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Objective: To examine the relationship of eating disorder (ED) symptoms with the severity of alcohol use among adolescents in treatment for alcohol and other substance use disorders (AOSUDs). Method: A sample consisted of 177 adolescents who participated in outpatient AOSUD treatment programs in Connecticut. Chi square tests, one-way ANOVAs and Pearson's correlation coefficients were used to describe the prevalence and correlates of any eating disorders, and the related symptoms. Multivariate regression was used to test the associations between ED symptoms and alcohol consumption. Results: 26.4% of the participants had at least one ED symptom, with the highest number of symptoms occurring in females. The number of ED symptoms was associated with increases in the number of times that they became intoxicated in the year before entering treatment, the number of alcohol-related social problems, and the number of alcohol-related physical symptoms after taking into consideration the effects of age and gender. Conclusions: The prevalence of symptoms of EDs is high in adolescents with AOSUDs, with the number of ED symptoms correlating with increased alcohol consumption. Further studies on the course and treatment of adolescents with AOSUDs and symptoms of EDs are warranted. [ABSTRACT FROM AUTHOR]

The widespread adoption of microfluidic devices among the neuroscience and neurobiology communities has enabled addressing a broad range of questions at the molecular, cellular, circuit, and system levels. Here, we review biomedical engineering approaches that harness the power of microfluidics for bottom-up generation of neuronal cell types and for the assembly and analysis of neural circuits. Microfluidics-based approaches are instrumental to generate the knowledge necessary for the derivation of diverse neuronal cell types from human pluripotent stem cells, as they enable the isolation and subsequent examination of individual neurons of interest. Moreover, microfluidic devices allow to engineer neural circuits with specific orientations and directionality by providing control over neuronal cell polarity and permitting the isolation of axons in individual microchannels. Similarly, the use of microfluidic chips enables the construction not only of 2D but also of 3D brain, retinal, and peripheral nervous system model circuits. Such brain-on-a-chip and organoid-on-a-chip technologies are promising platforms for studying these organs as they closely recapitulate some aspects of in vivo biological processes. Microfluidic 3D neuronal models, together with 2D in vitro systems, are widely used in many applications ranging from drug development and toxicology studies to neurological disease modeling and personalized medicine. Altogether, microfluidics provide researchers with powerful systems that complement and partially replace animal models.

We determine the presence of four open-form configurational isomers for an unsubstituted metastable-state photoacid (mPAH) of the tricyanofuran (TCF) type in solution, at room temperature, via 2D NMR experiments. Electronic structure calculations are carried out to predict the relative stability of the isomers found experimentally and their isomerization barriers. According to the calculated rate constants for isomerization, the molecule can freely interconvert between the open-form isomers, thereby providing a thermal pathway between the isomers that might be better suited to access the cyclized closed-form configuration and those that are not. In establishing the open form isomeric makeup of the TCF mPAH under study, this work establishes the need to consider the four isomers in further studies on the thermal and excited-state isomerization processes and substituent effect thereon., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Anti-Vascular Endothelial Growth Factor (VEGF) agents are the first-line treatment for retinal neovascular diseases, which represent the most prevalent causes of acquired vision loss world-wide. VEGF-Trap (Aflibercept, AFL), a recombinant decoy receptor recognizing ligands of both VEGFR-1 and -2, was recently reported to be highly efficient in improving visual acuity and preserving retinal anatomy in individuals affected by diabetic macular edema. However, the precise molecular and cell biological mechanisms underlying the beneficial effects of this novel tool have yet to be elucidated. Using the mouse oxygen-induced retinopathy (OIR) model as a surrogate of retinopathies with sterile post-ischemic inflammation, such as late proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and diabetic macular edema (DME), we provide evidence that AFL modulates inflammation in response to hypoxia by regulating the morphology of microglial cells, a parameter commonly used as a proxy for changes in their activation state. We show that AFL administration during the hypoxic period of OIR leads to an increased number of ramified Iba1 + microglial cells/macrophages while subsequently limiting the accumulation of these cells in particular retinal layers. Our results suggest that, beyond its well-documented beneficial effects on microvascular regeneration, AFL might exert important modulatory effects on post-ischemic retinal inflammation.

