Structure and Intercalation of Cysteine-Asparagine-Serine Peptide into Montmorillonite as an Anti-Inflammatory Agent Preparation-A DFT Study.

Peptides are receiving significant attention in pharmaceutical sciences due to their applications as anti-inflammatory drugs; however, many aspects of their interactions and mechanisms at the molecular level are not well-known. This work explores the molecular structure of two peptides-(i) cysteine (Cys)-asparagine (Asn)-serine (Ser) (CNS) as a molecule in the gas phase and solvated in water in zwitterion form, and (ii) the crystal structure of the dipeptide serine-asparagine (SN), a reliable peptide indication whose experimental cell parameters are well known. A search was performed by means of atomistic calculations based on density functional theory (DFT). These calculations matched the experimental crystal structure of SN, validating the CNS results and useful for assignments of our experimental spectroscopic IR bands. Our calculations also explore the intercalation of CNS into the interlayer space of montmorillonite (MNT). Our quantum mechanical calculations show that the conformations of these peptides change significantly during intercalation into the confined interlayer space of MNT. This intercalation is energetically favorable, indicating that this process can be a useful preparation for therapeutic anti-inflammatory applications and showing high stability and controlled release processes.

Imidazole and nitroimidazole derivatives as NADH-fumarate reductase inhibitors: Density functional theory studies, homology modeling, and molecular docking.

Chagas disease is caused by Trypanosoma cruzi. Benznidazole and nifurtimox are drugs used for its therapy; nevertheless, they have collateral effects. NADH-fumarate (FUM) reductase is a potential pharmacological target since it is essential for survival of parasite and is not found in humans. The objectives are to design and characterize the electronic structure of imidazole and nitroimidazole derivatives at DFT-M06-2X level in aqueous solution; also, to model the NADH-FUM reductase and analyze its intermolecular interactions by molecular docking. Quantum-chemical descriptors allowed to select the molecules with the best physicochemical properties and lowest toxicity. A high-quality three-dimensional structure of NADH-FUM reductase was obtained by homology modeling. Water molecules do not have influence in the interaction between FUM and NADH-FUM reductase. The main hydrogen-binding interactions for FUM were identified in NADH, Lys172, and Arg89; while hydrophobic interactions in Phe479, Thr174, Met63. The molecules S3-8, S2-8, and S1-8 could be inhibitors of NADH-FUM reductase.

Crystal polymorphism and spectroscopical properties of sulfonamides in solid state by means of First Principles calculations.

Sulfonamides are an important class of therapeutic agents. The increase in the number of new sulfonamide derivatives makes it necessary to study more rationally the chemical structure, because the solid forms often display different mechanical, thermal and physicochemical properties that can influence the bioavailability and stability of the drugs; consequently, the polymorphic structures are of great interest to the pharmaceutical industry because of their ability to modify the physical properties of the active pharmaceutical ingredient. The molecular interactions of these drugs in their crystal lattice are important for the stability of the crystals and polymorphism and for preparing composite complexes for optimizing the use of these drugs. In this work, the crystal structure of these drugs and crystal polymorphism is investigated. So, the crystal forms of antibiotics derivatives of the sulfonamides, sulfamethoxazole, sulfamethazine, sulfachloropyridazine, and sulfacetamide are studied at the molecular and supramolecular level by using computational modeling approach at quantum mechanical level. The spectroscopic properties of these systems are also studied explaining assignments of previous experimental data. The results of DFT calculations reproduce the crystal structures of sulfonamides determined experimentally and the polymorphism in these molecules have been clarified. Likewise, the main intermolecular interactions in all crystal forms of these sulfonamides are H-bonds among the sulfonic and amino groups and SNH groups, and also some π-π interactions. Also, these 3-D periodical models allow the exploration of the intermolecular interactions included in the crystal structures and some of these interactions can alter the vibration modes of the molecules. Therefore, the use of these models can be useful for experimental spectroscopy studies where use actual crystal solids.

Current practice of rectal biopsies for the diagnosis of Hirschsprung's disease in Latin America: an international online survey.

