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14 pages, 4143 KiB  
Article
Standardization of Dual-Energy CT Iodine Uptake of the Abdomen and Pelvis: Defining Reference Values in a Big Data Cohort
by Ibrahim Yel, Christian Booz, Tommaso D’Angelo, Vitali Koch, Leon D. Gruenewald, Katrin Eichler, Aynur Gökduman, Davide Giardino, Michele Gaeta, Silvio Mazziotti, Eva Herrmann, Thomas J. Vogl, Scherwin Mahmoudi and Ludovica R. M. Lanzafame
Diagnostics 2024, 14(18), 2051; https://doi.org/10.3390/diagnostics14182051 (registering DOI) - 15 Sep 2024
Abstract
Background: To establish dual-energy-derived iodine density reference values in abdominopelvic organs in a large cohort of healthy subjects. Methods: 597 patients who underwent portal venous phase dual-energy CT scans of the abdomen were retrospectively enrolled. Iodine distribution maps were reconstructed, and regions [...] Read more.
Background: To establish dual-energy-derived iodine density reference values in abdominopelvic organs in a large cohort of healthy subjects. Methods: 597 patients who underwent portal venous phase dual-energy CT scans of the abdomen were retrospectively enrolled. Iodine distribution maps were reconstructed, and regions of interest measurements were placed in abdominal and pelvic structures to obtain absolute iodine values. Subsequently, normalization of the abdominal aorta was conducted to obtain normalized iodine ratios. The values obtained were subsequently analyzed and differences were investigated in subgroups defined by sex, age and BMI. Results: Overall mean iodine uptake values and normalized iodine ratios ranged between 0.31 and 6.08 mg/mL and 0.06 and 1.20, respectively. Women exhibited higher absolute iodine concentration across all organs. With increasing age, normalized iodine ratios mostly tend to decrease, being most significant in the uterus, prostate, and kidneys (p < 0.015). BMI was the parameter less responsible for variations in iodine concentrations; normal weighted patients demonstrated higher values of both absolute and normalized iodine. Conclusions: Iodine concentration values and normalized iodine ratios of abdominal and pelvic organs reveal significant gender-, age-, and BMI-related differences, underscoring the necessity to integrate these variables into clinical practice. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>Study flowchart.</p>
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<p>Exemplary demonstration of ROI placement on axial portal–venous phase iodine maps for liver, pancreas, and spleen.</p>
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<p>Box-and-whiskers plots showing iodine concentration values (<b>A</b>) and normalized iodine ratio (<b>B</b>) in abdominopelvic organs.</p>
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<p>Scatter plots of normalized abdominopelvic iodine ratios values at different ages.</p>
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21 pages, 5888 KiB  
Article
A Novel Non-Invasive Murine Model of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes
by Elise A. Lemanski, Bailey A. Collins, Andrew T. Ebenezer, Sudha Anilkumar, Victoria A. Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M. Schwarz and Elizabeth C. Wright-Jin
Cells 2024, 13(18), 1551; https://doi.org/10.3390/cells13181551 (registering DOI) - 14 Sep 2024
Viewed by 280
Abstract
Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive [...] Read more.
Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. There was significant upregulation of inflammatory genes in microglia 24 h after hypoxia. Single-cell RNA sequencing (scRNAseq) revealed two microglia subclusters of interest following HIE. Pseudobulk analysis revealed increased microglia motility gene expression and upregulation of epigenetic machinery and neurodevelopmental genes in macrophages following HIE. No sex differences were found in any measures. These results support a two-hit noninvasive model pairing MIA and hypoxia as a model for HIE in humans. This model results in a milder phenotype compared to established HIE models; however, HIE is a clinically heterogeneous injury resulting in a variety of outcomes in humans. The pathways identified in our model of HIE may reveal novel targets for therapy for neonates with HIE. Full article
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<p>Two-hit HIE model: (<b>A</b>) A representation of our two-hit model of HIE and experimental design. (<b>B</b>) Representative graph of oxygen levels present and pup behavior during the 8 min hypoxia protocol (<span class="html-italic">n</span> = 3 litters).</p>
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<p>HIE results in a trend toward smaller brains 24 h after injury, and motor developmental delays in the neonatal period: (<b>A</b>) Whole-brain volume obtained on P7 through ex vivo MRI for control animals, and two-hit HIE animals. Analyzed with two-way ANOVA (<span class="html-italic">n</span> = 4 control male, 4 control female; 4 HIE male, 4 HIE female). (<b>B</b>–<b>J</b>) Date of acquisition for neonatal developmental behaviors is shown for the average values for males and females in each litter. (<span class="html-italic">n</span> = 6 control male, 6 control female; 4 HIE male, 5 HIE female). The dashed line indicates P6, the day of hypoxia exposure. Developmental behaviors were analyzed with a two-way ANOVA. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>HIE results in distal muscle weakness and gait disturbances in adulthood: (<b>A</b>) forepaw (FP) and (<b>A2</b>) hindpaw (HP) stride lengths measured by the catwalk ~P105 (two-way ANOVA). (<b>B</b>) Forepaw and (<b>B2</b>) hindpaw swing time measured by the catwalk (two-way ANOVA). (<b>C</b>) Average body speed on the catwalk. (catwalk <span class="html-italic">n</span> = 13 control male, 11 control female; HIE = 10 control male, 10 control female, two-way ANOVA) (<b>D</b>) Forepaw strength measured by a grip strength meter on ~P60 (<span class="html-italic">n</span> = 22 control male, 24 control female; 12 HIE male, 20 HIE female, two-way ANOVA). (<b>E</b>) Survival curve showing the proportion of animals still on the rotating rod across time using a Cox mixed-effects model on ~P61. Males and females are collapsed on this graph due to visibility considerations (<span class="html-italic">n</span> = 22 control male, 24 control female; 12 HIE male, 20 HIE female, Cox mixed-effects model). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>HIE results in acute transcriptional changes within microglia: (<b>A</b>) Genes identified by both DESeq2 and edgeR with an FDR adjusted <span class="html-italic">p</span>-value &lt; 0.05 within CD11b+ cells on P7, one-day post hypoxia (<span class="html-italic">n</span> = 2 control male, 2 control female, 4 HIE male). (<b>B</b>) Gene set enrichment plots of significantly upregulated proinflammatory gene sets within HIE microglia. (<b>C</b>) Gene set enrichment plots of significantly proliferation-related gene sets within HIE microglia. (<b>D</b>) Gene set enrichment plots of significantly upregulated damage checkpoint/apoptosis gene sets within HIE microglia.</p>
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<p>No unique subclusters emerge following HIE. ScRNAseq data from P8 and P10 combined (<span class="html-italic">n</span> = 6 control P8, 6 HIE P8, 6 control P10, 6 HIE P10): (<b>A</b>) Representative UMAP of all cell types identified by scRNA-Seq. (<b>B</b>) Representative UMAP of identified microglia subclusters. (<b>C</b>) Representative UMAP of identified macrophage subclusters.</p>
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<p>Microglia subclusters 7 and 12 emerge as clusters of interest following HIE in scRNAseq analysis: (<b>A</b>) Pathway enrichment analysis of microglia subcluster 7. (<b>B</b>) Pathway enrichment analysis of microglia subcluster 12. (<span class="html-italic">n</span> = 6 control P8, 6 HIE P8, 6 control P10, 6 HIE P10). (GO:BP, GOCC, GO:MF: Gene Ontology Biological Processes, Cellular Components, Molecular Functions, respectively; KEGG: KEGG PATHWAY Database; REAC: Reactome Pathway Database).</p>
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<p>Microglia have significant transcriptional changes following HIE: (<b>A</b>) MA plot of the differentially expressed genes in microglia (P8 and P10). (<b>B</b>) Plot of the significantly different functional pathways in microglia. (<span class="html-italic">n</span> = 6 control P8, 6 HIE P8, 6 control P10, 6 HIE P10).</p>
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<p>Macrophages have significant transcriptional changes following HIE: (<b>A</b>) Volcano plot of the differentially expressed genes in macrophages (P8 and P10). (<b>B</b>) Plot of the significantly different pathways in macrophages. (<span class="html-italic">n</span> = 6 control P8, 6 HIE P8, 6 control P10, 6 HIE P10).</p>
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13 pages, 382 KiB  
Article
Trends in Cancer Incidence and Mortality in US Adolescents and Young Adults, 2016–2021
by Li Zhang, Joshua E. Muscat, Vernon M. Chinchilli and Chandrika G. Behura
Cancers 2024, 16(18), 3153; https://doi.org/10.3390/cancers16183153 (registering DOI) - 14 Sep 2024
Viewed by 209
Abstract
(1) Background: The incidence rate of early onset-cancer (<50) has increased since 1995. Among younger people, cancers in AYAs (aged 15–39 y) are often biologically distinct tumors from those treated in the pediatric and older adult population. The current study describes trends in [...] Read more.