Ischemic retinal dystrophies are leading causes of acquired vision loss. Although the dysregulated expression of the hypoxia-responsive VEGF-A is a major driver of ischemic retinopathies, implication of additional VEGF-family members in their pathogenesis has led to the development of multivalent anti-angiogenic tools. Designed as a decoy receptor for all ligands of VEGFR1 and VEGFR2, Aflibercept is a potent anti-angiogenic agent. Notwithstanding, the molecular mechanisms mediating Aflibercept's efficacy remain only partially understood. Here, we used the oxygen-induced retinopathy (OIR) mouse as a model system of pathological retinal vascularization to investigate the transcriptional response of the murine retina to hypoxia and of the OIR retina to Aflibercept. While OIR severely impaired transcriptional changes normally ensuing during retinal development, analysis of gene expression patterns hinted at alterations in leukocyte recruitment during the recovery phase of the OIR protocol. Moreover, the levels of Angiopoietin-2, a major player in the progression of diabetic retinopathy, were elevated in OIR tissues and consistently downregulated by Aflibercept. Notably, GO term, KEGG pathway enrichment, and expression dynamics analyses revealed that, beyond regulating angiogenic processes, Aflibercept also modulated inflammation and supported synaptic transmission. Altogether, our findings delineate novel mechanisms potentially underlying Aflibercept's efficacy against ischemic retinopathies., (© 2021. The Author(s).)

Human pluripotent stem cells (hPSCs) offer an unprecedented opportunity to model diverse cell types and tissues. To enable systematic exploration of the programming landscape mediated by transcription factors (TFs), we present the Human TFome, a comprehensive library containing 1,564 TF genes and 1,732 TF splice isoforms. By screening the library in three hPSC lines, we discovered 290 TFs, including 241 that were previously unreported, that induce differentiation in 4 days without alteration of external soluble or biomechanical cues. We used four of the hits to program hPSCs into neurons, fibroblasts, oligodendrocytes and vascular endothelial-like cells that have molecular and functional similarity to primary cells. Our cell-autonomous approach enabled parallel programming of hPSCs into multiple cell types simultaneously. We also demonstrated orthogonal programming by including oligodendrocyte-inducible hPSCs with unmodified hPSCs to generate cerebral organoids, which expedited in situ myelination. Large-scale combinatorial screening of the Human TFome will complement other strategies for cell engineering based on developmental biology and computational systems biology.

The advent of single-cell sequencing started a new era of transcriptomic and genomic research, advancing our knowledge of the cellular heterogeneity and dynamics. Cell type annotation is a crucial step in analyzing single-cell RNA sequencing data, yet manual annotation is time-consuming and partially subjective. As an alternative, tools have been developed for automatic cell type identification. Different strategies have emerged to ultimately associate gene expression profiles of single cells with a cell type either by using curated marker gene databases, correlating reference expression data, or transferring labels by supervised classification. In this review, we present an overview of the available tools and the underlying approaches to perform automated cell type annotations on scRNA-seq data., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Retinal hypoxia triggers abnormal vessel growth and microvascular hyper-permeability in ischemic retinopathies. Whereas vascular endothelial growth factor A (VEGF-A) inhibitors significantly hinder disease progression, their benefits to retinal neurons remain poorly understood. Similar to humans, oxygen-induced retinopathy (OIR) mice exhibit severe retinal microvascular malformations and profound neuronal dysfunction. OIR mice are thus a phenocopy of human retinopathy of prematurity, and a proxy for investigating advanced stages of proliferative diabetic retinopathy. Hence, the OIR model offers an excellent platform for assessing morpho-functional responses of the ischemic retina to anti-angiogenic therapies. Using this model, we investigated the retinal responses to VEGF-Trap (Aflibercept), an anti-angiogenic agent recognizing ligands of VEGF receptors 1 and 2 that possesses regulatory approval for the treatment of neovascular age-related macular degeneration, macular edema secondary to retinal vein occlusion and diabetic macular edema. Our results indicate that Aflibercept not only reduces the severity of retinal microvascular aberrations but also significantly improves neuroretinal function. Aflibercept administration significantly enhanced light-responsiveness, as revealed by electroretinographic examinations, and led to increased numbers of dopaminergic amacrine cells. Additionally, retinal transcriptional profiling revealed the concerted regulation of both angiogenic and neuronal targets, including transcripts encoding subunits of transmitter receptors relevant to amacrine cell function. Thus, Aflibercept represents a promising therapeutic alternative for the treatment of further progressive ischemic retinal neurovasculopathies beyond the set of disease conditions for which it has regulatory approval. Cover Image for this issue: doi: 10.1111/jnc.14743., (© 2019 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

