Comparing preservation substrates under field conditions for efficient DNA recovery in bone.

Often bones are the only biological material left for the identification of human remains. As situations may occur where samples need to be stored for an extended period without access to cooling, appropriate storage of the bone samples is necessary for maintaining the integrity of DNA for profiling. To simulate DNA preservation under field conditions, pig rib bones were used to evaluate the effects of bone cleaning, buffer composition, storage temperature, and time on DNA recovery from bone samples. Bones were stored in three different buffers: TENT, solid sodium chloride, and ethanol-EDTA, at 20 °C and 35 °C for 10, 20, and 30 days. Bones were subsequently dried and ground to powder. DNA was extracted and quantified. Results show that temperature and storage time have no significant influence on DNA yield. DNA recovery from bones stored in solid sodium chloride or ethanol-EDTA was significantly higher compared to bones stored in TENT, and grinding of bones was facilitated by the extent of dehydration in solid sodium chloride and ethanol-EDTA compared to TENT. Overall, solid sodium chloride was found to be superior over ethanol-EDTA; when it comes to transportation, dry material such as salt eliminates the risk of leaking; it is non-toxic and in contrast to ethanol not classified as dangerous goods. Based on this study's results, we recommend NaCl as a storage substrate for forensic samples in cases where no cooling/freezing conditions are available.

Pharmacomicrobiomics and Drug-Infection Interactions: The Impact of Commensal, Symbiotic and Pathogenic Microorganisms on a Host Response to Drug Therapy.

Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. In this context, we introduce the concept of "drug-infection interaction" to describe the influence of pathogenic microorganisms on drug response. This review analyzes the current state of knowledge regarding the relevance of microorganisms in the host's response to drugs. It also highlights promising areas for future research and proposes the term "drug-infection interaction" as an extension of pharmacomicrobiomics.

A VCO-Based CMOS Readout Circuit for Capacitive MEMS Microphones.

Microelectromechanical systems (MEMS) microphone sensors have significantly improved in the past years, while the readout electronic is mainly implemented using switched-capacitor technology. The development of new battery powered "always-on" applications increasingly requires a low power consumption. In this paper, we show a new readout circuit approach which is based on a mostly digital Sigma Delta ( Σ Δ ) analog-to-digital converter (ADC). The operating principle of the readout circuit consists of coupling the MEMS sensor to an impedance converter that modulates the frequency of a stacked-ring oscillator-a new voltage-controlled oscillator (VCO) circuit featuring a good trade-off between phase noise and power consumption. The frequency coded signal is then sampled and converted into a noise-shaped digital sequence by a time-to-digital converter (TDC). A time-efficient design methodology has been used to optimize the sensitivity of the oscillator combined with the phase noise induced by 1 / f and thermal noise. The circuit has been prototyped in a 130 nm CMOS process and directly bonded to a standard MEMS microphone. The proposed VCO-based analog-to-digital converter (VCO-ADC) has been characterized electrically and acoustically. The peak signal-to-noise and distortion ratio (SNDR) obtained from measurements is 77.9 dB-A and the dynamic range (DR) is 100 dB-A. The current consumption is 750 µ A at 1.8 V and the effective area is 0.12 mm 2 . This new readout circuit may represent an enabling advance for low-cost digital MEMS microphones.

Association analysis of calpain 10 gene variants/haplotypes with gestational diabetes mellitus among Mexican women.

Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays.  The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.

Implementation of a Piezo-diagnostics Approach for Damage Detection Based on PCA in a Linux-Based Embedded Platform.