(1) Background: The incidence rate of early onset-cancer (<50) has increased since 1995. Among younger people, cancers in AYAs (aged 15–39 y) are often biologically distinct tumors from those treated in the pediatric and older adult population. The current study describes trends in the United States for the most recent years including the first year of the COVID-19 epidemic. We aimed to describe the recent incidence and mortality trends of cancers in AYAs (aged 15–39 y). (2) Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER 22) from 1 January 2016 to 31 December 2021. Age-adjusted incidence and mortality rates were assessed by SEER*Stat 8.4.3 for major cancer types by sex, race/ethnicity, age, and metropolitan/nonmetropolitan status. Time trends of age-adjusted incidence and mortality rates were examined by sex and metropolitan/nonmetropolitan status. (3) Results: Age-adjusted overall cancer incidence and mortality rates were stable during this study period. The age-adjusted incidence rates declined significantly for ependymoma, melanoma, carcinomas of lung, bronchus, and trachea, unspecified malignant neoplasms, and non-Hodgkin’s lymphoma. Significant increases were found for gastrointestinal tract cancers and non-Kaposi sarcomas. The age-adjusted mortality rate decreased for acute myeloid leukemia, melanoma, carcinomas of liver and intrahepatic bile ducts, kidney and, in women, leukemia. For some cancers, rates differed by sex, race, ethnicity, and geography. Monitoring the rates and time trends of AYA cancer emphasizes the distinct health concern for this age group. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
16 pages, 1215 KiB  
Article
Levels of Empathy in Students and Professors with Patients in a Faculty of Dentistry
by Víctor P. Díaz-Narváez, Joyce Huberman-Casas, Jorge Andrés Nakouzi-Momares, Chris Alarcón-Ureta, Patricio Alberto Jaramillo-Cavieres, Maricarmen Espinoza-Retamal, Blanca Patricia Klahn-Acuña, Leonardo Epuyao-González, Gabriela Leiton Carvajal, Mariela Padilla, Lindsay W. Vilca, Alejandro Reyes-Reyes and Fernando Reyes-Reyes
Behav. Sci. 2024, 14(9), 817; https://doi.org/10.3390/bs14090817 (registering DOI) - 14 Sep 2024
Viewed by 180
Abstract
Background: Empathy is an attribute that plays an essential role in the dentist–patient therapeutic relationship, clinical care, and treatment adherence, along with providing other benefits. The main objective of this research was to establish the validity, reliability, and invariance of the Jefferson Scale [...] Read more.
Background: Empathy is an attribute that plays an essential role in the dentist–patient therapeutic relationship, clinical care, and treatment adherence, along with providing other benefits. The main objective of this research was to establish the validity, reliability, and invariance of the Jefferson Scale of Empathy and then characterize the empathy levels of students and teachers at a dental school. Materials and Methods: An observational and cross-sectional study analyzed a sample of undergraduate students and professors from the Universidad Andrés Bello Faculty of Dentistry (Chile) (n = 1727 and n = 267, respectively). The Empathy Scale for Health Professionals (HP) and the same scale for students (HPS) were applied. Results: The Jefferson Empathy Scale presents adequate psychometric properties. The empathy measure has adequate reliability and construct validity, confirming a fit of the three-factor empathy model to the data. The measurement is invariant within the university campus, the sex of the student, and between teacher and student. Teachers present greater empathy than students except in the Perspective Adoption dimension. Conclusions: The Jefferson Empathy Scale is reliable, valid, and invariant among Chilean dental students and professors. Students do not differ from their professors in the cognitive component of empathy, but they present a lower score in the affective component and global empathy. It is inferred that students can develop the affective component of empathy in their interactions with their professors, increasing their overall empathy. Understanding and fostering empathy in dental students and professors can significantly improve patient care and treatment adherence and increase patient and dentist satisfaction. Full article
(This article belongs to the Section Social Psychology)
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<p>Confirmatory Factor Analysis of the empathy scale in university students.</p>
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<p>Confirmatory Factor Analysis of the Empathy Scale in Professors.</p>
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10 pages, 11612 KiB  
Article
The Ultramorphology and Sexual Dimorphism of Antennae and Sensilla in the Pale Grass Blue, Pseudozizeeria maha (Lepidoptera: Lycaenidae)
by Qing-Xiao Chen, Ying Han and Ya-Fei Li
Insects 2024, 15(9), 698; https://doi.org/10.3390/insects15090698 (registering DOI) - 14 Sep 2024
Viewed by 127
Abstract
The pale grass blue, Pseudozizeeria maha, is a small lycaenid butterfly widely distributed across Asia. Due to its exclusively diurnal lifestyle and conspicuous sexual dimorphism in wing coloration, vision has traditionally been regarded as the primary sensory system driving various behaviors. However, [...] Read more.
