. This property is peculiar among amine-targeting reactions and can reduce combinatorial diversity when many available reactive amines are available, such as in the formation of antibody-drug conjugates. Unlike amides, the modification undergoes very slow reversion under high pH conditions. The reaction offers a thermodynamically controlled route to single or multiple modifications of proteins for a wide range of applications.

Members of the haloacid dehalogenase (HAD) family of metabolite phosphatases play an important role in regulating multiple pathways in Plasmodium falciparum central carbon metabolism. We show that the P. falciparum HAD protein, phosphoglycolate phosphatase (PGP), regulates glycolysis and pentose pathway flux in asexual blood stages via detoxifying the damaged metabolite 4-phosphoerythronate (4-PE). Disruption of the P. falciparum pgp gene caused accumulation of two previously uncharacterized metabolites, 2-phospholactate and 4-PE. 4-PE is a putative side product of the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, and its accumulation inhibits the pentose phosphate pathway enzyme, 6-phosphogluconate dehydrogenase (6-PGD). Inhibition of 6-PGD by 4-PE leads to an unexpected feedback response that includes increased flux into the pentose phosphate pathway as a result of partial inhibition of upper glycolysis, with concomitant increased sensitivity to antimalarials that target pathways downstream of glycolysis. These results highlight the role of metabolite detoxification in regulating central carbon metabolism and drug sensitivity of the malaria parasite. IMPORTANCE The malaria parasite has a voracious appetite, requiring large amounts of glucose and nutrients for its rapid growth and proliferation inside human red blood cells. The host cell is resource rich, but this is a double-edged sword; nutrient excess can lead to undesirable metabolic reactions and harmful by-products. Here, we demonstrate that the parasite possesses a metabolite repair enzyme (PGP) that suppresses harmful metabolic by-products (via substrate dephosphorylation) and allows the parasite to maintain central carbon metabolism. Loss of PGP leads to the accumulation of two damaged metabolites and causes a domino effect of metabolic dysregulation. Accumulation of one damaged metabolite inhibits an essential enzyme in the pentose phosphate pathway, leading to substrate accumulation and secondary inhibition of glycolysis. This work highlights how the parasite coordinates metabolic flux by eliminating harmful metabolic by-products to ensure rapid proliferation in its resource-rich niche., (Copyright © 2019 Dumont et al.)

Objective: This study investigated whether using thermometers clipped on workers' shoes would result in different heat exposure estimation and work-rest schedules compared with using area-level meteorological data alone., Methods: Alabama workers (n = 51) were individually monitored using thermometers on shoes. Wet bulb globe temperature (WBGT) was estimated using thermometer temperatures (WBGT [personal]) or nearby weather station temperatures (WBGT [WS]). Work-rest schedules were determined from WBGT, clothing, and hourly metabolic rates estimated from self-reported tasks and bodyweight., Results: The percent of hours exceeding the threshold limit value (TLV, ACGIH, Cincinnati, OH) were estimated at 47.8% using WBGT (personal) versus 42.1% using WBGT (WS). For work-rest recommendations, more hours fell into the most protective schedule (0 to 15 min work/45 to 60 min rest) using WBGT (personal) versus WBGT (WS) (17.4% vs 14.4%)., Conclusions: Temperatures from wearable thermometers, together with meteorological data, can serve as an additional method to identify occupational heat stress exposure and recommend work-rest schedules.

A polymer-based electrode capable of specific detection of human serum albumin, and its glycated derivatives, is described. The sensor is constructed from a glass microscope slide coated with a synthesized, polythiophene film bearing a protected, iminodiacetic acid motif. The electrode surface is then further elaborated to a functional biosensor through deprotection of the iminodiacetic acid, followed by metal-affinity immobilization of a specific and high-affinity, albumin ligand. Albumin was then quantified in buffer and synthetic urine via electrochemical impedance spectroscopy. Glycated albumin was next bound to a boronic acid-modified, single-cysteine dihydrofolate reductase variant to quantify glycation ratios by square-wave voltammetry. The platform offers high sensitivity, specificity, and reproducibility in an inexpensive arrangement. The detection limits exceed the requirements for intermediate-term glycemic control monitoring in diabetes patients at 5 and 1 nM for albumin and its glycated forms, respectively.