The implementation of damage-detection methods for continuously assessing structural integrity entails systems with attractive features such as storage capabilities, memory capacity, computational complexity and time-consuming processing. In this sense, embedded hardware platforms are a promising technology for developing integrated solutions in Structural Health Monitoring. In this paper, design, test, and specifications for a standalone inspection prototype are presented, which take advantage of piezo-diagnostics principle, statistical processing via Principal Component Analysis (PCA) and embedded systems. The equipment corresponds to a piezoelectric active system with the capability to detect defects in structures, by using a PCA-based algorithm embedded in the Odroid-U3 ARM Linux platform. The operation of the equipment consists of applying, at one side of the structure, wide guided waves by means of piezoelectric devices operated in actuation mode and to record the wave response in another side of the structure by using the same kind of piezoelectric devices operated in sensor mode. Based on the nominal response of the guide wave (no damages), represented by means of a PCA statistical model, the system can detect damages between the actuated/sensed points through squared prediction error (Q-statistical index). The system performance was evaluated in a pipe test bench where two kinds of damages were studied: first, a mass is added to the pipe surface, and then leaks are provoked to the pipe structure by means of a drill tool. The experiments were conducted on two lab structures: (i) a meter carbon-steel pipe section and (ii) a pipe loop structure. The wave response was recorded between the instrumented points for two conditions: (i) The pipe in nominal conditions, where several repetitions will be applied to build the nominal statistical model and (ii) when damage is caused to the pipe (mass adding or leak). Damage conditions were graphically recognized through the Q-statistic chart. Thus, the feasibility to implement an automated real-time diagnostic system is demonstrated with minimum processing resources and hardware flexibility.

SNDR Limits of Oscillator-Based Sensor Readout Circuits.

This paper analyzes the influence of phase noise and distortion on the performance of oscillator-based sensor data acquisition systems. Circuit noise inherent to the oscillator circuit manifests as phase noise and limits the SNR. Moreover, oscillator nonlinearity generates distortion for large input signals. Phase noise analysis of oscillators is well known in the literature, but the relationship between phase noise and the SNR of an oscillator-based sensor is not straightforward. This paper proposes a model to estimate the influence of phase noise in the performance of an oscillator-based system by reflecting the phase noise to the oscillator input. The proposed model is based on periodic steady-state analysis tools to predict the SNR of the oscillator. The accuracy of this model has been validated by both simulation and experiment in a 130 nm CMOS prototype. We also propose a method to estimate the SNDR and the dynamic range of an oscillator-based readout circuit that improves by more than one order of magnitude the simulation time compared to standard time domain simulations. This speed up enables the optimization and verification of this kind of systems with iterative algorithms.

Thioxylated cyclosporin A for studying protein-drug interactions.

Single atom substitution of cyclosporin A (CsA) through thioxylation has been used to study the structure-activity relationship of the immunosuppressive complex, involving the CsA receptor protein cyclophilin 18 (Cyp18) and the immunological target protein phosphatase calcineurin (CaN), illustrating the contributions of peptide backbone in protein-drug interaction. Moreover, the subtle difference between thioxylation positions in CsA has led to a remarkable change in the quenching effect on Cyp18 intrinsic fluorescence. Using the thioxylated compound Cs7 as an isosteric derivative of CsA in competition assay, the experiment has led to the determination of koff value in solution. Whereas the conformational heterogeneity of CsA has been found to be associated with its two-phase binding kinetics to Cyp18, the dissociation rate of CsA from complex is independent from the initial ligand structure.

[Novel central dopaminergic agents derived from atypical di-substituted 2-aminoindane-4, 7. Synthesis and central pharmacological profile]. / Novedosos agentes dopaminérgicos centrales derivados del 2-aminoindano-4,7 disustituido atipico. Síntesis y perfil farmacológico central.

In recent decades, many compounds with central dopaminergic activity have been designed, synthesized and evaluated pharmacologically. However, it has not been possible to obtain a drug able to improve or cure diseases involving dopaminergic regulation in the central nervous system, such as Parkinson's disease and schizophrenia, among others. Taking into consideration the term "atypical pharmacophore" and from the compound 5, the aralkyl fragment was incorporated, and the compounds 10, 11, 13a-h and 14a-h were synthesized. Both the compounds 10 and 13a-h under its methoxylated form and the compounds 11 and 14a-h under the phenolic form, were evaluated to determine their pharmacologically agonistic and antagonistic effects on central dopaminergic activity. For this, the effect of intracerebroventricular injection of said compounds on the hydromineral balance and stereotyped behavior in rats, was determined. The results of the preliminary pharmacological evaluation show a centrally acting action through dopamine mechanisms, in which the compounds 10, 11, 13d-h and 14a showed responses as agonists, whereas compounds 14b-h, had responses as antagonists.

Development of a new generation of ammonia sensors on printed polymeric hotplates.

