Premature Ovarian Insufficiency After Coronavirus Disease 2019 (COVID-19): Autoimmune Follicle-Stimulating Hormone (FSH) and FSH Receptor Blockade.

BACKGROUND: Since the onset of the coronavirus disease (COVID-19) pandemic, a variety of long-COVID-19 symptoms and autoimmune complications have been recognized. CASES: We report three cases of autoimmune premature poor ovarian response in patients aged 30-37 years after mild to asymptomatic COVID-19 before vaccination, with nucleotide antibody confirmation. Two patients failed to respond to maximum-dose gonadotropins for more than 4 weeks, despite a recent history of response before having COVID-19. After a month of prednisone 30 mg, these two patients had normal follicle-stimulating hormone (FSH) levels, high oocyte yield, and blastocyst formation in successful in vitro fertilization cycles. All three patients have above-average anti-müllerian hormone levels that persisted throughout their clinical ovarian insufficiency. Two patients had elevated FSH levels, perhaps resulting from FSH receptor blockade. One patient, with a history of high response to gonadotropins 75 international units per day and below-normal FSH levels, had no ovarian response to more than a month of gonadotropins (525 international units daily), suggesting autoimmune block of the FSH glycoprotein and possible FSH receptor blockade. CONCLUSION: Auto-antibody production in response to COVID-19 before vaccination may be a rare cause of autoimmune poor ovarian response. Although vaccination is likely protective, further study will be required to evaluate the effect of vaccination and duration of autoimmune FSH or FSH receptor blockade.

Angiotensin II type 1 receptor antibodies and native kidney function in pediatric liver and intestinal transplant recipients.

BACKGROUND: Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored. METHODS: Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period. Estimated glomerular filtration rate (eGFR) was determined using creatinine based CKiD U25 equation and measured at time of AT1R-Ab measurement, at 1 year post-AT1R-Ab measurement, at 5 years post-AT1R-Ab measurement, and at the most recent routine clinic visit. The prevalence of hypertension and antihypertensive medication use were also evaluated. RESULTS: Younger age at time of AT1R-Ab measurement was associated with AT1R-Ab positivity in liver transplant recipients. There was no association between AT1R-Ab status and change in eGFR, prevalence of hypertension, or use of antihypertensive medications at the described time points. CONCLUSIONS: AT1R-Ab positivity was not associated with a decline in eGFR or hypertension in pediatric liver and intestinal transplant recipients. Further studies are needed using other markers of kidney function, such as cystatin C, to validate this finding. A higher resolution version of the Graphical abstract is available as Supplementary information.

Unmet health-related needs of community-dwelling older adults during COVID-19 lockdown in a diverse urban cohort.

BACKGROUND: Shelter-in-place orders during the COVID-19 pandemic created unmet health-related and access-related needs among older adults. We sought to understand the prevalence of these needs among community-dwelling older adults. METHODS: We performed a retrospective chart review of pandemic-related outreach calls to older adults between March and July 2020 at four urban, primary care clinics: a home-based practice, a safety net adult medicine clinic, an academic geriatrics practice, and a safety net clinic for adults living with HIV. Participants included those 60 or older at three sites, and those 65 or older with a chronic health condition at the fourth. We describe unmet health-related needs (the need for medication refills, medical supplies, or food) and access-related needs (ability to perform a telehealth visit, need for a call back from the primary care provider). We performed bivariate and multivariate analyses to examine the association between unmet needs and demographics, medical conditions, and healthcare utilization. RESULTS: Sixty-two percent of people had at least one unmet need. Twenty-six percent had at least one unmet health-related need; 14.0% needed medication refills, 12.5% needed medical supplies, and 3.0% had food insecurity. Among access-related needs, 33% were not ready for video visits, and 36.4% asked for a return call from their provider. Prevalence of any unmet health-related need was the highest among Asian versus White (36.4% vs. 19.1%) and in the highest versus lowest poverty zip codes (30.8% vs. 18.2%). Those with diabetes and COPD had higher unmet health-related needs than those without, and there was no change in healthcare utilization. CONCLUSIONS: During COVID, we found that disruptions in access to services created unmet needs among older adults, particularly for those who self-identified as Asian. We must foreground the needs of this older population group in the response to future public health crises.

