Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice.

Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low-folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual's age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

Minimally invasive total pancreatectomy with islet autotransplantation for chronic pancreatitis: the robotic approach.

INTRODUCTION: Total pancreatectomy with islet autotransplantation (TPIAT) treats refractory pain in chronic pancreatitis, prevents episodes of acute exacerbation, and mitigates postoperative brittle diabetes. The minimally invasive (MIS) approach offers a decreased surgical access trauma and enhanced recovery. Having established a laparoscopic TPIAT program, we adopted a robotic approach (R-TPIAT) and studied patient outcomes compared to open TPIAT. METHODS: Between 2013 and 2021, 61 adult patients underwent TPIAT after a comprehensive evaluation (97% chronic pancreatitis). Pancreatic islets were isolated on-site during the procedure. We analyzed and compared intraoperative surgical and islet characteristics, postoperative morbidity and mortality, and 1-year glycemic outcomes. RESULTS: MIS-TPIAT was performed in 41 patients (67%, 15 robotic and 26 laparoscopic), and was associated with a shorter mean length of intensive care unit stay compared to open TPIAT (2.9 vs 4.5 days, p = 0.002). R-TPIAT replaced laparoscopic TPIAT in 2017 as the MIS approach of choice and demonstrated decreased blood loss compared to open TPIAT (324 vs 843 mL, p = 0.004), similar operative time (609 vs 562 min), 30-day readmission rate (7% vs 15%), and 90-day complication rate (13% vs 20%). The glycemic outcomes including C-peptide detection at 1-year (73% vs 88%) and insulin dependence at 1-year (75% vs 92%) did not differ. The mean length of hospital stay after R-TPIAT was 8.6 days, shorter than for laparoscopic (11.5 days, p = 0.031) and open TPIAT (12.6 days, p = 0.017). Both MIS approaches had a 1-year mortality rate of 0%. CONCLUSIONS: R-TPIAT was associated with a 33% reduction in length of hospital stay (4-day benefit) compared to open TPIAT. R-TPIAT was similar to open TPIAT on measures of feasibility, safety, pain control, and 1-year glycemic outcomes. Our data suggest that robotic technology, a new component in the multidisciplinary therapy of TPIAT, is poised to develop into the primary surgical approach for experienced pancreatic surgeons.

Nickel binding enables isolation and reactivity of previously inaccessible 7-aza-2,3-indolynes.

N-Heteroaromatics are key elements of pharmaceuticals, agrochemicals, and materials. N-Heteroarynes provide a scaffold to build these essential molecules but are underused because five-membered N-heteroarynes have been largely inaccessible on account of the strain of a triple bond in that small of a ring. On the basis of principles of metal-ligand interactions that are foundational to organometallic chemistry, in this work we report the stabilization of five-membered N-heteroarynes in the nickel coordination sphere. A series of 1,2-bis(dicyclohexylphosphino)ethane nickel 7-azaindol-2,3-yne complexes were synthesized and characterized crystallographically and spectroscopically. Ambiphilic reactivity of the nickel 7-azaindol-2,3-yne complexes was observed with multiple nucleophilic, electrophilic, and enophilic coupling partners.

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups.

BACKGROUND AND OBJECTIVES: Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti-HBc) prevents transfusion-transmitted HBV infection but can lead to significant donor loss. As isolated anti-HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti-HBc testing and the representation of rare blood groups in anti-HBc-positive donors. MATERIALS AND METHODS: Three hundred ninety-seven HBV surface antigen-negative and anti-HBc initially reactive blood donor samples were tested by five different anti-HBc assays. RESULTS: Eighty percentage of samples reactive in Architect anti-HBc assay were positive by the Murex assay and anti-HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty-eight percentage of anti-HBc-positive donors identified as minority ethnic groups compared with 11% representation in anti-HBc-negative donors (p < 0.0001); the frequency of the Ro blood group in anti-HBc-positive donors was 18 times higher in non-white ethnic groups. CONCLUSION: Using two anti-HBc assays effectively enabled the identification of HBV-exposed and potentially infectious donors, their deferral and potential clinical follow-up. However, the exclusion of confirmed anti-HBc-positive donors will still impact the supply of rare blood such as Ro.

Ligand-Controlled Regioinduction in a PHOX-Ni Aryne Complex.