Conducting polyaniline-based chemiresistors on printed polymeric micro-hotplates were developed, showing sensitive and selective detection of ammonia vapor in air. The devices consist of a fully inkjet-printed silver heater and interdigitated electrodes on a polyethylene naphthalate substrate, separated by a thin dielectric film. The integrated heater allowed operation at elevated temperatures, enhancing the ammonia sensing performance. The printed sensor designs were optimized over two different generations, to improve the thermal performance through careful design of the shape and dimension of the heater element. A vapor-phase deposition polymerization technique was adapted to produce polyaniline sensing layers doped with poly(4-styrenesulfonic acid). The resulting sensor had better thermal stability and sensing performance when compared with conventional polyaniline-based sensors, and this was attributed to the polymeric dopant used in this study. Improved long-term stability of the sensors was achieved by electrodeposition of gold on the silver electrodes. Response to sub-parts-per-million concentrations of ammonia even under humid conditions was observed.

Algorithm for the Construction of a Global Enzymatic Network to be Used for Gene Network Reconstruction.

Relationships between genes are best represented using networks constructed from information of different types, with metabolic information being the most valuable and widely used for genetic network reconstruction. Other types of information are usually also available, and it would be desirable to systematically include them in algorithms for network reconstruction. Here, we present an algorithm to construct a global metabolic network that uses all available enzymatic and metabolic information about the organism. We construct a global enzymatic network (GEN) with a total of 4226 nodes (EC numbers) and 42723 edges representing all known metabolic reactions. As an example we use microarray data for Arabidopsis thaliana and combine it with the metabolic network constructing a final gene interaction network for this organism with 8212 nodes (genes) and 4606,901 edges. All scripts are available to be used for any organism for which genomic data is available.

STAT4 Gene Variant rs7574865 Is Associated with Rheumatoid Arthritis Activity and Anti-CCP Levels in the Western but Not in the Southern Population of Mexico.

Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in Western and Southern Mexico populations. Genotyping was performed on 476 samples (cases = 240; controls = 236) using the Taqman® system and qPCR probes. Disease activity was assessed using DAS28 and HAQ DI. CRP, ESR, RF, and anti-CCP were determined for clinical assessment. Our study showed there is a statistically significant association with susceptibility to RA for the rs7574865 variant in the Western population for the GT and TT genotypes. The same genotypes also showed a moderate-to-high activity according to DAS28 and positive anti-CCP compared to the control group. This association was not found in the Southern population. This work confirms the association of the rs7574865 variant with RA, as well as a moderate-to-high activity and positive anti-CCP in the Western population but not in the Southern population. No association of the rs897200 variant was found in any of the studied populations.

Ray tracing optimization: a new method for intraocular lens power calculation in regular and irregular corneas.

To develop a novel algorithm based on ray tracing, simulated visual performance and through-focus optimization for an accurate intraocular lens (IOL) power calculation. Custom-developed algorithms for ray tracing optimization (RTO) were used to combine the natural corneal higher-order aberrations (HOAs) with multiple sphero-cylindrical corrections in 210 higher order statistical eye models for developing keratoconus. The magnitude of defocus and astigmatism producing the maximum Visual Strehl was considered as the optimal sphero-cylindrical target for IOL power calculation. Corneal astigmatism and the RMS HOAs ranged from - 0.64 ± 0.35D and 0.10 ± 0.04 µm (0-months) to - 3.15 ± 1.38D and 0.82 ± 0.47 µm (120-months). Defocus and astigmatism target was close to neutral for eyes with low amount of HOAs (0 and 12-months), where 91.66% of eyes agreed within ± 0.50D in IOL power calculation (RTO vs. SRK/T). However, corneas with higher amounts of HOAs presented greater visual improvement with an optimized target. In these eyes (24- to 120-months), only 18.05% of eyes agreed within ± 0.50D (RTO vs. SRK/T). The power difference exceeded 3D in 42.2% while the cylinder required adjustments larger than 3D in 18.4% of the cases. Certain amounts of lower and HOAs may interact favourably to improve visual performance, shifting therefore the refractive target for IOL power calculation.

The Influence of Lifestyle on High-Density Lipoprotein Concentration among Mexican Emerging Adults.