MicroRNAs (miRNAs) are small RNA molecules with important roles in post-transcriptional regulation of gene expression. In recent years, the predicted number of miRNAs has skyrocketed, largely as a consequence of high-throughput sequencing technologies becoming ubiquitous. This dramatic increase in miRNA candidates poses multiple challenges in terms of data deposition, curation, and validation. Although multiple databases containing miRNA annotations and targets have been developed, ensuring data quality by validating miRNA-target interactions requires the efforts of the research community. In order to generate databases containing biologically active miRNAs, it is imperative to overcome a multitude of hurdles, including restricted miRNA expression patterns, distinct miRNA biogenesis machineries, and divergent miRNA-mRNA interaction dynamics. In the present review, we discuss recent advances and limitations in miRNA prediction, identification, and validation. Lastly, we focus on the most enriched neuronal miRNA, miR-124, and its gene regulatory network in human neurons, which has been revealed using a combined computational and experimental approach., Competing Interests: None

The health and function of our visual system relies on accurate gene expression. While many genetic mutations are associated with visual impairment and blindness, we are just beginning to understand the complex interplay between gene regulation and retinal pathologies. MicroRNAs (miRNAs), a class of non-coding RNAs, are important regulators of gene expression that exert their function through post-transcriptional silencing of complementary mRNA targets. According to recent transcriptomic analyses, certain miRNA species are expressed in all retinal cell types, while others are cell type-specific. As miRNAs play important roles in homeostasis, cellular function, and survival of differentiated retinal cell types, their dysregulation is associated with retinal degenerative diseases. Thus, advancing our understanding of the genetic networks modulated by miRNAs is central to harnessing their potential as therapeutic agents to overcome visual impairment. In this review, we summarize the role of distinct miRNAs in specific retinal cell types, the current knowledge on their implication in inherited retinal disorders, and their potential as therapeutic agents.

Small changes in the pH gradient play a critical role in numerous biological and chemical pathways. Systems capable of monitoring and regulating these changes with high sensitivity and minimum photo-fatigue are in demand. Herein, we propose a visible light-triggered molecular system that allows for reversible regulation of acidity and fluorescence. This robust bi-functional system opens a new horizon towards novel studies that rely on small changes in acid-mediated controlled processes with high sensitivity. The two photosensitive compounds employed, a metastable-state photoacid (mPAH) and a boron-dipyrromethene (BODIPY) derivative, allow for consistent modulation of both fluorescence (based on the working principle of the inner filter effect) and pH (around a magnitude) over multiple cycles.

