Unraveling the Interplay between Quantum Transport and Geometrical Conformations in Monocyclic Hydrocarbons' Molecular Junctions.

In the field of molecular electronics, especially in quantum transport experiments, determining the geometrical configurations of a single molecule trapped between two electrodes can be challenging. To address this challenge, we employed a combination of molecular dynamics (MD) simulations and electronic transport calculations based on density functional theory to determine the molecular orientation in our break-junction experiments under ambient conditions. The molecules used in this study are common solvents used in molecular electronics, such as benzene, toluene (aromatic), and cyclohexane (aliphatic). Furthermore, we introduced a novel criterion based on the normal vector of the surface formed by the cavity of these ring-shaped monocyclic hydrocarbon molecules to clearly define the orientation of the molecules with respect to the electrodes. By comparing the results obtained through MD simulations and density functional theory with experimental data, we observed that both are in good agreement. This agreement helps us to uncover the different geometrical configurations that these molecules adopt in break-junction experiments. This approach can significantly improve our understanding of molecular electronics, especially when using more complex cyclic hydrocarbons.

[Systematic karyotyping before ICSI: A necessary procedure? Analysis of case studies in the Nancy University Hospital Fertility Centre]. / Le caryotype avant ICSI, une procédure à abandonner ? Étude de pratiques au centre d'AMP du CHRU de Nancy.

INTRODUCTION: A constitutional karyotype is often assayed for the couple before ICSI management. The objective of this study was to assess the prevalence of chromosomal abnormality in an infertile population, the impact on the care of couples and its cost. METHODS: A single-center retrospective study was carried out at the Fertility Center of the University Hospital of Nancy, including all infertile couples who underwent a karyotype analysis from June 2009 to December 2016. RESULTS: 1252 couples were included. 7.9% had at least one abnormal karyotype. A change in care affected 22% of these couples, i.e. 1.7% of the total population. 9% of couples with karyotype abnormality underwent PGD. In the male population, the percentage of abnormal spermograms is significantly higher in the group with karyotype abnormality compared to the control group (85.7% vs. 46.5%, P<0.001). DISCUSSION: The constitutional karyotype, due to its high economic and human cost, and limited interest, is a screening method for chromosomal abnormalities that has no place systematically before performing IVF. The future lies in the restriction of the indications for prescribing the karyotype as well as in the realization of PGS in targeted situations.

[Additional non-contraceptive effects of contraception: CNGOF Contraception Guidelines]. / Bénéfices non contraceptifs des contraceptions. RPC Contraception CNGOF.

Hormonal and intrauterine contraceptive methods provide women with highly efficient protection against undesired pregnancy. Additional non-contraceptive effects are now well documented. Combined hormonal contraceptives use, either through the oral transdermal and vaginal route, allow a reduction in menorrhagia, dysmenorrhea, functional ovarian cysts, benign breast and uterine disease, endometriosis-related pain and recurrence. A reduction in ovarian cancer risks, including in women with BRCA syndrome, endometrial and colon cancer is documented. This effect is prolonged for years after contraception discontinuation. Non-contraceptive benefits of progestin-only contraceptives are less documented. Use of the levonorgestrel IUD is associated with a reduction in menorrhagia, dysmenorrhea including in case of endometriosis. Copper IUD use is associated with a decrease in cervix and endometrial cancer risk.

Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Key issues in hymenoptera venom allergy: an update

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis (AU)

En esta revisión el Comité de Alergia a Himenópteros de la SEAIC ha analizado la literatura científica más reciente sobre los principales problemas diagnósticos de la alergia a himenópteros, así como sobre las dificultades que pueden surgir durante la inmunoterapia con venenos. Se revisan especialmente las novedades relacionadas con el diagnóstico molecular y los perfiles moleculares de riesgo. También se describe la alergia a himenópteros poco habituales y los problemas diagnósticos y terapéuticos que esta conlleva. Por último, se tratan los síndromes de activación mastocitaria clonal, íntimamente relacionados con la alergia a himenópteros, que se han convertido en un nuevo reto diagnóstico para el alergólogo (AU)

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

INTRODUCTION: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. MATERIALS AND METHODS: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. RESULTS: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. CONCLUSIONS: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Factors modulating circulation of hematopoietic progenitor cells in cord blood and neonates.

