Nevin Manimala

Brain Behav. 2023 Mar 14:e2932. doi: 10.1002/brb3.2932. Online ahead of print.

ABSTRACT

OBJECTIVE: The contribution of large vessel stenosis to the development of white matter hyperintensities (WMHs) has not been fully elucidated. This study aims to explore the correlation between ipsilateral white matter hyperintensities (WMHs) and the severity of large vessel stenosis in the anterior circulation and cerebral perfusion level, as well as analyze the factors influencing WMHs.

METHODS: A cross-sectional study of 150 patients with unilateral anterior circulation large vessel stenosis of ≥50% was conducted. The severity of ipsilateral WMHs was assessed by Fazekas scale on T2-weighted image and/or fluid-attenuated inversion recovery MR imaging, vascular stenosis severity was evaluated on computed tomography angiography images, and the level of cerebral perfusion was rated according to a staging system for abnormal cerebral perfusion based on CTP results. The relationships between the stenosis severity, cerebral perfusion level and ipsilateral WMHs severity were analyzed. A multivariate logistic regression analysis was performed to determine the factors independently influencing WMHs.

RESULTS: Among 150 patients (mean age, 63.12 ± 10.55 years), there was a statistically significant positive correlation between cerebral perfusion level and the severity of DWMHs and PWMHs (Gamma = 0.561, p < .001; Gamma = 0.600, p < .001), and a positive correlation between cerebral perfusion level and the severity of vascular stenosis (Gamma = 0.495, p < .001).While, there was no statistically significant correlation between the severity of vascular stenosis and the severity of DWMHs and PWMHs (Gamma = 0.188, p = .08; Gamma = 0.196, p = .06). The multivariate logistic regression analysis results demonstrated that age (OR = 1.047, 95% CI 1.003-1.093; p = .035), stroke/TIA history (OR = 2.880, 95% CI 1.154-7.190; p = .023) and stage II of cerebral perfusion (OR = 2.880, 95% CI 1.154-7.190; p = .023) were independent influencing factors on ipsilateral DWMHs. Age (OR = 1.051, 95% CI 1.009-1.094; p = .018), and stage II of cerebral perfusion (OR = 12.871, 95% CI 3.576-46.322; p < .001) were factors independently influencing ipsilateral PWMHs.

CONCLUSION: White matter hyperintensities may be attributed to cerebral hypoperfusion secondary to vascular stenosis but not directly to the severity of stenosis in the large vessels of anterior circulation. Moreover, longitudinal studies with sequential imaging exams may further reveal the impact of cerebral perfusion secondary to vascular stenosis on the development and progression of WMHs.

PMID:36917737 | DOI:10.1002/brb3.2932

Brain Behav. 2023 Mar 14:e2940. doi: 10.1002/brb3.2940. Online ahead of print.

ABSTRACT

BACKGROUND: Whole-brain longitudinal diffusion studies are crucial to examine changes in structural connectivity in neurodegeneration. Here, we investigated the longitudinal alterations in white matter (WM) microstructure across the timecourse of Huntington’s disease (HD).

METHODS: We examined changes in WM microstructure from premanifest to early manifest disease, using data from two cohorts with different disease burden. The TrackOn-HD study included 67 controls, 67 premanifest, and 10 early manifest HD (baseline and 24-month data); the PADDINGTON study included 33 controls and 49 early manifest HD (baseline and 15-month data). Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity from baseline to last study visit were investigated for each cohort using tract-based spatial statistics. An optimized pipeline was employed to generate participant-specific templates to which diffusion tensor imaging maps were registered and change maps were calculated. We examined longitudinal differences between HD expansion-carriers and controls, and correlations with clinical scores, including the composite UHDRS (cUHDRS).

RESULTS: HD expansion-carriers from TrackOn-HD, with lower disease burden, showed a significant longitudinal decline in FA in the left superior longitudinal fasciculus and an increase in MD across subcortical WM tracts compared to controls, while in manifest HD participants from PADDINGTON, there were significant widespread longitudinal increases in diffusivity compared to controls. Baseline scores in clinical scales including the cUHDRS predicted WM microstructural change in HD expansion-carriers.

