Nevin Manimala

Radiat Res. 2023 Aug 8. doi: 10.1667/RADE-23-00057. Online ahead of print.

ABSTRACT

Recent studies suggest ultra-high dose rate radiation treatment (UHDR-RT) reduces normal tissue damage compared to conventional radiation treatment (CONV-RT) at the same dose. In this study, we compared first, the kinetics and degree of skin damage in wild-type C57Bl/6 mice, and second, tumor treatment efficacy in GL261 and B16F10 dermal tumor models, at the same UHDR-RT and CONV-RT doses. Flank skin of wild-type mice received UHDR-RT or CONV-RT at 25 Gy and 30 Gy. Normal skin damage was tracked by clinical observation to determine the time to moist desquamation, an endpoint which was verified by histopathology. Tumors were inoculated on the right flank of the mice, then received UHDR-RT or CONV-RT at 1 × 11 Gy, 1 × 15, 1 × 25, 3 × 6 and 3 × 8 Gy, and time to tumor tripling volume was determined. Tumors also received 1 × 11, 1 × 15, 3 × 6 and 3 × 8 Gy doses for assessment of CD8+/CD4+ tumor infiltrate and genetic expression 96 h postirradiation. All irradiations of the mouse tumor or flank skin were performed with megavoltage electron beams (10 MeV, 270 Gy/s for UHDR-RT and 9 MeV, 0.12 Gy/s for CONV-RT) delivered via a clinical linear accelerator. Tumor control was statistically equal for similar doses of UHDR-RT and CONV-RT in B16F10 and GL261 murine tumors. There were variable qualitative differences in genetic expression of immune and cell damage-associated pathways between UHDR and CONV irradiated B16F10 tumors. Compared to CONV-RT, UHDR-RT resulted in an increased latent period to skin desquamation after a single 25 Gy dose (7 days longer). Time to moist skin desquamation did not significantly differ between UHDR-RT and CONV-RT after a 30 Gy dose. The histomorphological characteristics of skin damage were similar for UHDR-RT and CONV-RT. These studies demonstrated similar tumor control responses for equivalent single and fractionated radiation doses, with variable difference in expression of tumor progression and immune related gene pathways. There was a modest UHDR-RT skin sparing effect after a 1 × 25 Gy dose but not after a 1 × 30 Gy dose.

PMID:37590482 | DOI:10.1667/RADE-23-00057

J Child Adolesc Psychopharmacol. 2023 Aug 17. doi: 10.1089/cap.2022.0081. Online ahead of print.

ABSTRACT

Background: There has been a debate on whether sluggish cognitive tempo (SCT) differs from attention-deficit/hyperactivity disorder (ADHD). Although there have been many studies on metabolic parameters in relation to ADHD, no similar studies have been conducted on patients with SCT. We investigated whether there are differences between SCT and ADHD in terms of these factors. Subjects and Methods: Sixty-two participants with ages ranging from 11 to 18 who have diagnosis of ADHD (33 subjects) and SCT (29 subjects) were included in this study. The parents of all participants completed the 48-item Conners’ Parent Rating Scale (CPRS) and the Barkley Child Attention Scale (BCAS) forms, and all participants’ blood was taken to compare metabolic, oxidative stress, and antioxidant status of the SCT and ADHD groups. A child and adolescent psychiatrist interviewed the parents and children to assess the diagnosis of SCT and ADHD using standard diagnostic procedures. Results: In the comparison between the SCT and ADHD groups in terms of metabolic parameters, statistically significant differences were found in terms of total oxidant status, total antioxidant status, Oxidative Stress Index, total thiol, native thiol, disulfide, interleukin (IL)-1β, IL-6, and DNA damage (p < 0.05), but not in terms of tumor necrosis factor-α (p > 0.05). Conclusions: Our data showed that these two disorders may be different, but we believe that the data that indicate their differences remain inconclusive overall, but this study may be a potential pathway for future research.

PMID:37590480 | DOI:10.1089/cap.2022.0081

Dermatitis. 2023 Aug 17. doi: 10.1089/derm.2023.0130. Online ahead of print.

