Nevin Manimala

PLoS One. 2023 Mar 29;18(3):e0283531. doi: 10.1371/journal.pone.0283531. eCollection 2023.

ABSTRACT

Little is known about the most important factors that inform a nephrologist’s decision to treat (DTT) pre-dialysis chronic kidney disease (CKD) patients with vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT). The objective of this study was to identify such factors and their relative importance in the DTT with a vitamin D therapy. A web-based, adaptive design conjoint analysis discrete-choice survey was developed to study factors that informed the DTT among a sample of 200 nephrologists located throughout the United States. Based on literature review and clinician input, eight attributes were selected that could influence a provider’s DTT: age, race, CKD stage, serum 25-hydroxyvitamin D (25D), parathyroid hormone (PTH), serum calcium (Ca), serum phosphorus (P), and history of comorbidities. Respondents were asked to select one patient profile most suitable for treatment from three profiles with varying attribute levels. Each attribute’s relative importance score was computed using hierarchical-Bayesian statistics to measure the influence of each factor where higher scores represented greater DTT consideration. The pooled analysis revealed the four most important factors: serum 25D (31.4%), serum Ca (22.7%), plasma PTH (11.5%) levels, and history of comorbidities (8.5%). Age (8.2%), serum P (7.7%), CKD stage (5.7%), and race (4.4%) were relatively less important. Patients’ 25D and Ca levels contributed to more than half of nephrologists’ DTT, with the consideration of PTH levels being less of a factor. Further understanding of the driving forces behind the factors that inform the DTT may help to standardize the management of CKD patients with SHPT and VDI and improve outcomes.

PMID:36989323 | DOI:10.1371/journal.pone.0283531

Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2220469120. doi: 10.1073/pnas.2220469120. Epub 2023 Mar 29.

ABSTRACT

First-order optimization algorithms are widely used today. Two standard building blocks in these algorithms are proximal operators (proximals) and gradients. Although gradients can be computed for a wide array of functions, explicit proximal formulas are known for only limited classes of functions. We provide an algorithm, HJ-Prox, for accurately approximating such proximals. This is derived from a collection of relations between proximals, Moreau envelopes, Hamilton-Jacobi (HJ) equations, heat equations, and Monte Carlo sampling. In particular, HJ-Prox smoothly approximates the Moreau envelope and its gradient. The smoothness can be adjusted to act as a denoiser. Our approach applies even when functions are accessible only by (possibly noisy) black box samples. We show that HJ-Prox is effective numerically via several examples.

PMID:36989305 | DOI:10.1073/pnas.2220469120

PLoS One. 2023 Mar 29;18(3):e0282301. doi: 10.1371/journal.pone.0282301. eCollection 2023.

ABSTRACT

When ascending to high altitude, it is a rigorous challenge to people who living in the low altitude area to acclimatize to hypoxic environment. Hypoxia exposure can cause dramatic disturbances of metabolism. This longitudinal cohort study was conducted to delineate the plasma metabolomics profile following exposure to altitude environments and explore potential metabolic changes after return to low altitude area. 25 healthy volunteers living in the low altitude area (Nor; 40m) were transported to high altitude (HA; 3,650m) for a 7-day sojourn before transported back to the low altitude area (HAP; 40m). Plasma samples were collected on the day before ascending to HA, the third day on HA(day 3) and the fourteenth day after returning to low altitude(14 day) and analyzed using UHPLC-MS/MS tools and then the data were subjected to multivariate statistical analyses. There were 737 metabolites were obtained in plasma samples with 133 significantly changed metabolites. We screened 13 differential metabolites that were significantly changed under hypoxia exposure; enriched metabolic pathways under hypoxia exposure including tryptophan metabolism, purine metabolism, regulation of lipolysis in adipocytes; We verified and relatively quantified eight targeted candidate metabolites including adenosine, guanosine, inosine, xanthurenic acid, 5-oxo-ETE, raffinose, indole-3-acetic acid and biotin for the Nor and HA group. Most of the metabolites recovered when returning to the low altitude area, however, there were still 6 metabolites that were affected by hypoxia exposure. It is apparent that high-altitude exposure alters the metabolic characteristics and two weeks after returning to the low altitude area a small portion of metabolites was still affected by high-altitude exposure, which indicated that high-altitude exposure had a long-term impact on metabolism. This present longitudinal cohort study demonstrated that metabolomics can be a useful tool to monitor metabolic changes exposed to high altitude, providing new insight in the attendant health problem that occur in response to high altitude.

PMID:36989280 | DOI:10.1371/journal.pone.0282301

PLoS One. 2023 Mar 29;18(3):e0283159. doi: 10.1371/journal.pone.0283159. eCollection 2023.