Previous studies have highlighted the role of lifestyle on HDL-C concentrations in adults. To our knowledge, the health and nutritional status of emerging adults have been understudied. The present study aimed to explore the most important lifestyle factors, including micronutrient intake adequacy and the percentage of energy from food processing, according to HDL-C concentrations in emerging adults. In this context, a cross-sectional analysis was conducted on 261 Mexican emerging adults who were apparently healthy. Lifestyle factors were collected through a structured survey and the prevalence of micronutrient intake inadequacy was estimated using the estimated average requirement cut-point method. The percentage of energy from ultra-processed foods was assessed using the NOVA system. HDL-C was determined using the enzymatic colorimetric method. Statistical analyses were conducted in SPSS. The results revealed that lifestyle factors do not differ according to HDL-C status. The participants showed a poor nutritional diet that was energy-dense and micronutrient-inadequate. Nearly half of their energy came from processed and ultra-processed foods. Most participants did not meet the recommendations for key nutrients (ϖ3 fatty acids and phytosterols) that promote a healthy lipid status. In conclusion, regardless of their HDL-C levels, emerging adults exhibited lifestyle-related risk factors. The persistence of these findings over time could contribute to the development of metabolic disorders in the future. It is crucial to increase understanding and to develop effective nutritional interventions during this critical phase of life.

Accuracy of Eye and Hair Color Prediction in Mexican Mestizos from Monterrey City Based on ForenSeqTM DNA Signature Prep.

Forensic genomic systems allow simultaneously analyzing identity informative (iiSNPs), ancestry informative (aiSNPs), and phenotype informative (piSNPs) genetic markers. Among these kits, the ForenSeq DNA Signature prep (Verogen) analyzes identity STRs and SNPs as well as 24 piSNPs from the HIrisPlex system to predict the hair and eye color. We report herein these 24 piSNPs in 88 samples from Monterrey City (Northeast, Mexico) based on the ForenSeq DNA Signature prep. Phenotypes were predicted by genotype results with both Universal Analysis Software (UAS) and the web tool of the Erasmus Medical Center (EMC). We observed predominantly brown eyes (96.5%) and black hair (75%) phenotypes, whereas blue eyes, and blond and red hair were not observed. Both UAS and EMC showed high performance in eye color prediction (p ≥ 96.6%), but a lower accuracy was observed for hair color prediction. Overall, UAS hair color predictions showed better performance and robustness than those obtained with the EMC web tool (when hair shade is excluded). Although we employed a threshold (p > 70%), we suggest using the EMC enhanced approach to avoid the exclusion of a high number of samples. Finally, although our results are helpful to employ these genomic tools to predict eye color, caution is suggested for hair color prediction in Latin American (admixed) populations such as those studied herein, principally when no black color is predicted.

Effect of Human Adenovirus 36 on Response to Metformin Monotherapy in Obese Mexican Patients with Type 2 Diabetes: A Prospective Cohort Study.

Human adenovirus 36 (HAdV-36) has been associated with obesity and changes in glucose and lipid metabolism. The virus has been reported to increase insulin sensitivity and paradoxically promote weight gain. Because of its effects on metabolism, infection with the virus could alter the response to several drugs used to treat type 2 diabetes (DM2), such as metformin. The aim of this study was to test whether HAdV-36 affects the response to metformin in a group of obese patients with DM2. METHODS: In a prospective cohort study, 103 obese patients with newly diagnosed DM2 were divided into two groups based on their HAdV-36 seropositivity (+HAdV-36 and -HAdV-36). Weight, glucose, cholesterol, triglycerides, body mass index, body fat percentage, and waist and hip circumference were measured and compared in both groups at baseline and after 45 days of metformin treatment. RESULTS: Only glucose was significantly lower in the +HAdV-36 group at baseline, while all other variables were similar between the two study groups. After 45 days of follow-up, it was observed that the effect of metformin did not differ between the groups, but the variables improved significantly after treatment. CONCLUSIONS: In this study, we did not find that HAdV-36 had an effect on the response to metformin in obese patients with DM2.

Bioinformatic identification of cassava miRNAs differentially expressed in response to infection by Xanthomonas axonopodis pv. manihotis.

