Control in relation to suicidal ideation and nonfatal suicidal behavior among older adults: a systematic review.

OBJECTIVES: This review aims to evaluate and synthesize quantitative and qualitative findings on perceived control and value placed on control within the context of suicidal ideation or nonfatal suicidal behaviors in older adults. METHOD: A comprehensive literature search was completed in June 2022, October 2022, and November 2023. Included studies focused on perceived control or value placed on control and on suicidal ideation or nonfatal suicidal behavior. Studies were published in English and included older adults (≥ 60 years) in separate analyses. Studies focusing on self-efficacy were excluded. RESULTS: Twelve studies with 10 unique samples of 1487 total participants from eight countries were assessed. Quantitative studies indicated that perceived control and value placed on control are significant correlates of suicidal ideation and nonfatal suicidal behaviors, while qualitative studies highlighted that individuals who survive suicide attempts often specify decreased perceived control as a reason for their attempts. CONCLUSION: Results of this review indicate that perceived control and value placed on control are relevant variables when studying suicidal ideation and nonfatal suicidal behavior. This conclusion should be considered preliminary. Future research should examine heterogeneous samples, adopt gold standard assessments, and assess covariates in the associations.

Assessing age invariance of the Male Depression Risk Scale-22 in younger and older adult males.

OBJECTIVES: Women are twice as likely to be diagnosed with major depressive disorder as men. Yet suicide rates are four times higher in men than women, increasing to six times when comparing older men to older women. Investigators have begun researching if depression presents differently in individuals who adhere to masculine norms, leading to the conceptualization of masculine depression. Despite validity evidence for the Male Depression Risk Scale-22 (MDRS-22) in mixed-age samples, few studies have investigated the possibility of age-related differences in masculine depression. The present study aimed to test for age invariance of the MDRS-22. METHOD: Age invariance for the MDRS-22 was tested via a multi-group confirmatory factor analysis with groups of younger (18-64 years) and older (65+ years) males (N = 469). RESULTS: Age invariance for the MDRS-22 was not established, ΔX2 = 451.47, Δdf = 16, p < 0.001. CONCLUSION: Results of the study indicate that masculine depression may present differently between younger and older men. To fully understand the construct of masculine depression, it is important to investigate how symptoms may present in individuals of all ages. Overall, the study highlights the importance of investigating how masculine depression may present differently in older men.

An update on lipophilic efficiency as an important metric in drug design.

INTRODUCTION: Lipophilic efficiency (LipE) and lipophilic metabolic efficiency (LipMetE) are valuable tools that can be utilized as part of a multiparameter optimization process to advance a hit to a clinical quality compound. AREAS COVERED: This review covers recent, effective use cases of LipE and LipMetE that have been published in the literature over the past 5 years. These use cases resulted in the delivery of high-quality molecules that were brought forward to in vivo work and/or to clinical studies. The authors discuss best-practices for using LipE and LipMetE analysis, combined with lipophilicity-focused compound design strategies, to increase the speed and effectiveness of the hit to clinical quality compound optimization process. EXPERT OPINION: It has become well established that increasing LipE and LipMetE within a series of analogs facilitates the improvement of broad selectivity, clearance, solubility, and permeability and, through this optimization, also facilitates the achievement of desired pharmacokinetic properties, efficacy, and tolerability. Within this article, we discuss lipophilic efficiency-focused optimization as a tool to yield high-quality potential clinical candidates. It is suggested that LipE/LipMetE-focused optimization can facilitate and accelerate the drug-discovery process.

Burnout and Depression Among Sandwich Generation Caregivers: A Brief Report.

Twenty-nine percent of adults in the U.S. care for children, and 12% to 24.3% of those adults are multigenerational caregivers who also provide unpaid care for one or more adults. These adults are considered members of the "sandwich generation," which is a term for multigenerational caregivers who provide care, financial support, and emotional support for both their children and parents. The present study characterized the sandwich generation and examined how sandwich generation caregivers differed from caregivers of children, caregivers of parents, and non-caregivers regarding burnout and depression. We found that sandwich generation caregivers and caregivers of parents reported significantly higher levels of informal caregiving burnout than caregivers of children. Compared to non-caregivers, all caregivers reported significantly higher levels of personal burnout. Burnout is higher in sandwich generation caregivers and those who care for parents than burnout among those who care only for children. Future studies should investigate additional variables that affect burnout.