BACKGROUND: Hematopoietic progenitor cells (HPC) circulate at high levels at birth and disappear rapidly afterwards, but the underlying mechanism it is not known. The aim of this study was to assess circulating HPC in cord blood at different gestational ages and shortly after birth and concomitantly study the biologic markers involved in this phenomenon. METHODS: All samples were analyzed for CD34(+) cells, colony-forming units (CFU) and cytokines. RESULTS: The results obtained confirmed a slight decrease in HPC concentration during the late stage of fetal life (R(2)=0.41). After birth, CD34(+) cells showed a rapid decline from circulation: 25+/-29% at 3 h, 51+/-42% at 12 h and 80+/-48% at 60 h. CFU cleared following a similar pattern. Cord plasma showed higher concentrations of stem cell factor (SCF), fetal liver tyrosine kinase 3-ligand (FLT3l), erythrpoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and interleukin-11 (IL-11) compared with an adult control. Interestingly, the EPO concentration in newborn plasma correlated with the kinetics of HPC decline after birth. Moreover, we observed an up-regulation of l-selectin and a down-regulation of CXCR4 expression in CD34(+) cells 3 h after birth. DISCUSSION: These data combined suggest that an active homing process results in the clearance of HPC from the circulation immediately after birth.

[Ciliary changes with abscence of dynein arms in Kartagener's syndrome]. / Alteración ciliar con ausencia de los brazos de dineina en el síndrome de Kartagener.

A 33 years-old female with a diagnosis of Kartagener's syndrome was studied. She had a clinical history of chronic sinusitis with nasal obstruction and rhinorrea, and a chronic cough with mucopurulent sputum. A paranasal sinus CT showed hypertrophyc mucosa. A thoracic CT showed a situs inversus and chronic bronchitis with bronchiectasis. The saccharin test lasted 55 minutes. The electron microscopy study showed in a a cross-sectional axoneme a total absence of the outer and inner arm of the 9th outer doublet in over a 100 cilias studied. No others ultrastructure anormalities were observed.

Alteración ciliar con ausencia de los brazos de dineina en el síndrome de Kartagener / Ciliary changes with abscence of dynein arms in Kartagener's syndrome

Presentamos el caso de una mujer de 33 años diagnosticada de síndrome de Kartagener. La paciente refiere una historia de rinorrea y obstrucción nasal de larga evolución sugestiva de sinusitis crónica y de tos acompañada de expectoración mucopurulenta. En TC de senos paranasales se aprecia una mucosa sinusal hipertrófica. En TC de tórax de observa un situs inversus y bronquiectasias. El tiempo del test de la sacarina fue de 55 minutos. El estudio ciliar con microscopío electrónico mostró una ausencia completa de los dos brazos del doblete número nueve en más de 100 cilios estudiados. No se observaron otras alteraciones ultraestructurales (AU)

A 33 years-old female with a diagnosis of Kartagener's syndrome was studied. She had a clinical history of chronic sinusitis with nasal obstruction and rhinorrea, and a chronic cough with mucopurulent sputum. A paranasal sinus CT showed hypertrophyc mucosa. A thoracic CT showed a situs inversus and chronic bronchitis with bronchiectasis. The saccharin test lasted 55 minutes. The electron microscopy study showed in a a cross-sectional axoneme a total absence of the outer and inner arm of the 9th outer doublet in over a 100 cilias studied. No others ultrastructure anormalities were observed (AU)

Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue.