BACKGROUND: microRNAs (miRNAs) are short RNA molecules that control gene expression by silencing complementary mRNA. They play a crucial role in stress response in plants, including biotic stress. Some miRNAs are known to respond to bacterial infection in Arabidopsis thaliana but it is currently unknown whether these responses are conserved in other plants and whether novel species-specific miRNAs could have a role in defense. RESULTS: This work addresses the role of miRNAs in the Manihot esculenta (cassava)-Xanthomonas axonopodis pv. manihotis (Xam) interaction. Next-generation sequencing was used for analyzing small RNA libraries from cassava tissue infected and non-infected with Xam. A full repertoire of cassava miRNAs was characterized, which included 56 conserved families and 12 novel cassava-specific families. Endogenous targets were predicted in the cassava genome for many miRNA families. Some miRNA families' expression was increased in response to bacterial infection, including miRNAs known to mediate defense by targeting auxin-responding factors as well as some cassava-specific miRNAs. Some bacteria-repressed miRNAs included families involved in copper regulation as well as families targeting disease resistance genes. Putative transcription factor binding sites (TFBS) were identified in the MIRNA genes promoter region and compared to promoter regions in miRNA target genes and protein coding genes, revealing differences between MIRNA gene transcriptional regulation and other genes. CONCLUSIONS: Taken together these results suggest that miRNAs in cassava play a role in defense against Xam, and that the mechanism is similar to what's known in Arabidopsis and involves some of the same families.

Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis.

Recovery from skeletal muscle injury is often incomplete because of the formation of fibrosis and inadequate myofiber regeneration; therefore, injured muscle could benefit significantly from therapies that both stimulate muscle regeneration and inhibit fibrosis. To this end, we focused on blocking myostatin, a member of the transforming growth factor-ß superfamily and a negative regulator of muscle regeneration, with the myostatin antagonist follistatin. In vivo, follistatin-overexpressing transgenic mice underwent significantly greater myofiber regeneration and had less fibrosis formation compared with wild-type mice after skeletal muscle injury. Follistatin's mode of action is likely due to its ability to block myostatin and enhance neovacularization. Furthermore, muscle progenitor cells isolated from follistatin-overexpressing mice were significantly superior to muscle progenitors isolated from wild-type mice at regenerating dystrophin-positive myofibers when transplanted into the skeletal muscle of dystrophic mdx/severe combined immunodeficiency mice. In vitro, follistatin stimulated myoblasts to express MyoD, Myf5, and myogenin, which are myogenic transcription factors that promote myogenic differentiation. Moreover, follistatin's ability to enhance muscle differentiation is at least partially due to its ability to block myostatin, activin A, and transforming growth factor-ß1, all of which are negative regulators of muscle cell differentiation. The findings of this study suggest that follistatin is a promising agent for improving skeletal muscle healing after injury and muscle diseases, such as the muscular dystrophies.

Altered functional connectivity between the insula and the cingulate cortex in patients with temporomandibular disorder: a pilot study.

BACKGROUND: Among the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3-15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain. OBJECTIVE: The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain. The current study sought specifically to investigate IC-CC functional connectivity in TMD patients and healthy controls (HCs), both during resting state and during the application of a painful stimulus. METHODS: Eight patients with TMD, and 8 age- and sex-matched HCs were enrolled in the present study. Functional magnetic resonance imaging data during resting state and during the performance of a pressure pain stimulus to the temple were acquired. Predefined seed regions were placed in the IC (anterior and posterior insular cortices) and the extracted signal was correlated with brain activity throughout the whole brain. Specifically, we were interested whether TMD patients and HCs would show differences in IC-CC connectivity, both during resting state and during the application of a painful stimulus to the face. RESULTS: As a main finding, functional connectivity analyses revealed an increased functional connectivity between the left anterior IC and pregenual anterior cingulate cortex (ACC) in TMD patients, during both resting state and applied pressure pain. Within the patient group, there was a negative correlation between the anterior IC-ACC connectivity and clinical pain intensity as measured by a visual analog scale. CONCLUSIONS: Since the pregenual region of the ACC is critically involved in antinociception, we hypothesize that an increase in anterior IC-ACC connectivity is indicative of an adaptation of the pain modulatory system early in the chronification process.

Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data.

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m2, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).