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Purpose: To investigate the perceptions of parents/caregivers about the impact of oral conditions on the oral health-related quality of life (OHRQoL) of children/adolescents with autism spectrum disorder (ASD) compared to the perceptions of parents/caregivers of children/adolescents without ASD. Methods: A comparative cross-sectional study was conducted involving 80 children/adolescents with ASD three to 16 years of age matched by sex and age with 80 children/adolescents without ASD and their parents/caregivers. Clinical examinations were performed for the diagnosis of dental caries experience (DMFT/dmft), clinical consequences of untreated dental caries (PUFA/pufa), visible plaque (VPI), bleeding on probing (BPI), malocclusion and traumatic dental injury (TDI). Parents/caregivers answered a questionnaire addressing sociodemographic characteristics and the Brazilian version of the Parental-Caregiver Perceptions Questionnaire (P-CPQ), which measures OHRQoL from the perspective of parents/caregivers. Data analysis involved the Wilcoxon test, chi-squared test and Poisson regression. Results: Dental caries experience impacted OHRQoL in the group with ASD regarding the total P-CPQ score (p < 0.001) as well as the "oral symptoms" (p = 0.011) and "wellbeing" (p < 0.011) domains. No differences were found between the perceptions of parents/caregivers of children/adolescents with ASD and perceptions of parents/caregivers of children/adolescents without ASD (p = 0.721). Conclusion: Dental caries experience can have a negative impact on the OHRQoL of children/adolescents with ASD.

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Abstract Background Long-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD. Methods This retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported. Results Patients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients’ total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment. Conclusions The significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations.

Abstract Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Context: Cytochrome C oxidase (COX) is the fourth component of the respiratory chain and is located within the internal membrane of mitochondria. COX deficiency causes an inherited mitochondrial disease with significant genetic and phenotypic heterogeneity. Four clinical subtypes have been identified, each with distinct phenotypes and genetic variants. Mitochondrial complex IV deficiency nuclear type 4 (MC4DN4) is a form of COX deficiency associated with pathogenic variants in the SCO1 gene. Case description: We describe three patients with MC4DN4 with developmental and epileptic encephalopathy (DEE), hypopituitarism, and SCO1 pathogenic variants. These patients’ phenotypes considerably differ from previously reported MC4DN4 phenotypes as they associate DEE with progressive hypopituitarism and survival beyond the first months after birth. Pituitary deficiency in these patients progressively worsened and mainly involved growth hormone secretion and thyroid function. Conclusions: Our findings expand knowledge of phenotypic variability in MC4DN4 and suggest that SCO1 is a candidate gene for genetic hypopituitarism and DEE. Significance statement Our paper describes three patients affected by MC4DN4 with hypopituitarism and developmental and epileptic encephalopathy (DEE), two features that have never been associated with this condition. In addition, we reviewed the clinical features of all previous cases of MC4DN4 to give the other clinicians a wide picture of the clinical phenotype of this genetic disease. We hope that the publication of our data may help others to identify this disease and consider the chance to analyze the SCO1 gene in cases of DEE associated with pituitary dysfunction. Our article contributes to expanding the spectrum of genetic hypopituitarism and proposes a model to explain an association between this condition, mitochondrial anomalies, and neurodevelopmental defects.

Academic underachievement refers to school performance which falls below expectations. Focusing on the pivotal first stage of education, we explored a quantitative measure of underachievement using genomically predicted achievement delta (GPA[delta]), which reflects the difference between observed and expected achievement predicted by genome-wide polygenic scores. We analyzed the relationship between GPA[delta] at age 7 and achievement trajectories from ages 7 to 16, using longitudinal data from 4175 participants in the Twins Early Development Study to assess empirically the extent to which students regress to their genomically predicted levels by age 16. We found that the achievement of underachievers and overachievers who deviated from their genomic predictions at age 7 regressed on average by one-third towards their genomically predicted levels. We also found that GPA[delta] at age 7 was as predictive of achievement trajectories as a traditional ability-based index of underachievement. Targeting GPA[delta] underachievers might prove cost-effective because such interventions seem more likely to succeed by going with the genetic flow rather than swimming upstream, helping GPA[delta] underachievers reach their genetic potential as predicted by their GPS. However, this is a hypothesis that needs to be tested in intervention research investigating whether GPA[delta] underachievers respond better to the intervention than other underachievers. We discuss the practicality of genomic indices in assessing underachievement.