Objective: There are limited studies in Latin America regarding the chronic consequences of the Chikungunya virus (CHIK), such as post-CHIK chronic inflammatory rheumatism (pCHIK-CIR). We assessed the largest cohort so far of pCHIK-CIR in Latin America, at the municipality of La Virginia, Risaralda, a new endemic area of CHIK in Colombia., Methods: We conducted a cohort retrospective study in Colombia of 283 patients diagnosed with CHIK that persisted with pCHIK-CIR after a minimum of 6 weeks and up to a maximum of 26.1 weeks. pCHIK cases were identified according to validated criteria via telephone., Results: Of the total CHIK-infected subjects, 152 (53.7%) reported persistent rheumatological symptoms (pCHIK-CIR). All of these patients reported joint pains (chronic polyarthralgia, pCHIK-CPA), 49.5% morning stiffness, 40.6% joint edema, and 16.6% joint redness. Of all patients, 19.4% required and attended for care prior to the current study assessment (1.4% consulting rheumatologists). Significant differences in the frequency were observed according to age groups and gender. Patients aged >40 years old required more medical attention (39.5%) than those ≤40 years-old (12.1%) (RR=4.748, 95%CI 2.550-8.840)., Conclusions: According to our results, at least half of the patients with CHIK developed chronic rheumatologic sequelae, and from those with pCHIK-CPA, nearly half presented clinical symptoms consistent with inflammatory forms of the disease. These results support previous estimates obtained from pooled data of studies in La Reunion (France) and India and are consistent with the results published previously from other Colombian cohorts in Venadillo (Tolima) and Since (Sucre).

In an effort to develop alternate techniques to recover metals from waste electrical and electronic equipment (WEEE), this research evaluated the bioleaching efficiency of gold (Au), copper (Cu) and nickel (Ni) by two strains of Aspergillus niger in the presence of gold-plated finger integrated circuits found in computer motherboards (GFICMs) and cellular phone printed circuit boards (PCBs). These three metals were analyzed for their commercial value and their diverse applications in the industry. Au-bioleaching ranged from 42 to 1% for Aspergillus niger strain MXPE6; with the combination of Aspergillus niger MXPE6 + Aspergillus niger MX7, the Au-bioleaching was 87 and 28% for PCBs and GFICMs, respectively. In contrast, the bioleaching of Cu by Aspergillus niger MXPE6 was 24 and 5%; using the combination of both strains, the values were 0.2 and 29% for PCBs and GFICMs, respectively. Fungal Ni-leaching was only found for PCBs, but with no significant differences among treatments. Improvement of the metal recovery efficiency by means of fungal metabolism is also discussed.

Objective: To develop a technological tool that improves the initial learning of sign language in hearing impaired children., Methods: The development of this research was conducted in three phases: the lifting of requirements, design and development of the proposed device, and validation and evaluation device. Through the use of information technology and with the advice of special education professionals, we were able to develop an electronic device that facilitates the learning of sign language in deaf children. This is formed mainly by a graphic touch screen, a voice synthesizer, and a voice recognition system. Validation was performed with the deaf children in the Filadelfia School of the city of Bogotá., Results: A learning methodology was established that improves learning times through a small, portable, lightweight, and educational technological prototype., Conclusions: Tests showed the effectiveness of this prototype, achieving a 32 % reduction in the initial learning time for sign language in deaf children.

Background: Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1-4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans., Methods: To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population., Results: Patients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T > G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C > T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T > G); and 11.11%, 8.82% and 9.00% for T (c.458C > T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33., Conclusions: The novel loss-of function mutation of CTSC gene (c.203 T > G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.

The chemical influence in the phase separation phenomenon that occurs in perovskite manganites is discussed by means of ab initio calculations. Supercells have been used to simulate a phase separated state, that occurs at Ca concentrations close to the localized itinerant crossover. We have first considered a model with two types of magnetic ordering coexisting within the same compound. This is not stable. However, a non-isotropic distribution of chemical dopants is found to be the ground state. This leads to regions in the system with different effective concentrations, that would always accompany the magnetic phase separation at the same nanometric scale, with hole-rich regions being more ferromagnetic in character and hole-poor regions being in the antiferromagnetic region of the phase diagram, as long as the system is close to a phase crossover.