Phosphinooxazoline (PHOX) ligands have been used to control the regio- and enantioselectivity in a wide variety of metal-catalyzed reactions. Despite their widespread use, PHOX ligands have never been studied in metal-aryne complexes. Herein we report the first example of a PHOX-Ni aryne complex. As demonstrated in other systems, the differentiated P versus N donors and different steric environments of the unsymmetric ligand are able to induce regiocontrol. A 81:19 mixture of o-methoxy substituted aryne complexes is observed. Single-crystal X-ray crystallographic analysis, UV/vis spectroscopy, and cyclic voltammetry are used to gain further insight into the molecular and electronic structure of these complexes. Lastly, a methylation/deuteration sequence shows retention of the PHOX ligand-induced regiocontrol in the difunctionalized products and that the regiospecificity of these difunctionalizations is due to the trans influence of the P donor.

Late-life dietary folate restriction reduces biosynthetic processes without compromising healthspan in mice.

Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual's age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

Redox-Neutral Decarboxylative and Desulfonylative C(sp3) Trifluoromethylation: Method Development and Mechanistic Inquiry.

Sodium triflinate (CF3SO2Na) is an inexpensive bench-stable radical CF3 source that is often activated by external oxidants such as peroxides. However, despite the commercial accessibility of CF3SO2Na, the salt has never been applied to decarboxylative trifluoromethylation due to challenges in controlled cross-radical coupling. We report a redox-neutral approach to decarboxylative C(sp3) trifluoromethylation of carboxylic acid derivatives. Mechanistic inquiry is performed to address the limitations in scope.

Redox Inversion: A Radical Analogue of Umpolung Reactivity for Base- and Metal-Free Catalytic C(sp3)-C(sp3) Coupling.

The construction of alkyl-alkyl bonds is a powerful tool in organic synthesis. Redox inversion, defined as switching the donor/acceptor profile of a functional group to its acceptor/donor profile, is used for C(sp3)-C(sp3) coupling. We report a photocatalytic coupling of carboxylic acids to form bibenzyls through a radical-radical coupling. Mechanistic insight is gained through control reactions. This unexplored redox-opposite relationship between a carboxylic acid and its redox-active ester is implemented in catalysis.

Radical-Polar Crossover Catalysis with a d0 Metal Enabled by a Redox-Active Ligand.

Radical-polar crossover mechanisms are invoked in numerous late transition metal and photocatalyzed reactions. To the best of our knowledge, reductive radical-polar crossover mechanisms are not invoked for group 3 early transition metals due to their propensity to exist in high oxidation states. Through use of a redox-active (tris)amido ligand we have accessed this mechanism for use with early transition metals. This mechanism is showcased through enabling product formation for a wide variety of elimination products from α-halo substituted benzylic bromides. The mechanism of this new type of reactivity with Sc is explored, and Hammett analysis reveals an anionic intermediate. The wide functional group tolerance of this reaction is also demonstrated.

The dynamics of trust and communication in COVID-19 vaccine decision making: A qualitative inquiry.

In response to the COVID-19 pandemic, scientists coordinated a complex immunization effort that developed and distributed vaccines by December 2020. This study aimed to explain COVID-19 vaccination decision-making process to inform vaccine communication with patients and the public. Building on quantitative research on COVID-19 vaccine hesitancy, we conducted a grounded theory study, collecting 30 qualitative interviews with employees at a U.S. university that provided vaccine eligibility in December 2020. Analysis followed the Sort and Sift, Think and Shift method. Participants who had chosen to receive the vaccine and those who had not both described five factors that impacted their decision-making: emotional response, understanding, personal values, culture, and social norms. Across these factors, we identified three cross-cutting themes: time, trust, and communication tactics. In a time of emerging science and changing answers, the constant introduction of new information created information overload for participants. COVID-19 vaccine development was a "grand experiment globally," which required trust, not only knowledge, to overcome hesitancy. The complex information environment surrounding COVID-19 vaccination requires multi-level intervention that cannot rely on knowledge translation alone. We need to help patients build trusting relationships with experts that can create scaffolding for future information processing.

Gatekeeper training needs of community pharmacy staff.

