Nevin Manimala

J Pain Symptom Manage. 2022 Feb 27:S0885-3924(22)00416-X. doi: 10.1016/j.jpainsymman.2022.02.334. Online ahead of print.

ABSTRACT

CONTEXT: Most patient-reported outcomes (PRO) are not directly tailored to an individual patient’s values, partially because tailored PROs require clinical interviews or are difficult to use in statistical analyses.

OBJECTIVES: This study tested a method for tailoring pain PROs, Precision PROs, that can be implemented and analyzed using standard statistical tests.

METHODS: People with cancer and pain (n=231) completed an online survey and then a second survey (n=161) one to two weeks later. Participants reviewed the PROMIS pain interference item bank, chose the four items most important to their quality of life and then completed those items. Kappas compared choices between the two surveys. Participants completed measures of pain intensity, physical function, and a standard pain interference measure.

RESULTS: All participants were able to select four items that were personally meaningful. Only one item (enjoyment of life) was chosen by more than half the sample (50.6%). Kappas for item choice were in the moderate to nearly perfect range for 32 of 35 items. The majority of the sample (59%) preferred tailoring their own PRO questions to completing a previously determined, non-patient-specific PRO. The Precision PRO scores had similar associations with pain intensity and physical function as the standard pain interference measure.

CONCLUSIONS: The Precision PRO approach was feasible, more preferred by patients, and showed consistency over a short timeframe. This approach could be used to make PRO assessment in clinical care and clinical trials more patient-centered. Additional research is needed to determine the generalizability of this approach to other outcomes and populations.

PMID:35235855 | DOI:10.1016/j.jpainsymman.2022.02.334

Sci Total Environ. 2022 Feb 27:154205. doi: 10.1016/j.scitotenv.2022.154205. Online ahead of print.

ABSTRACT

The main aim of this research was to determine the transport and deposition velocities of ⁷Be and ²¹⁰Pb based on a vast database containing the results of measurements of ⁷Be and ²¹⁰Pb in fallout and aerosol samples carried out at several stations located throughout Poland in the period from 2000 to 2016. The monthly deposition flux of ⁷Be and ²¹⁰Pb showed an unequivocal downward trend but was also subject to seasonal changes, with maximum values in the summer period. The same patterns were found in the case of the deposition rate, the average values of which were 0.7 cm s^-1 for ⁷Be and 0.5 cm s^-1 for ²¹⁰Pb. A strong, statistically significant dependence of the deposition rate on the amount of dust was demonstrated, whereby a 10 μg m^-3 decrease in dust increases the ⁷Be deposition rate by 0.1 cm s^-1. Reduction of the concentration of carrier particles reduces the share of dry deposition in favour of precipitation convection, which is much more significant for the transport of both isotopes to the surface. Study of the effect of meteorological parameters showed that the concentrations of ⁷Be in fallout and aerosol samples and ²¹⁰Pb in fallout increase with increasing temperature, indicating a significant share of convection processes in isotope transport. The concentrations of ²¹⁰Pb in aerosols did not show any significant statistical changes over time. Their maximum values were observed in the winter period, indicating an additional source of this isotope related to combustion processes in the heating season. The studies confirmed the dominant role of convective precipitation and large-scale precipitation processes in the elution of ⁷Be from the atmosphere by showing the monthly deposition of this isotope to be strongly dependent on the total precipitation (r = 0.618).

PMID:35235848 | DOI:10.1016/j.scitotenv.2022.154205

Cell Rep. 2022 Mar 1;38(9):110444. doi: 10.1016/j.celrep.2022.110444.

ABSTRACT

Accumulation of senescent cells affects organismal aging and the prevalence of age-associated disease. Emerging evidence suggests that activation of autophagy protects against age-associated diseases and promotes longevity, but the roles and regulatory mechanisms of autophagy in cellular senescence are not well understood. Here, we identify the transcription factor, MondoA, as a regulator of cellular senescence, autophagy, and mitochondrial homeostasis. MondoA protects against cellular senescence by activating autophagy partly through the suppression of an autophagy-negative regulator, Rubicon. In addition, we identify peroxiredoxin 3 (Prdx3) as another downstream regulator of MondoA essential for mitochondrial homeostasis and autophagy. Rubicon and Prdx3 work independently to regulate senescence. Furthermore, we find that MondoA knockout mice have exacerbated senescence during ischemic acute kidney injury (AKI), and a decrease of MondoA in the nucleus is correlated with human aging and ischemic AKI. Our results suggest that decline of MondoA worsens senescence and age-associated disease.

PMID:35235784 | DOI:10.1016/j.celrep.2022.110444

Curr Biol. 2022 Feb 26:S0960-9822(22)00261-5. doi: 10.1016/j.cub.2022.02.039. Online ahead of print.