CONCLUSION: The present study showed significant longitudinal changes in WM microstructure across the HD timecourse. Changes were evident in larger WM areas and across more metrics as the disease advanced, suggesting a progressive alteration of WM microstructure with disease evolution.

PMID:36917716 | DOI:10.1002/brb3.2940

Am J Dent. 2023 Feb;36(1):21-24.

ABSTRACT

PURPOSE: To evaluate in a retrospective practice-based clinical study, the effects of additional laser therapy on side effects following the removal of all four impacted third molars. The secondary objective was, based on those results, to rationalize a protocol for low-level laser therapy (LLLT) in terms of irradiation settings.

METHODS: 96 subjects requiring simultaneous surgical removal of the four third molars were treated from 2017 to 2019. For each subject, one side was randomly assigned to laser treatment, the other receiving the placebo. LLLT was performed by applying an infrared diode laser of 810 nm. In the LLLT irradiated side of the mouth, three groups were randomly assigned to a specific protocol of irradiation. Controllable settings include power, energy density and also scanning technique. The main outcome was pain, registered on a visual analog scale (VAS) performed by the patients.

RESULTS: There was a statistically significant difference for one of the tested protocols. Self-reported annoyance and pain scores were lower for the side submitted to a 30-second laser radiation at a power of 0.3 W with the slow scanning technique (P< 0.05).

CLINICAL SIGNIFICANCE: The present treatment approach, using a one-time low-level laser therapy intra-oral application, showed a beneficial effect of LLLT reducing pain after third molar surgery, which should be confirmed through further study.

PMID:36917711

Am J Dent. 2023 Feb;36(1):15-20.

ABSTRACT

PURPOSE: To evaluate the role of improvement in inflammatory oxidative stress by periodontal therapy (NSPT) in chronic kidney disease (CKD) subjects.

METHODS: 50 stable subjects of CKD (stage III-IV) and having chronic periodontitis were enrolled for the present study. Group A (control group) subjects who did not receive NSPT and Group B (test group) subjects who received NSPT. Oral hygiene instructions were given to both groups, malondialdehyde (MDA) in gingival crevicular fluid (GCF) and serum, albumin creatinine ratio (ACR), urine protein creatinine ratio (UPCR), pocket depth (PD), clinical attachment loss (CAL), plaque index (PI), gingival index (GI), Interleukin 1-beta (IL-1β), high sensitivity C-reactive protein (hs-CRP) in serum were assessed at baseline and 6 months.

RESULTS: There was a significant difference observed in PD, CAL, PI, GI and MDA-GCF, hs-CRP, IL-1β in serum following NSPT in the test group compared to the control group at 6 months follow up. Within the limitations of the study, the results revealed that NSPT can be used as an effective method to reduce inflammatory oxidative stress in CKD subjects and improve renal health. Further well-designed longitudinal trials with larger sample size and longer follow ups are needed.

CLINICAL SIGNIFICANCE: The non-surgical periodontal intervention showed statistically significant improvement on oxidative and inflammatory stress markers in gingival crevicular fluid and serum in subjects suffering from chronic kidney disease which suggests that periodontal treatment may be beneficial for these subjects.

PMID:36917710

Anal Chem. 2023 Mar 14. doi: 10.1021/acs.analchem.2c03575. Online ahead of print.

ABSTRACT

Research on graphene-related two-dimensional (2D) materials (GR2Ms) in recent years is strongly moving from academia to industrial sectors with many new developed products and devices on the market. Characterization and quality control of the GR2Ms and their properties are critical for growing industrial translation, which requires the development of appropriate and reliable analytical methods. These challenges are recognized by International Organization for Standardization (ISO 229) and International Electrotechnical Commission (IEC 113) committees to facilitate the development of these methods and standards which are currently in progress. Toward these efforts, the aim of this study was to perform an international interlaboratory comparison (ILC), conducted under Versailles Project on Advanced Materials and Standards (VAMAS) Technical Working Area (TWA) 41 “Graphene and Related 2D Materials” to evaluate the performance (reproducibility and confidence) of the thermogravimetric analysis (TGA) method as a potential new method for chemical characterization of GR2Ms. Three different types of representative and industrially manufactured GR2Ms samples, namely, pristine few-layer graphene (FLG), graphene oxide (GO), and reduced graphene oxide (rGO), were used and supplied to ILC participants to complete the study. The TGA method performance was evaluated by a series of measurements of selected parameters of the chemical and physical properties of these GR2Ms including the number of mass loss steps, thermal stability, temperature of maximum mass change rate (T_p) for each decomposition step, and the mass contents (%) of moisture, oxygen groups, carbon, and impurities (organic and non-combustible residue). TGA measurements determining these parameters were performed using the provided optimized TGA protocol on the same GR2Ms by 12 participants across academia, industry stakeholders, and national metrology institutes. This paper presents these results with corresponding statistical analysis showing low standard deviation and statistical conformity across all participants that confirm that the TGA method can be satisfactorily used for characterization of these parameters and the chemical characterization and quality control of GR2Ms. The common measurement uncertainty for each parameter, key contribution factors were identified with explanations and recommendations for their elimination and improvements toward their implementation for the development of the ISO/IEC standard for chemical characterization of GR2Ms.

