Association Between Autism Spectrum Disorders and Cardiometabolic Diseases: A Systematic Review and Meta-analysis.

Importance: Although the increased risk of obesity among individuals with autism has been well established, evidence on the association between autism, cardiometabolic disorders, and obesity remains inconclusive. Objective: To examine the association between autism spectrum disorders and cardiometabolic diseases in a systematic review and meta-analysis. Data Sources: PubMed, Scopus, Web of Science, ProQuest, Embase, and Ovid databases were searched from inception through July 31, 2022, without restrictions on date of publication or language. Study Selection: Observational or baseline data of interventional studies reporting the prevalence of cardiometabolic risk factors (ie, diabetes, hypertension, dyslipidemia, atherosclerotic macrovascular disease) among children and/or adults with autism and matched with participants without autism were included. Data Extraction and Synthesis: Screening, data extraction, and quality assessment were performed independently by at least 2 researchers. DerSimonian-Laird random-effects meta-analyses were performed using the meta package in R. Main Outcomes and Measures: Relative risks (RRs) of diabetes, hypertension, dyslipidemia, and atherosclerotic macrovascular disease among individuals with autism were the primary outcomes. Secondary outcomes included the RR of type 1 and type 2 diabetes, heart disease, stroke, and peripheral vascular disease. Results: A total of 34 studies were evaluated and included 276 173 participants with autism and 7 733 306 participants without autism (mean [range] age, 31.2 [3.8-72.8] years; pooled proportion [range] of female individuals, 47% [0-66%]). Autism was associated with greater risks of developing diabetes overall (RR, 1.57; 95% CI, 1.23-2.01; 20 studies), type 1 diabetes (RR, 1.64; 95% CI, 1.06-2.54; 6 studies), and type 2 diabetes (RR, 2.47; 95% CI, 1.30-4.70; 3 studies). Autism was also associated with increased risks of dyslipidemia (RR, 1.69; 95% CI, 1.20-2.40; 7 studies) and heart disease (RR, 1.46; 95% CI, 1.42-1.50; 3 studies). Yet, there was no significantly associated increased risk of hypertension and stroke with autism (RR, 1.22; 95% CI, 0.98-1.52; 12 studies; and RR, 1.19; 95% CI, 0.63-2.24; 4 studies, respectively). Meta-regression analyses revealed that children with autism were at a greater associated risk of developing diabetes and hypertension compared with adults. High between-study heterogeneity was a concern for several meta-analyses. Conclusions and Relevance: Results suggest that the associated increased risk of cardiometabolic diseases should prompt clinicians to vigilantly monitor individuals with autism for potential contributors, signs of cardiometabolic disease, and their complications.

Efficacy and safety of immune checkpoint inhibitors in young adults with metastatic melanoma.

BACKGROUND: The integration of immune checkpoint inhibitors (ICI) for the treatment of melanoma has resulted in remarkable and durable responses. Given the potential role of immunosenescence, age may contribute to differential ICI efficacy and toxicity. While older patients have been studied in detail, outcomes from ICI in young patients (≤40 years) are not well characterised. METHODS: We performed a multi-institutional, retrospective study of patients with advanced melanoma treated with anti-PD-1 monotherapy or ICI combination (ipilimumab and anti-PD-1). Response rates, survival, and toxicities were examined based on age comparing those under 40 years of age with older patients (age 41-70 and ≥ 71 years). RESULTS: A total of 676 patients were included: 190 patients (28%) aged ≤40 years, 313 (46%) between ages 41-70, and 173 patients (26%) aged ≥71. Patients ≤40 years had higher response rates (53% vs 38%, p = 0.035) and improved progression-free survival (median 13.7 vs 4.0 months, p = 0.032) with combination ICI compared to monotherapy. Progression-free survival was similar among groups while overall survival was inferior in patients >70 years, who had low response rates to combination therapy (28%). ICIs had a similar incidence of severe toxicities, though hepatotoxicity was particularly common in younger patients vs. patients >40 with monotherapy (9% vs. 2%, p = 0.007) or combination ICI (37% vs. 10%, p < 0.001). CONCLUSIONS: ICIs had comparable efficacy between younger and older patients, although outcomes were superior with combination ICI compared to monotherapy in patients aged ≤40 years. Toxicity incidence was similar across age groups, though organs affected were substantially different.

Chitin-psyllium based aerogel for the efficient removal of crystal violet from aqueous solutions.