ABSTRACT

Aesthetic experience seems both regular and idiosyncratic. On one hand, there are powerful regularities in what we tend to find attractive versus unattractive (e.g., beaches versus mud puddles).^1-4 On the other hand, our tastes also vary dramatically from person to person:^5-8 what one of us finds beautiful, another might find distasteful. What is the nature of such differences? They may in part be arbitrary-e.g., reflecting specific past judgments (such as liking red towels over blue ones because they were once cheaper). However, they may also in part be systematic-reflecting deeper differences in perception and/or cognition. We assessed the systematicity of aesthetic taste by exploring its typicality for the first time across seeing and hearing. Observers rated the aesthetic appeal of ordinary scenes and objects (e.g., beaches, buildings, and books) and environmental sounds (e.g., doorbells, dripping, and dialtones). We then measured “taste typicality” (separately for each modality) in terms of the similarity between each individual’s aesthetic preferences and the population’s average. The data revealed two primary patterns. First, taste typicality was not arbitrary but rather was correlated to a moderate degree across seeing and hearing: people who have typical taste for images also tend to have typical taste for sounds. Second, taste typicality captured most of the explainable variance in people’s impressions, showing that it is the primary dimension along which aesthetic tastes systematically vary.

PMID:35235766 | DOI:10.1016/j.cub.2022.02.039

Bioengineered. 2022 Mar;13(3):6908-6918. doi: 10.1080/21655979.2022.2026709.

ABSTRACT

Ischemic stroke is one of the leading causes of morbidity and mortality in humans. Cerebral ischemia-reperfusion (CIR) injury serves as a leading cause of stroke. Schisandra chinensis is a well-known Chinese traditional medicine. In this study, we explored the role of Gomisin J (GJ), a compound of S. chinensis, in CIR using a middle cerebral artery occlusion/reperfusion rat model and the possible mechanisms. We identified that GJ reduced neurological scores, cerebral infarction, and water content in the I/R rat brain. Importantly, GJ rescued I/R treatment-reduced neuron survival in the hippocampus, inhibited apoptosis of ischemic tissues in I/R rats, increased B-cell lymphoma-extra-large (Bcl-XL) expression, and reduced the levels of cleaved caspase-3, Bax, cyclooxygenase-2, nuclear factor kappa-B, and nitric oxide in I/R rat brain tissues. Furthermore, GJ treatment enhanced nuclear factor E2 related factor 2 (Nrf2) translocation, heme oxygenase-1 (HO-1) expression, superoxide dismutase and glutathione peroxidase activities, and glutathione level. Overall, GJ treatment GJ attenuates CIR injury by inducing anti-apoptotic, antioxidant, and anti-inflammatory effects in vivo.

PMID:35235758 | DOI:10.1080/21655979.2022.2026709

J Clin Psychiatry. 2022 Mar 1;83(2):21m14274. doi: 10.4088/JCP.21m14274.

ABSTRACT

Objective: Measurement-based care (MBC) improves patient outcomes. However, there has been minimal focus on MBC for psychotic disorders. This study examines the use of patient-reported outcome measures (PROMs) in the Veterans Health Administration (VHA) to characterize their use among Veterans with psychotic disorders and to inform candidate measures for psychosis-related MBC.

Methods: Data on Veterans with and without ICD-10 psychotic disorders and at least 1 PROM during fiscal years (FYs) 2016-2019 (FY16-FY19) were collected. The sample included 3,935,504 PROM administrations among 1,192,897 Veterans. Included PROMs spanned multiple symptom and non-symptom domains. Percentages of total PROM administrations were calculated by aggregating across time and diagnosis. Facility-level statistics were also calculated. Absolute change in the percentage of unique Veterans administered a particular and repeated PROMs over time were calculated.

Results: The core PROMs for VHA MBC (Patient Health Questionnaire-9 [PHQ-9], General Anxiety Disorder-7 Scale, PTSD Checklist-5, and Brief Addiction Monitor) accounted for the majority of PROMs for Veterans with (88.18%) and without (92.56%) psychotic disorders. The PHQ-9 accounted for the largest proportion (psychotic disorder: 45.89%; other diagnosis: 46.70%). The absolute changes in percentages of repeated PROM administration were similar over time across groups.

Conclusions: The use of PROMs in VHA mental health care increased during FY16-FY19 for Veterans with and without psychosis. The rates of PROM use were similar for both groups, and PROM use predominately consisted of the core measures. While the similar rates of PROM administration are encouraging, these findings highlight the need for psychosis-specific measures to tailor MBC for Veterans with these diagnoses.

PMID:35235719 | DOI:10.4088/JCP.21m14274

Ecol Lett. 2022 Mar 2. doi: 10.1111/ele.13982. Online ahead of print.

ABSTRACT

Life-history strategies differ with respect to investment in current versus ‘future’ reproduction, but when is this future? Under the novel ‘temporality in reproductive investment hypothesis’, we postulate variation should exist in the time frame over which reproductive costs are paid. Slow-paced individuals should pay reproductive costs over short (e.g. inter-annual) time scales to prevent reproductive costs accumulating, whereas fast-paced individuals should allow costs to accumulate (i.e. senescence). Using Fourier transforms, we quantify adjustments in clutch size with age, across four populations of blue tits (Cyanistes caeruleus). Fast populations had more prevalent and stronger long-term changes in reproductive investment, whereas slower populations had more prevalent short-term adjustments. Inter-annual environmental variation partly accounted for short-, but not long-term changes in reproductive investment. Our study reveals individuals differ in when they pay the cost of reproduction and that failure to partition this variation across different temporal scales and environments could underestimate reproductive trade-offs.