The aim of this study was to evaluate the effects of supplementing OC enriched in polyphenols (EOC) to mid-lactating Holstein cows on milk quality, metabolic response, and rumen fermentation and microbiota. Twenty multiparous Holstein dairy cows (10 cows/group) were enrolled for 30 d in two homogeneous groups according to milk yield, days in milking, parity, and body condition score. The control group (CTR) received no supplemented concentrate, whereas the EOC group received concentrate with a 7% inclusion of EOC. Milk and blood samples were collected at 0 d and 30 d of treatment, while rumen fluid samples were collected after 30 d of treatment. Overall, the dietary supplementation of EOC did not affect milk yield and its quality, rumen pH, and rumen VFA. However, milk of EOC cows had lower C10:0, C12:0, C14:0, and C16:0 content, and greater C18:0, C18:1 cis-9, and C18:2 n6 content, compared with CTR cows. Regarding the rumen microbiota composition, EOC diet increased the relative abundance of Bacteroidales_RF16_group, Absconditabacteriales_(SR1), and Fibrobacteracea in the rumen. On cow’s metabolism, EOC cows showed lower blood haptoglobin and greater ferric reducing antioxidant power (FRAP), cholesterol, and Zn levels compared with CTR cows. The supplementation of EOC led to a milder low-grade inflammatory response of cows and a positive modulation of cholesterol synthesis (probably at both intestinal and hepatic level). Supplementing EOC modulated rumen microbiota and improved the lipid profile of milk. Thereby, OC may be considered a valid feed to be included in the dairy cow’s diet leading to a positive effects on dairy cattle metabolism (less low-grade inflammatory response and oxidative stress) and at the same time giving an added value to the milk with a better profile of the fatty acids.

Objectives. This study aimed to analyze an indication of physical exercise on the increase of cardiac troponin (cTn) levels as a marker of myocardial infarction from the physiological perspective. Materials and methods. A search of journal databases including MEDLINE-Pubmed, Web of Science, Scopus, and Science Direct was used in this systematic review study. The inclusion criteria were papers that addressed cardiac troponin (cTn), physical activity, and myocardial infarction, and were published within the last five years. Using the databases Science Direct, Pubmed, and Web of Science, 83 recognized publications were found. For this systematic review, finally ten publications that fulfilled the requirements for inclusion were chosen and examined. This study evaluated standard operating procedures using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results. This systematic review reports that physical exercise has been found to increase cardiac troponin (cTn) levels as a marker of myocardial infarction, but this increase is triggered by the body’s physiological response during exercise and is not considered as a pathological response. Conclusions. According to the findings of the study, physical exercise has been proven to elevate the risk of heart muscle damage by triggering an increase in cardiac troponin (cTn). However, this feature occurs in a physiological state and represents an exercise adaptation process. An analysis of the relevant articles reveals that this increase in cardiac troponin (cTn) has not been shown to have a negative influence on developing cardiovascular disease.

Abstract Background Individuals with type 2 diabetes (T2D) face an increased mortality risk, not fully captured by canonical risk factors. Biological age estimation through DNA methylation (DNAm), i.e. the epigenetic clocks, is emerging as a possible tool to improve risk stratification for multiple outcomes. However, whether these tools predict mortality independently of canonical risk factors in subjects with T2D is unknown. Methods Among a cohort of 568 T2D patients followed for 16.8 years, we selected a subgroup of 50 subjects, 27 survived and 23 deceased at present, passing the quality check and balanced for all risk factors after propensity score matching. We analyzed DNAm from peripheral blood leukocytes using the Infinium Human MethylationEPIC BeadChip (Illumina) to evaluate biological aging through previously validated epigenetic clocks and assess the DNAm-estimated levels of selected inflammatory proteins and blood cell counts. We tested the associations of these estimates with mortality using two-stage residual-outcome regression analysis, creating a reference model on data from the group of survived patients. Results Deceased subjects had higher median epigenetic age expressed with DNAmPhenoAge algorithm (57.49 [54.72; 60.58] years. vs. 53.40 [49.73; 56.75] years; p = 0.012), and accelerated DunedinPoAm pace of aging (1.05 [1.02; 1.11] vs. 1.02 [0.98; 1.06]; p = 0.012). DNAm PhenoAge (HR 1.16, 95% CI 1.05–1.28; p = 0.004) and DunedinPoAm (HR 3.65, 95% CI 1.43–9.35; p = 0.007) showed an association with mortality independently of canonical risk factors. The epigenetic predictors of 3 chronic inflammation-related proteins, i.e. CXCL10, CXCL11 and enRAGE, C-reactive protein methylation risk score and DNAm-based estimates of exhausted CD8 + T cell counts were higher in deceased subjects when compared to survived. Conclusions These findings suggest that biological aging, as estimated through existing epigenetic tools, is associated with mortality risk in individuals with T2D, independently of common risk factors and that increased DNAm-surrogates of inflammatory protein levels characterize deceased T2D patients. Replication in larger cohorts is needed to assess the potential of this approach to refine mortality risk in T2D.

We present a morphological-systematic study of new fossil specimens of equisetaleans (horsetails) from the Cortaderita Formation, Sorocayense Group, Middle Triassic, Cuyana Basin, southwest of the San Juan Province, Argentina. In this unit, nine fossiliferous strata with plant remains have been recognized (EF4–12). The fossils studied come from EF4, located in the lower member of the formation, and correspond to impressions-compressions. The fossils are assigned to the family Equisetaceae and the genus Equicalastrobus, being the oldest record of the genus and the first record of this taxon for Argentina and Gondwana. The samples are closed and open strobili composed of peltate sporangio-phores, with glabrous hexagonal discs and with an umbo on its external face which projects, acquiring a leaf shape. Some specimens are found in organic connection with leaf sheaths and axis fragments, allowing the whole plant to be reconstructed.