"Genotype-first" approaches on a curious case of idiopathic progressive cognitive decline

Background In developing countries, many cases with rare neurological diseases remain undiagnosed due to limited diagnostic experience. We encountered a case in China where two siblings both began to develop idiopathic progressive cognitive decline starting from age six, and were suspected to have an undiagnosed neurological disease. Methods Initial clinical assessments included review of medical history, comprehensive physical examination, genetic testing for metabolic diseases, blood tests and brain imaging. We performed exome sequencing with Agilent SureSelect exon capture and Illumina HiSeq2000 platform, followed by variant annotation and selection of rare, shared mutations that fit a recessive model of inheritance. To assess functional impacts of candidate variants, we performed extensive biochemical tests in blood and urine, and examined their possible roles by protein structure modeling. Results Exome sequencing identified NAGLU as the most likely candidate gene with compound heterozygous mutations (chr17:40695717C > T and chr17:40693129A > G in hg19 coordinate), which were documented to be pathogenic. Sanger sequencing confirmed the recessive patterns of inheritance, leading to a genetic diagnosis of Sanfilippo syndrome (mucopolysaccharidosis IIIB). Biochemical tests confirmed the complete loss of activity of alpha-N-acetylglucosaminidase (encoded by NAGLU) in blood, as well as significantly elevated dermatan sulfate and heparan sulfate in urine. Structure modeling revealed the mechanism on how the two variants affect protein structural stability. Conclusions Successful diagnosis of a rare genetic disorder with an atypical phenotypic presentation confirmed that such “genotype-first” approaches can particularly succeed in areas of the world with insufficient medical genetics expertise and with cost-prohibitive in-depth phenotyping

Clinical and mutational features of three Chinese children with congenital generalized lipodystrophy

Objective: To investigate the clinical and molecular features of congenital generalized lipodystrophy (CGL) in three Chinese patients with various typical manifestations. Methods: Data on clinical symptoms, results of laboratory analyses, and previous treatments in three Chinese patients were collected by a retrospective review of medical records. All coding regions and adjacent exon–intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase chain reaction and sequenced.Results: Generalized lipodystrophy, acanthosis nigricans, muscular hypertrophy, severe hypertriglyceridemia, and hepatomegaly were features in all three patients. Patient 1 developed diabetes mellitus at the early age of 2 months and he was the youngest CGL patient reported with overt diabetes. Patient 2 was found to have cardiomyopathy when she was aged 6 months. All of the patients were found to have mutations in the BSCL2 gene, but none of these was a novel mutation. We did not find any AGPAT2 mutation in our patients.Conclusion: All of our patients exhibited characteristic features of CGL due to mutations in the BSCL2 gene

Poly(m-Phenylenediamine) Nanospheres and Nanorods: Selective Synthesis and Their Application for Multiplex Nucleic Acid Detection

In this paper, we demonstrate for the first time that poly(m-phenylenediamine) (PMPD) nanospheres and nanorods can be selectively synthesized via chemical oxidation polymerization of m-phenylenediamine (MPD) monomers using ammonium persulfate (APS) as an oxidant at room temperature. It suggests that the pH value plays a critical role in controlling the the morphology of the nanostructures and fast polymerization rate favors the anisotropic growth of PMPD under homogeneous nucleation condition. We further demonstrate that such PMPD nanostructures can be used as an effective fluorescent sensing platform for multiplex nucleic acid detection. A detection limit as low as 50 pM and a high selectivity down to single-base mismatch could be achieved. The fluorescence quenching is attributed to photoinduced electron transfer from nitrogen atom in PMPD to excited fluorophore. Most importantly, the successful use of this sensing platform in human blood serum system is also demonstrated

Cadmium Addition Effects on Anaerobic Digestion with Elevated Temperatures

Anaerobic fermentation with biogas as an energy source is influenced by the presence of heavy metals. However, the availability of the heavy metals is dependent on the digestion temperature. In this study, the impacts of Cd on the characteristics of biogas, substrate biodegradation, and enzyme activity during anaerobic co-digestion were investigated under varying digestion temperatures. The results showed that 1 mg/L initial Cd concentration improved cumulative biogas yields by 404.96%, 16.93%, and 5.56% at 55 °C, 45 °C, and 35 °C, respectively. In contrast, at low temperatures (25 °C), the yield decreased by 0.77%. In the 55 °C group, Cd addition improved the activity of cellulase (p < 0.05) and coenzyme F420 (p < 0.01). The total chemical oxygen demand (COD) during the peak period and the transformation of hydrolytic organic components into volatile fatty acids (VFAs) influenced the CH4 and biogas yields. There were no significant differences in cellulase, dehydrogenase, and coenzyme F420 activities with or without Cd addition when the digestion temperature was 45 °C, 35 °C, and 25 °C. Therefore, thermophilic digestion is recommended for the efficient degradation of Cd-contaminated biowaste. Moreover, the impact of metals on the performance of anaerobic digestion should be considered together with temperature conditions in future research and practice

Triglyceride-glucose index as a valuable predictor for aged 65-years and above in critical delirium patients: evidence from a multi-center study