PMID:36917706 | DOI:10.1021/acs.analchem.2c03575

Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2215278120. doi: 10.1073/pnas.2215278120. Epub 2023 Mar 14.

ABSTRACT

Heatwaves damage societies worldwide and are intensifying with global warming. Several mechanistic drivers of heatwaves, such as atmospheric blocking and soil moisture-atmosphere feedback, are well-known for their ability to raise surface air temperature. However, what limits the maximum surface air temperature in heatwaves remains unclear; this became evident during recent Northern Hemisphere heatwaves which achieved temperatures far beyond the upper tail of the observed statistical distribution. Here, we present evidence for the hypothesis that convective instability limits annual maximum surface air temperatures (TXx) over midlatitude land. We provide a theory for the corresponding upper bound of midlatitude temperatures, which accurately describes the observed relationship between temperatures at the surface and in the midtroposphere. We show that known heatwave drivers shift the position of the atmospheric state in the phase space described by the theory, changing its proximity to the upper bound. This theory suggests that the upper bound for midlatitude TXx should increase 1.9 times as fast as 500-hPa temperatures at the time and location of TXx occurrences. Using empirical 500-hPa warming, we project that the upper bound of TXx over Northern Hemisphere midlatitude land (40°N to 65°N) will increase about twice as fast as global mean surface air temperature, and TXx will increase faster than this bound over regions that dry on the hottest days.

PMID:36917663 | DOI:10.1073/pnas.2215278120

Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2220313120. doi: 10.1073/pnas.2220313120. Epub 2023 Mar 14.

ABSTRACT

Multivariate climate change presents an urgent need to understand how species adapt to complex environments. Population genetic theory predicts that loci under selection will form monotonic allele frequency clines with their selective environment, which has led to the wide use of genotype-environment associations (GEAs). This study used a set of simulations to elucidate the conditions under which allele frequency clines are more or less likely to evolve as multiple quantitative traits adapt to multivariate environments. Phenotypic clines evolved with nonmonotonic (i.e., nonclinal) patterns in allele frequencies under conditions that promoted unique combinations of mutations to achieve the multivariate optimum in different parts of the landscape. Such conditions resulted from interactions among landscape, demography, pleiotropy, and genetic architecture. GEA methods failed to accurately infer the genetic basis of adaptation under a range of scenarios due to first principles (clinal patterns did not evolve) or statistical issues (clinal patterns evolved but were not detected due to overcorrection for structure). Despite the limitations of GEAs, this study shows that a back-transformation of multivariate ordination can accurately predict individual multivariate traits from genotype and environmental data regardless of whether inference from GEAs was accurate. In addition, frameworks are introduced that can be used by empiricists to quantify the importance of clinal alleles in adaptation. This research highlights that multivariate trait prediction from genotype and environmental data can lead to accurate inference regardless of whether the underlying loci display clinal or nonmonotonic patterns.

PMID:36917658 | DOI:10.1073/pnas.2220313120

Oncologist. 2023 Mar 14:oyad028. doi: 10.1093/oncolo/oyad028. Online ahead of print.

ABSTRACT

BACKGROUND: There is a lack of consensus regarding the optimal method of assessing health-related quality of life (HR-QOL) among patients with metastatic renal cell carcinoma (mRCC). This study explored the perceived relevance of items that make up the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), as judged by patients with mRCC.