Trauma re-engagement and PTSD in older medically ill veterans: implications for trauma-informed care.

OBJECTIVES: We characterize rates and correlates of PTSD and of trauma re-engagement without PTSD in medically ill older Veterans, as well as supportive strategies, with the goal of advancing trauma-informed care. METHODS: We interviewed medically ill older Veterans (N = 88, M age 75.13, SD = 6.14) with primary care screening measures for PTSD and trauma re-engagement, and open-ended questions to assess supportive strategies. RESULTS: One-fifth (20.5%) presented with probable PTSD, associated with greater trauma exposures (r=.57, p<.001), whereas two-fifths (43.2%) reported re-engagement with military memories without PTSD, associated with having a spouse/partner (t = 2.27, p=.028). Of those who experienced trauma, half reported thinking more about the trauma recently and becoming more emotional on certain days. In response to the question 'What gives you strength as you think about the future with your illness' Veterans described support of family, healthcare, worldview, personal control, acceptance, and health behaviors. CONCLUSION: Memories of trauma are common with medical illness. Age-friendly trauma-informed care could consider factors that patients describe as sources of strength with illness.

Assessing What Matters Most in Older Adults With Multicomplexity.

BACKGROUND AND OBJECTIVES: Abilities and activities that are often simultaneously valued may not be simultaneously achievable for older adults with multicomplexity. Because of this, the Geriatrics 5Ms framework prioritizes care on "what matters most." This study aimed to evaluate and refine the What Matters Most-Structured Tool (WMM-ST). RESEARCH DESIGN AND METHODS: About 105 older adults with an average of 4 chronic conditions completed the WMM-ST along with open-ended questions from the Serious Illness Conversation Guide. Participants also provided demographic and social information, completed cognitive screening with the Telephone-Montreal Cognitive Assessment-Short and frailty screening with the Frail scale. Quantitative and qualitative analyses aimed to (a) describe values; (b) evaluate the association of patient characteristics with values; and (c) assess validity via the tool's acceptability, educational bias, and content accuracy. RESULTS: Older adults varied in what matters most. Ratings demonstrated modest associations with social support, religiosity, cognition, and frailty, but not with age or education. The WMM-ST was rated as understandable (86%) and applicable to their current situation (61%) independent of education. Qualitative analyses supported the content validity of WMM-ST, while revealing additional content. DISCUSSION AND IMPLICATIONS: It is possible to assess what matters most to older adults with multicomplexity using a structured tool. Such tools may be useful in making an abstract process clearer but require further validation in diverse samples.

Advancing Your Confidence as an Educator (ACE): An Academic-VA Partnership to Enhance Educator Skills and Improve Attitudes About Careers in Aging.

Previous research suggests some psychologists may not consider academic careers because of doubts about their teaching competency, and this is especially true for psychologists interested in aging (i.e., geropsychologists). To enhance competencies in the practice of education, we developed a webinar series, Advancing Your Confidence as an Educator, to bolster skills and attitudes toward teaching and improve attitudes about careers in aging. Seven hour-long webinars addressed key skills in developing and executing courses and professional presentations, and 2 panel sessions addressed attitudes toward teaching by featuring early- and later-career professionals discussing their paths to and satisfaction with jobs as educators. Attendance across the highly interactive sessions was robust (M = 50). Evaluation data suggest the webinar was effective in meeting educational needs. To promote sustainable impact, the webinars are archived and freely available online. Challenges in marketing and evaluation arose, but overall, this effort is one way of cultivating a more vigorous interest and self-confidence in teaching.

1,2-Difunctionalized bicyclo[1.1.1]pentanes: Long-sought-after mimetics for ortho/meta-substituted arenes.

The development of a versatile platform for the synthesis of 1,2-difunctionalized bicyclo[1.1.1]pentanes to potentially mimic ortho/meta-substituted arenes is described. The syntheses of useful building blocks bearing alcohol, amine, and carboxylic acid functional handles have been achieved from a simple common intermediate. Several ortho- and meta-substituted benzene analogs, as well as simple molecular matched pairs, have also been prepared using this platform. The results of in-depth ADME (absorption, distribution, metabolism, and excretion) investigations of these systems are presented, as well as computational studies which validate the ortho- or meta-character of these bioisosteres.