Effect of a Novel, Evidence-Based, Standardized Discharge Checklist on 30-Day All-Cause Readmissions in Patients Hospitalized for Heart Failure in an Urban Safety Net Hospital.

Safety net hospitals frequently incur financial penalties for high readmission rates. Heart failure (HF) is a common driver of readmissions, but effectively lowering readmission rates in patients with HF has proved challenging. There are few evidence-based interventions validated within safety net systems. Between October 2018 and April 2019, we implemented an evidence-based discharge checklist. We evaluated the hypothesis that it would reduce 30-day all-cause readmissions in patients admitted for HF at an urban safety net hospital. We retrospectively compared all-cause 30-day readmission rates between the cohort discharged using the checklist and historical controls. Demographics were similar between the intervention (n = 103) and control (n = 187) groups and reflected the diverse and vulnerable population cared for in the safety net. The mean age was 60 years, 71% were male, 42% were Black, 22% were Hispanic/Latinx, 28% were not housed, 35% used illicit stimulants, and 73% had a left ventricular ejection fraction ≤40%. Use of the checklist was associated with a 12.4% absolute reduction in the 30-day readmission rate (29.9% vs 17.5%, p = 0.02). The intervention group was more likely to be discharged on appropriate guideline-directed medical therapy for reduced systolic function, including ß blockers (93% vs 73%, p = 0.0004), angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (92% vs 66%, p <0.0001) and mineralocorticoid receptor antagonists (50% vs 27%, p = 0.0007). Multivariable analysis demonstrated that using the discharge checklist was associated with a lower risk of 30-day all-cause readmission (risk ratio 0.54, 0.33 to 0.90). Therefore, a low-cost, novel, evidence-based discharge checklist significantly reduced 30-day all-cause readmission rates in patients hospitalized for HF at a safety net hospital.

Listener Ratings of Male Singer Technical Ability.

Perceptual judgments of singer technical ability have not been widely researched. A few studies have examined perceptions of singers versus nonsingers (Usha 2017) and evaluations of vocal beauty in the male voice (Robison 1992). The investigators used recordings of male voices singing [i] in an online survey instrument using a Likert-type scale. Listeners were divided into four groups (nonmusicians, music ensemble participants, music students, and music professionals). Listeners rated the technical ability of each singer (27 recordings) on a 6-point scale from beginning to advanced. Survey responses of the four listener groups were compared with vibrato rate, extent, and jitter of the recorded samples. We hypothesized that musical training would affect how listeners rate male singers overall, with the expectation that the most musically experienced and trained listeners' ratings would be the most severe.

A case of failure to thrive secondary to primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 is a rare genetic condition characterized by oxalate deposition in the kidneys. We report findings of an 8-month old female presenting with failure to thrive, poor oral intake, and kidney stones resulting in the diagnosis of primary hyperoxaluria type 1. The patient exhibits a unique presentation without renal failure at the time of diagnosis suggesting a previously unreported comorbidity in early stages of disease.

The Power Of Access To Affordable Care.

A patient and student with severe asthma chases adequate insurance coverage until the Affordable Care Act provides something more.

Visualizing the structure and motion of the long noncoding RNA HOTAIR.

Long noncoding RNA molecules (lncRNAs) are estimated to account for the majority of eukaryotic genomic transcripts, and have been associated with multiple diseases in humans. However, our understanding of their structure-function relationships is scarce, with structural evidence coming mostly from indirect biochemical approaches or computational predictions. Here we describe direct visualization of the lncRNA HOTAIR (HOx Transcript AntIsense RNA) using atomic force microscopy (AFM) in nucleus-like conditions at 37°. Our observations reveal that HOTAIR has a discernible, although flexible, shape. Fast AFM scanning enabled the quantification of the motion of HOTAIR, and provided visual evidence of physical interactions with genomic DNA segments. Our report provides a biologically plausible description of the anatomy and intrinsic properties of HOTAIR, and presents a framework for studying the structural biology of lncRNAs.