METHODS: This was a multinational cross-sectional survey. Eligible patients responded to a questionnaire composed of 18 items that assessed the perceived relevance of each item in the FKSI-19 questionnaire. Open-ended questions assessed additional issues deemed relevant by patients. Responses were grouped as relevant (scores 2-5) or nonrelevant (score 1). Descriptive statistics were collated, and open-ended questions were analyzed and categorized into descriptive categories. Spearman correlation statistics were used to test the association between relevance and clinical characteristics.

RESULTS: A total of 151 patients were included (gender: 78.1 M, 21.9F; median age: 64; treatment: 38.4 immunotherapy, 29.8 targeted therapy, 13.9 immuno-TKI combination therapy) in the study. The most relevant questions evaluated fatigue (77.5), lack of energy (72.2), and worry that their condition will get worse (71.5). Most patients rated blood in urine (15.2), fevers (16.6), and lack of appetite (23.2) as least relevant. Qualitative analysis of open-ended questions revealed several themes, including emotional and physical symptoms, ability to live independently, effectiveness of treatment, family, spirituality, and financial toxicity.

CONCLUSION: There is a need to refine widely used HR-QOL measures that are employed among patients diagnosed with mRCC treated with contemporary therapies. Guidance was provided for the inclusion of more relevant items to patients’ cancer journey.

PMID:36917626 | DOI:10.1093/oncolo/oyad028

Elife. 2023 Mar 14;12:e81446. doi: 10.7554/eLife.81446. Online ahead of print.

ABSTRACT

The beta rhythm (13-30 Hz) is a prominent brain rhythm. Recordings in primates during instructed-delay reaching tasks have shown that different types of traveling waves of oscillatory activity are associated with episodes of beta oscillations in motor cortex during movement preparation. We propose here a simple model of motor cortex based on local excitatory-inhibitory neuronal populations coupled by long-range excitation, where additionally inputs to the motor cortex from other neural structures are represented by stochastic inputs on the different model populations. We show that the model accurately reproduces the statistics of recording data when these external inputs are correlated on a short time scale (25 ms) and have two different components, one that targets the motor cortex locally and another one that targets it in a global and synchronized way. The model reproduces the distribution of beta burst durations, the proportion of the different observed wave types, and wave speeds, which we show not to be linked to axonal propagation speed. When the long-range connectivity or the local input targets are anisotropic, traveling waves are found to preferentially propagate along the axis where connectivity decays the fastest. Different from previously proposed mechanistic explanations, the model suggests that traveling waves in motor cortex are the reflection of the dephasing by external inputs, putatively of thalamic origin, of an oscillatory activity that would otherwise be spatially synchronized by recurrent connectivity.

PMID:36917621 | DOI:10.7554/eLife.81446

PLoS One. 2023 Mar 14;18(3):e0280620. doi: 10.1371/journal.pone.0280620. eCollection 2023.

ABSTRACT

Food insecurity is prevalent and associated with poor health outcomes, but little is known about its geographical nature. The aim of this study is to utilize geospatial modeling of individual-level food insecurity screening data ascertained in health care settings to test for neighborhood hot and cold spots of food insecurity in a large metropolitan area, and then compare these hot spot neighborhoods to cold spot neighborhoods in terms of the CDC’s Social Vulnerability Index. In this cross-sectional secondary data analysis, we geocoded the home addresses of 6,749 unique participants screened for food insecurity at health care locations participating in CMS’s Accountable Health Communities (AHC) Model, as implemented in Houston, TX. Next, we created census-tract level incidence profiles of positive food insecurity screens per 1,000 people. We used Anselin’s Local Moran’s I statistic to test for statistically significant census tract-level hot/cold spots of food insecurity. Finally, we utilized a Mann-Whitney-U test to compare hot spot tracts to cold spot tracts in relation to the CDC’s Social Vulnerability Index. We found that hot spot tracts had higher overall social vulnerability index scores (P <0.001), higher subdomain scores, and higher percentages of individual variables like poverty (P <0.001), unemployment (P <0.001), limited English proficiency (P <0.001), and more. The combination of robust food insecurity screening data, geospatial modeling, and the CDC’s Social Vulnerability Index offers a solid method to understand neighborhood food insecurity.

PMID:36917592 | DOI:10.1371/journal.pone.0280620