OBJECTIVES: The aims of this study were to evaluate the following: 1) the prevalence of hypertransaminasemia (HT) in a pediatric celiac disease (CD) and its relation with clinical parameters; 2) the frequency of HT as the only manifestation of pediatric CD; and 3) the evolution of HT after a gluten free diet. METHODS: A total of 114 consecutive pediatric CD patients were studied (60% with classical and 40% with atypical forms). Antiendomisyum antibodies and anti-tissue transglutaminase antibodies were determined in patients with a clinical suspicion of CD (including unexplained chronic HT), in patients at risk, and in patients with preoperative increased ALT activity for minor surgery. CD was confirmed by duodenal biopsy. At baseline, the relationship between clinical factors and aminotransferase status was univariately and multivariately assessed. After starting a gluten free diet, patients were followed up, until serological markers cleared and serum aminotransferase normalized. RESULTS: HT occurred in 32% of patients (37 of 114) at diagnosis. HT was the only manifestation of CD in five patients (4.3%). Patients with HT were younger (2.9 +/- 0.4 yr) than patients with normal aminotransferases (5.1 +/- 0.5 yr) (p = 0.007). A higher percentage of patients with classical CD tend to have abnormal aminotransferases (73%; 95% CI = 65-81%) than do patients with atypical CD (27%; 95% CI = 19-35%) (p = 0.068). Logistic regression analysis showed that only younger age was significantly associated with HT (p = 0.039; OR = 0.8; 95% CI = 0.71-0.99). Aminotransferases normalized with a gluten free diet in all 35 patients who were followed-up, either before (n = 18) or at the same time (n = 17) as serological markers cleared. CONCLUSIONS: HT is a frequent finding in pediatric CD patients and, in a substantial proportion, may be the only manifestation of CD. Thus, serological markers of CD should be introduced in the first step of the diagnostic workup of liver diseases in pediatric patients.

Brote epidémico de acarosis en una unidad de cuidados intensivos por exposición ocupacional / Epidemic bud of acarosis in an intensive unit of cares by exposition occupational

El presente estudio muestra la experiencia de un brote epidémico intrahospitalario en trabajadores de salud por exposición al S.scabiei, a partir de un caso de Sarna Costrosa, diagnosticado tardíamente en nuestra Unidad de Cuidados Intensivos; las medidas que se tomaron para el control de la propagación, las fallas en la bioseguridad y las consecuencias que de ella derivan, la importancia de la vigilancia epidemiológica y la experiencia en el uso de permetrina 5 por ciento en un brote de acarosis.

Bartonelosis (fiebre de la Oroya o verruga peruana): reporte de un caso-revisión de la literatura / Bartonellosis(Oroya fever or verruga paruana): a case report and literature review

Se presenta un caso típico de verruga peruana atendido en el Servicio de Dermatología del Hospital Alberto Sabogal Sologuren, y a raíz de ello revisamos esta interesante enfermedad emergente mundial. La bartonelosis humana al principio fue asociada básicamente a la especie Bartonella bacilliformis, pero hoy en día se han descubierto hasta 18 Bartonellas que afectan al humano y a varios animales domésticos. La Bartonella bacilliformis es una parásito bacteriano intracelular facultativo de los eritrocitos humanos y de las células endoteliales. La enfermedad de Carrión, fiebre de la Oroya y verruga peruana son todos términos que describen las consecuencias patológicas de la infección humana por Bartonella bacilliformis. Aunque las infecciones que involucran especies de Bartonella, tales como Bartonella henselae quintan, ocurren en todo el mundo, la enfermedad de Carrión es endémica únicamente en Sudamérica. Las infecciones por B. bacilliformis son un problema de salud en numerosas áreas rurales de Sudamérica y para los viajeros que visitan estas regiones montañosas de Perú, Ecuador y Colombia. La Lutzomya verrucarum es el principal vector para la transmisión de la bacteria al ser humano; la hembra del mosquito transmite el patógeno durante su alimentación nocturna de sangre humana. Presumiblemente el insecto se alimenta de la sangre de un individuo infectado y disemina el patógeno por medio de su saliva durante la siguiente ingesta de sangre. La bacteria no es contagiosa entre humanos.

Identification of active molecular sites using quantum-self-similarity measures.