Objective: It was hypothesized that exposure to mild temperatures above the human thermoneutral zone would decrease caloric intake in a sedentary office environment., Methods: Women (n = 25) were randomized in a crossover design to perform seated office work for 7 hours in a thermoneutral condition (control, 19°C-20°C) and a condition above the thermoneutral zone (warm, 26°C-27°C). Food intake was estimated by weight and bomb calorimetry, peripheral temperature by thermal imaging, and thermal comfort and productivity by questionnaires. Mixed effects models were used to examine the effects of thermal condition on caloric intake., Results: Participants ate, on average, 357 kcal less in the warm condition, adjusting for BMI and peripheral temperature (P = 0.0219). According to the survey results at midday (after 3.5 hours of exposure), 96% of the participants in the warm condition reported being comfortable (n = 24) compared with 32% in the control condition (n = 8). More participants reported being as productive or more productive than usual in the warm condition (n = 22, 88%) than in the control condition (n = 12, 48%)., Conclusions: This line of research is worthy of further exploration. Untightening climate control toward warmer conditions during summer to increase comfort and productivity while decreasing caloric intake may prove both effective and comfortable., (© 2018 The Obesity Society.)

Purpose Academic healthcare systems face great challenges in coordinating services across a continuum of care that spans hospital, community providers, home and chronic care facilities. The Johns Hopkins Community Health Partnership (J-CHiP) was created to improve coordination of acute, sub-acute and ambulatory care for patients, and improve the health of high-risk patients in surrounding neighborhoods. The paper aims to discuss this issue. Design/methodology/approach J-CHiP targeted adults admitted to the Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center, patients discharged to participating skilled nursing facilities (SNFs), and high-risk Medicare and Medicaid patients receiving primary care in eight nearby outpatient sites. The primary drivers of the program were redesigned acute care delivery, seamless transitions of care and deployment of community care teams. Findings Acute care interventions included risk screening, multidisciplinary care planning, pharmacist-driven medication management, patient/family education, communication with next provider and care coordination protocols for common conditions. Transition interventions included post-discharge health plans, hand-offs and follow-up with primary care providers, Transition Guides, a patient access line and collaboration with SNFs. Community interventions involved forming multidisciplinary care coordination teams, integrated behavioral care and new partnerships with community-based organizations. Originality/value This paper offers a detailed description of the design and implementation of a complex program to improve care coordination for high-risk patients in an urban setting. The case studies feature findings from each intervention that promoted patient engagement, strengthened collaboration with community-based organizations and improved coordination of care.

A reliable, scalable, cost-effective, and chromatography-free synthesis of 4-azido-l-phenylalanine beginning from l-phenylalanine is described. Investigations into the safety of the synthesis reveal that the Ullman-like Cu(I)-catalyzed azidation step does not represent a significant risk. The isolated 4-azido-l-phenylalanine product, however, exhibits previously undocumented explosive characteristics.

Background: To support hospital efforts to improve coordination of care, a tool is needed to evaluate care coordination from the perspective of inpatient healthcare professionals., Objectives: To develop a concise tool for assessing care coordination in hospital units from the perspective of healthcare professionals, and to assess the performance of the tool in measuring dimensions of care coordination in 2 hospitals after implementation of a care coordination initiative., Methods: We developed a survey consisting of 12 specific items and 1 global item to measure provider perceptions of care coordination across a variety of domains, including teamwork and communication, handoffs, transitions, and patient engagement. The questionnaire was distributed online between October 2015 and January 2016 to nurses, physicians, social workers, case managers, and other professionals in 2 tertiary care hospitals., Results: A total of 841 inpatient care professionals completed the survey (response rate = 56.6%). Among respondents, 590 (75%) were nurses and 37 (4.7%) were physicians. Exploratory factor analysis revealed 4 subscales: (1) Teamwork, (2) Patient Engagement, (3) Handoffs, and (4) Transitions (Cronbach's alpha 0.84-0.90). Scores were fairly consistent for 3 subscales but were lower for patient engagement. There were minor differences in scores by profession, department, and hospital., Conclusions: The new tool measures 4 important aspects of inpatient care coordination with evidence for internal consistency and construct validity, indicating that the tool can be used in monitoring, evaluating, and planning care coordination activities in hospital settings., (© 2017 Society of Hospital Medicine)

We report the total synthesis of (R)-tuberculostearic acid-containing Mycobacterium tuberculosis phosphatidylglycerol (PG). The approach features a two-step synthesis of (R)-tuberculostearic acid, involving an (S)-citronellyl bromide linchpin, and the phosphoramidite-assisted assembly of the full PG structure. Collision-induced dissociation mass spectrometry of two chemically-synthesized PG acyl regioisomers revealed diagnostic product ions formed by preferential loss of carboxylate at the secondary (sn-2) position.