OBJECTIVE: To develop an online suicide prevention gatekeeper training program to prepare community pharmacy staff to communicate with patients who exhibit warning signs of suicide. METHOD: A convenience sample of 17 community pharmacy staff members completed a 1-hr semi-structured interview during which they viewed content from an existing gatekeeper training program and provided suggestions for improvement. Once thematic saturation was achieved, interviews were digitally recorded, transcribed, and analyzed by two independent coders who reached consensus on the themes present in each transcript. RESULTS: Participants noted barriers to communicating about suicide, including lack of time and privacy, discomfort with using the word "suicide" and limited referral options. Participants wanted gatekeeper training to include local suicide prevention referral resources, take less than 30 min to complete, and incorporate 3-4 realistic role play scenarios, including a phone interaction. CONCLUSIONS: Many environmental, interpersonal, and individual-level barriers complicate pharmacy staff members' ability to act as gatekeepers and communicate about suicide with at-risk patients. To maximize the public health impact of pharmacy staff, skills-based training on how to identify, communicate with, and refer at-risk patients is needed. Gatekeeper training should model brief, realistic interactions with patients and provide pharmacy staff with local referral resources.

Men's Attitudes and Behaviors About Skincare and Sunscreen Use Behaviors.

IMPORTANCE: Skin cancer is the most common cancer in the United States, and men experience higher rates of skin cancer than women. Despite publicized preventative measures, men are less likely than women to use sunscreen. OBJECTIVE: To assess men's motivations, behaviors, and preferred product characteristics towards daily sunscreen use. DESIGN AND SETTING: Cross-sectional online survey of 705 men, administered July– August 2019, using Survey Monkey and distributed through Amazon Mechanical Turk. PARTICIPANTS: Men ages 20–70, having completed at least High School/GED, and living in the United States were eligible. Sampling strategy ensured diversity in terms of race, ethnicity, and sexual orientation. Main Outcome(s) and Measures: Men’s sunscreen use, behaviors, and preferred skincare product characteristics. RESULTS: Final participants included 705 men. The most frequent skincare products used regularly were liquid soap/body wash (65%), bar soap (47%), and moisturizers (32%). Most men (n=612; 83%) reported not using sunscreen daily, and 38% reported using sunscreen weekly. Income was related to daily and weekly sunscreen use, as males who earned between $40-$50,000 annually used sunscreen less often compared to people who earned $100,000 annually (OR 0.54%, 95% CI −0.34% to .88%; P = .01). Age, sexual orientation, race, ethnicity, and region were not related to daily or weekly sunscreen use. Main motivators for daily sunscreen use included reducing skin cancer risk (n=575; 82%) and looking younger (n=299; 42%). CONCLUSIONS AND RELEVANCE: This survey shows lapses in evidenced-based sunscreen behaviors to reduce skin cancer among men. Campaigns to reduce skin cancer should focus on increasing men's interest in daily sunscreen use and adherence to wearing sun-protective products. J Drugs Dermatol. 2021;20(1):88-93. doi:10.36849/JDD.5470.

Exploring community members' perceptions to adopt a Tele-COPD program in rural counties.

Background: Patients diagnosed with COPD residing in rural areas report a lower quality of life. Telehealth addresses geographic barriers by offering routine, technology-based visits, and remote patient monitoring. Objective: The study objective was to explore adoption perceptions of a tele-COPD program among community members in rural Western North Carolina (WNC) counties. Methods: A convenience sample of 17 community members were recruited to participate in one of five 45-min focus groups. Before the focus group, all participants completed a brief demographic survey. Focus groups were digitally recorded, transcribed verbatim, imported into MAXQDA v10, and analyzed thematically using established qualitative coding procedures. SPSS v22 was used to calculate descriptive statistics. Results: Participants were primarily Non-Hispanic White (100%), male (59%), insured (100%), and had at least a high school education (80%). Only 25% of participants had any prior knowledge of telehealth programs. The majority (94%) of participants expressed interest in receiving a tele-COPD program due to convenience factors. Yet, most participants expressed a lack of interest and comfort in using Internet-capable devices (e.g., mobile devices, tablets, computers). Participants noted that to be successful, telehealth visits must be described and shown to them by their own provider or other trusted individual(s), such as a pharmacist. Privacy and cost were also expressed as telehealth concerns. Conclusion: Interest in a tele-COPD program was high among community residents in rural WNC. However, to increase patient willingness to adopt a tele-COPD program, patients' providers must overcome challenges, such as patients' awareness and knowledge of telehealth, privacy and cost concerns, and access to and comfort with using new technologies. Pharmacists may mitigate these challenges by increasing patients' trust and comfort with telehealth programs.

Measuring patient perspectives on community pharmacy quality: psychometric evaluation of a brief survey.