A novel approach to construct theoretical QSAR models is proposed. This technique, based on the systematic use of quantum similarity measures as theoretical molecular descriptors, opens the possibility to localize and to identify the position of the bioactive part of drug molecules in situations, where the nature of the pharmacophore is not known. To test the reliability of this new approach, the method has been applied to the study of steroids binding to corticosteroid-binding human globulin. The studied molecules involved the set of 31 Cramer's steroids, often used as a benchmark set in QSAR studies. It has been shown that theoretical QSAR models based on the present procedure are superior to those derived from alternative existing approaches. In addition, a new method to measure the statistical significance of multiparameter QSAR models is also proposed.

Dermografismo secundario a alergia a picadura de avispa / Secondary dermographism in wasp sting allergy

Se presenta el caso de una mujer de 55 años que inició dermografismo a partir de una picadura de avispa. Tenía antecedentes de reacción local gigante retardada y reacción sistémica grado I tras picadura de avispa y, en ese momento, las pruebas cutáneas y la IgE específica habían sido positivas para Polistes spp (intradermorreacción 1 µg/mL: 7x7/25x27 mm; 0,51 kU/L). Tres años más tarde, después de una picadura de avispa, inició dermografismo y los valores de IgE específica aumentaron de manera marcada (>100 kU/L). Al cabo de 5 meses persistían la clínica cutánea e idénticos valores de IgE específica. No se han encontrado casos descritos de dermografismo asociado a alergia a veneno de himenópteros. (AU)

Molecular electronic density fitting using elementary Jacobi rotations under atomic shell approximation

Fitted electron density functions constitute an important step in quantum similarity studies. This fact not only is presented in the published papers concerning quantum similarity measures (QSM), but also can be associated with the success of the developed fitting algorithms. As has been demonstrated in previous work, electronic density can be accurately fitted using the atomic shell approximation (ASA). This methodology expresses electron density functions as a linear combination of spherical functions, with the constraint that expansion coefficients must be positive definite, to preserve the statistical meaning of the density function as a probability distribution. Recently, an algorithm based on the elementary Jacobi rotations (EJR) technique was proven as an efficient electron density fitting procedure. In the preceding studies, the EJR algorithm was employed to fit atomic density functions, and subsequently molecular electron density was built in a promolecular way as a simple sum of atomic densities. Following previously established computational developments, in this paper the fitting methodology is applied to molecular systems. Although the promolecular approach is sufficiently accurate for quantum QSPR studies, some molecular properties, such as electrostatic potentials, cannot be described using such a level of approximation. The purpose of the present contribution is to demonstrate that using the promolecular ASA density function as the starting point, it is possible to fit ASA-type functions easily to the ab initio molecular electron density. A comparative study of promolecular and molecular ASA density functions for a large set of molecules using a fitted 6-311G atomic basis set is presented, and some application examples are also discussed.

Use of electron-electron repulsion energy as a molecular descriptor in QSAR and QSPR studies.

Electron-electron repulsion energy () is presented as a new molecular descriptor to be employed in QSAR and QSPR studies. Here it is shown that this electronic energy parameter is connected to molecular quantum similarity measures (MQSM), and as a consequence can be considered as a complement to steric and electronic parameters in description of molecular properties and biological responses of organic compounds. The present strategy considers the molecule as a whole, thus there is no need to employ contributions of isolated fragments as in many calculations of molecular descriptors, like log P or the Free-Wilson analysis. The procedure has been tested in a widespread set of molecules: alcohols, alkanamides, indole derivatives and 1-alkylimidazoles. Molecular properties, as well as toxicity, are correlated using as a parameter, and extensions to the method are given for handling difficult systems. In almost all studied cases, satisfactory linear relationships were finally obtained.

Simple linear QSAR models based on quantum similarity measures.