The pale grass blue, Pseudozizeeria maha, is a small lycaenid butterfly widely distributed across Asia. Due to its exclusively diurnal lifestyle and conspicuous sexual dimorphism in wing coloration, vision has traditionally been regarded as the primary sensory system driving various behaviors. However, non-visual sensory systems related to sex-specific behavioral responses, such as antennae, have received far less attention. This study investigated the morphological characteristics and sensilla types of the antennae in adult P. maha using scanning electron microscopy, with a focus on potential sexual dimorphism. The antennae of adult P. maha are clavate, with no significant sexual differences in overall morphology. Six types of antennal sensilla were identified: Böhm bristles, sensilla squamiformia, sensilla trichodea, sensilla chaetica, sensilla basiconica, and sensilla coeloconica, with no sexual dimorphism observed in their morphological types or dimensions. Remarkably, the sensilla coeloconica exhibit significant sexual dimorphism, with a more prominent presence in females. This finding suggests that female P. maha may rely more on olfactory cues for some sex-specific behaviors, such as oviposition site selection. Full article
(This article belongs to the Section Insect Physiology, Reproduction and Development)
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<p>SEM micrographs of <span class="html-italic">Pseudozizeeria maha</span> antennae. (<b>A</b>) A pair of antennae. (<b>B</b>) Basal region of the antenna. (<b>C</b>) Pedicel and proximal flagellomeres. (<b>D</b>) Distal flagellomeres forming the antennal club. BB, Böhm’s bristle; CE, compound eye; F, flagellum; Fl, flagellomere; P, pedicel; S, scape; SC, sensillium chaeticum; Sca1, scale with pores; Sca2, scale without pores. Scale bars: (<b>A</b>) = 600 µm; (<b>B</b>,<b>C</b>) = 60 µm; (<b>D</b>) = 100 µm.</p>
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<p>Cuticular modifications on the antennae. (<b>A</b>) Proximal flagellomeres with scales. (<b>B</b>) Dorsal view of the apical flagellomeres. (<b>C</b>) Scales with pores. (<b>D</b>) A magnified view of the subtype 1 of scale. (<b>E</b>) Scales without pores. (<b>F</b>) A magnified view of the subtype 2 of scale. SC, sensillium chaeticum; Sca1, scale with pores; Sca2, scale without pores; SSq, sensillium squamiformium. Scale bars: (<b>A</b>,<b>B</b>) = 20 µm; (<b>C</b>,<b>E</b>) = 8 µm; (<b>D</b>,<b>F</b>) = 1 µm.</p>
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<p>Antennal sensilla. (<b>A</b>) Böhm’s bristles on the pedicel. (<b>B</b>) Sensillium squamiformium on a flagellomere with scales. (<b>C</b>) Rows of sensilla chaetica on the scaleless flagellomeres. (<b>D</b>) Sensillium chaeticum. BB, Böhm’s bristle; Fl, flagellomere; P, pedicel; SC, sensillium chaeticum; Sca1, scale with pores; SSq, sensillium squamiformium; ST, sensillium trichodeum. Scale bars: (<b>A</b>,<b>B</b>,<b>D</b>) = 8 µm; (<b>C</b>) = 40 µm.</p>
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<p>Sensilla on the antennal club. (<b>A</b>) Ventral view of the fifth to eighth apical flagellomeres, showing numerous sensilla trichodea and sensilla coeloconica (arrows). (<b>B</b>) Dorsal view of the apical flagellomeres. Arrows indicate sensilla coeloconica. (<b>C</b>) Sensilla trichodea and basiconica. (<b>D</b>) Sensillium trichodeum. Fl, flagellomere; SB1, sensillium basiconicum 1; SB2, sensillium basiconicum 2; SC, sensillium chaeticum; ST, sensillium trichodeum. Scale bars: (<b>A</b>,<b>B</b>) = 30 µm; (<b>C</b>,<b>D</b>) = 3 µm.</p>
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<p>Sensilla coeloconica and basiconica. (<b>A</b>) Sensillium coeloconicum. (<b>B</b>) Two subtypes of sensilla basiconica. (<b>C</b>) Ventral view of the apical flagellomere. Arrows indicate sensilla basiconica 1. (<b>D</b>) Sensillium basiconicum 2. SB1, sensillium basiconicum 1; SB2, sensillium basiconicum 2; SC, sensillium chaeticum; SCo, sensillium coeloconicum; ST, sensillium styloconicum. Scale bars: (<b>A</b>,<b>B</b>,<b>D</b>) = 1 µm; (<b>C</b>) = 10 μm.</p>
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9 pages, 2224 KiB  
Article
Playing High: Strategic Use of the Lob in Professional Padel
by Antonio Villar-León, Diego Muñoz, Bernardino J. Sánchez-Alcaraz, Iván Martín-Miguel, Rafael Conde-Ripoll and Adrián Escudero-Tena
Appl. Sci. 2024, 14(18), 8261; https://doi.org/10.3390/app14188261 - 13 Sep 2024
Viewed by 140
Abstract
The aim of this study was to analyze the lob in professional padel, taking into account sex, the player’s side of play, the direction of the lob and the efficiency of the lob. For this purpose, 2063 lobs (933 in men’s and 1130 [...] Read more.
The aim of this study was to analyze the lob in professional padel, taking into account sex, the player’s side of play, the direction of the lob and the efficiency of the lob. For this purpose, 2063 lobs (933 in men’s and 1130 in women’s) corresponding to 10 matches of the 2024 season of the Premier Padel circuit were analyzed through systematic observation. The results indicated that there is no association between the player who makes the lob according to the side of play in professional padel (p = 0.796) and the category of play (men’s and women’s). The distribution of lobs in these categories, both men’s and women’s, was distributed 50% between both players from the same pair. On the other hand, in men’s professional padel, right-side players made more cross-court lobs (RTC = 3.3), while left-side players made more down-the-middle lobs (RTC = 2.0). In addition, in women’s professional padel, right-side players made more cross-court lobs (RTC = 3.6), while left-side players made more down-the-middle lobs (RTC = 6.0). Finally, in men’s padel, the lobs tended to overpass the opponents when they were down the middle (RTC = 4.1) and tended to not overpass when they were cross-court (RTC = 2.5). In conclusion, there are differences in the characteristics of lobs in professional padel according to sex. These results can be very useful for coaches for performing specific training on the lob according to the sex of their players. Full article
(This article belongs to the Special Issue Exercise Physiology and Biomechanics in Human Health)
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<p>Side of play and lob directions.</p>
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<p>Lobs in men’s professional padel: degree of association between the player’s side of play (black line: left side; blue line: right side) and direction ((<b>A</b>): down-the-line; (<b>B</b>): central zone; (<b>C</b>): cross-court).</p>
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<p>Lobs in women’s professional padel: degree of association between the player’s side of play (black line: left side; blue line: right side) and direction ((<b>A</b>): down-the line; (<b>B</b>): central zone; (<b>C</b>): cross-court).</p>
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<p>Lobs in men’s professional padel: degree of association between lob efficacy and direction.</p>
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<p>Lobs in women’s professional padel: degree of association between lob efficacy and direction.</p>
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11 pages, 1190 KiB  
Article
Comparative Analysis of Korean Nasal Morphology Using Cone-Beam Computed Tomography
by Jeong-Hyun Lee and Jong-Tae Park
Healthcare 2024, 12(18), 1839; https://doi.org/10.3390/healthcare12181839 - 13 Sep 2024
Viewed by 163
Abstract
Background/Objectives: Nasal morphology is a significant aspect of facial anatomy and is often used for forensic identification and aesthetic surgery. This study aims to compare nasal dimensions based on sex, facial index (FI), and nasal index (NI) using cone-beam computed tomography (CBCT) and [...] Read more.
Background/Objectives: Nasal morphology is a significant aspect of facial anatomy and is often used for forensic identification and aesthetic surgery. This study aims to compare nasal dimensions based on sex, facial index (FI), and nasal index (NI) using cone-beam computed tomography (CBCT) and 3D modeling. Methods: To observe differences in nasal dimensions by sex and analyze the relationships between facial shapes (FI) and nasal forms (NI), a total of 100 participants (50 males, 50 females) in their 20s were selected from Dankook University Dental Hospital. CBCT scans were performed, and 3D models were created using Mimics software (version 22.0). The measurement items included the alaria distance between (AL), the distance between N (nasion) and SN (subnasale), the distance between N (nasion) and PRN (pronasale), and the distance between SN (subnasale) and PRN (pronasale). A T-test was used for the sex-based analysis of the nasal dimensions, and the facial index- and nasal index-based nasal dimensions were analyzed using a one-way ANOVA with Scherffe’s post hoc test. Additionally, all the statistical analyses were performed using SPSS software (version 23.0). Results: The results indicated that males generally have larger nasal dimensions than females. Additionally, the mesoprosopic facial type (round face) showed the largest nasal dimensions in the FI classification, while the platyrrhine nasal type (broad and short nose) exhibited the largest dimensions in the NI classification. Conclusions: This study demonstrates that the nasal size varies significantly with sex, facial shape, and nasal form. The findings can contribute to forensic identification and provide valuable data for clinical practices in facial reconstruction and nasal surgery. Full article
(This article belongs to the Special Issue Innovations in Forensic Medicine)
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<p>Facial index measurement items. (1) Facial height (FH): the distance between the nasion (N) and the gnathion (GN); (2) facial width (FW): the bizygomatic distance from right to left zygion (ZY).</p>
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<p>Nasal index measurement items. (1) Nasal height (NH): the distance between the nasion (N) and the subnasale (SN); (2) nasal width (NW): the distance between each alaria (AL).</p>
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<p>Nasal size measurements items. (1) Nasal bridge length: the distance between the nasion (N) and the pronasale (PRN); (2) nasal tip protrusion: the distance between the subnasale (SN) and the pronasale (PRN).</p>
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9 pages, 2072 KiB  
Article
The Potential Role of Cell-Death Mechanisms in the Pathogenesis of Familial Mediterranean Fever Attacks: Granzyme A and Beyond
by Ece Yaglikara, Oguz Boluk, Yagmur Bayindir, Yelda Bilginer, Medine Aysin Tasar, Seza Ozen and Erdal Sag
Diagnostics 2024, 14(18), 2031; https://doi.org/10.3390/diagnostics14182031 - 13 Sep 2024
Viewed by 176
Abstract
Background: FMF is the most common autoinflammatory disease. The activation of the pyrin inflammasome is the mainstay of the pathogenesis, which might lead to a specific cell-death mechanism, pyroptosis. Pyroptosis is a programmed inflammatory cell death mediated by gasdermin proteins, featuring cell swelling, [...] Read more.