Development of a Late-Stage Diversification Strategy for the 4- and 5-Positions of 4,5,6-Trisubstituted Indazoles.

Indazoles represent a privileged motif in drug discovery. However, the formation of highly substituted indazoles can require the execution of lengthy synthetic routes with minimal opportunities to introduce diversity. In this report, we disclose the development of a late-stage diversification strategy for the 4- and 5-positions of 4,5,6-trisubstituted indazoles. A regioselective C-H functionalization and subsequent nucleophilic aromatic substitution provide two sequential points of diversification. The synthetic sequence delivers rapid access to an array of 4,5,6-trisubstituted indazoles in only four steps from readily available starting materials.

Differential Diagnoses and Clinical Implications of Medication Nonadherence in Older Patients with Chronic Kidney Disease: A Review.

Older adults with chronic kidney disease (CKD) often have many comorbidities, which requires them to take multiple medications. As the number of daily medications prescribed increases, the risk for polypharmacy increases. Understanding and improving medication adherence in this patient population is vital to avoiding the drug-related adverse events of polypharmacy. The primary objective of this review is to summarize the existing literature and to understand the factors leading to medication nonadherence in older patients with CKD. In this review, we discuss the prevalence of polypharmacy, the current lack of consensus on the incidence of medication nonadherence, the heterogeneity of assessing medication adherence, and the most common differential diagnoses for medication nonadherence in this population. Specifically, the most common differential diagnoses for medication nonadherence in older adults with CKD are (1) medication complexity; (2) cognitive impairment; (3) low health literacy; and (4) systems-based barriers. We provide tailored strategies to address these differential diagnoses and subsequently improve medication adherence. The clinical implications include deprescribing to decrease medication complexity and polypharmacy, utilizing a team-based approach to identify and support patients with cognitive impairment, enriching communication between health providers and patients with low health literacy, and improving health care access to address systems-based barriers. Further research is needed to determine the effects of addressing these differential diagnoses and medication adherence in older adults with CKD.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Rapid Integration of Home Telehealth Visits Amidst COVID-19: What Do Older Adults Need to Succeed?

OBJECTIVE: Our objective was to identify and address patient-perceived barriers to integrating home telehealth visits. DESIGN: We used an exploratory sequential mixed-methods design to conduct patient needs assessments, a home telehealth pilot, and formative evaluation of the pilot. SETTING: Veterans Affairs geriatrics-renal clinic. PARTICIPANTS: Patients with scheduled clinic visits from October 2019 to April 2020. MEASUREMENTS: We conducted an in-person needs assessment and telephone postvisit interviews. RESULTS: Through 50 needs assessments, we identified patient-perceived barriers in interest, access to care, access to technology, and confidence. A total of 34 (68%) patients were interested in completing a home telehealth visit, but fewer (32 (64%)) had access to the necessary technology or were confident (21 (42%)) that they could participate. We categorized patients into four phenotypes based on their interest and capability to complete a home telehealth visit: interested and capable, interested and incapable, uninterested and capable, and uninterested and incapable. These phenotypes allowed us to create trainings to overcome patient-perceived barriers. We completed 32 home telehealth visits and 12 postvisit interviews. Our formative evaluation showed that our pilot was successful in addressing many patient-perceived barriers. All interviewees reported that the home telehealth visits improved their well-being. Home telehealth visits saved participants an average of 166 minutes of commute time. Five participants borrowed a device from a family member, and five visits were finished via telephone. All participants successfully completed a home telehealth visit. CONCLUSIONS: We identified patient-perceived barriers to home telehealth visits and classified patients into four phenotypes based on these barriers. Using principles of implementation science, our home telehealth pilot addressed these barriers, and all patients successfully completed a visit. Future study is needed to understand methods to deploy larger-scale efforts to integrate home telehealth visits into the care of older adults.

Toward Long-Term Accurate and Continuous Monitoring of Nitrate in Wastewater Using Poly(tetrafluoroethylene) (PTFE)-Solid-State Ion-Selective Electrodes (S-ISEs).