Optical excitation spectra of Ag(n) and Ag(n)@He(60) (n = 2, 8) clusters are investigated in the framework of the time-dependent density functional theory (TDDFT) within the linear response regime. We have performed the ab initio calculations for two different exact exchange functionals (GGA-exact and LDA-exact). The computed spectra of Ag(n)@He(60) clusters with the GGA-exact functional accounting for exchange-correlation effects are found to be generally in a relatively good agreement with the experiment. A strategy is proposed to obtain the ground-state structures of the Ag(n)@He(60) clusters and in the initial process of the geometry optimization, the He environment is simulated with buckyballs. A redshift of the silver clusters spectra is observed in the He environment with respect to the ones of bare silver clusters. This observation is discussed and explained in terms of a contraction of the Ag-He bonding length and a consequent confinement of the s valence electrons in silver clusters. Likewise, the Mie-Gans predictions combined with our TDDFT calculations also show that the dielectric effect produced by the He matrix is considerably less important in explaining the redshifting observed in the optical spectra of Ag(n)@He(60) clusters.

We have performed collinear and noncollinear calculations on neutral Bi(4)Mn and collinear ones on ionized Bi(4)Mn with charges +1 and -1 to find out why theoretical calculations will not predict the magnetic state found in the experiment. We have used the density functional theory to find a fit between the theoretical prediction of the magnetic moment and the experimental value. Our calculations have consisted in a structural search of local energy minima, and the lowest energy magnetic state for each resulting isomer. The geometry optimization found three local minima whose fundamental state is the doublet spin state. These isomers could not be found in previous theoretical works, but they are higher in energy than the lowest-lying isomer by ≈1.75 eV. This magnetic state could help understand the experiment. Calculations of noncollinear magnetic states for the Bi(4)Mn do not lower the total magnetic moment. We conclude arguing how the three isomers with doublet state could actually be the ones measured in the experiment.

We have performed ab initio calculations in the Density Functional Theory framework on unsupported small gold clusters with size ranging from three to seven atoms. In our calculations we have introduced a single O2 molecule on different places around the cluster surface, and in both parallel and perpendicular position with respect to the cluster surface. We have found that the oxygen molecule bonds in-plane with the bidimensional Au cluster when the number of Au atoms is even, and it will be adsorbed off-plane if the number of Au atoms is odd. The latter case, despite not presenting a true chemical bonding, has great stability due to spin pairing and electrostatic interactions, and the structures will be distorted respect to the geometry of their pure Au cluster equivalents.

We have studied the energetic and structural stability of the interaction of molecular oxygen with small neutral, anionic and cationic silver clusters, Ag(n) (3 < or = n < or = < 8). The calculations have been carried out using a linear combination of atomic Gaussian-type orbitals within the density functional theory as it is implemented in the demon-ks3.5 code. The O2 molecule has been placed in different positions surrounding the cluster, in order to increase the configurational space of the structural minima. We have found that the oxidized cation and neutral clusters undergo a 2D-3D structural transition even before than the nonoxidized counterparts. Moreover, our results show that the adsorption energies on the cationic and neutral silver oxide clusters manifest an odd-even alternation pattern. Likewise, the average magnetic moment of the O2 radical in the charged and neutral silver environment tends to be greater than the charged and neutral bare diatomic oxygen molecule.

Magnetic nanoparticles with controlled magnetocaloric properties are a good candidate to lower the temperature of nanosized systems: they are easy to manipulate and to distribute into different geometries, as wires or planes. Using a Monte Carlo technique we study the entropy change and refrigerant capacity of an assembly of fine magnetic particles as a function of their anisotropy and magnetization, key-parameters of the magnetic behavior of the system. We focus our attention on the anisotropy energy/dipolar energy ratio by means of the related parameter c0 = 2K/M(S)2, where K is the anisotropy constant and M(S) is the saturation magnetization of the nanoparticles. Making to vary the value of co parameter by choosing different K-M(S) combinations, allows us to discuss how the magnetocaloric response of an assembly of magnetic nanoparticles may be tuned by an appropriate choice of the magnetic material composition.