ABSTRACT

Background: Allergic contact dermatitis (ACD) in older adults (OA) represents a significant health burden, but few studies examine the prevalence and characteristics of contact allergy and ACD in this population. Objective: To compare positive and clinically relevant patch test results in OA versus younger adults (YA) and children. Methods: Retrospective analysis of patch test results obtained in OA (≥65 years), YA (19-64 years), and children (≤18 years) by the North American Contact Dermatitis Group, 2009 to 2020. Results: Of 28,177 patients patch tested, 5366 (19.0%) were OA. OA were more likely to have a final primary diagnosis of ACD as compared with YA (50.8% vs 49.2%, P = 0.035) and children (44.6%, P < 0.0001). The primary site of dermatitis also differed by age group, with OA having a higher proportion of dermatitis affecting the trunk, scalp, anogenital region, and “under clothing,” and a lower proportion of dermatitis affecting the face, lips, and feet. Limitations: Retrospective design, lack of follow-up, and referral population. Conclusion: OA were as likely and were statistically even more likely to have a final primary diagnosis of ACD compared with YA and children. Anatomic site of dermatitis also differed by age group. This underscores the need for patch testing in OA when ACD is suspected.

PMID:37590477 | DOI:10.1089/derm.2023.0130

Multivariate Behav Res. 2023 Aug 17:1-23. doi: 10.1080/00273171.2023.2240779. Online ahead of print.

ABSTRACT

In a cluster randomized trial clusters of persons, for instance, schools or health centers, are assigned to treatments, and all persons in the same cluster get the same treatment. Although less powerful than individual randomization, cluster randomization is a good alternative if individual randomization is impossible or leads to severe treatment contamination (carry-over). Focusing on cluster randomized trials with a pretest and post-test of a quantitative outcome, this paper shows the equivalence of four methods of analysis: a three-level mixed (multilevel) regression for repeated measures with as levels cluster, person, and time, and allowing for unstructured between-cluster and within-cluster covariance matrices; a two-level mixed regression with as levels cluster and person, using change from baseline as outcome; a two-level mixed regression with as levels cluster and time, using cluster means as data; a one-level analysis of cluster means of change from baseline. Subsequently, similar equivalences are shown between a constrained mixed model and methods using the pretest as covariate. All methods are also compared on a cluster randomized trial on mental health in children. From these equivalences follows a simple method to calculate the sample size for a cluster randomized trial with baseline measurement, which is demonstrated step-by-step.

PMID:37590444 | DOI:10.1080/00273171.2023.2240779

J Occup Environ Med. 2023 Aug 14. doi: 10.1097/JOM.0000000000002941. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of interventions to improve sleep, reduce fatigue, and advance the well-being of team truck drivers.

METHODS: In a randomized controlled trial (k = 24 teams; n = 49 drivers; 62.5% of planned sample), intervention teams were exposed to baseline (3-4 weeks), cab enhancements (active suspension seat, therapeutic mattress; 3-4 weeks), and cab enhancements plus a behavioral sleep-health program (1-2 months). Control teams worked as usual during the same period.

RESULTS: Trends in sleep-related outcomes favored the intervention. Large and statistically significant intervention effects were observed for objectively measured physical activity (a behavioral program target). The discussion of results addresses effect sizes, statistical power, intervention exposure, and work organization.

CONCLUSION: Trends, effect sizes, and significant findings in this rare trial provide valuable guidance for future efforts to improve working conditions and outcomes for team drivers.

PMID:37590443 | DOI:10.1097/JOM.0000000000002941

J Occup Environ Med. 2023 Aug 14. doi: 10.1097/JOM.0000000000002944. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to determine the association between workplace violence and sickness absenteeism.

METHODS: We analyzed the data from the fifth and sixth waves of the Korean Working Conditions Surveys. Individuals aged under 18 years and self-employed or unpaid family workers were excluded. Descriptive statistics, chi-square tests, and multiple logistic regression analysis were conducted.

RESULTS: After adjusting for sociodemographic, occupational, and job-related characteristics, we found that the workers who had experienced workplace violence had higher rates of sickness absenteeism, especially when the perpetrator of violence was a co-worker.

CONCLUSIONS: Daily contact with the perpetrator at the workplace can cause distress and recollection of painful memories; thus, the aftermath of being harassed inside the workplace can be even more devastating than the event itself. A sensitive approach to recognizing the perpetrators of violence is needed.