BACKGROUND: Measuring patient perspectives of the quality of health care delivery is an essential component of building a patient-centered model of care, which has garnered increasing emphasis under value-based payment models. Although measurements of patient perspectives of physician practices are common, few validated measures are currently available to assess patient perspectives of pharmacy quality. OBJECTIVE: To assess the reliability and validity of a brief measure that assesses patient experiences with the quality of community pharmacy services, referred to as the "patient experience" measure. METHODS: This article focuses on the second phase of a 2-phase survey development study. In the second phase, a convenience sample of 400 adult patients with chronic health conditions completed the final 7-item version of the patient experience measure via an online survey. An exploratory factor analysis was performed to determine the number of factors underlying the patient experience measure. Internal consistency reliability was assessed with Cronbach's alpha, and construct validity was evaluated by examining relationships between the patient experience measure, a quality of pharmacy services item, and patient demographic variables. RESULTS: Eigenvalues and scree plots suggested a 1-factor solution, with this single factor explaining 64% of the variance in the patient experience measure. Cronbach's alpha indicated excellent reliability (α = 0.90). Individuals with more positive patient experience scores rated the quality of their pharmacies' services significantly higher (Pearson r = 0.73, P < 0.001). Mean patient experience scores for those who had gone to their pharmacies for 7-11 months (mean = 3.66) were significantly lower than for those who had been going to their pharmacies for 5 or more years (mean = 4.22). CONCLUSIONS: The patient experience measure demonstrated excellent reliability and was correlated with patient perceptions of pharmacy quality. The measure also differentiated between individuals based on the length of time they had been going to their pharmacies. The scale could be used to quickly assess patient experience with community pharmacy services. DISCLOSURES: This work was supported by the National Community Pharmacists Association Innovation Center through a grant from the Community Pharmacy Foundation. Farley reports an unrelated grant from AstraZeneca and fees from Takeda for expert testimony. The other authors have nothing to disclose. This work was presented as a virtual poster at the American Pharmacists Association (APhA) Annual Meeting & Exposition, March 2020, Washington, DC.

Figure-of-Merit Characterization of Hydrogen-Bond Acidic Sorbents for Waveguide-Enhanced Raman Spectroscopy.

The optical properties of several hydrogen-bond acidic sorbent materials are evaluated in situ to assess their suitability for waveguide-enhanced Raman spectroscopy (WERS) of vapor-phase organophosphonates. A number of characteristics critical to WERS are evaluated for each sorbent: infrared absorption, Raman spectral background, and the limit of detection for a test hydrogen-bond-basic analyte (dimethyl methylphosphonate, DMMP). We describe the chemical properties of the sorbents that differentiate their optical properties for sensing. Then, we introduce a sorbent figure-of-merit that quantifies these differences and provides a framework to assess the quality of newly developed sorbent materials.

Nickel(II/IV) Manifold Enables Room-Temperature C(sp3)-H Functionalization.

This Article demonstrates a mild oxidatively induced C(sp3)-H activation at a high-valent Ni center. In contrast with most C(sp3)-H activation reactions at NiII, the transformation proceeds at room temperature and generates an isolable NiIV σ-alkyl complex. Density functional theory studies show two plausible mechanisms for this C-H activation process involving triflate-assisted C-H cleavage at either a NiIV or a NiIII intermediate. The former pathway is modestly favored over the latter (by ∼3 kcal/mol). The NiIV σ-alkyl product of C-H cleavage reacts with a variety of nucleophiles to form C(sp3)-X bonds (X = halide, oxygen, nitrogen, sulfur, or carbon). These stoichiometric transformations can be coupled using N-fluoro-2,4,6-trimethylpyridinium triflate as a terminal oxidant in conjunction with chloride as a nucleophile to achieve a proof-of-principle NiII/IV-catalyzed C(sp3)-H functionalization reaction.

Impact of Oxidation State on Reactivity and Selectivity Differences between Nickel(III) and Nickel(IV) Alkyl Complexes.