Background: FMF is the most common autoinflammatory disease. The activation of the pyrin inflammasome is the mainstay of the pathogenesis, which might lead to a specific cell-death mechanism, pyroptosis. Pyroptosis is a programmed inflammatory cell death mediated by gasdermin proteins, featuring cell swelling, membrane rupture, and release of inflammatory contents Aim: In this study we aimed to analyze the cell-death mechanisms in the pathogenesis of FMF attacks. Methods: Twenty-five FMF patients were included, and PFAPA patients (n = 10) and healthy controls (HC, n = 10) served as controls. We collected plasma samples from FMF and PFAPA patients during the attack and the attack-free period. We measured the soluble plasma levels of sFas, sFasL, granzyme A, granzyme B, perforin, granulysin, IL-2, IL-4, IL-10, IL-6, IL-17A, TNF-α, and IFN-γ by commercial pre-defined cytometric bead array kits. Results: There was no significant difference between groups in terms of sex and age between FMF patients and HCs, but PFAPA patients were younger than other groups due to the nature of the disease. We then analyzed the components of apoptosis and pyroptosis. The levels of sFasL (p = 0.035) and granzyme A (p = 0.038) in FMF patients were significantly increased during the attack period and decreased to levels comparable to HCs during the attack-free period. This increase was not seen in the PFAPA patients, with comparable levels with the HC group both during attack period and attack-free period. During the attack period of FMF patients, granzyme B (p = 0.145) and perforin (p = 0.203) levels were also increased; however, the differences were not statistically significant. The levels of sFasL, granzyme A, granzyme B, and perforin were closely correlated with each other during the attack period of FMF patients. Conclusions: Our study on death pathways during an FMF attack, suggests an upregulation in both pyroptosis through the granzyme-gasdermin pathway and apoptosis with the increased FasL and perforin levels, which was different from PFAPA patients. These findings might shed light on the reason for the nature of self-limited attacks, but further studies are needed to prove this hypothesis. Full article
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<p>Plasma levels of different cytokines during attack and attack-free periods. FMF (familial mediterranean fever); PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis); HC, (healthy control). (* <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Plasma levels of apoptosis and pyroptosis markers during the attack and attack-free period. FMF (familial mediterranean fever); PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis); HC, (healthy control). (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Correlations of the plasma levels of cell-death markers with each other.</p>
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17 pages, 340 KiB  
Article
Factors Associated with Older People’s Anxiety Symptom Positioning after COVID-19: Cross-Sectional Findings from a Canadian Sample
by Gail Low, Anila Naz AliSher, Juceli Morero, Zhiwei Gao, Gloria Gutman, Alex Franca and Sofia von Humboldt
Healthcare 2024, 12(18), 1837; https://doi.org/10.3390/healthcare12181837 - 13 Sep 2024
Viewed by 243
Abstract
This study sheds light on the personal characteristics of older Canadians self-identifying as severely anxious and the coping strategies that they gravitated to mitigate their anxiety. Our studied sample consisted of 606 Canadians aged 60 and above who took part in an e-survey [...] Read more.
This study sheds light on the personal characteristics of older Canadians self-identifying as severely anxious and the coping strategies that they gravitated to mitigate their anxiety. Our studied sample consisted of 606 Canadians aged 60 and above who took part in an e-survey across all 10 of Canada’s provinces, launched in July 2022, when social distancing was lifted across the country. Participants completed a personal characteristics questionnaire, the Geriatric Anxiety Scale or GAS-10, and a checklist of everyday coping strategies for mitigating anxiety. A seemingly greater number of severely anxious Canadians were born female, self-identified as a cisgender woman, and were in their 60s and in poor to fair health. A univariate logistic regression analysis revealed that all such personal characteristics were associated with statistically significantly greater odds of experiencing severe anxiety. In our multivariate logistic regression analysis, no significant differences were observed between the sexes (AOR = 0.590, p = 0.404), and non-binary and cisgender men (AOR = 0.689, p = 0.441) and women (AOR = 0.657, p = 0.397). Nor were there statistically significant differences in the odds of experiencing severe anxiety for those living with versus without a life partner and chronic illnesses. Older Canadians experiencing severe anxiety were far more likely to normalize their fear and anxiety (AOR = 4.76, p < 0.001), challenge their worries (AOR = 5.21, p < 0.001), and to relax or meditate (AOR = 2.36, p = < 0.001). They were less inclined to decrease other sources of stress in their lives, to stay active, and to get enough sleep. We offer anticipatory guidance for mental health program planners and practitioners, and fruitful avenues of inquiry for researchers. Full article
(This article belongs to the Special Issue The Impact of COVID-19 on Mental Health across Diverse Populations)
17 pages, 903 KiB  
Article
Parental Psychological Control and Risk-Taking among Taiwanese Adolescents and Emerging Adults: Benefit Perception as a Mediator
by Catherine P. Chou
Int. J. Environ. Res. Public Health 2024, 21(9), 1207; https://doi.org/10.3390/ijerph21091207 - 13 Sep 2024
Viewed by 200
Abstract
Youth risk-taking behaviors present important public health concerns due to their prevalence and potential adverse consequences, underscoring the need for research and prevention strategies to promote youth’s healthy development. The present research examined the relationship between parental psychological control and risk-taking behaviors via [...] Read more.