PURPOSE: The gold standard for the diagnosis of Hirschsprung's disease (HD) is a rectal biopsy. The sample may be obtained using a transanal excisional biopsy (TEB) or suction technique. Rectal suction biopsy (RSB) is not a standard procedure in Latin-America. AIM: To evaluate the current practice in rectal biopsy for HD among pediatric surgeons. METHODS: We distributed an online questionnaire among Latin-American pediatric surgeons. RESULTS: One hundred forty-nine pediatric surgeons from 15 countries completed the anonymous survey (71.4% of Latin-American countries), grouped into 81.9% pediatric surgeons; 8.9% pediatric colorectal surgeons, 8.9% trainees, and 1 pediatric colorectal surgeon fellow. 50.4% reported less than 5 new patients with HD per year, 36.2% 5-10 new cases, and 13.4% more than 10. Only 14.1% of surgeons have access to perform a RSB in the diagnostic work-up of patients with suspected HD, 90% in our study perform an TEB under general anesthesia. When we ask if they could perform both procedures in babies up to 6 months, 52.3% indicate that they prefer an RSB, and for patients older than 6 months, 35.4% favor an RSB. Regarding the number of samples obtained performing an TEB, 30.9% get one biopsy, 29.5% two biopsies, and 39.6% three or more samples. Surgeons obtained the most proximal biopsy at a median of 2.3 cm (range 1-4 cm) above the pectinate line. 67.8% of surgeons prescribed antibiotic prophylaxis. Overall, 16.1% experienced complications, including rectal blood loss (n = 18), and rectal perforation (n = 3). The most frequently used staining methods for rectal biopsies are hematoxylin/eosin (87%), calretinin (56, 8%), and acetylcholinesterase (21.9%). CONCLUSIONS: In Latin-America, the accessibility for RSB is limited only 18 out of 149 surgeons have access to rectal suction tool. There is no consensus regarding sample number, site of proximal biopsy, and antibiotics use. The complications associated with the procedure seems to be less than reported with RSB. Therefore, we should standardize this common surgical practice and establish universal guidelines for rectal biopsy procedure (RBP).

Family Member Incarceration, Psychological Stress, and Subclinical Cardiovascular Disease in Mexican Women (2012-2016).

Objectives. To examine the association between family member incarceration, psychological stress, and subclinical cardiovascular disease (CVD).Methods. Between 2012 and 2016, 1849 CVD-free women from the Mexican Teachers' Cohort responded to questions on family incarceration from the Life Stressor Checklist. Perceived stress and hair cortisol levels were measured in a subset of participants. Carotid intima-media thickness was measured, and carotid atherosclerosis was determined in all participants. We used multivariable quantile, linear, and logistic regression models to evaluate the association between family member incarceration, stress, and subclinical CVD.Results. Among women with a mean age of 49.7 years (SD ±5.2), 15.3% reported family member incarceration. We found that both perceived stress and hair cortisol levels were significantly higher in women with an incarcerated family member relative to women without one. After multivariable adjustment, women who reported family member incarceration had 41% (95% confidence interval = 1.04, 2.00) higher odds of carotid atherosclerosis compared with those who did not.Conclusions. Family member incarceration was associated with robust markers of stress and cardiovascular risk. Mass incarceration may have a long-lasting impact on physical health of affected families.

Hydrothermal carbonization of dry toilet residues as an added-value strategy - Investigation of process parameters.

Human faeces from a dry toilet are converted via hydrothermal carbonization to obtain a sterilized carbonaceous material. During this process the original material undergoes consecutively hydrolysis, water elimination and polymerization reactions. Consequently, the oxygen content is reduced, leading to a material with a better dewaterability and an attractive higher heating value (HHV = 22-28 MJ kg-1). The influence of pH-value, set by the addition of citric acid, the reaction time and the reaction temperature are investigated. By thermogravimetric analysis it is shown that especially higher acid concentration as well as higher reaction temperatures and longer reaction times are necessary to fully convert the feedstock into a stable carbon-rich material. As pathogens are destroyed by hydrothermal carbonization, nutrient recovery becomes a relevant aspect. The analysis shows that alkali salts such as sodium and potassium are dissolved in the aqueous phase, but an important proportion of the phosphorus and nitrogen remain in the hydrochar. This finding is the basis for phosphorus recycling or to produce an organic fertilizer.

Mesenteric Primitive Myxoid Mesenchymal Tumor in a 7-Month-Old Boy.

Mesenteric tumors are rare, especially in the pediatric population. We present a case of a 7-month-old boy with an incidental abdominal mass identified as a Primitive Myxoid Mesenchymal Tumor of Infancy derived from the small bowel mesentery. This neoplasm is part of a spectrum of myofibroblastic lesions, with distinct clinical, morphologic, IHQ reactivity, and an aggressive clinical course. There is a paucity of evidence for the management of these tumors, and surgical resection remains the mainstay of treatment.

Good health indicators in children with Down syndrome: High frequency of exclusive breastfeeding at 6 months. / Buenos indicadores de salud en niños con síndrome de Down: Alta frecuencia de lactancia materna exclusiva a los 6 meses.