Described is a systematic comparison of factors impacting the relative rates and selectivities of C(sp3 )-C and C(sp3 )-O bond-forming reactions at high-valent Ni as a function of oxidation state. Two Ni complexes are compared: a cationic octahedral NiIV complex ligated by tris(pyrazolyl)borate and a cationic octahedral NiIII complex ligated by tris(pyrazolyl)methane. Key features of reactivity/selectivity are revealed: 1) C(sp3 )-C(sp2 ) bond-forming reductive elimination occurs from both centers, but the NiIII complex reacts up to 300-fold faster than the NiIV , depending on the reaction conditions. The relative reactivity is proposed to derive from ligand dissociation kinetics, which vary as a function of oxidation state and the presence/absence of visible light. 2) Upon the addition of acetate (AcO- ), the NiIV complex exclusively undergoes C(sp3 )-OAc bond formation, while the NiIII analogue forms the C(sp3 )-C(sp2 ) coupled product selectively. This difference is rationalized based on the electrophilicity of the respective M-C(sp3 ) bonds, and thus their relative reactivity towards outer-sphere SN 2-type bond-forming reactions.

Economic and objective burden of caregiving on informal caregivers of patients with systemic vasculitis.

INTRODUCTION: Systemic vasculitis (SV) is associated with substantial economic impact to patients and the healthcare system but little is known about the burden of SV on informal caregivers. We evaluated the objective caregiving burden experienced by informal caregivers of patients with SV. METHODS: We surveyed adult patients and their informal caregivers on the physical, emotional, social and economic impacts of SV. We asked patients about the extent to which they felt they were a burden to their identified caregivers. Caregivers reported the direct and indirect economic impact of SV, including employment disturbance, income loss and relative time investment of caregiving for their care recipient's SV. We used the Inventory of Caregiving Activities Questionnaire to compute the objective caregiving burden. RESULTS: We analysed data from 68 SV patient-caregiver dyads. Patients reported moderate levels of subjective burden to their caregivers. Over one-quarter of caregivers reported ever having lost some income owing to caregiving for SV. Caregivers reported spending a median of 19 weekly hours on various caregiving tasks, including a median 17 weekly hours on household activities. DISCUSSION: Given the extended hours that caregivers spend caring for their care recipient, intervention targets should aim to reduce caregiver burnout in the SV population. Future research should examine the relationship between the objective burden of caregiving for SV and the overall physical health, mental health and quality of life of caregivers.

Factors associated with how often community pharmacists offer and dispense naloxone.

BACKGROUND: A recent Surgeon General's report encourages people to ask pharmacists about naloxone, but whether pharmacists are well-prepared to respond to these requests is unclear. OBJECTIVES: Determine factors that are associated with how often pharmacists offer and dispense naloxone. METHODS: A convenience sample of 457 community pharmacists in North Carolina completed a 5-min online survey. Linear regressions were conducted to identify factors that are associated with how often pharmacists offer and dispense naloxone. Pharmacists' self-reported barriers to teaching naloxone administration were identified. RESULTS: Most pharmacists (81.2%) worked in pharmacies that stocked naloxone, but many never offered (36.6%) or dispensed (19.4%) naloxone. Pharmacists offered (ß = 0.15, p < 0.01) and dispensed (ß = 0.15, p < 0.01) naloxone more often when their pharmacy stocked more naloxone formulations. Pharmacists who were more comfortable discussing naloxone offered it more often (ß = 0.26, p = 0.001). Pharmacists who worked in regional/local/grocery chain pharmacies dispensed and offered naloxone less often than other pharmacy types. Barriers to teaching naloxone administration included: time constraints, inadequate training, and perceived lack of patient comprehension. CONCLUSIONS: Many community pharmacists do not offer or dispense naloxone. Pharmacists who are uncomfortable discussing naloxone or work at smaller chain pharmacies may benefit from targeted naloxone training.

A Review of Portable Electronic Spirometers: Implications for Asthma Self-Management.

PURPOSE OF REVIEW: Although portable electronic spirometers allow for at-home lung function monitoring, a comprehensive review of these devices has not yet been conducted. We conducted a systematic search and review of commercially available portable electronic spirometers designed for asthma patient use. RECENT FINDINGS: All devices (N = 16) allowed for monitoring of basic lung function parameters, but only 31% provided in-app videos on how to perform breathing maneuvers. Most devices (63%) provided graphical representations of lung function results, but only 44% gave immediate feedback on the quality of the breathing maneuver. Several devices (25%) were FDA-approved and cost ranged from US$99 to $1390. Information on data security (63%), measurement accuracy (50%), and association with patient outcomes (0%) was commonly limited. This review found that providers' ability to make informed decisions about whether asthma patients may benefit from portable electronic spirometers is limited due to lack of patient outcome data.