Youth risk-taking behaviors present important public health concerns due to their prevalence and potential adverse consequences, underscoring the need for research and prevention strategies to promote youth’s healthy development. The present research examined the relationship between parental psychological control and risk-taking behaviors via benefit perception among high school and college students in Taiwan. Using a cross-sectional design, the study surveyed 378 participants to assess maternal and paternal psychological control, benefit perception, and engagement in risk-taking behaviors. Results indicated no significant difference in psychological control or benefit perception between high school and college students. However, college students reported higher levels of risk-taking behaviors, such as risky driving, alcohol use, and unprotected sex. Both maternal and paternal psychological control positively correlated with benefit perception and risk-taking behaviors. Furthermore, benefit perception mediated the relationship between psychological control and risk-taking behavior among high school and college students. These findings suggested that parental psychological control indirectly influenced youth risk-taking by shaping their perceptions of the benefits of such behaviors. The study highlights the importance of promoting autonomy-supportive parenting to reduce risk-taking behaviors and advocates for programs that enhance decision-making skills among adolescents and emerging adults. Full article
(This article belongs to the Special Issue Health and Risk Behaviors in Adolescents and Youths)
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<p>Maternal mediation model. Note: * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01 (2-tailed). MPsy Control: maternal psychological control.</p>
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<p>Paternal mediation model. Note: * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01 (2-tailed). PPsy Control: paternal psychological control.</p>
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13 pages, 622 KiB  
Article
Comparative Study of Different Respiratory Muscle Training Methods: Effects on Cardiopulmonary Indices and Athletic Performance in Elite Short-Track Speedskaters
by Tomasz Kowalski, Andrzej Klusiewicz, Kinga Rębiś, Adrian Wilk and Michał Starczewski
Life 2024, 14(9), 1159; https://doi.org/10.3390/life14091159 - 13 Sep 2024
Viewed by 246
Abstract
Respiratory muscle training (RMT) improves endurance performance, balance, and ability to repeat high-intensity exercise bouts, providing a rationale to be applied in short-track speedskating. To establish a preferable RMT method for short-track speedskating, the influence of inspiratory pressure threshold loading (IPTL) and voluntary [...] Read more.
Respiratory muscle training (RMT) improves endurance performance, balance, and ability to repeat high-intensity exercise bouts, providing a rationale to be applied in short-track speedskating. To establish a preferable RMT method for short-track speedskating, the influence of inspiratory pressure threshold loading (IPTL) and voluntary isocapnic hyperpnoea (VIH) on cardiopulmonary indices and athletic performance was investigated. Sixteen elite short-track speedskaters completed 6 weeks of RMT based on IPTL or VIH. Wingate Anaerobic Tests (WAnTs), cardiopulmonary exercise tests (CPETs), spirometry assessments, and on-ice time trials were performed before and after RMT intervention. Repeated measures ANOVA was used to assess the differences between each method’s influence. No statistically significant (p > 0.05) differences between RMT methods were found in performance during the WAnT, CPET, or specific on-ice time trials. Spirometry measures were similar between both methods. Significant effects were found for the interaction between maximum breathing frequency during CPET (BFmax) and method (p = 0.009), as well as for the interaction between BFMax, method, and sex (p = 0.040). BFmax decreased for IPTL and increased for VIH. The interaction between method and sex revealed that BFmax increased only in males performing VIH. Our findings suggest that IPTL and VIH lead to analogous effects in the study participants, highlighting a negligible practical disparity in the impact of different RMT methods in elite short-track speedskaters. Full article
(This article belongs to the Special Issue Resistance Training Is Medicine)
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<p>Illustrative application of two RMT methods. (<b>A</b>) Presentation of inspiratory pressure threshold loading. (<b>B</b>) Presentation of voluntary isocapnic hyperpnoea.</p>
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14 pages, 6502 KiB  
Article
A Morphometric Study on the Dimensions of the Vertebral Canal and Intervertebral Discs from Th1 to S1 in Cats and Their Relevance for Spinal Diseases
by Jessica Richter, Christoph K. W. Mülling and Nicole Röhrmann
Vet. Sci. 2024, 11(9), 429; https://doi.org/10.3390/vetsci11090429 - 13 Sep 2024
Viewed by 186
Abstract
As part of the spine, the vertebral canal represents a central structure protecting the spinal cord running within it. Since alterations to the spinal canal and adjacent structures can have a significant impact on the spinal cord, knowledge of the physiological vertebral canal [...] Read more.
As part of the spine, the vertebral canal represents a central structure protecting the spinal cord running within it. Since alterations to the spinal canal and adjacent structures can have a significant impact on the spinal cord, knowledge of the physiological vertebral canal dimensions is essential. Compression of spinal nerves at the lumbosacral junction is the primary cause of cauda equina syndrome (CES). Although CES is common in dogs, it is rarely documented in cats. Given the lack of information on normal vertebral canal dimensions in cats, it is necessary to collect data and verify currently used measurements, to determine if and to what extent comparisons with dogs are valid. In 50 cats, interpedicular (ID) and midsagittal (SD) diameters were examined from the first thoracic (Th1) to the first sacral vertebra (S1). In 28 of these animals, the intervertebral disc width (IVDW) was measured. All data were gathered through gross anatomical dissection of the cats. Significant lumen reduction was evident in all cats from L6 to S1 with the narrowest point at S1. Narrowings were also found in the thoracic spine. The widest points coincide with the spinal cord enlargements. IVDW shows relatively constant values up to Th10–Th11 and peaks at L7–S1 in 95.65% of cats. While distinct similarities to dogs were observed, differences exist. The findings allow conclusions as to whether relations between the parameters and resulting predispositions to pathological changes can be derived. This could help the understanding of the pathogenesis of feline spinal diseases, particularly compressive myelopathies. Further studies are necessary to investigate the impact of age, sex and breed. Full article
(This article belongs to the Section Anatomy, Histology and Pathology)
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<p>Exemplary picture of the paramedian section in a cat.</p>
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<p>Overview of measuring parameters and their composition in transverse plane. ID = interpedicular diameter, SD = midsagittal diameter, dl = radius of the left half of the vertebra, dr = radius of the right half of the vertebra, v = saw blade loss.</p>
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<p>Illustration of the lumbosacral junction on right body half in one examined cat. Tapering of the vertebral canal in caudal orientation and reaching the narrowest point at the level of S1 are comprehensible. cr = cranial, ca = caudal, L6 = body of L6, L7 = body of L7, S1 = sacral basis, * narrowest point, ↓ = lumbosacral junction.</p>
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<p>(<b>A</b>) Interpedicular diameters (ID) and (<b>B</b>) midsagittal diameters (SD) measured at the center of each vertebra from Th1 up to S1 with respect to the mean length of the vertebral canal from Th1 to L7. Mean values are shown as squares and median values as horizontal lines inside the boxes. Outliers are displayed as black diamonds outside the boxes. The height of the box represents the interquartile range (IQR), which spans from the 25th (Q1) to the 75th (Q3) percentile. The whiskers are defined as lower extreme (Q1 − 1.5 × IQR) and upper extreme (Q3 + 1.5 × IQR), representing the maximum values within 1.5 × IQR, and may appear non-symmetrical due to variations in the data distribution.</p>
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<p>(<b>A</b>) Intervertebral disc widths (IVDW) from disc Th1–Th2 up to disc L7–S1 with respect to the mean length of the vertebral canal from Th1 to L7. Mean values are shown as squares and median values as horizontal lines inside the boxes. Outliers are displayed as black diamonds outside the boxes. The height of the box represents the interquartile range (IQR), which spans from the 25th (Q1) to the 75th (Q3) percentile. The whiskers are defined as lower extreme (Q1 − 1.5 × IQR) and upper extreme (Q3 + 1.5 × IQR), representing the maximum values within 1.5 × IQR, and may appear non-symmetrical due to variations in the data distribution. (<b>B</b>) Course of the intervertebral disc widths from disc Th9–Th10 up to disc L7–S1 shown as mean values with corresponding trend line. A distinct increase in the intervertebral disc width starting from disc Th11–Th12 and the peak at disc L7–S1 are visible.</p>
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<p>Combining illustration of interpedicular (ID) and midsagittal diameter (SD) as well as intervertebral disc width (IVDW) from Th1 to S1. The parameters are shown as mean values.</p>
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15 pages, 4185 KiB  
Article
Sex-Specific Behavioral and Molecular Responses to Maternal Lipopolysaccharide-Induced Immune Activation in a Murine Model: Implications for Neurodevelopmental Disorders
by Jing Xu, Rujuan Zhao, Mingyang Yan, Meng Zhou, Huanhuan Liu, Xueying Wang, Chang Lu, Qiang Li, Yan Mo, Paihao Zhang, Xingda Ju and Xianlu Zeng
Int. J. Mol. Sci. 2024, 25(18), 9885; https://doi.org/10.3390/ijms25189885 - 13 Sep 2024
Viewed by 229
Abstract
Maternal immune activation (MIA) during pregnancy has been increasingly recognized as a critical factor in the development of neurodevelopmental disorders, with potential sex-specific impacts that are not yet fully understood. In this study, we utilized a murine model to explore the behavioral and [...] Read more.