ABSTRACT

The use of fresh tissue for molecular studies is preferred but often impossible. Instead, frozen or formalin-fixed, paraffin-embedded (FFPE) tissues are widely used and constitute valuable resources for retrospective studies. We assessed the utility of cardiac tissue stored in different ways for gene expression analyses by whole transcriptome sequencing of paired fresh, frozen, and FFPE tissues. RNA extracted from FFPE was highly degraded. Sequencing of RNA from FFPE tissues yielded higher proportions of intronic and intergenic reads compared to RNA from fresh and frozen tissues. The global gene expression profiles varied with the storage conditions, particularly mitochondrial and long non-coding RNAs. However, we observed high correlations among protein-coding transcripts (ρ > 0.94) with the various storage conditions. We did not observe any significant storage effect on the allele-specific gene expression. However, FFPE had statistically significantly (p < 0.05) more discordant variant calls compared to fresh and frozen tissue. In conclusion, we found that frozen and FFPE tissues can be used for reliable gene expression analyses, provided that proper quality control is performed and caution regarding the technical variability is withheld.

PMID:36989279 | DOI:10.1371/journal.pone.0283159

PLoS One. 2023 Mar 29;18(3):e0283020. doi: 10.1371/journal.pone.0283020. eCollection 2023.

ABSTRACT

Recent research has revealed the diversity and biomass of life across ecosystems, but how that biomass is distributed across body sizes of all living things remains unclear. We compile the present-day global body size-biomass spectra for the terrestrial, marine, and subterranean realms. To achieve this compilation, we pair existing and updated biomass estimates with previously uncatalogued body size ranges across all free-living biological groups. These data show that many biological groups share similar ranges of body sizes, and no single group dominates size ranges where cumulative biomass is highest. We then propagate biomass and size uncertainties and provide statistical descriptions of body size-biomass spectra across and within major habitat realms. Power laws show exponentially decreasing abundance (exponent -0.9±0.02 S.D., R2 = 0.97) and nearly equal biomass (exponent 0.09±0.01, R2 = 0.56) across log size bins, which resemble previous aquatic size spectra results but with greater organismal inclusivity and global coverage. In contrast, a bimodal Gaussian mixture model describes the biomass pattern better (R2 = 0.86) and suggests small (~10-15 g) and large (~107 g) organisms outweigh other sizes by one order magnitude (15 and 65 Gt versus ~1 Gt per log size). The results suggest that the global body size-biomass relationships is bimodal, but substantial one-to-two orders-of-magnitude uncertainty mean that additional data will be needed to clarify whether global-scale universal constraints or local forces shape these patterns.

PMID:36989258 | DOI:10.1371/journal.pone.0283020

PLOS Glob Public Health. 2023 Mar 29;3(3):e0001716. doi: 10.1371/journal.pgph.0001716. eCollection 2023.

ABSTRACT

BACKGROUND: Averse birth-outcomes still affect newborns worldwide. Although high-quality prenatal care is the main strategy to prevent these outcomes, the effect of prenatal care based on Kotelchuck index combined with consultation contents is still unclear. Thus, this article to evaluate the effect of the quality of prenatal care (PC) process on birth indicators in a cohort of puerperaes who attended maternity hospitals in Brazilian western Amazon, city of Rio Branco, in the state of Acre, Brazil, in 2015.

METHODS: This research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in the city between April 6 and June 30, 2015. This research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in Rio Branco between April 6th. and June 30th., 2015. Prenatal care was classified as fully adequate when started ≤4th month; ≥80.0-109% expected consultations for GA according to the Kotelchuck Index; ≥5 records of blood pressure, weight, GA, fundal height, ≥4 records of fetal heart rate, fetal movements or equivalent to 75% of the number of consultations; in addition to recording ABO/RH, hemoglobin, VDRL, urine, glucose, anti-HIV and anti-toxoplamosis during the 1st trimester. The evaluated outcomes were low birth weight (LBW), preterm birth and vertical transmission of human immunodeficiency virus (HIV)/hepatitis/syphilis. Differences between proportions were assessed using the X² test, and the crude and adjusted odds ratios (OR) (95% CI) were estimated using unconditional logistic regression.

RESULTS: Overall cohort, the outcomes incidences were 8.8% for LBW, 9.2% for preterm birth, and 1.1% for vertical transmission (syphilis/HIV/hepatitis). Crude and adjusted OR showed that inadequate PC increased the risk statistically significant of LBW (ORcrude: 1.84; 95%CI: 0.99-3.44; ORadjusted: 1.87; 95%CI: 1.00-3.52), and preterm birth (ORcrude: 1.79; 95%CI: 1.00-3.29; ORadjusted: 3.98; 95%CI: 1.40-11.29).

CONCLUSION: The results draw attention to the importance of quality PC in reducing the risks of LBW, preterm birth, and vertical transmission of syphilis/HIV/hepatitis. Moreover, using this proposed quality prenatal care indicator based on Kotelchuck index combined with consultations contents adjusted by GA may accurately predict unfavorable outcomes.

PMID:36989229 | DOI:10.1371/journal.pgph.0001716

PLOS Glob Public Health. 2023 Mar 29;3(3):e0001761. doi: 10.1371/journal.pgph.0001761. eCollection 2023.

ABSTRACT

INTRODUCTION: Mortality prediction aids clinical decision-making and is necessary for trauma quality improvement initiatives. Conventional injury severity scores are often not feasible in low-resource settings. We hypothesize that clinician assessment will be more feasible and have comparable discrimination of mortality compared to conventional scores in low and middle-income countries (LMICs).

METHODS: Between 2017 and 2019, injury data were collected from all injured patients as part of a prospective, four-hospital trauma registry in Cameroon. Clinicians used physical exam at presentation to assign a highest estimated abbreviated injury scale (HEAIS) for each patient. Discrimination of hospital mortality was evaluated using receiver operating characteristic curves. Discrimination of HEAIS was compared with conventional scores. Data missingness for each score was reported.

RESULTS: Of 9,635 presenting with injuries, there were 206 in-hospital deaths (2.2%). Compared to 97.5% of patients with HEAIS scores, only 33.2% had sufficient data to calculate a Revised Trauma Score (RTS) and 24.8% had data to calculate a Kampala Trauma Score (KTS). Data from 2,328 patients with all scores was used to compare models. Although statistically inferior to the prediction generated by RTS (AUC 0.92-0.98) and KTS (AUC 0.93-0.99), HEAIS provided excellent overall discrimination of mortality (AUC 0.84-0.92). Among 9,269 patients with HEAIS scores was strongly predictive of mortality (AUC 0.93-0.96).

CONCLUSION: Clinical assessment of injury severity using HEAIS strongly predicts hospital mortality and far exceeds conventional scores in feasibility. In contexts where traditional scoring systems are not feasible, utilization of HEAIS could facilitate improved data quality and expand access to quality improvement programming.

PMID:36989211 | DOI:10.1371/journal.pgph.0001761

PLoS One. 2023 Mar 29;18(3):e0281822. doi: 10.1371/journal.pone.0281822. eCollection 2023.

ABSTRACT

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis.

PMID:36989207 | DOI:10.1371/journal.pone.0281822

J Am Geriatr Soc. 2023 Mar 29. doi: 10.1111/jgs.18349. Online ahead of print.

ABSTRACT

BACKGROUND: Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults.

METHODS: This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018. Outcomes included new incidence of injury (concussion, contusion, dislocation, fall, fracture, or other injuries) and delirium. The cohort was followed from the initiation of therapy until the first occurrence of any of the following events: end of the index drug exposure, end of health plan membership, death, or the study end date of December 31st, 2019. Descriptive statistics were used to compare baseline patient characteristics between baclofen and tizanidine treatment groups. Cox proportional hazards model was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals.

RESULTS: The final study cohort included 12,101 and 6,027 older adults in the baclofen and tizanidine group respectively (mean age 72.2 ± 6.2 years old, 59% female). Older adults newly started on baclofen had a greater risk of injury (HR = 1.54, 95% CI = 1.21-1.96, P = < 0.001) and delirium (HR = 3.33, 95% CI = 2.11-5.26, p = <0.001) compared to those started on tizanidine.

CONCLUSION: The results of this study suggest that baclofen is associated with higher incidences of injury and delirium compared to tizanidine when used for the treatment of musculoskeletal pain. Future studies should investigate if these risks are dose-related and include a comparison group not exposed to either drug.

PMID:36989193 | DOI:10.1111/jgs.18349

Drug Alcohol Rev. 2023 Mar 29. doi: 10.1111/dar.13644. Online ahead of print.

ABSTRACT

INTRODUCTION: Causal relationships between alcohol outlets and crime are inferred from their statistical associations across neighbourhoods. However, many unobserved covariates may confound these effects. Recognising that outlet sales vary by time of day and day of week, we assess whether areas with more bars/pubs, restaurants or off-premise outlets have more crime during days and times when alcohol sales are greatest.

METHODS: Annual administrative crime counts, sociodemographic data and other area characteristics of 336 Census block groups in Oakland, California, USA, were related to outlet densities from 2000 to 2015. Bayesian space-time Poisson models were used to measure associations between outlet densities and crime during: (i) weekday daytime; (ii) weekday nighttime; (iii) weekend daytime; and (iv) weekend nighttime periods (four seemingly unrelated equations). Comparisons of parameter estimates across equations provided an assessment of outlet effects on crime across days and times within the same analysis units using the same constellation of confounding covariates.

RESULTS: Assault and driving under the influence crime incidents during weekend evening hours were more frequent in Census block group areas with greater numbers of bar/pubs. Burglaries were consistently greater in areas with greater densities of restaurants.

DISCUSSION AND CONCLUSIONS: The spatiotemporal signature relating densities of bars/pubs over weekend evening hours to assault and driving under the influence incidents suggests that these outlets are a critical source of these crimes across neighbourhoods. Prevention programs and policies that focus upon specific drinking establishments, days and times may be most effective in reducing assault and impaired driving incidents in neighbourhoods.

PMID:36989160 | DOI:10.1111/dar.13644