Glutamine synthetase in avian muscle contributes to a positive myogenic response to ammonia compared with mammalian muscle.

In mammalian models of cirrhosis, plasma ammonia concentration increases, having numerous adverse effects, including sarcopenia. The objective of this study was to identify differences between avian and mammalian myogenic response to applied ammonia and glutamine. Primary chicken breast and thigh, primary rat, and C2C12 myotubes were treated with ammonium acetate (AA, 10 mM) or glutamine (10 mM) for 24 h and compared with sodium acetate (10 mM) and untreated controls. Myostatin mRNA was significantly higher in C2C12 and rat myotubes treated with AA compared with glutamine and controls (P < 0.01), whereas myostatin was unchanged in chicken myotubes. AA-treated C2C12 myotubes had significantly higher glutamine synthetase (GS) mRNA expression compared with controls, but GS protein expression was unchanged. In contrast, GS mRNA expression was unchanged in thigh myotubes, but GS protein expression was significantly higher in AA-treated thigh myotubes (P < 0.05). In both breast and thigh myotubes, intracellular glutamine concentration was significantly increased in AA- and glutamine-treated myotubes compared with controls but was only increased in glutamine-treated C2C12 and rat myotubes (P < 0.05). Glutamine concentration was significantly higher in all treatment media collected from avian myotube cultures compared with both C2C12 and rat media (P < 0.01). Myotube diameter was significantly larger in avian myotubes after treatment with both AA and glutamine (P < 0.05). C2C12 and rat myotubes had a significantly smaller myotube diameter after AA treatment (P < 0.001). Altogether, these data support species differences in skeletal muscle ammonia metabolism and suggest that glutamine synthesis is a mechanism of ammonia utilization in avian muscle.

Differential ammonia metabolism and toxicity between avian and mammalian species, and effect of ammonia on skeletal muscle: A comparative review.

Comparative aspects of ammonia toxicity, specific to liver and skeletal muscle and skeletal muscle metabolism between avian and mammalian species are discussed in the context of models for liver disease and subsequent skeletal muscle wasting. The purpose of this review is to present species differences in ammonia metabolism and to specifically highlight observed differences in skeletal muscle response to excess ammonia in avian species. Ammonia, which is produced during protein catabolism and is an essential component of nucleic acid and protein biosynthesis, is detoxified mainly in the liver. While the liver is consistent as the main organ responsible for ammonia detoxification, there are evolutionary differences in ammonia metabolism and nitrogen excretory products between avian and mammalian species. In patients with liver disease and all mammalian models, inadequate ammonia detoxification and successive increased circulating ammonia concentration, termed hyperammonemia, leads to severe skeletal muscle atrophy, increased apoptosis and reduced protein synthesis, altogether having deleterious effects on muscle size and strength. Previously, an avian embryonic model, designed to determine the effects of increased circulating ammonia on muscle development, revealed that ammonia elicits a positive myogenic response. Specifically, induced hyperammonemia in avian embryos resulted in a reduction in myostatin, a well-known inhibitor of muscle growth, expression, whereas myostatin expression is significantly increased in mammalian models of hyperammonemia. These interesting findings imply that species differences in ammonia metabolism allow avians to utilize ammonia for growth. Understanding the intrinsic physiological mechanisms that allow for ammonia to be utilized for growth has potential to reveal novel approaches to muscle growth in avian species and will provide new targets for preventing muscle degeneration in mammalian species.

Patient Engagement In Health Care Safety: An Overview Of Mixed-Quality Evidence.