Maternal immune activation (MIA) during pregnancy has been increasingly recognized as a critical factor in the development of neurodevelopmental disorders, with potential sex-specific impacts that are not yet fully understood. In this study, we utilized a murine model to explore the behavioral and molecular consequences of MIA induced by lipopolysaccharide (LPS) administration on embryonic day 12.5. Our findings indicate that male offspring exposed to LPS exhibited significant increases in anxiety-like and depression-like behaviors, while female offspring did not show comparable changes. Molecular analyses revealed alterations in pro-inflammatory cytokine levels and synaptic gene expression in male offspring, suggesting that these molecular disruptions may underlie the observed behavioral differences. These results emphasize the importance of considering sex as a biological variable in studies of neurodevelopmental disorders and highlight the need for further molecular investigations to understand the mechanisms driving these sex-specific outcomes. Our study contributes to the growing evidence that prenatal immune challenges play a pivotal role in the etiology of neurodevelopmental disorders and underscores the potential for sex-specific preventative approaches of MIA. Full article
(This article belongs to the Special Issue Molecular Investigations in Neurodevelopmental Disorders)
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<p>LPS-induced MIA male offspring showed elevated anxiety in elevated plus maze test. (<b>A</b>) Schematic of the experimental design. Pregnant C57BL/6J mice were i.p. injected with lipopolysaccharide (LPS) (60 μg/kg) or Phosphate Buffered Saline (PBS) on E12.5 to induce maternal immune activation (MIA). E12.5, Embryonic day 12.5. Red box: the center of the chamber. (<b>B</b>) Maternal serum concentrations of IL-6 (PBS, <span class="html-italic">n</span> = 5, LPS, <span class="html-italic">n</span> = 4) at 3 h after PBS or LPS injection into pregnant dams at E12.5. Unpaired Student’s <span class="html-italic">t</span>-tests. *** <span class="html-italic">p</span> &lt; 0.001, Mean ± SEM. red line: the mean value. (<b>C</b>) Relative IL-6 mRNA expression in E12.5 at 3 h after PBS and LPS injection in placentas of pregnant mice (PBS, <span class="html-italic">n</span> = 10, LPS, <span class="html-italic">n</span> = 13). Unpaired Student’s <span class="html-italic">t</span> test. ** <span class="html-italic">p</span> &lt; 0.01. Mean ± SEM. (<b>D</b>) Heatmap of mouse movement in the elevated plus maze test in 5 min. (<b>E</b>) Number of entries to the close zone. (<b>F</b>) Time in the close zone. (<b>G</b>) Number of entries to the open zone. (<b>H</b>) Time in the open zone. (<b>E</b>–<b>H</b>) <span class="html-italic">n</span> = 16 per group; two-way ANOVA with Tukey’s post hoc tests. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. Means ± SEM.</p>
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<p>LPS-induced MIA male offspring showed elevated anxiety in open field test. (<b>A</b>) Heatmap of mouse movement in the open-field test in 5 min. (<b>B</b>) Average speed. (<b>C</b>) Total distance traveled. (<b>D</b>) Time in the center zone. (<b>E</b>) Total distance traveled in the center zone. (<b>F</b>) Time in the outside zone. (<b>G</b>) Total distance traveled in the outside zone. <span class="html-italic">n</span> = 18 per group; two-way ANOVA with Tukey’s post hoc tests. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001. Means ± SEM. LPS, lipopolysaccharide. MIA, maternal immune activation.</p>
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<p>LPS-induced MIA male offspring showed elevated levels of depression in tail suspension test. (<b>A</b>) Total time mobile. (<b>B</b>) Maximum movement speed. <span class="html-italic">n</span> = 17 per group; two-way ANOVA with Tukey’s post hoc tests. ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001. Means ± SEM. LPS, lipopolysaccharide. MIA, maternal immune activation.</p>
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<p>Maternal weight and offspring development in response to LPS exposure. (<b>A</b>) Maternal weight changes across embryonic days 12.5 to 18.5 post-PBS or LPS treatment. <span class="html-italic">n</span> = 4–19 per group, two-way ANOVA with Tukey’s post hoc tests. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001. Mean ± SEM. (<b>B</b>) Litter size differences between PBS and LPS groups. <span class="html-italic">n</span> = 5–7 per group, Mann–Whitney U test. (<b>C</b>) Offspring weight progression by sex. <span class="html-italic">n</span> = 4–15 per group, two-way ANOVA with Tukey’s post hoc tests. PBS-Female vs. LPS-Female, * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001. PBS-Male vs. LPS-Male, ++++ <span class="html-italic">p</span> &lt; 0.0001. Means ± SEM. LPS, lipopolysaccharide. MIA, maternal immune activation.</p>
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<p>LPS-induced MIA did not lead to noticeable alterations in the size of the offspring’s brain. (<b>A</b>) Schematic representation of brain statistics of PBS and LPS offspring. The horizontal blue arrow represents the width of brain, the vertical blue arrow indicates the length of brain, the cortical area is marked with a red line, and the red arrow signifies the length of the cortex. Scale bar = 5 mm. (<b>B</b>) Brain of PBS and LPS adult offspring. (<b>C</b>) Length of brain. (<b>D</b>) Width of brain. E Length of cortex. PBS male, <span class="html-italic">n</span> = 20; PBS female, <span class="html-italic">n</span> = 20; LPS male, <span class="html-italic">n</span> = 14; LPS female, <span class="html-italic">n</span> = 14; two-way ANOVA with Tukey’s post hoc tests. Means ± SEM. LPS, lipopolysaccharide. MIA, maternal immune activation.</p>
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<p>LPS-induced MIA promoted significant alterations in the synaptic-related genes of male offspring. (<b>A</b>) Luminex to measure the protein expression levels of various cytokines in the cortex of P0 offspring mice in PBS-M group, LPS-M group, PBS-F group, and LPS-F group (<span class="html-italic">n</span> = 3–5 per group). (<b>B</b>) PCR array experiments showing differential expression of genes associated with synaptic plasticity in the cortex of P0 offspring of mice of PBS-M, LPS-M, PBS-F, and LPS-F group. (<b>C</b>) Selected Gene ontology (GO) annotations enriched in the LPS-M and PBS-M groups. (<b>D</b>) Selected Gene ontology (GO) annotations enriched in the LPS-F and PBS-F groups. Bar plot shows the top 10 enrichment score [−log<sub>10</sub> (Q-value)] of DEGs involving a biological process. (<b>E</b>) Venn diagram showing shared and unique upregulated genes in the KEGG pathways within the cortices of PBS and LPS offspring of different sexes. (<b>F</b>) Venn diagram showing shared and unique downregulated genes in the KEGG pathways within the cortices of PBS and LPS offspring of different sexes. PBS-M, PBS-Male; LPS-M, LPS-Male; PBS-F, PBS-Female and LPS-F, LPS-Female. LPS, lipopolysaccharide. MIA, maternal immune activation.</p>
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12 pages, 511 KiB  
Article
A Retrospective Analysis of 1311 Oral Surgery Procedures Performed in a Pediatric Hospital in Barcelona: A Study of Their Characteristics and Age-Related Diagnoses
by Elvira Ferrés-Amat, Francisco Guinot-Jimeno, Ana Veloso-Durán, Josselyn Ñaupari-Pocomucha, Eduard Ferrés-Amat, Jordi Prats-Armengol, Javier Mareque-Bueno and Eduard Ferrés-Padró
J. Clin. Med. 2024, 13(18), 5427; https://doi.org/10.3390/jcm13185427 - 13 Sep 2024
Viewed by 231
Abstract
Background: Oral surgery involves the diagnosis and surgical treatment of diseases affecting the soft and hard tissues of the oral cavity and encompasses a wide range of surgical interventions. The aim of this investigation was to study the characteristics and age-related diagnoses of [...] Read more.