A new alternative aerogel was prepared from low-cost chitin and psyllium biopolymers to adsorb crystal violet (CV) dye from liquid media and possibly treat effluents containing other dyes. The aerogel was characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), which demonstrated that aerogel has a typical structure of amorphous materials and presented a randomly interconnected porous structure that resembles an open pore network. 2.5 g L-1 of aerogel was able to remove 86.00% of CV from solutions, and the natural pH of the CV solution was considered the more adequate for adsorption. The pseudo-second-order (PSO) model satisfactorily described the adsorption kinetics, and the Freundlich model was suitable to represent the adsorption equilibrium. The maximum experimental capacity achieved was 227.11 mg g-1, which indicates that aerogel is very efficient and competitive with several adsorbents. Tests using a simulated effluent showed that aerogel has excellent potential to treat real colored effluents.

New Evidence of Ancient Mitochondrial DNA of the Southern Andes (Calchaquí Valleys, Northwest Argentina, 3,600-1,900 Years before Present).

Genetic studies on pre-Hispanic populations of the Southern Andes have been increasing steadily in the last decade. Nevertheless, ancient DNA characterization of Formative Period archaeological human remains is particularly scant, especially for Northwest Argentina. To expand current information on genetic characterization of the first agricultural communities of the southern Calchaquí Valleys, we present and discuss the first mitochondrial ancient DNA information obtained on samples dated to ca. 3,600-1,900 years before present from the Cajón Valley, Catamarca Province. Reproducible mtDNA hypervariable region 1 (HVR-1) sequences were obtained in seven individuals. Mitochondrial HVR-1 haplotypes were assigned to three of the four founding haplogroups, D1 (57.1%), C1 (28.5%), and B2 (14.2%), with absence of A2. Our results show that the Cajón Valley sample, with predominance of D1 and C1, differs from that commonly observed in ancient and modern Andean populations, which usually show a high prevalence of haplogroup B2. The fact that the Cajón Valley and Pampa Grande (Salta Province, Argentina) share a prevalence of haplogroup D1 could provide additional evidence to support possible genetic affinities between the valleys and the eastern sub-Andean region during the Formative Period in Northwest Argentina, expanding the archaeological evidence of contact between both populations. Future complete mitogenomic analysis will provide substantial information to formulate new hypotheses about the origins and phylogenetic relationships between the individuals of the Cajón Valley and other groups from the Andes, Gran Chaco, and the Amazon.

Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma.

PURPOSE: The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies. METHODS: This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point. RESULTS: After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%). CONCLUSION: Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.

Development of high quality activated carbon from biological sludge and its application for dyes removal from aqueous solutions.

A high quality activated carbon was developed from biological sludge of a beverage wastewater treatment plant (BWTP). The material was characterized and its adsorption potential to remove Allura Red AC and Crystal Violet dyes from aqueous media was verified. The ACBS (activated carbon from beverage sludge) revealed mesoporous features, presenting average pore diameter of 6.32 nm, pore volume of 0.5098 cm3 g-1 and surface area of 631.8 m2 g-1. Adsorption was adequate using 0.25 g L -1 of ACBS, and, the process was favored at pH 2.0 for Allura Red AC and pH 8.0 for Crystal Violet. From the kinetic viewpoint, the data were satisfactorily represented by the pseudo-second order model. Freundlich and Sips models were suitable to represent the adsorption equilibrium of the Allura Red and Crystal Violet, respectively. The maximum values for adsorption capacities were 287.1 mg g-1 for Allura Red and 640.7 mg g-1 for Crystal Violet. The adsorption of both dyes was thermodynamically spontaneous, favorable and endothermic. In brief, the residual sludge of a wastewater treatment plant may be used as an eco-friendly precursor for ACBS production. ACBS was an efficient adsorbent material able to uptake dyes from aqueous solutions.

Preparation of carbonaceous materials from pyrolysis of chicken bones and its application for fuchsine adsorption.

Activated carbon and biochar were obtained from chicken bone (CB), characterized, and applied to remove basic fuchsine from aqueous media. The adsorbent dosage and pH effects were studied, as well as kinetic, equilibrium, and thermodynamic curves were constructed. The values of BET surface area and total pore volume were 108.94 m2 g-1 and 0.219 cm3 g-1 for the activated carbon and, 18.72 m2 g-1 and 0.075 cm3 g-1 for the biochar. The dye removal percentages were 93.63 and 55.38% when 2.5 g L-1 of activated carbon and biochar were used, respectively. The adsorption was favored using 0.5 g L-1 of adsorbent and pH of 7.0. Adsorption kinetics was well represented by the pseudo-second-order model. Langmuir model was the best to represent the equilibrium. Maximum adsorption capacity was 260.8 mg g-1, obtained using activated carbon. The process was endothermic, favorable, and spontaneous. Results showed that alternative carbonaceous materials can be obtained from chicken bones and used as adsorbents to treat colored effluents containing fuchsine.