PMID:37590424 | DOI:10.1097/JOM.0000000000002944

Oncologist. 2023 Aug 17:oyad187. doi: 10.1093/oncolo/oyad187. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis.

MATERIALS AND METHODS: Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies.

RESULTS: Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028).

CONCLUSION: This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.

PMID:37590388 | DOI:10.1093/oncolo/oyad187

Science. 2023 Aug 18;381(6659):778-783. doi: 10.1126/science.adi6354. Epub 2023 Aug 17.

ABSTRACT

Ergodicity, the central tenet of statistical mechanics, requires an isolated system to explore all available phase space constrained by energy and symmetry. Mechanisms for violating ergodicity are of interest for probing nonequilibrium matter and protecting quantum coherence in complex systems. Polyatomic molecules have long served as a platform for probing ergodicity breaking in vibrational energy transport. Here, we report the observation of rotational ergodicity breaking in an unprecedentedly large molecule, ¹²C₆₀, determined from its icosahedral rovibrational fine structure. The ergodicity breaking occurs well below the vibrational ergodicity threshold and exhibits multiple transitions between ergodic and nonergodic regimes with increasing angular momentum. These peculiar dynamics result from the molecule’s distinctive combination of symmetry, size, and rigidity, highlighting its relevance to emergent phenomena in mesoscopic quantum systems.

PMID:37590361 | DOI:10.1126/science.adi6354

Science. 2023 Aug 18;381(6659):eabo3594. doi: 10.1126/science.abo3594. Epub 2023 Aug 18.

ABSTRACT

The cause, or causes, of the Pleistocene megafaunal extinctions have been difficult to establish, in part because poor spatiotemporal resolution in the fossil record hinders alignment of species disappearances with archeological and environmental data. We obtained 172 new radiocarbon dates on megafauna from Rancho La Brea in California spanning 15.6 to 10.0 thousand calendar years before present (ka). Seven species of extinct megafauna disappeared by 12.9 ka, before the onset of the Younger Dryas. Comparison with high-resolution regional datasets revealed that these disappearances coincided with an ecological state shift that followed aridification and vegetation changes during the Bølling-Allerød (14.69 to 12.89 ka). Time-series modeling implicates large-scale fires as the primary cause of the extirpations, and the catalyst of this state shift may have been mounting human impacts in a drying, warming, and increasingly fire-prone ecosystem.

PMID:37590347 | DOI:10.1126/science.abo3594

PLoS Negl Trop Dis. 2023 Aug 17;17(8):e0011573. doi: 10.1371/journal.pntd.0011573. Online ahead of print.

ABSTRACT

BACKGROUND: Trachoma is the chief cause of preventable blindness worldwide and has been earmarked for elimination as a public health problem by 2030. Despite the five-year Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE)-based interventions in the Andabet district, the prevalence of trachomatous follicular (TF) was 37%. With such a high prevalence of TF, the determinant factors were not revealed. Besides, there were no reports on the overall prevalence of active trachoma (i.e.TF and or trachomatous intense (TI)).

OBJECTIVE: To determine the prevalence and associated factors of active trachoma among 1-9 years of age children in the Andabet district.

METHOD: A community-based cross-sectional study was conducted among children aged under nine years from March 1-30, 2023 in Andabet district, Northwest Ethiopia. Multi-stage systematic random sampling was employed to reach 540 children. A multilevel mixed-effect logistic regression analysis was employed to assess factors associated with active trachoma. We fitted both random effect and fixed effect analysis. Finally, variables with p<0.05 in the multivariable multilevel analysis were claimed to be significantly associated with active trachoma.

RESULT: In this study, the overall prevalence of active trachoma was 35.37% (95% CI: 31.32%, 39.41%). The prevalence of TF and TI was 31.3% and 4.07% respectively. In the multilevel logistic regression analysis ocular discharge, fly-eye contact, latrine utilization, and source of water were significantly associated with the prevalence of active trachoma.

CONCLUSION: In this study, the prevalence of active trachoma was much higher than the World Health Organization (WHO) threshold prevalence. Ocular discharge, fly-eye contact, latrine utilization, and source of water were independent determinants of active trachoma among children (1-9 years). Therefore, paying special attention to these high-risk groups could decrease the prevalence of a neglected hyperendemic disease, active trachoma.

PMID:37590321 | DOI:10.1371/journal.pntd.0011573