Background: Oral surgery involves the diagnosis and surgical treatment of diseases affecting the soft and hard tissues of the oral cavity and encompasses a wide range of surgical interventions. The aim of this investigation was to study the characteristics and age-related diagnoses of these oral surgeries, as well as to describe the surgical procedures performed in a pediatric oral and maxillofacial surgery service. Methods: A descriptive, retrospective, observational, and relational study was conducted on children and adolescents aged from 0 to 22 years who were treated in a pediatric oral and maxillofacial surgery service at a children’s hospital. Results: We analyzed 1311 surgical interventions (51.4% were on boys and 48.6% on girls), consisting of 24.8% soft tissue surgeries, 65.9% bone and dental tissue surgeries, and 9.3% mixed tissue surgeries. The most common pathologies were tooth eruption disorders (65.9%), followed by ankyloglossia (20.5%). The most frequent treatment was wisdom teeth extraction (31.3%). A statistically significant association (p < 0.05) was found between surgical treatments and variables such as age, sex, tissue type, and biopsy. Conclusions: This study enhances our understanding of pediatric oral surgery, emphasizing that the most common pathology is altered tooth eruption, while the most frequent surgical intervention is the extraction of wisdom teeth at different stages of development. Full article
(This article belongs to the Special Issue Clinical Research in Pediatric Dentistry)
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<p>Association between oral and maxillofacial surgery treatments and gender in childhood and adolescence in a pediatric hospital.</p>
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Article
HLA-A, -B, -C and -DRB1 Association with Autism Spectrum Disorder Risk: A Sex-Related Analysis in Italian ASD Children and Their Siblings
by Franca Rosa Guerini, Elisabetta Bolognesi, Martina Maria Mensi, Michela Zanette, Cristina Agliardi, Milena Zanzottera, Matteo Chiappedi, Silvia Annunziata, Francisco García-García, Anna Cavallini and Mario Clerici
Int. J. Mol. Sci. 2024, 25(18), 9879; https://doi.org/10.3390/ijms25189879 - 12 Sep 2024
Viewed by 237
Abstract
Autism Spectrum disorders (ASD) are diagnosed more often in males than in females, by a ratio of about 3:1; this is likely to be due to a difference in risk burden between the sexes and/or to “compensatory skills” in females, that may delay [...] Read more.
Autism Spectrum disorders (ASD) are diagnosed more often in males than in females, by a ratio of about 3:1; this is likely to be due to a difference in risk burden between the sexes and/or to “compensatory skills” in females, that may delay the diagnosis of ASD. Identifying specific risk factors for ASD in females may be important in facilitating early diagnosis. We investigated whether HLA- class I: -A, -B, -C and class II -DRB1 alleles, which have been suggested to play a role in the development of ASD, can be considered as sex-related risk/protective markers towards the ASD. We performed HLA allele genotyping in 178 Italian children with ASD, 94 healthy siblings, and their parents. HLA allele distribution was compared between children with ASD, sex-matched healthy siblings, and a cohort of healthy controls (HC) enrolled in the Italian bone marrow donor registry. Allele transmission from parents to children with ASD and their siblings was also assessed. Our findings suggest that HLA-A*02, B*38, and C*12 alleles are more frequently carried by females with ASD compared to both HC and healthy female siblings, indicating these alleles as potential risk factors for ASD in females. Conversely, the HLA-A*03 allele was more commonly transmitted to healthy female siblings, suggesting it might have a protective effect. Additionally, the HLA-B*44 allele was found to be more prevalent in boys with ASD, indicating it is a potential risk factor for male patients. This is the first Italian study of sex-related HLA association with ASD. If confirmed, these results could facilitate early ASD diagnosis in female patients, allowing earlier interventions, which are crucial in the management of neurodevelopmental disorders. Full article
(This article belongs to the Special Issue Genetic Basis of Autism Spectrum Disorder)
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<p>(<b>A</b>): HLA-A allele distribution in 3571 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 178 ASD children (ASD vs. HC <span class="html-italic">p<sub>c</sub></span> = 0.05, df = 19), and 47 healthy SIBS (ASD vs. SIBS <span class="html-italic">p<sub>c</sub></span> = 0.06, df = 13). (<b>B</b>): HLA-A allele distribution in 3571 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 41 female ASD (fASD) (HC vs. fASD <span class="html-italic">p<sub>c</sub></span> = 0.05, df = 19), and 137 male ASD (mASD) (HC vs. mASD <span class="html-italic">p<sub>c</sub></span> = 0.09, df = 19). (<b>C)</b>: HLA-A allele distribution in 41 fASD and 31 female sibs (fSIBS) (<span class="html-italic">p<sub>c</sub></span> = 0.07, df = 12) * (<span class="html-italic">p</span> = 0.03, <span class="html-italic">p<sub>c</sub></span> = 0.36; OR: 2.4; 95%CI: 1.1–5.5); § (<span class="html-italic">p</span> = 0.006, <span class="html-italic">p<sub>c</sub></span> = 0.07; OR: 0.27; 95%CI: 0.1–0.7. (<b>D</b>): HLA-A allele distribution in 137 mASD and 16 male sibs (mSIBS) (<span class="html-italic">p<sub>c</sub></span> = 0.11, df = 13).</p>
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<p>(<b>A</b>): HLA-B allele distribution in 7591 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 178 ASD children (ASD vs. HC <span class="html-italic">p<sub>c</sub></span> &lt; 0.001, df = 36) and 47 healthy SIBS (ASD vs. SIBS <span class="html-italic">p<sub>c</sub></span> = 0.29, df = 29). * (<span class="html-italic">p</span> = 0.002, <span class="html-italic">p<sub>c</sub></span>= 0.07 OR: 0.4; 95%CI: 0.2–0.8); ^ (<span class="html-italic">p</span> &lt; 0.0001, <span class="html-italic">p<sub>c</sub></span> &lt; 0.001 OR: 2.9; 95%CI: 1.9–4.4); § (<span class="html-italic">p</span> = 0.03, <span class="html-italic">p<sub>c</sub></span>=0.72 OR: 1.5; 95%CI: 1.1–2.1) (<b>B</b>): HLA-B allele distribution in 7591 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 41 female ASD (fASD) (fASD vs. HC <span class="html-italic">p<sub>c</sub></span> &lt; 0.001, df=35), and 137 male ASD (mASD) (mASD vs. HC <span class="html-italic">p<sub>c</sub></span>&lt; 0.001, df = 34) * (<span class="html-italic">p</span> = 0.01, <span class="html-italic">p<sub>c</sub></span> = 0.36 OR: 0.5; 95%CI: 0.2–0.8) ° (<span class="html-italic">p</span> &lt; 0.001, <span class="html-italic">p<sub>c</sub></span> = 0.01 OR: 4.9; 95%CI: 2.2–3.4); ^ (<span class="html-italic">p</span> = 0.006, <span class="html-italic">p<sub>c</sub></span> = 0.21 OR: 2.4; 95%CI: 1.3–3.9); § (<span class="html-italic">p</span> = 0.02, <span class="html-italic">p<sub>c</sub></span> = 0.70 OR: 1.6; 95%CI: 1.1–2.4) (<b>C</b>): HLA-B allele distribution in 41 female ASD (fASD) and 31 female sibs (fSIBS) (fASD vs. fSIBS <span class="html-italic">p<sub>c</sub></span> = 0.44, df = 24) * (<span class="html-italic">p<sub>f</sub></span> = 0.01, <span class="html-italic">p<sub>c</sub></span> = 0.24 df = 24); (<b>D</b>): HLA-B allele distribution in 137 male ASD (mASD) and 16 male sibs (mSIBS) (mASD vs. mSIBS <span class="html-italic">p<sub>c</sub></span> = 0.005, df = 27) * (<span class="html-italic">p</span> = 0.0001, <span class="html-italic">p<sub>c</sub></span> = 0.003 OR: 0.08; 95%CI: 0.02–0.3).</p>
Full article ">Figure 2 Cont.