A novel QSAR approach based on quantum similarity measures was developed and tested in this paper. This approach consists of replacing the usual physicochemical parameters employed in QSAR analysis, such as octanol-water partition coefficient or Hammett sigma constant, by appropriate quantum chemical descriptors. The methodological basis for this substitution is found in recent theoretical studies [J. Comput. Chem. 1998, 19, 1575-1583, J. Comput. -Aided Mol. Des. 1999, 13, 259-270], in which it was demonstrated that both molecular hydrophobic character and electronic substituent effect can be modeled by appropriately chosen quantum self-similarity measures (QS-SM). The most important aim of this study was to prove that selected QS-SM descriptors can be advantageously used in empirical QSAR analysis instead of classical descriptors. For this purpose several QSAR correlations are proposed, in which empirical descriptors such as Hammett sigma constants or log P values are replaced by the appropriate QS-SM. These examples involve: (i) a set of benzenesulfonamides which bind to human carbonic anhydrase, (ii) a set of benzylamines as competitive inhibitors of the enzyme trypsin, and (iii) a set of indole derivatives which are benzodiazepine receptor inverse agonist site ligands. Simple linear QSAR models were developed in order to obtain mathematical relationships between the biological activity and the pertinent quantum chemical descriptors. The validity of the obtained QSAR models is supported by comparison of the observed and predicted values of the biological activity and by a statistical analysis based on a randomization test.

Diagnosis and follow-up of a case of peroxisomal disorder with peroxisomal mosaicism.

Peroxisomal disorder phenotypes are the result of mutations that cause defective peroxisomal assembly or alterations in the import mechanism of peroxisomal proteins that lead to multiple peroxisomal dysfunctions, or the result of a peroxisomal enzymatic deficiency with a single peroxisomal dysfunction. With complementation analysis, 16 groups have been found. Assignment of the genetic defect has been described for some of the complementation groups. We describe the clinical evolution and follow-up over 10 years of a patient who belongs to complementation group 4, although he showed a milder clinical course. It has been found in fibroblasts different peroxisome populations, normal processing and expression of beta-oxidation PTS1 and PTS2 proteins, abnormal ALD protein distribution and normal plasmalogen biosynthesis; abnormal beta-oxidation metabolites have also been detected in serum. Ultrastructural studies in liver showed peroxisomal mosaicism as in fibroblasts. It has been taken into account that peroxisomal mosaicism may lead to variability in peroxisomal diagnostic parameters, making difficult the final diagnosis in these patients.

Effect of glycosylation of recombinant human granulocytic colony-stimulating factor on expansion cultures of umbilical cord blood CD34+ cells.

BACKGROUND AND OBJECTIVE: Granulocytic colony-stimulating factor (G-CSF) is a cytokine widely used for several purposes such as stem cell mobilization, treatment of neutropenia or in vitro cultures. Recombinant human G-CSF (rh-G-CSF) is available in two forms: a non-glycosylated (E. Coli-derived), and a glycosylated CHO-derived rhG-CSF. As previously shown, glycosylation gives a higher degree of homology between the recombinant and the wild human G-CSF molecule. This study analyses the role of glycosylation in expansion cultures comparing the biological effects of the two forms of G-CSF. DESIGN AND METHODS: CD34+ cells from nine cord blood samples were positively selected (median purity 84%) and cultured in the presence of 50 ng/mL of stem cell factor and 1, 10 or 100 ng/mL of glycosylated rh-G-CSF (GG) or a deglycosylated form (DG). After 5 days of a static, serum-dependent culture fed on day 0, nucleated cells (NC), CD34+ cells and colony-forming units were evaluated and compared using the paired Student's t-test. RESULTS: For all concentrations tested, GG was able to generate more NC and progenitors than DG was able to (p<0.05). This effect was mainly observed in CFU-GM colonies, and in CFU-Mix, and indeed no influence was detected in terms of BFU-E expansion. The presence of GG in culture causes the generation of more mature granulocytic cells, assessed by the expression of CD11b/CD15 on CD13+ population, than the presence of DG. In order to check the role of the molecule's stability in this difference, the effect of daily supplementation was tested. Continuous presence of cytokines using either form of G-CSF (daily feeding) significantly increased the rate of expansion, but again GG produced higher generation than its DG counterpart. INTERPRETATION AND CONCLUSIONS: Our results suggest that the stability of the G-CSF molecule has a predominant effect on the higher biological activity found. A glycosylated form of G-CSF is recommended for in vitro cultures using serum-dependent conditions.