Patients and caregivers play a central role in health care safety in the hospital, ambulatory care setting, and community. Despite this, interventions to promote patient engagement in safety are still underexplored. We conducted an overview of review articles on patient engagement interventions in safety to examine the current state of the evidence. Of the 2,795 references we evaluated, 52 articles met our full-text inclusion criteria for synthesis in 2018. We identified robust evidence supporting patients' self-management of anticoagulation medications and mixed-quality evidence supporting patient engagement in medication and chronic disease self-management, adverse event reporting, and medical record accuracy. Promising modes of patient engagement in safety, such as anticoagulation management and patient portal access, are not widely implemented. We discuss major implementation priorities and propose directions for future research and policy to enhance patient partnership within safety efforts.

A symbiotic-like biologically-driven regenerating fabric.

Living organisms constantly maintain their structural and biochemical integrity by the critical means of response, healing, and regeneration. Inanimate objects, on the other hand, are axiomatically considered incapable of responding to damage and healing it, leading to the profound negative environmental impact of their continuous manufacturing and trashing. Objects with such biological properties would be a significant step towards sustainable technology. In this work we present a feasible strategy for driving regeneration in fabric by means of integration with a bacterial biofilm to obtain a symbiotic-like hybrid - the fabric provides structural framework to the biofilm and supports its growth, whereas the biofilm responds to mechanical tear by synthesizing a silk protein engineered to self-assemble upon secretion from the cells. We propose the term crossbiosis to describe this and other hybrid systems combining organism and object. Our strategy could be implemented in other systems and drive sensing of integrity and response by regeneration in other materials as well.

Molecular Robots Obeying Asimov's Three Laws of Robotics.

Asimov's three laws of robotics, which were shaped in the literary work of Isaac Asimov (1920-1992) and others, define a crucial code of behavior that fictional autonomous robots must obey as a condition for their integration into human society. While, general implementation of these laws in robots is widely considered impractical, limited-scope versions have been demonstrated and have proven useful in spurring scientific debate on aspects of safety and autonomy in robots and intelligent systems. In this work, we use Asimov's laws to examine these notions in molecular robots fabricated from DNA origami. We successfully programmed these robots to obey, by means of interactions between individual robots in a large population, an appropriately scoped variant of Asimov's laws, and even emulate the key scenario from Asimov's story "Runaround," in which a fictional robot gets into trouble despite adhering to the laws. Our findings show that abstract, complex notions can be encoded and implemented at the molecular scale, when we understand robots on this scale on the basis of their interactions.

Ammonia elicits a different myogenic response in avian and murine myotubes.

Increased myostatin expression, resulting in muscle loss, has been associated with hyperammonemia in mammalian models of cirrhosis. However, there is evidence that hyperammonemia in avian embryos results in a reduction of myostatin expression, suggesting a proliferative myogenic environment. The present in vitro study examines species differences in myotube and liver cell response to ammonia using avian and murine-derived cells. Primary myoblasts and liver cells were isolated from embryonic day 15 and 17 chick embryos to be compared with mouse myoblasts (C2C12) and liver (AML12) cells. Cells were exposed to varying concentrations of ammonium acetate (AA; 2.5, 5, or 10 mM) to determine the effects of ammonia on the cells. Relative expression of myostatin mRNA, determined by quantitative real-time PCR, was significantly increased in AA (10 mM) treated C2C12 myotubes compared to both ages of chick embryonic myotube cultures after 48 h (P < 0.02). Western blot analysis of myostatin protein confirmed an increase in myostatin expression in AA-treated C2C12 myotubes compared to the sodium acetate (SA) controls, while myostatin expression was decreased in the chick embryonic myotube cultures when treated with AA. Myotube diameter was significantly decreased in AA-treated C2C12 myotubes compared to controls, while avian myotube diameter increased with AA treatment (P < 0.001). There were no significant differences between avian and murine liver cell viability, assessed using 2', 7'- bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein, acetoxymethyl ester, when treated with AA. However, after 24 h, AA-treated avian myotubes showed a significant increase in cell viability compared to the C2C12 myotubes (P < 0.05). Overall, it appears that there is a positive myogenic response to hyperammonemia in avian myotubes compared to murine myotubes, which supports a proliferative myogenic environment.