Abstract Background The triglyceride-glucose index (TyG), an established indicator of insulin resistance, is closely correlated with the prognosis of several metabolic disorders. This study aims to investigate the association between the TyG index and the incidence of critical delirium in patients aged 65 years and older. Methods We focused on evaluating patients aged 65 years and older diagnosed with critical delirium. Data were obtained from the Medical Information Database for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Multivariate logistic regression and restricted cubic spline (RCS) regression were used to determine the relationship between the TyG index and the risk of delirium. Results Participants aged 65 years and older were identified from the MIMIC-IV (n = 4,649) and eICU-CRD (n = 1,844) databases. Based on optimal thresholds derived from RCS regression, participants were divided into two cohorts: Q1 (< 8.912), Q2 (≥ 8.912). The logistic regression analysis showed a direct correlation between the TyG index and an increased risk of critical delirium among ICU patients aged 65 and older. These findings were validated in the eICU-CRD dataset, and sensitivity analysis further strengthened our conclusions. In addition, the subgroup analysis revealed certain differences. Conclusion This study highlights a clear, independent relationship between the TyG index and the risk of critical delirium in individuals aged 65 years and older, suggesting the importance of the TyG index as a reliable cardio-cerebrovascular metabolic marker for risk assessment and intervention

Does ICU admission dysphagia independently contribute to delirium risk in ischemic stroke patients? Results from a cohort study

Abstract Background Delirium is prevalent in ischemic stroke patients, particularly those in the intensive care unit (ICU), and it poses a significant burden on patients and caregivers, leading to increased mortality rates, prolonged hospital stays, and impaired cognitive function. Dysphagia, a common symptom in critically ill patients with ischemic stroke, further complicates their condition. However, the association between dysphagia and delirium in this context remains unclear. The objective of this study was to investigate the correlation between dysphagia and delirium in ICU patients with ischemic stroke. Methods A retrospective analysis was conducted on adult patients diagnosed with ischemic stroke at a medical center in Boston. Ischemic stroke cases were identified using the ninth and tenth revisions of the International Classification of Diseases. Dysphagia was defined as a positive bedside swallowing screen performed by medical staff on the day of ICU admission, while delirium was assessed using the ICU Confusion Assessment Method and review of nursing notes. Logistic regression models were used to explore the association between dysphagia and delirium. Causal mediation analysis was employed to identify potential mediating variables. Results The study comprised 1838 participants, with a median age of approximately 70 years, and 50.5% were female. Among the total study population, the prevalence of delirium was 43.4%, with a higher prevalence observed in the dysphagia group (60.7% vs. 40.8%, p < 0.001) compared to the non-dysphagia group. After adjusting for confounding factors including age, sex, race, dementia, depression, sedative medications, history of falls, visual or hearing deficit, sequential organ failure score, and Glasgow coma score, multifactorial logistic regression analysis demonstrated a significant association between dysphagia and an increased likelihood of delirium (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07–2.05; p = 0.018; E-value = 1.73). Causal mediation analysis revealed that serum albumin levels partially mediated the association between dysphagia and delirium in critically ill patients with ischemic stroke (average causal mediated effect [ACME]: 0.02, 95% CI: 0.01 to 0.03; p < 0.001). Conclusion ICU admission dysphagia may independently contribute to the risk of delirium in patients with ischemic stroke. Early identification and intervention in ischemic stroke patients with dysphagia may help mitigate the risk of delirium and improve patient prognosis

Effects of Media and Social Standing on Smoking Behaviors among Adolescents in China

Many studies have documented associations between peer influences and smoking among US and Chinese adolescents. Few studies, however, have shown how these influences occur in relation to adolescents\u27 positions in their social networks. Social media channels such as online social networking and text messaging extend adolescents\u27 networks and sphere of influence. This study examines the interplay between social media channels, peer influences, and smoking outcomes. Data were collected from 6,073 students from 24 high schools in Chengdu, China. Multilevel models suggest that mobile phone use (AOR = 1.45, p \u3c .0001) and social Internet activity are risk factors for smoking (AOR = 1.18, p = .002), whereas informational Internet activity is protective (AOR = 0.87, p = .038). High social status was also positively associated with smoking (AOR = 1.16, p = .001), whereas the relationship with smoking intentions was moderated by mobile phone use (AOR = 1.11, p = .013). Findings suggest that media usage and social standing may have differential effects on smoking and other risky adolescent behaviors

Comparative Analysis of Single-stage and Two-stage Fermentation Systems under Various Process Conditions

A comparative study of single-stage fermentation (wet or dry) and two-stage (wet-dry and dry-wet) fermentation systems was carried out under medium temperature conditions. The effect of the length of the first wet or dry fermentation stage (5-, 10-, 15-, 20-, and 25-d) in the two-stage anaerobic fermentation was investigated. The results showed that the gas production of wet fermentation and two-stage wet-dry fermentation was better than that of the dry fermentation and two-stage dry-wet fermentation. The cumulative gas production increased gradually with increased stage conversion times for the two-stage wet-dry fermentation. The gas production for the 20-d experimental group of the two-stage wet-dry fermentation system was the best. The cumulative biogas production in the anaerobic fermentation of straw correlated significantly with the changes in the degradation rates of volatile solids, cellulose, and hemicellulose (P < 0.01). The kinetic fitting analysis showed that the Reaction Curve (RC) model was more suitable for data modeling of the single-stage wet fermentation and two-stage wet-dry fermentation with straw than the Modified Gompertz (GM) and Modified Logistic (LM) models. The results of this study provided a theoretical basis for choosing a fermentation process for large-scale biogas production with straw