Preparation of chitin nanowhiskers and its application for crystal violet dye removal from wastewaters.

Chitin (Ch) and chitin nanowhiskers (ChNW) were prepared, characterized, and applied as adsorbent to remove crystal violet (CV) dye from aqueous solutions. Ch was obtained from shrimp wastes and submitted to acid hydrolysis in order to find ChNW. The increase in average pore size and the rod-like shape of ChNW were probably the main characteristics which contributed to the increase in adsorption potential, when compared with raw Ch. The adsorbent dosage considered more adequate was 5 g L-1, and the most suitable pH was 8.0. A pseudo-second-order model was adequate to represent the kinetic profile. Sips and Hill models were suitable to fit the equilibrium curves. The maximum adsorption capacity of CV on ChNW was 59.52 mg g-1, and the process was endothermic, favorable, and spontaneous. These findings indicated that ChNW have potential to be used as adsorbent in the treatment of colored wastewaters.

Identification of a novel K311 ubiquitination site critical for androgen receptor transcriptional activity.

The androgen receptor (AR) is the main driver of prostate cancer (PC) development and progression, and the primary therapeutic target in PC. To date, two functional ubiquitination sites have been identified on AR, both located in its C-terminal ligand binding domain (LBD). Recent reports highlight the emergence of AR splice variants lacking the LBD that can arise during disease progression and contribute to castrate resistance. Here, we report a novel N-terminal ubiquitination site at lysine 311. Ubiquitination of this site plays a role in AR stability and is critical for its transcriptional activity. Inactivation of this site causes AR to accumulate on chromatin and inactivates its transcriptional function as a consequence of inability to bind to p300. Additionally, mutation at lysine 311 affects cellular transcriptome altering the expression of genes involved in chromatin organization, signaling, adhesion, motility, development and metabolism. Even though this site is present in clinically relevant AR-variants it can only be ubiquitinated in cells when AR retains LBD suggesting a role for AR C-terminus in E2/E3 substrate recognition. We report that as a consequence AR variants lacking the LBD cannot be ubiquitinated in the cellular environment and their protein turnover must be regulated via an alternate pathway.

Biosorption of gold from computer microprocessor leachate solutions using chitin.

The biosorption of gold from discarded computer microprocessor (DCM) leachate solutions was studied using chitin as a biosorbent. The DCM components were leached with thiourea solutions, and two procedures were tested for recovery of gold from the leachates: (1) biosorption and (2) precipitation followed by biosorption. For each procedure, the biosorption was evaluated considering kinetic, equilibrium, and thermodynamic aspects. The general order model was able to represent the kinetic behavior, and the equilibrium was well represented by the BET model. The maximum biosorption capacities were around 35 mg g(-1) for both procedures. The biosorption of gold on chitin was a spontaneous, favorable, and exothermic process. It was found that precipitation followed by biosorption resulted in the best gold recovery, because other species were removed from the leachate solution in the precipitation step. This method enabled about 80% of the gold to be recovered, using 20 g L(-1) of chitin at 298 K for 4 h.

(2SR,3RS)-Methyl 2-(adamantan-1-yl)-3-phenyl-sulfonyl-3-(pyridin-2-ylsulfan-yl)propano-ate dichloro-methane hemisolvate.

The title compound, C(25)H(29)NO(4)S(2) 0.5CH(2)Cl(2), was obtained as a racemate. The pyridine and phenyl rings are arranged face-to-face, giving a weak intra-molecular π-π inter-action [centroid-centroid separation = 3.759 (3) Å]. These inter-actions are extended inter-molecularly, forming chains of stacked rings along [001] with separations of 3.859 (3) and 3.916 (3) Å. The solvent used for crystallization, CH(2)Cl(2), is located in voids between the chains of mol-ecules, with a site occupancy of 0.5.

Identification of latexin by a proteomic analysis in rat normal articular cartilage.