Long-term accurate and continuous monitoring of nitrate (NO3-) concentration in wastewater and groundwater is critical for determining treatment efficiency and tracking contaminant transport. Current nitrate monitoring technologies, including colorimetric, chromatographic, biometric, and electrochemical sensors, are not feasible for continuous monitoring. This study addressed this challenge by modifying NO3- solid-state ion-selective electrodes (S-ISEs) with poly(tetrafluoroethylene) (PTFE, (C2F4)n). The PTFE-loaded S-ISE membrane polymer matrix reduces water layer formation between the membrane and electrode/solid contact, while paradoxically, the even more hydrophobic PTFE-loaded S-ISE membrane prevents bacterial attachment despite the opposite approach of hydrophilic modifications in other antifouling sensor designs. Specifically, an optimal ratio of 5% PTFE in the S-ISE polymer matrix was determined by a series of characterization tests in real wastewater. Five percent of PTFE alleviated biofouling to the sensor surface by enhancing the negative charge (-4.5 to -45.8 mV) and lowering surface roughness (Ra: 0.56 ± 0.02 nm). It simultaneously mitigated water layer formation between the membrane and electrode by increasing hydrophobicity (contact angle: 104°) and membrane adhesion and thus minimized the reading (mV) drift in the baseline sensitivity ("data drifting"). Long-term accuracy and durability of 5% PTFE-loaded NO3- S-ISEs were well demonstrated in real wastewater over 20 days, an improvement over commercial sensor longevity.

Opioid Management in Older Adults with Chronic Kidney Disease: A Review.

Chronic pain, a common comorbidity of chronic kidney disease, is consistently under-recognized and difficult to treat in older adults with nondialysis chronic kidney disease. Given the decreased kidney function associated with aging and chronic kidney disease, these patients are at increased risk for drug accumulation and adverse events. Emerging research has demonstrated the efficacy of opioids in chronic kidney disease patients, but research specifically focusing on older, nondialysis chronic kidney disease patients is scarce. The primary objective of this review is to determine which oral and transdermal opioids are the safest for older, nondialysis chronic kidney disease patients. We discuss the limited existing evidence on opioid prescription in older, nondialysis chronic kidney disease patients and provide recommendations for the management of oral and transdermal opioids in this patient population. Specifically, transdermal buprenorphine, transdermal fentanyl, and oral hydromorphone are the most tolerable opioids in these patients; hydrocodone, oxycodone, and methadone are useful but require careful monitoring; and tramadol, codeine, morphine, and meperidine should be avoided due to risk of accumulation and adverse events. Because older adults with nondialysis chronic kidney disease are at increased risk for adverse events, vigilant monitoring of opioid prescription is critical. Lastly, collaboration among an interprofessional clinical team can ensure safe prescription of opioids in older adults with nondialysis chronic kidney disease.

Using stereoretention for the synthesis of E-macrocycles with ruthenium-based olefin metathesis catalysts.

The synthesis of E-macrocycles is achieved using stereoretentive, Ru-based olefin metathesis catalysts supported by dithiolate ligands. Kinetic studies elucidate marked differences in activity among the catalysts tested, with catalyst 4 providing meaningful yields of products in much shorter reaction times than stereoretentive catalysts 2 and 3. Macrocycles were generated with excellent selectivity (>99% E) and in moderate to high yields (47-80% yield) from diene starting materials bearing two E-configured olefins. A variety of rings were constructed, ranging from 12- to 18-membered macrocycles, including the antibiotic recifeiolide.

Stereoretentive Olefin Metathesis: An Avenue to Kinetic Selectivity.

Olefin metathesis is an incredibly valuable transformation that has gained widespread use in both academic and industrial settings. Lately, stereoretentive olefin metathesis has garnered much attention as a method for the selective generation of both E- and Z-olefins. Early studies employing ill-defined catalysts showed evidence for retention of the stereochemistry of the starting olefins at low conversion. However, thermodynamic ratios E/Z were reached as the reaction proceeded to equilibrium. Recent studies in olefin metathesis have focused on the synthesis of catalysts that can overcome the inherent thermodynamic preference of an olefin, providing synthetically useful quantities of a kinetically favored olefin isomer. These reports have led to the development of stereoretentive catalysts that not only generate Z-olefins selectively, but also kinetically produce E-olefins, a previously unmet challenge in olefin metathesis. Advancements in stereoretentive olefin metathesis using tungsten, ruthenium, and molybdenum catalysts are presented.

Effect of hydroxyapatite concentration on high-modulus composite for biodegradable bone-fixation devices.