Background: Environmental heat exposure is a public health concern. The impacts of environmental heat on mortality and morbidity at the population scale are well documented, but little is known about specific exposures that individuals experience., Objectives: The first objective of this work was to catalyze discussion of the role of personal heat exposure information in research and risk assessment. The second objective was to provide guidance regarding the operationalization of personal heat exposure research methods., Discussion: We define personal heat exposure as realized contact between a person and an indoor or outdoor environment that poses a risk of increases in body core temperature and/or perceived discomfort. Personal heat exposure can be measured directly with wearable monitors or estimated indirectly through the combination of time-activity and meteorological data sets. Complementary information to understand individual-scale drivers of behavior, susceptibility, and health and comfort outcomes can be collected from additional monitors, surveys, interviews, ethnographic approaches, and additional social and health data sets. Personal exposure research can help reveal the extent of exposure misclassification that occurs when individual exposure to heat is estimated using ambient temperature measured at fixed sites and can provide insights for epidemiological risk assessment concerning extreme heat., Conclusions: Personal heat exposure research provides more valid and precise insights into how often people encounter heat conditions and when, where, to whom, and why these encounters occur. Published literature on personal heat exposure is limited to date, but existing studies point to opportunities to inform public health practice regarding extreme heat, particularly where fine-scale precision is needed to reduce health consequences of heat exposure. https://doi.org/10.1289/EHP556.

Potential obesity-related policy approaches have recently been receiving more attention. Although some have been implemented and others only proposed, few have been formally evaluated. We discuss the relevance, and in some cases irrelevance, of some of the types of evidence that are often brought to bear in considering obesity-related policy decisions. We discuss major methods used to generate such evidence, emphasizing study design and the varying quality of the evidence obtained. Third, we consider what the standards of evidence should be in various contexts, who ought to set those standards, as well as the inherent subjectivity involved in making policy decisions. Finally, we suggest greater transparency from both academics and policymakers in the acknowledgment of subjectivities so they can distinguish and communicate the roles of empirical evidence and subjective values in the formulation of policy.

The fidelity of acylation regioselectivity in the synthesis of mixed glycosyl diacylglycerols can be accurately measured by quantitative 13 C NMR spectroscopy using a 1- 13 C-labelled fatty acid and a paramagnetic relaxation enhancement agent. Exquisite regioselectivity is achieved using a stepwise acylation/substitution of a glycosyl β-bromohydrin, which is applied to the total synthesis of Streptococcus pneumoniae Glc-DAG-s2.

Mycobacterium tuberculosis H37Ra produces a range of immunogenic β-gentiobiosyl diacylglycerides. We report the total synthesis of several candidate structures and show that these compounds signal weakly through mouse, but not human, Mincle. Structure-activity relationships reveal a striking dependence upon acyl chain length for gentiobiosyl diacylglyceride signalling through Mincle. Significantly, a truncated β-glucosyl diglyceride was shown to provide potent signalling through both human and mouse Mincle and could activate murine bone marrow derived dendritic cells.

Macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle) comprise part of an extensive repertoire of pattern recognition receptors with the ability to sense damage-associated and pathogen-associated molecular patterns. In this review, we cover the discovery and molecular characterization of these C-type lectin receptors, and highlight recent advances in the understanding of their roles in orchestrating the response of the immune system to bacterial and fungal infection, and damaged self. We also discuss the identification and structure-activity relationships of activating ligands, particularly trehalose dimycolate and related mycobacterial glycolipids, which have significant potential in the development of TH1/TH17 vaccination strategies.

A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12-C19) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12-C14) or the C15 and C16 lactones pentadecanolide (for iso-C15-C17) and hexadecanolide (for iso-C18-C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13-C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S)-2,15-dimethylpalmitic acid, (S)-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

Glucuronosyl diacylglycerides (GlcAGroAc2) are functionally important glycolipids and membrane anchors for cell wall lipoglycans in the Corynebacteria. Here we describe the complete synthesis of distinct acyl-isoforms of GlcAGroAc2 bearing both acylation patterns of (R)-tuberculostearic acid (C19:0) and palmitic acid (C16:0) and their mass spectral characterization. Collision-induced fragmentation mass spectrometry identified characteristic fragment ions that were used to develop "rules" allowing the assignment of the acylation pattern as C19:0 (sn-1), C16:0 (sn-2) in the natural product from Mycobacterium smegmatis, and the structural assignment of related C18:1 (sn-1), C16:0 (sn-2) GlcAGroAc2 glycolipids from M. smegmatis and Corynebacterium glutamicum. A synthetic hydrophobic octyl glucuronoside was used to characterize the GDP-mannose-dependent mannosyltransferase MgtA from C. glutamicum that extends GlcAGroAc2. This enzyme is an Mg(2+)/Mn(2+)-dependent metalloenzyme that undergoes dramatic activation upon reduction with dithiothreitol.