AIM: To describe the frequency of exclusive breastfeeding at 6 months in binomial of mother and in fants with Down Syndrome (DS) attending at the Health net UC CHRISTUS (PSSPSD-UC), and iden tify the main factors associated with exclusive breastfeeding cessation. PATIENTS AND METHODS: Prevalence study of exclusively breastfeeding at 6 months of age that includes mother-child binomial of Chilean infants with (DS) aged 6-24 months, who attend the PSSPSD-UC. An on-line questionnaire was conducted, which included demographic data, child's background and experience in breastfee ding. RESULTS: The total sample consisted of 73 binomials. Forty-six percent (34/73) of the mothers exclusively breastfed until 6 months or longer, 67.1% (49/73) of the infants had a disease or malfor mation that interfere with breast feeding. Among the 39 mothers who did not exclusively breastfeed until 6 months, 25 (64.1%) referred child factors. Hospitalization during the first 6 months was the most significant factor affecting the cessation of breastfeeding (OR = 6,13). CONCLUSIONS: First study in Chile that describes the frequency of exclusive breastfeeding at 6 months of age in children with DS, which shows a large rate of exclusively breastfeeding in the studied sample. The adequate support and education in breastfeeding could allow to achieve a better rate of exclusive breastfeeding in this vulnerable group.

Hepatoblastoma and Abernethy Malformation Type I: Case Report.

A 2-year-old boy presented with pneumonia and an abdominal mass was noted incidentally. A right lobe hepatic mass classified as PRETEXT III and congenital absence of the portal vein with drainage of the superior mesenteric vein to the inferior vena cava (Abernethy malformation type I) were confirmed by computed tomography and angiography. After a clinical diagnosis of hepatoblastoma had been made, he was treated with 4 cycles of doxorubicin and cisplatin and hepatic arterial chemoembolization with doxorubicin, after which the tumor was classified as POSTEXT III. He underwent a right extended hepatic lobectomy with resection of the caudate lobe but died on postoperative day 4 due to hepatic failure. The Abernethy malformation type I is associated with the development of hepatic tumors, and the abnormal blood flow might predispose to hepatic failure after liver resection. Extensive study of the hepatic vasculature is warranted in patients with suspected malformations. Liver transplant could be considered in patients with congenital portosystemic shunt and malignant liver tumors.

Contact Burn with Blister Formation in Children Treated with Sennosides.

Eight children treated for severe constipation with sennosides unexpectedly developed contact burns with blisters secondary to the use of these laxatives. All patients wore diapers, and the injuries occurred overnight. To avoid this side effect, we recommend that patients treated with sennosides, especially those in diapers, receive the medication at a time that allows for bowel movements to occur during the day and not overnight.

Success stories in genomic medicine from resource-limited countries.

In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments.

Study of the Chemical Space of Selected Bacteriostatic Sulfonamides from an Information Theory Point of View.

The relative structural location of a selected group of 27 sulfonamide-like molecules in a chemical space defined by three information theory quantities (Shannon entropy, Fisher information, and disequilibrium) is discussed. This group is composed of 15 active bacteriostatic molecules, 11 theoretically designed ones, and para-aminobenzoic acid. This endeavor allows molecules that share common chemical properties through the molecular backbone, but with significant differences in the identity of the chemical substituents, which might result in bacteriostatic activity, to be structurally classified and characterized. This is performed by quantifying the structural changes on the electron density distribution due to different functional groups and number of electrons. The macroscopic molecular features are described by means of the entropy-like notions of spatial electronic delocalization, order, and uniformity. Hence, an information theory three-dimensional space (IT-3D) emerges that allows molecules with common properties to be gathered. This space witnesses the biological activity of the sulfonamides. Some structural aspects and information theory properties can be associated, as a result of the IT-3D chemical space, with the bacteriostatic activity of these molecules. Most interesting is that the active bacteriostatic molecules are more similar to para-aminobenzoic acid than to the theoretically designed analogues.

Primary sigmoidectomy and appendicostomy for chronic idiopathic constipation.

PURPOSE: To present our experience in patients with chronic idiopathic constipation complicated by megarectosigmoid and fecal incontinence who underwent a primary sigmoidectomy and appendicostomy. METHODS: We reviewed eight patients referred to the Colorectal Center from 2014 to 2016 with chronic idiopathic constipation and undergoing a sigmoidectomy and appendicostomy. We analyzed the previous medical treatment, indications for the surgical procedure, and outcomes. RESULTS: Age at operation was 5-19 years. Time with constipation was 4-15 years. All patients received multiple laxatives, mainly polyethylene glycol, and all had severe social problems. Four patients have autism. The indication for surgery was an unsuccessful laxative trial, refusal to continue with rectal enemas or both, and social fear of continued fecal incontinence. Post-operatively, all patients were having daily bowel movements without fecal accidents. CONCLUSION: Selected patients with chronic idiopathic constipation complicated by megarectosigmoid and fecal incontinence can obtain great benefit from primary sigmoidectomy and appendicostomy.

