Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.     

Guardianship: A medicolegal review for clinicians

Guardianship may pose an ethical dilemma for physicians, who must balance protecting vulnerable patients from potential safety concerns with respecting their autonomy. Older adults with dementia are particularly susceptible to loss of independence and the ability to participate in medical decision making. To have the capacity for medical decision making, individuals must understand relevant information, appreciate their circumstances, demonstrate reasoning, and express a consistent choice free from coercion. Although capacity assessments are usually task-specific, geriatricians and other specialists may be asked to comment on capacity more globally. These determinations may be used to support a Petition for the Appointment of a Guardian of a Legally Incapacitated Adult, the legal process of pursuing guardianship in probate court. Assigned guardians may be known to the incapacitated individual (e.g., a family member or friend) or may be professional guardians with no prior relationship to the ward. Guardians are encouraged to use substituted decision-making, taking into account the ward's previously expressed values and preferences. Although a number of viable alternatives to guardianship exist, numerous systemic barriers may prevent these from being fully explored. The ongoing need for guardianship should be periodically revisited and reassessed. Data about guardians and wards is shockingly sparse, as there are no centralized databases. Laws and regulations for guardianships vary significantly between states. Physicians can serve as important allies and advocates for patients with cognitive impairment at risk of incapacity, can help preserve their autonomy for as long as possible, and ensure appropriate protections are in place if the patient does lose their decision-making ability.     

The source of relaxin in pregnant Syrian hamsters

Serum immunoreactive relaxin (IR) was measured on days 8, 10, and 14 of gestation in intact and ovariectomized (day 8 of pregnancy) hamsters. In intact hamsters, IR increased from 3-4 ng/ml on day 8 to 20 ng/ml by day 14 of pregnancy. After ovariectomy on day 8, pregnancy failed, and IR decreased rapidly to 0.29 ng/ml on day 14. However, when pregnancy was maintained in ovariectomized hamsters by daily injections of 0.1 microgram 17 beta-estradiol and 4 mg progesterone, serum IR rose to levels similar to those in intact hamsters on days 10 and 14 of pregnancy (i.e. 15 and 20 ng/ml, respectively). Placentas were obtained from other groups of hamsters on days 11, 14, and 15 of pregnancy and homogenized for bioassay by the classical guinea pig pubic symphysis palpation bioassay. Homogenates of placentas obtained on days 14 and 15 contained, respectively, 4 and 10 micrograms eq porcine relaxin/serum relaxin/g fresh tissue. The placenta, rather than the ovary, appears to be the source of during pregnancy in the hamster.     

Measurement properties of the Wheelchair Skills Test for scooters among experienced users

Purpose: To investigate the score distribution, reliability, and validity of the objective Wheelchair Skills Test (WST) for scooter users.

Method: A study using a test–retest design was conducted with 20 people who had mobility limitations that prevented them from ambulating more than one city block without a mobility aid, and who had owned a scooter for ≥3 months. Objective scooter skills, confidence, and physical accessibility were measured at both time points, while anxiety, depression, visual attention and task switching, functional independence, and visual acuity were measured only at baseline.

Results: The mean total WST scores at Time 1 and Time 2 were 86.3% and 87.5%. The WST ICC was 0.889. The WST had a SEM of 2.50 and a Cronbach’s alpha of 0.74. The total WST scores were significantly correlated with total subjective WST-Q scores (r?=?0.547, p?=?0.013), scooter confidence (r?=?0.466, p?=?0.038), and were affected by gender (p?=?0.005).

Conclusion: The WST for scooters has good test–retest reliability and generally varies as anticipated with other measures. Although further study is needed, the WST for scooters appears to have promise for use in research and clinical practice.

• Implications for Rehabilitation

• It is important to understand the measurement properties of the tools we use in rehabilitation so the results can be interpreted correctly.

• As scooter use increases, better measurement of skills is required.