Aim: To examine attitudes toward and acceptability of HPV vaccination among a community-based sample of women in the Philippines., Methods: Self-administered surveys were completed by 435 adult women. Intent to receive the HPV vaccine was assessed at low, moderate, and high vaccine price through responses on Likert scale items. The theory-grounded survey assessed attitudinal correlates, as well as sociodemographic, behavioral, and health-related characteristics., Results: Over half of the sample (54%) was accepting of HPV vaccination at the low price, but only 30% and 31% were accepting at the moderate and high price, respectively. Negative intent to receive the vaccine was significantly associated with women's indication that their mothers or partners were influential in their vaccination decisions. Perceived social support, access to transportation, perceived benefits of vaccination, perceived susceptibility to HPV, history of pap testing, and having been exposed to vaccine-promoting media were among factors independently associated with positive intent to receive the vaccine., Conclusions: HPV vaccine acceptance among Filipina women is contingent on affordable pricing. A successful vaccine initiative in the region must minimize structural barriers, foster familial and social support for vaccination, incorporate HPV education, and work within cultural norms.

Previous methods for the control of zearalenone (ZEN)-induced hyperestrogenism in animals have proven largely ineffective. The main objective in this study was to identify an enterosorbent that decreases the dietary bioavailability, and subsequent estrogenic effects, of ZEN. Initial in vitro screenings in aqueous solution (4 microg ZEN/ml) indicated that an activated carbon (AC) was the most efficient sorbent (99%), followed by a combination of 2 parts AC plus 3 parts HEC (hectorite) (69%), cetylpyridinium-exchanged low-pH montmorillonite (CP-LPHM) clay (58%), hexadecyltrimethylammonium-exchanged low-pH montmorillonite (HDTMA-LPHM) clay (54%), and HEC alone (28%). Results from the adult hydra bioassay suggested that the addition of either AC or HEC effectively decreased the effects of ZEN on Hydra attenuata without toxicity, as was observed with the use of either CP-LPHM or HDTMA-LPHM. Based on these results, AC, HEC, and 2AC:3HEC were evaluated in prepubertal mice. At a dietary inclusion level of 0.8% (w/w), AC alone significantly protected mice against the estrogenic effects induced by 35 mg ZEN/kg feed. Inclusion of 1.2% HEC with the 0.8% AC showed no additional protection; whereas 1.2% HEC alone failed to decrease the estrogenic effects. Ground flaxseed (25% w/w) in the diet also elicited protection, but to a lesser extent. Preliminary studies suggested that three similar carbons failed to decrease ZEN bioavailability. These findings suggest that the AC used in this study may be efficacious as an enterosorbent in animals consuming ZEN-contaminated diets. However, further studies are needed to evaluate the binding specificity, as well as the safety of chronic exposure.

Complex mixtures of hazardous chemicals such as polycyclic aromatic hydrocarbons (PAHs) in contaminated soil and groundwater can have severe and long-lasting effects on health. The evidence that these contaminants can cause adverse health effects in animals and humans is rapidly expanding. The frequent and wide-spread occurrence of PAHs in groundwater makes appropriate intervention strategies for their remediation highly desirable. The core objective of this research was to assess the ability of a clay-based composite to sorb and remove toxic contaminants from groundwater at a wood-preserving chemical waste site. Treatment efficiencies were evaluated using either effluent from an oil-water separator (OWS) or a bioreactor (B2). The effluent water from these units was passed through fixed bed columns containing either an organoclay composite or granular activated carbon. The sorbent columns were placed in-line using existing sampling ports at the effluent of the OWS or B2. Individual one-liter samples of treated and untreated effluent were collected in Kimax bottles over the course of 78 h (total of 50 samples). Subsequently each sample was extracted by solid phase extraction methodology, and pentachlorophenol (PCP) and PAH concentrations were quantitated via GC/MS. Columns containing porous organoclay composite, i.e. sand-immobilized cetylpyridinium-exchanged low-pH montmorillonite clay (CP/LPHM), were shown to reduce the contaminant load from the OWS effluent stream by 97%. The concentrations of benzo[a]pyrene (BaP) and PCP were considerably reduced (i.e. >99%). An effluent stream from the bioreactor was also filtered through columns packed with composite or an equivalent amount of GAC. Although the composite reduced the majority of contaminants (including BaP and PCP), it was less effective in diminishing the levels of lower ring versus higher ring PAHs. Conversely, GAC was more effective in removing the lower ring PAHs, except for naphthalene and PCP. The effectiveness of sorption of PCP from the OWS effluent by the composite was confirmed using a PCP-sensitive adult hydra bioassay previously described in our laboratory. The findings of this initial study have delineated differences between CP/LPHM and GAC for groundwater remediation, and suggest that GAC (instead of sand) as the solid support for organoclay may be more effective for the treatment of contaminated groundwater under field conditions than GAC or CP/LPHM alone. Further work is ongoing to confirm this conclusion.