BACKGROUND: Osteoarthritis (OA) is characterized by degeneration of articular cartilage. Animal models of OA induced are a widely used tool in the study of the pathogenesis of disease. Several proteomic techniques for selective extraction of proteins have provided protein profiles of chondrocytes and secretory patterns in normal and osteoarthritic cartilage, including the discovery of new and promising biomarkers. In this proteomic analysis to study several proteins from rat normal articular cartilage, two-dimensional electrophoresis and mass spectrometry (MS) were used. Interestingly, latexin (LXN) was found. Using an immunohistochemical technique, it was possible to determine its localization within the chondrocytes from normal and osteoarthritic articular cartilage. RESULTS: In this study, 147 proteins were visualized, and 47 proteins were identified by MS. A significant proportion of proteins are involved in metabolic processes and energy (32%), as well as participating in different biological functions including structural organization (19%), signal transduction and molecular signaling (11%), redox homeostasis (9%), transcription and protein synthesis (6%), and transport (6%). The identified proteins were assigned to one or more subcellular compartments.Among the identified proteins, we found some proteins already recognized in other studies such as OA-associated proteins. Interestingly, we identified LXN, an inhibitor of mammalian carboxypeptidases, which had not been described in articular cartilage. Immunolabeling assays for LXN showed a granular distribution pattern in the cytoplasm of most chondrocytes of the middle, deep and calcified zones of normal articular cartilage as well as in subchondral bone. In osteoarthritic cartilage, LXN was observed in superficial and deep zones. CONCLUSIONS: This study provides the first proteomic analysis of normal articular cartilage of rat. We identified LXN, whose location was demonstrated by immunolabeling in the chondrocytes from the middle, deep and calcified zones of normal articular cartilage, and superficial and deep zones of osteoarthritic cartilage.

Effects of the insecticides malathion and diazinon on the early oogenesis in mice in vitro.

Malathion and diazinon are two of the most commonly used organophosphorous (OP) agrochemicals. Several studies show that these pesticides exert several effects on mammalian spermatogenesis. Nevertheless, there are no studies concerning their effects on oogenesis. The objective of this study was to evaluate the effects of these insecticides on the viability of in vitro cultured mouse oocytes during the early oogenesis and to get a further understanding of the molecular mechanisms by which OP insecticides act and affect germinal cells. Oocytes were cultured from fetal ovaries for 10 days, when most oocytes had reached the diplotene stage (germinal vesicle stage). Cultures were exposed to different concentrations of malathion or diazinon for 24 h, and the effect on oocyte viability was assessed. Gene expression in oocytes exposed to the insecticides was analyzed by generating cDNA libraries and performing differential screenings. Results show a significant decrease in oocytes survival after 24-h exposure to 250 microM malathion or 900 nM diazinon, and the effect of these insecticides on the regulation of genes encoding proteins involved in transcription (BP75), translation (ribosomal protein S5), and mitochondrial function (cytochrome oxidase subunits I and III), providing evidence for OP insecticides as toxicants for mammals oocytes during the early oogenesis.

Gene expression analysis on the early development of pig embryos exposed to malathion.

Malathion is a widely used pesticide and there is evidence that it could alter mammal's germ and somatic cells, as well as cell lines. There are not enough studies showing how the nonacute malathion doses affect gene expression. This study analyzes gene expression alterations in pig morular embryos exposed in vitro, for 96 h, to several malathion concentrations after in vitro fertilization. cDNA libraries of isolated morular embryos were created and differential screenings performed to identify target genes. Seven clones were certainly identified. Genes related to mitochondrial metabolism as cytochrome c subunits I and III, nuclear genes such as major histocompatibility complex I (MHC I), and a hypothetical protein related with a splicing factor were the target of malathion's deregulation effect. The widespread use of malathion as a pesticide should be regarded with reproductive implications and more detailed analysis would yield more about molecular mechanisms of malathion injury on embryo cells.

Differential gene expression in lymphocytes from malnourished children.

Malnutrition, which is widespread in developing countries, may be particularly devastating during childhood, when tissue development is occurring and nutrient requirements are great. Since protein-energy malnutrition potentially involves many cellular alterations, we have evaluated gene expression changes in lymphocytes from malnourished children using differential hybridization cloning. A cDNA library was generated from well-nourished children and differential screenings were performed with cDNAs obtained from well-nourished and malnourished children who presented with bacterial gastrointestinal infections. Differential expression was detected for genes involved in cell development and differentiation, and for genes involved in lymphocyte and mitochondrial functions. The genes detected in the present study suggest mechanisms for the changes in cell growth and immune function that are associated with protein-energy malnutrition. Two down-regulated genes in malnourished children may represent mechanisms of protection against immunosuppression. This finding clearly merits further investigation.

Radical contraction of 1,3,2-dioxaphosphepanes to 1,3,2-dioxaphosphorinanes: a kinetic and (17)O NMR spectroscopic study.

Two diastereomeric 5-bromo-4-phenyl-2-phenoxy-2-oxo-1,3,2-dioxophosphepanes have been synthesized and used to study the contraction of 4-phenyl-2-phenoxy-2-oxo-1,3,2-dioxophosphorinan-5-yl radicals. Kinetics were determined by competition methods and demonstrate Arrhenius parameters typical of rearrangements of this kind. Isotopic labeling reveals that all rearrangements are formally of the 1,2-type with retention of configuration at phosphorus. Analysis of the stereochemistry of the rearrangements, however, reveals the two diastereomers to take different paths with respect to the geometry of the presumed alkene radical cation intermediate.