There are over 3 million bone fractures in the United States annually; over 30% of which require internal mechanical fixation devices to aid in the healing process. The current standard material used is a metal plate that is implanted onto the bone. However, metal fixation devices have many disadvantages, namely stress shielding and metal ion leaching. This study aims to fix these problems of metal implants by making a completely biodegradable material that will have a high modulus and exhibit great toughness. To accomplish this, long-fiber poly-l-lactic acid (PLLA) was utilized in combination with a matrix composed of polycaprolactone (PCL) and hydroxyapatite (HA) nano-rods. Through single fibril tensile tests, it was found that the PLLA fibers have a Young's modulus of 8.09 GPa. Synthesized HA nanorods have dimensions in the nanometer range with an aspect ratio over 6. By dip coating PLLA fibers in a suspension of PCL and HA and hot pressing the resulting coated fibers, dense fiber-reinforced samples were made having a flexural modulus up to 9.2 GPa and a flexural strength up to 187 MPa. The flexural modulus of cortical bone ranges from 7 to 25 GPa, so the modulus of the composite material falls into the range of bone. The typical flextural strength of bone is 130 MPa, and the samples here greatly exceed that with a strength of 187 MPa. After mechanical testing to failure the samples retained their shape, showing toughness with no catastrophic failure, indicating the possibility for use as a fixation material. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1963-1971, 2017.

Comparison of reproductive performance of primiparous dairy cattle following revaccination with either modified-live or killed multivalent viral vaccines in early lactation.

The objective of this randomized clinical trial was to compare the effect of revaccination in primiparous dairy cows with modified live viral (MLV) or killed viral (KV) vaccines containing bovine viral diarrhea virus (BVDV) and bovine herpesvirus-1 (BoHV-1) on (1) pregnancy rate following estrus synchronization-timed artificial insemination (TAI), (2) serum progesterone concentrations, and (3) serum neutralizing antibody titers at revaccination and at TAI. Primiparous dairy cows (n=692) that had been previously vaccinated with 4 doses of MLV vaccine as calves or heifers were randomized to receive either an MLV or a KV vaccine between 21 and 28 d in milk and 17 d before initiation of a double-Ovsynch-TAI protocol. Serum was collected within the double-Ovsynch protocol for determination of progesterone concentrations, and at vaccination and TAI for serum neutralizing antibody titers. Ultrasound pregnancy determinations were made at 30 and 60 d after TAI. No differences in pregnancy rates were observed between cows receiving MLV vaccine (44%; n=326) or KV vaccine (43%; n=336). No differences were observed in serum progesterone concentrations during a double-Ovsynch-TAI protocol between cows receiving MLV and KV vaccines. No differences were observed in BVDV 1 or BVDV 2 antibody titers at vaccination and TAI between cows receiving MLV or KV vaccine; however, BoHV-1 antibody titers were greater at TAI in cows receiving KV vaccine. Overall response to vaccination-defined as the percent of all individual cows that had any detectable increase in antibody titer from vaccination to TAI-was 39% for BVDV 1, 45% for BVDV 2, and 61% for BoHV-1. In this research, use of an MLV vaccine did not impede reproduction when revaccination was performed between 21 and 28 DIM and just before enrollment in an estrus synchronization-TAI program in primiparous dairy cows; however, response to vaccination as defined by increases in virus-specific antibody titers could be considered less than ideal for this population of cattle.

Ruthenium-catalyzed C-C coupling of amino alcohols with dienes via transfer hydrogenation: redox-triggered imine addition and related hydroaminoalkylations.

Ruthenium-catalyzed hydrogen transfer from 4-aminobutanol to butadiene results in the pairwise generation of 3,4-dihydro-2H-pyrrole and an allylruthenium complex, which combine to form products of imine anti-crotylation. In couplings of 1-substituted-1,3-dienes, novel C2 regioselectivity is observed. As corroborated by deuterium labeling studies, kinetically preferred hydrometalation of the terminal olefin of the 1-substituted-1,3-diene delivers a 1,1-disubstituted π-allylruthenium complex that isomerizes to a thermodynamically more stable monosubstituted π-allylruthenium complex, which undergoes imine addition with allylic inversion through a closed transition structure. Direct ruthenium-catalyzed diene hydroaminoalkylations with pyrrolidine also are described.