PMID:35235709 | DOI:10.1111/ele.13982

Alzheimers Dement. 2022 Mar 2. doi: 10.1002/alz.12615. Online ahead of print.

ABSTRACT

This perspective is a companion to a recent editorial on the use of Bayesian analysis in clinical research. We aim to introduce and highlight the relevance and advantages that Bayesian inference offers to clinical trials using the data on the amyloid antibody aducanumab presented at a Food and Drug Administration hearing in November 2020 as an applied example. We apply Bayesian analysis of model plausibility and effect sizes based on simulated data of the two phase 3 trials of aducanumab in prodromal and mild dementia stages of Alzheimer’s disease (AD). Bayesian analysis can quantify evidence in favor of, or against, the presence of an effect (i.e., provide evidence of absence), as well as assess the strength of the effect. This is in contrast to the binary conclusions provided by frequentist tests.

PMID:35235700 | DOI:10.1002/alz.12615

Math Med Biol. 2022 Mar 2:dqac001. doi: 10.1093/imammb/dqac001. Online ahead of print.

ABSTRACT

Mycobacterium tuberculosis (TB) infection can involve all immune system components and can result in different disease outcomes. The antibiotic TB drugs require strict adherence to prevent both disease relapse and mutation of drug- and multidrug-resistant strains. To overcome the constraints of pathogen-directed therapy, host-directed therapy has attracted more attention in recent years as an adjunct therapy to enhance host immunity to fight against this intractable pathogen. The goal of this paper is to investigate in-host TB models to provide insights into therapy development. Focusing on therapy-targeting parameters, the parameter regions for different disease outcomes are identified from an established ODE model. Interestingly, the ODE model also demonstrates that the immune responses can both benefit and impede disease progression, depending on the number of bacteria engulfed and released by macrophages. We then develop two Itô SDE models, which consider the impact of demographic variations at the cellular level and environmental variations during therapies along with demographic variations. The SDE model with demographic variation suggests that stochastic fluctuations at the cellular level have significant influences on (1) the T-cell population in all parameter regions, (2) the bacterial population when parameters located in the region with multiple disease outcomes and (3) the uninfected macrophage population in the parameter region representing active disease. Further, considering environmental variations from therapies, the second SDE model suggests that disease progression can slow down if therapies (1) can have fast return rates and (2) can bring parameter values into the disease clearance regions.

PMID:35235658 | DOI:10.1093/imammb/dqac001

J Clin Endocrinol Metab. 2022 Mar 2:dgac104. doi: 10.1210/clinem/dgac104. Online ahead of print.

ABSTRACT

CONTEXT: PLIN1 encodes Perilipin-1 which coats lipid droplets in adipocytes and is involved in droplet formation, triglyceride storage and lipolysis. Rare PLIN1 frameshift variants that extend the translated protein have been described to cause lipodystrophy.

OBJECTIVE: To test whether PLIN1 protein-truncating variants cause lipodystrophy in a large population-based cohort.

DESIGN: We identified individuals with PLIN1 PTVs in individuals with exome data in UK Biobank. We performed gene-burden testing for individuals with PLIN1 PTVs. We replicated the associations using data from the T2D Knowledge portal. We performed a phenome-wide association study using publicly available association statistics.

SETTING: A population-based cohort and a T2D case/control study.

PARTICIPANTS: 362,791 individuals in UK Biobank and 43,125 individuals in the T2D Knowledge portal.Main Outcome Measures: Twenty-two diseases and traits relevant to lipodystrophy.

RESULTS: The 735 individuals with PLIN1 protein-truncating variants had a favourable metabolic profile. These individuals had increased HDL cholesterol (0.12mmol/L, 95% CI: 0.09, 0.14, P=2×10 -18), reduced triglycerides (-0.22 mmol/L 95% CI: -0.29, -0.14, P=3×10 -11), reduced waist hip ratio (-0.02, 95% CI: -0.02, -0.01, P=9×10 -12) and reduced systolic blood pressure (-1.67 mmHg, -3.25, -0.09, P=0.05). These associations were consistent in the smaller T2D knowledge portal cohort. In UK Biobank, PLIN1 PTVs were associated with reduced risk of myocardial infarction (OR=0.59, 95% CI: 0.35, 0.93, P=0.02) and hypertension (OR=0.85, 95% CI: 0.73, 0.98, P=0.03), but not Type 2 diabetes (OR=0.99 95% CI: 0.63,1.51, P=0.99).

CONCLUSION: Our study suggests that PLIN1 haploinsufficiency causes a favourable metabolic profile and may protect against cardiovascular disease.

PMID:35235652 | DOI:10.1210/clinem/dgac104