We have performed Monte Carlo simulations to treat the effect of the dipolar interaction in assemblies of superparamagnetic nanoparticles. Our simulations reproduce correctly the increase of the blocking temperature (T(B)) as the concentration increases, as observed experimentally. Interestingly, we have observed a progressive displacement of the M2 versus H/M isotherms (Arrott plots) from the origin as the concentration of nanoparticles increases. Moreover, the curvature of the isotherms at T > T(B) changes from positive to negative slope at high sample concentrations, resembling the shape of a first order phase transition. These results are surprisingly similar to that found in a conventional magnetic phase transition under the effect of a random anisotropy or a random field.

We sought to determine the effect of ischemic preconditioning (IPC) on secondary ischemia in myocutaneous flaps in a rat model. Forty rectus abdominis myocutaneous flaps were elevated in 40 rats, and the animals were randomized into control or IPC groups (20 flaps each group). All flaps were then subject to primary ischemia for 2 hours via pedicle clamping. Twenty-four hours later, the control and IPC flaps were randomized to two groups each of 1 or 2 hours of secondary ischemia (4 groups, 10 flaps per group). Flap survival was evaluated on postoperative day 5 by measuring the percentage area of flap survival by a blinded observer. Mean flap survival area and total necrosis rates were compared between the groups. In the 1-hour secondary ischemia groups, IPC improved mean flap survival area from 11 +/- 7% to 36 +/- 22%, and the total necrosis rates from 40 to 0%. These differences were statistically significant (p < 0.006, p < 0.05, respectively). In the 2-hour secondary ischemia groups, differences were not statistically significant (p = 0.2, p = 0.4, respectively). IPC improves the survival of myocutaneous flaps subjected to secondary ischemia of 1 hour in this rat free flap model., (Copyright Thieme Medical Publishers.)

Introduction: Macrocephaly-capillary malformation syndrome is characterized by cutaneous vascular lesions, including cutis marmorata telangiectatica and hemangiomas, associated with congenital anomalies, including macrocephaly, macrosomia, asymmetry and mental retardation. In addition to these cardinal signs, several other clinical conditions have been reported in people with this condition. However, to the best of our knowledge, the presence of tetralogy of Fallot has not previously been reported in association with this syndrome., Case Presentation: We present a case of a Mexican newborn girl with tetralogy of Fallot associated with macrocephaly-capillary malformation. We discuss the clinical treatment of the patient and its consequences., Conclusion: Since physiologic cutis marmorata is a common condition in newborns, the information provided in this report could be helpful in future cases in preventing severe clinical consequences or sudden death in patients with similar symptoms.

Klinefelter's syndrome is a frequent genetic sexual alteration in males, associated with the 47,XXY aneuploidy. Several syndrome variants are caused by different X and Y polysomy and mosaicisms, including the 49,XXXXY condition described by some authors as Fraccaro's syndrome. Mosaics with three or more different chromosomal lines are very rare. Here, we describe a case with XXY/XXXY/XXXXY mosaic in a newborn with clinical features of Fraccaro's syndrome, but also with obstructive hydrocephaly which has not been reported previously.

The complexity of the monitored data available in modern intensive care units suggests that they may be best processed, for presentation to medical staff, by expert system techniques. However, standard expert system shells are ill-fitted to either the basic sequential monitoring tasks of data acquisition and storage, or to handling the temporal considerations inherent in monitoring and in the recognition and processing of sporadic alarm signals. A solution to this dilemma is described: an expert system that has an appropriately designed inference engine and manages data acquisition via a medical information bus (MIB). Use of this MIB standard allows great flexibility as regards the monitoring apparatuses employed; in particular, the connection or disconnection of any apparatus is recognised and triggers the automatic reconfiguration of the network.

At present, units designed to diagnose the state of the foetus during labour base their decisions on relatively short segments of the monitored foetal heart rate and uterine pressure signals. This article describes a new method which takes a sequence of such local diagnoses of individual contractions, extracts the most relevant pathological features and predicts the neuro-physiological performance of the child at birth.