Contribution of Non-Covalent Interactions and Electronic Effects on the Conformational Landscape and Tautomeric Equilibria of Molecules and Molecular Complexes: Structural and Dynamical Data from Rotational Spectroscopy

This thesis concerns the study of complex conformational surfaces and tautomeric equilibria of molecules and molecular complexes by quantum chemical methods and rotational spectroscopy techniques. In particular, the focus of this research is on the effects of substitution and noncovalent interactions in determining the energies and geometries of different conformers, tautomers or molecular complexes. The Free-Jet Absorption Millimeter Wave spectroscopy and the Pulsed-Jet Fourier Transform Microwave spectroscopy have been applied to perform these studies and the obtained results showcase the suitability of these techniques for the study of conformational surfaces and intermolecular interactions. The series of investigations of selected medium-size molecules and complexes have shown how different instrumental setups can be used to obtain a variety of results on molecular properties. The systems studied, include molecules of biological interest such as anethole and molecules of astrophysical interest such as N-methylaminoethanol. Moreover halogenation effects have been investigated on halogen substituted tautomeric systems (5-chlorohydroxypyridine and 6-chlorohydroxypyridine), where it has shown that the position of the inserted halogen atom affects the prototropic equilibrium. As for fluorination effects, interesting results have been achieved investigating some small complexes where a molecule of water is used as a probe to reveal the changes on the electrostatic potential of different fluorinated compounds: 2-fluoropyridine, 3-fluoropyridine and penta-fluoropyridine. While in the case of the molecular complex between water and 2-fluoropyridine and 3-fluoropyridine the geometry of the complex with one water molecule is analogous to that of pyridine with the water molecule linked to the pyridine nitrogen, the case of pentafluoropyridine reveals the effect of perfluorination and the water oxygen points towards the positive center of the pyridine ring. Additional molecular adducts with a molecule of water have been analyzed (benzylamine-water and acrylic acid-water) in order to reveal the stabilizing driving forces that characterize these complexes.

Oral mucosal findings related to tobacco use and alcohol consumption: a study on Swiss army recruits involving self-reported and clinical data

PURPOSE: The aim of the present study was to assess the oral mucosal health status of young male adults (aged 18 to 24 years) in Switzerland and to correlate their clinical findings with self-reported risk factors such as tobacco use and alcohol consumption. MATERIALS AND METHODS: Data on the oral health status of 615 Swiss Army recruits were collected using a standardised self-reported questionnaire, followed by an intraoral examination. Positive clinical findings were classified as (1) common conditions and anatomical variants, (2) reactive lesions, (3) benign tumour lesions and (4) premalignant lesions. The main locations of the oral mucosal findings were recorded on a topographical classification chart. Using correlational statistics, the findings were further associated with the known risk factors such as tobacco use and alcohol consumption. RESULTS: A total of 468 findings were diagnosed in 327 (53.17%) of the 615 subjects. In total, 445 findings (95.09%) were classified as common conditions, anatomical variants and reactive soft-tissue lesions. In the group of reactive soft-tissue lesions, there was a significantly higher percentage of smokers (P < 0.001) and subjects with a combination of smoking and alcohol consumption (P < 0.001). Eight lesions were clinically diagnosed as oral leukoplakias associated with smokeless tobacco. The prevalence of precursor lesions in the population examined was over 1%. CONCLUSIONS: Among young male adults in Switzerland, a significant number of oral mucosal lesions can be identified, which strongly correlate with tobacco use. To improve primary and secondary prevention, young adults should therefore be informed more extensively about the negative effects of tobacco use on oral health.

Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data

In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM).

Mobile phone technologies and advanced data analysis towards the enhancement of diabetes self-management

Advances in the area of mobile and wireless communication for healthcare (m-Health) along with the improvements in information science allow the design and development of new patient-centric models for the provision of personalised healthcare services, increase of patient independence and improvement of patient's self-control and self-management capabilities. This paper comprises a brief overview of the m-Health applications towards the self-management of individuals with diabetes mellitus and the enhancement of their quality of life. