Category: Nevin Manimala

Exp Eye Res. 2021 Jun 20:108680. doi: 10.1016/j.exer.2021.108680. Online ahead of print.

ABSTRACT

Accumulation of bisretinoids such as A2E and its isomer iso-A2E is thought to mediate blue light-induced oxidative damage associated with age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). We hypothesize that increasing dietary intake of the macular carotenoids lutein and zeaxanthin in individuals at risk of AMD and STGD1 can inhibit the formation of bisretinoids A2E and iso-A2E, which can potentially ameliorate macular degenerative diseases. To study the beneficial effect of macular carotenoids in a retinal degenerative diseases model, we used ATP-binding cassette, sub-family A member 4 (Abca4^-/-)/β,β-carotene-9′,10′-oxygenase 2 (Bco2^-/-) double knockout (KO) mice that accumulate elevated levels of A2E and iso-A2E in the retinal pigment epithelium (RPE) and macular carotenoids in the retina. Abca4^-/-/Bco2^-/- and Abca4^-/- mice were fed a lutein-supplemented chow, zeaxanthin-supplemented chow or placebo chow (∼2.6 mg of carotenoid/mouse/day) for three months. Visual function and electroretinography (ERG) were measured after one month and three months of carotenoid supplementation. The lutein and zeaxanthin supplemented Abca4^-/-/Bco2^-/- mice had significantly lower levels of RPE/choroid A2E and iso-A2E compared to control mice fed with placebo chow and improved visual performance. Carotenoid supplementation in Abca4^-/- mice minimally raised retinal carotenoid levels and did not show much difference in bisretinoid levels or visual function compared to the control diet group. There was a statistically significant inverse correlation between carotenoid levels in the retina and A2E and iso-A2E levels in the RPE/choroid. Supplementation with retinal carotenoids, especially zeaxanthin, effectively inhibits bisretinoid formation in a mouse model of STGD1 genetically enhanced to accumulate carotenoids in the retina. These results provide further impetus to pursue oral carotenoids as therapeutic interventions for STGD1 and AMD.

PMID:34161819 | DOI:10.1016/j.exer.2021.108680

Am J Med Sci. 2021 Jun 20:S0002-9629(21)00240-8. doi: 10.1016/j.amjms.2021.06.009. Online ahead of print.

ABSTRACT

BACKGROUND: The therapeutic benefits and rationale for treating fevers with external cooling methods remain unclear. We aimed to describe the clinical settings in which cooling blankets (CBs) are used.

DESIGN: We conducted a retrospective chart review of CB use in adult patients admitted to our tertiary care center over a one-year period. We measured how they are used and correlations between clinical variables and their duration of use.

RESULTS: 561 patients were included in our study. The mean highest temperature during hospitalization was 39.35°C (SD, 0.67). Shivering occurred in 176 patients (31.4%) while on a CB although 303 patients (54%) had no data regarding shivering. Discontinuation of CBs was recorded in only 177 (30.5%) cases. Among these, the median duration of use was 33.37 hours (IQR: 18.13-80.38) while the median duration of fever was 22.13 hours (IQR 6.67-51.98). Duration of CB use was highly correlated with fever duration (Spearman’s rho, 0.771, p<.001), moderately with length of stay (LOS) (rho, 0.425, p<.001), LOS after CB initiation (rho, 0.475, p<.001) and antipyretic use (rho, 0.506, p<.001). No other statistically significant correlations were observed.

CONCLUSION: Documentation of CB use including temperature set points, time of discontinuation and duration in EMRs was poor. We could not establish benefits of CB use in this study but observed that almost a third of patients developed adverse effects in the form of shivering. Thus, adverse effects of CB use may outweigh potential benefits. Their use should be reevaluated and institutional protocols developed for their use.

PMID:34161829 | DOI:10.1016/j.amjms.2021.06.009

J Oral Maxillofac Surg. 2021 May 19:S0278-2391(21)00518-8. doi: 10.1016/j.joms.2021.05.019. Online ahead of print.

ABSTRACT

PURPOSE: We aim to reveal postoperative morphological correlations between the nasolabial components in patients with unilateral cleft lip (UCL). The hypothetical correlations are first, a correlation between the vertical height of the cleft-side alar base and the length of the cleft-side red lip, and second, a correlation between the length of the cleft-side red lip and the vertical position of the cleft-side oral commissure. We explain how these morphological balances are controlled by surgery.

METHODS: Three-dimensional bilateral measurements of the length of the red lip, vertical height of the nasal alar base, and vertical height of the oral commissure were conducted retrospectively on 31 patients with UCL and palate (complete UCL: 26; incomplete UCL: 5) who underwent primary lip plasty at Osaka Women’s and Children’s Hospital from 2017 to 2019.

RESULTS: We found a statistically significant correlation between the vertical height of the cleft-side alar base and cleft-side red lip length (P = .012, r = 0.45); thus, the longer the red lip, the lower was the nasal alar base. The correlation between the cleft-side red lip length and the vertical height of the cleft-side oral commissure also showed a statistically significant (P = .00074, r = 0.57); thus, the shorter the red lip, the higher was the oral commissure.

CONCLUSIONS: The present results provided objective evidence showing basic morphological relationships between the postoperative nasolabial features of patients with UCL. The results lead to a reasonable approach to define the proposed peak of the Cupid’s bow, an unsettled major controversy in cleft lip surgery.

PMID:34161809 | DOI:10.1016/j.joms.2021.05.019

Ann Epidemiol. 2021 Jun 20:S1047-2797(21)00154-X. doi: 10.1016/j.annepidem.2021.06.003. Online ahead of print.

NO ABSTRACT

PMID:34161794 | DOI:10.1016/j.annepidem.2021.06.003

Chembiochem. 2021 Jun 23. doi: 10.1002/cbic.202100193. Online ahead of print.

ABSTRACT

The oxidation of proteins generates reactive amino acid (AA) residue intermediates, leading to protein modification and cross-linking. Aerobic studies with peptides and photosensitizers allow for the controlled generation of reactive oxygen species (ROS) and reactive AA residue intermediates, providing mechanistic insights as to how natural protein modifications form. Such studies have inspired the development of abiotic methods for protein modification and crosslinking, including applications of biomedical importance. Dityrosine linkages derived from oxidation at tyrosine (Tyr) residues represent one of the more well-understood oxidation-induced modifications. Here we demonstrate an aerobic, visible light-dependent oxidation reaction of Tyr-containing substrates promoted by a water-soluble 4-amino-1,8-naphthalimide-based photosensitizer. The developed procedure converts Tyr-containing substrates into o,o’- Tyr-Tyr linked dimers. The regioselectively formed o,o’ -Tyr-Tyr linkage is consistent with dimeric standards prepared using a known enzymatic method. A crossover study with two peptides provides a statistical mixture of three distinct o,o’ -Tyr-Tyr linked dimers, supporting a mechanism that involves Tyr residue oxidation followed by intermolecular combination.

PMID:34161648 | DOI:10.1002/cbic.202100193

S D Med. 2021 Feb;74(2):54-57.

ABSTRACT

INTRODUCTION: Vaccinations are one of the greatest public health achievements of the 20th century, leading to a reduction in morbidity and mortality associated with the infectious diseases they prevent. Unfortunately, vaccination rates within the U.S. have been declining, and many of these vaccine-preventable diseases are again on the rise. Due to this, methods to increase vaccination rates are being explored. Vaccine standing orders are one method being employed. This pilot study explored the effects vaccine standing orders placed in the electronic medical record (EMR) had on the number of pediatric vaccinations administered in one South Dakota clinic.

METHODS: Nursing staff reviewed the EMR and state records to determine what immunizations the pediatric patients, defined as those 18 years of age and under, were due for according to the Center for Disease Control’s (CDC) recommended vaccination schedule. They then placed vaccine standing orders in the EMR for each delinquent vaccination based on these findings. The number of vaccines administered during a five-month period before (Jan. 1 – May 31, 2019) and a five-month period after (June 1 – Oct.31, 2019) implementation of standing orders were compared. Results were analyzed using an independent samples t-test.

RESULTS: The absolute number of vaccinations administered after standing orders were instituted was greater than those administered prior to standing orders. The average number of vaccines given per month more than doubled, resulting in a statistically significant increase in vaccination rates by 117 percent.

CONCLUSIONS: This pilot study demonstrated a significant increase in the number of immunizations administered with the use of standing orders.

PMID:34161683

Am J Hematol. 2021 Jun 23. doi: 10.1002/ajh.26276. Online ahead of print.

ABSTRACT

Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher disease type 1. In the Phase 3 ENGAGE trial of previously untreated adults with Gaucher disease type 1, eliglustat-treated patients had statistically significant improvements in organ volumes and hematologic parameters compared with placebo in the 9-month primary analysis. We report final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension. No patient deteriorated clinically or withdrew due to adverse events; 39/40 patients entered the open-label extension period and 34/40 (85%) remained in the trial until completion or switching to commercial eliglustat after its approval (2.3 to 6 years). Clinically meaningful improvements in Gaucher disease manifestations were seen in all patients concomitant with reductions in pathological lipid substrate levels (glucosylceramide and glucosylsphingosine). Among patients with 4.5 years of eliglustat exposure, mean spleen volume decreased by 66% (from 17.1 to 5.8 multiples of normal [MN], n=13)mean liver volume decreased by 23% (from 1.5 to 1.1 MN, n=13), mean hemoglobin increased 1.4 g/dL (from 11.9 to 13.4 g/dL, n=12), mean platelet count increased by 87% (from 67.6 to 122.6 x 10⁹ /L, n=12), median chitotriosidase decreased by 82% (from 13,394 to 2312 nmol/hr/ml, n=11), median glucosylceramide decreased by 79% (from 11.5 to 2.4 μg/mL, n=11), median glucosylsphingosine decreased by 84% (from 518.5 to 72.1 ng/mL, n=10), and mean spine T-score increased from -1.07 (osteopenia) to -0.53 (normal) (n=9). Together, these outcomes regardless of time on eliglustat showed comparable improvements in Gaucher manifestations and disease biomarkers. Eliglustat was well-tolerated and led to clinically significant improvements in previously untreated patients with Gaucher disease type 1 during 4.5 years of treatment. This article is protected by copyright. All rights reserved.

PMID:34161616 | DOI:10.1002/ajh.26276

Asia Pac J Clin Oncol. 2021 Jun 23. doi: 10.1111/ajco.13595. Online ahead of print.

ABSTRACT

OBJECTIVE: PSMA PET/CT has demonstrated superior sensitivity over conventional imaging in the detection of local and distant recurrence in biochemically relapsed (BCR) prostate cancer. We prospectively investigated the management impact of ⁶⁸ Ga-PSMA PET/CT imaging in men with BCR, with the aim of identifying baseline clinicopathological predictors for management change.

PATIENTS AND METHODS: Men with BCR who met eligibility criteria underwent ⁶⁸ Ga-PSMA-11 PET/CT at Monash Health (Melbourne, Australia). Intended management plans were prospectively documented before and after ⁶⁸ Ga-PSMA PET/CT imaging. Binary logistic regression analysis was performed to identify potential clinicopathological predictors of management change. Descriptive statistics were used to characterize the nature of these changes.

RESULTS: Seventy men underwent ⁶⁸ Ga-PSMA-11 PET/CT imaging. Median age was 67 years (IQR 63-72) and median PSA was 0.48 ng/ml (IQR 0.21-1.9). PSMA-avid disease was observed in 56% (39/70) of patients. Pre-scan management plan was altered following scanning in 43% (30/70) of patients. Management changes were significantly more common in patients with higher baseline PSA levels (PSA≥2 ng/ml, p = 0.01). 18/36 (50%) of the patients initially planned for watchful waiting had their management changed, including the use of salvage pelvic radiotherapy (n = 7) and stereotactic ablative body radiotherapy to oligometastatic disease (n = 6).

CONCLUSION: Management change after ⁶⁸ Ga-PSMA PET/CT for BCR is common and typically resulted in treatment intensification strategies in those planned for a watchful waiting approach. This study adds to the growing pool of evidence supporting the clinical utility of PSMA PET/CT imaging in the care of patients with BCR after definitive therapy.

PMID:34161628 | DOI:10.1111/ajco.13595

Am J Intellect Dev Disabil. 2021 Jul 1;126(4):324-340. doi: 10.1352/1944-7558-126.4.324.

ABSTRACT

Young children with developmental disabilities (DD) exhibit a range of strengths and weaknesses in cognitive, language, and adaptive skills. Identifying individual patterns of abilities across these domains is important for informing interventions. This study examines how 129 toddlers with significant developmental delays and less than 10 spoken words perform across different developmental domains and assessment methods (i.e., caregiver report and clinician-administered tests). Children exhibited statistically and clinically meaningful strengths and weaknesses across developmental domains, which may have important implications for differential interventions. Caregiver-reported and clinician-rated measures of cognition, language and adaptive functioning were highly related. However, the relation between caregiver report and clinician ratings was weaker for a subgroup of children with relatively more limited expressive language compared to other children in the sample.

PMID:34161562 | DOI:10.1352/1944-7558-126.4.324

Nicotine Tob Res. 2021 Jun 23:ntab134. doi: 10.1093/ntr/ntab134. Online ahead of print.

ABSTRACT

INTRODUCTION: Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual use is associated with decreases in exposure to toxicants.

METHODS: This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group, and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers.

RESULTS: In JUUL groups, median percent reductions in primary BOEs (Day 6-Baseline) were 90%- ≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps<0.025). Median reductions in primary BOEs in the Dual Use group were 43%-55% of Abstinence. Similar results were observed for secondary BOEs.

CONCLUSION: This study suggests that use of JUUL as a complete or partial substitute (i.e., dual use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking.

IMPLICATIONS: This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System (“JUUL”) in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.

PMID:34161586 | DOI:10.1093/ntr/ntab134