<p>(<b>A</b>): HLA-B allele distribution in 7591 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 178 ASD children (ASD vs. HC <span class="html-italic">p<sub>c</sub></span> &lt; 0.001, df = 36) and 47 healthy SIBS (ASD vs. SIBS <span class="html-italic">p<sub>c</sub></span> = 0.29, df = 29). * (<span class="html-italic">p</span> = 0.002, <span class="html-italic">p<sub>c</sub></span>= 0.07 OR: 0.4; 95%CI: 0.2–0.8); ^ (<span class="html-italic">p</span> &lt; 0.0001, <span class="html-italic">p<sub>c</sub></span> &lt; 0.001 OR: 2.9; 95%CI: 1.9–4.4); § (<span class="html-italic">p</span> = 0.03, <span class="html-italic">p<sub>c</sub></span>=0.72 OR: 1.5; 95%CI: 1.1–2.1) (<b>B</b>): HLA-B allele distribution in 7591 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 41 female ASD (fASD) (fASD vs. HC <span class="html-italic">p<sub>c</sub></span> &lt; 0.001, df=35), and 137 male ASD (mASD) (mASD vs. HC <span class="html-italic">p<sub>c</sub></span>&lt; 0.001, df = 34) * (<span class="html-italic">p</span> = 0.01, <span class="html-italic">p<sub>c</sub></span> = 0.36 OR: 0.5; 95%CI: 0.2–0.8) ° (<span class="html-italic">p</span> &lt; 0.001, <span class="html-italic">p<sub>c</sub></span> = 0.01 OR: 4.9; 95%CI: 2.2–3.4); ^ (<span class="html-italic">p</span> = 0.006, <span class="html-italic">p<sub>c</sub></span> = 0.21 OR: 2.4; 95%CI: 1.3–3.9); § (<span class="html-italic">p</span> = 0.02, <span class="html-italic">p<sub>c</sub></span> = 0.70 OR: 1.6; 95%CI: 1.1–2.4) (<b>C</b>): HLA-B allele distribution in 41 female ASD (fASD) and 31 female sibs (fSIBS) (fASD vs. fSIBS <span class="html-italic">p<sub>c</sub></span> = 0.44, df = 24) * (<span class="html-italic">p<sub>f</sub></span> = 0.01, <span class="html-italic">p<sub>c</sub></span> = 0.24 df = 24); (<b>D</b>): HLA-B allele distribution in 137 male ASD (mASD) and 16 male sibs (mSIBS) (mASD vs. mSIBS <span class="html-italic">p<sub>c</sub></span> = 0.005, df = 27) * (<span class="html-italic">p</span> = 0.0001, <span class="html-italic">p<sub>c</sub></span> = 0.003 OR: 0.08; 95%CI: 0.02–0.3).</p>
Full article ">Figure 3
<p>(<b>A</b>): HLA-C allele distribution in 4715 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 178 ASD children (ASD vs. HC <span class="html-italic">p<sub>c</sub></span> = 0.006, df = 13) and 47 healthy SIBS (ASD vs. SIBS <span class="html-italic">p<sub>c</sub></span> = 0.35, df = 12). * (<span class="html-italic">p</span> = 0.02, <span class="html-italic">p<sub>c</sub></span> = 0.26 OR: 0.7; 95%CI: 0.5–0.9); ° (<span class="html-italic">p</span> = 0.01, <span class="html-italic">p<sub>c</sub></span> = 0.13 OR: 1.5; 95%CI: 1.1–2.0). (<b>B</b>): HLA-C allele distribution in 4715 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 41 female ASD (fASD) (fASD vs. HC <span class="html-italic">p<sub>c</sub></span> = 0.23, df = 13), and 137 male ASD (mASD) (mASD vs. HC <span class="html-italic">p<sub>c</sub></span> = 0.14, df = 13); * (<span class="html-italic">p</span> = 0.04, <span class="html-italic">p<sub>c</sub></span> = 0.52 OR: 0.7; 95%CI: 0.5–1.0); ° (<span class="html-italic">p</span> = 0.05, <span class="html-italic">p<sub>c</sub></span> = 0.65 OR: 1.8; 95%CI: 1.0–3.1). (<b>C</b>): HLA-C allele distribution in 41 fASD and 31 female sibs (fSIBS) (fASD vs. fSIBS <span class="html-italic">p<sub>c</sub></span> = 0.12, df = 11) * (p<sub>f</sub> = 0.008, <span class="html-italic">p<sub>c</sub></span> = 0.09 OR: 6.6; 95%CI: 1.6–44.5). (<b>D)</b>: HLA-C allele distribution in 137 mASD and 16 male sibs (mSIBS) (mASD vs. mSIBS <span class="html-italic">p<sub>c</sub></span> = 0.69, df = 12).</p>
Full article ">Figure 4
<p>(<b>A</b>): HLA-DRB1 allele distribution in 57,345 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 178 ASD children (ASD vs. HC <span class="html-italic">p<sub>c</sub></span> &lt; 0.001, df = 12), and 47 healthy SIBS (ASD vs. SIBS <span class="html-italic">p<sub>c</sub></span> = 0.86, df = 12) * (<span class="html-italic">p</span> = 0.001, <span class="html-italic">p<sub>c</sub></span> = 0.01 OR: 0.7; 95%CI: 0.4–0.8); ° (<span class="html-italic">p</span> = 0.02, <span class="html-italic">p<sub>c</sub></span> = 0.24 OR: 1.4; 95%CI: 1.1–1.9). (<b>B</b>): HLA-DRB1 allele distribution in 57,345 HC [<a href="#B23-ijms-25-09879" class="html-bibr">23</a>], 41 female ASD (fASD) (fASD vs. HC <span class="html-italic">p<sub>c</sub></span> = 0.23, df = 12), and 137 male ASD (mASD) (mASD vs. HC <span class="html-italic">p<sub>c</sub></span> = 0.002, df = 12) * <span class="html-italic">p</span> = 0.001 <span class="html-italic">p<sub>c</sub></span> = 0.01 OR: 0.6; 95%CI: 0.5–0.8. (<b>C</b>): HLA-DRB1 allele distribution in 41 fASD and 31 female sibs (fSIBS) (fASD vs. fSIBS <span class="html-italic">p<sub>c</sub></span> = 0.96, df = 12). (<b>D</b>): HLA-DRB1 allele distribution in 137 mASD and 16 male sibs (mSIBS) (mASD vs. mSIBS <span class="html-italic">p<sub>c</sub></span> = 0.72, df = 12).</p>
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