[Morbidity profile among adolescents with Down syndrome]. / Perfil de morbilidad en adolescentes chilenos con síndrome de Down.

BACKGROUND: There is a paucity of information about morbidity and mortality of adolescents with Down syndrome (DS). AIM: To describe morbidity and mortality of a cohort of Chilean adolescents with DS. MATERIAL AND METHODS: Review of electronic clinical records of 67 ambulatory patients with DS aged 10 to 20 years (37 women), seen between the years 2007 and 2014 in outpatient clinics of a University hospital. RESULTS: The mean age at the last consultation was 13 ± 3 years. Ninety-eight percent of patients had a chronic condition: 37.1% where overweight or obese, 58.2% had a congenital heart disease, 11.9% where being evaluated or had the diagnosis of autism and 44.8% had hypothyroidism. Pubertal development was consistent with chronologic age in 93.7% of patients. In three patients puberty had been suppressed. In women, average age of menarche was 12.2 ± 1.1 years. There were no deaths reported. CONCLUSIONS: There was a high rate of comorbidities in this group of adolescents with DS, most of them with frequencies comparable to those reported in literature.

Predominant information quality scheme for the essential amino acids: an information-theoretical analysis.

In this work we undertake a pioneer information-theoretical analysis of 18 selected amino acids extracted from a natural protein, bacteriorhodopsin (1C3W). The conformational structures of each amino acid are analyzed by use of various quantum chemistry methodologies at high levels of theory: HF, M062X and CISD(Full). The Shannon entropy, Fisher information and disequilibrium are determined to grasp the spatial spreading features of delocalizability, order and uniformity of the optimized structures. These three entropic measures uniquely characterize all amino acids through a predominant information-theoretic quality scheme (PIQS), which gathers all chemical families by means of three major spreading features: delocalization, narrowness and uniformity. This scheme recognizes four major chemical families: aliphatic (delocalized), aromatic (delocalized), electro-attractive (narrowed) and tiny (uniform). All chemical families recognized by the existing energy-based classifications are embraced by this entropic scheme. Finally, novel chemical patterns are shown in the information planes associated with the PIQS entropic measures.

In Vivo Genotoxicity and Cytotoxicity Kinetics of Trimethoprim Sulfamethoxazole in Well-nourished and Undernourished Young Rats.

BACKGROUND/AIM: Undernutrition is a serious health problem prevalent in poor countries, affecting millions of people worldwide, especially young children, pregnant women, and sick elderly individuals. This condition increases vulnerability to infections, leading to widespread use of antibiotic treatments in undernourished populations. The objective of the present study was to determine the in vivo genotoxic and cytotoxic effects of trimethoprim-sulfamethoxazole (TMP-SMX) treatment according to nutritional conditions. MATERIALS AND METHODS: The effects of TMP-SMX treatment were measured by analyzing the kinetics of micronucleated reticulocytes (MN-RET) induced in the peripheral blood of young, well-nourished (WN) and undernourished (UN) rats. RESULTS: In the WN group, two distinct peaks of MN-RET were observed, while the UN group had a significantly higher basal frequency of MN-RET compared to the WN group and only a later peak. Reticulocyte (RET) frequency slightly decreased in WN, indicating a poor cytotoxic effect. In contrast, in the UN, the treatment caused a significant increase in RET frequency. The results indicate that SMX's aromaticity index decreases when formed with TMP, suggesting potentially fewer toxic effects. CONCLUSION: In vivo TMP-SMX produces two MN-RET induction peaks in WN animals, indicating two DNA damage induction mechanisms and consequent micronucleus production. The UN rats did not display the two peaks, indicating that the first MN induction mechanism did not occur in UN, possibly due to pharmacokinetic effects, decreased metabolism or effects on cell proliferation. TMP-SMX has a slight cytotoxic effect on WN. In contrast, in the UN, the antibiotic treatment seems to favor early erythropoiesis.

[Receiving the diagnosis of Down syndrome: what do the parents think?]. / ¿Cómo reciben los padres la noticia del diagnóstico de su hijo con síndrome de Down?

BACKGROUND: Having a child with Down syndrome (DS) is usually unexpected and stressful. AIM: To describe the experiences of parents of children with DS at the time of diagnosis. MATERIAL AND METHODS: A self-administered survey was answered by 345 parents (62% women) with an offspring with DS. RESULTS: Eighty four percent of parents received a postnatal diagnosis of DS, 32.3% were informed of the diagnosis in the presence of his or her partner and 19.3%o received some form of printed material regarding DS. Fifty six percent of respondents considered that the delivery of the diagnosis was inadequate. Factors associated with an overall positive experience were prenatal diagnosis (Odds Ratio (OR) 3.91 (95% Confidence Intervals (CI) 2.06-7.44)) and the presence of both parents at the time of the delivery of the diagnosis (OR 1.84 (95%> CI 1.16-2.91)). Fifty three percent of respondents believe that prenatal diagnosis of DS is preferable. CONCLUSIONS: The majority of parents are unsatisfied with the way the diagnosis of DS is delivered. Efforts should be made to educate health personnel regarding the delivery of the diagnosis of SD, to foster opportunities for prenatal diagnosis and to improve the delivery of printed material.

Adsorption of Capsaicin into the Nanoconfined Interlayer Space of Montmorillonite by DFT Calculations.

Capsaicin is the main compound responsible of the hot sense of the chili fruits. This compound has interesting therapeutic properties including anticancer, anti-inflammatory effects, and analgesic. However, its use has several secondary effects, such as skin irritation and allergies. Then, new therapeutic strategies are searched in order to overcome these problems. Montmorillonite has proved to be an excellent excipient for the release of pharmaceutical drugs. In this work, the molecular structure and crystal structure of capsaicin, and the adsorption of this molecule into the interlayer space of montmorillonite have been studied using quantum mechanical calculations based on Density Functional Theory (DFT) level of theory and molecular dynamics simulations. The crystal structure has been predicted with these calculations and the intermolecular interactions have been determined with a higher resolution than the previous experimental data. The adsorption of capsaicin into the confined interlayer space of montmorillonite is energetically favourable with low and high octahedral charge. This adsorption can be monitored by IR spectroscopy observing frequency shifts in some bands during the adsorption. This enhances the use of these clay minerals for capsaicin therapeutic formulations.

The role of ETFS amino acids on the stability and inhibition of p53-MDM2 complex of anticancer p53-derivatives peptides: Density functional theory and molecular docking studies.

Cancer is one of the leading causes of mortality in the world. Despite the existence of diverse antineoplastic treatments, these do not possess the expected efficacy in many cases. Knowledge of the molecular mechanisms involved in tumor processes allows the identification of a greater number of therapeutic targets employed in the study of new anticancer drugs. In the last decades, peptide-based therapy design using computational chemistry has gained importance in the field of oncology therapeutics. This work aims to evaluate the electronic structure, physicochemical properties, stability, and inhibition of ETFS amino acids and peptides derived from the p53-MDM2 binding domain with action in cancer cells; by means of chemical descriptors at the DFT-BHandHLYP level in an aqueous solution, and its intermolecular interactions through molecular docking studies. The results show that The ETFS fragment plays a critical role in the intermolecular interactions. Thus, the amino acids E17, T18 and S20 increase intermolecular interactions through hydrogen bonds and enhance structural stability. F19, W23 and V25 enhance the formation of the alpha-helix. The hydrogen bonds formed by the backbone atoms for PNC-27, PNC-27-B and PNC-28 stabilize the α-helices more than hydrogen bonds formed by the side chains atoms. Also, molecular docking indicated that the PNC27B-MDM2, PNC28B-MDM2, PNC27-MDM2 and PNC28A-MDM2 complexes show the best binding energy. Therefore, DFT and molecular docking studies showed that the proposed peptides: PNC-28B, PNC-27B and PNC-28A could inhibit the binding of MDM2 to the p53 protein, decreasing the translocation and degradation of p53 native protein.

Anorectal malformations in low and middle-income countries- spectrum, burden and management.

The clinical presentation, diagnosis and management of anorectal malformation has been well described in the literature, however the experience with these conditions in low-and middle-income countries is often shaped in unique ways due to the social, cultural and economic factors at work in these regions. This leads to adaptation of modifications in management options for these babies that usually present as delayed cases with added poor prognostic factors like sepsis leading to need for emergency resuscitation and overall increased morbidity and mortality. This article explores the anomaly from a global surgery lens and outlines the spectrum of the anomaly, burden faced in the resource constrained environment and the management options adopted for successful management under the available circumstances.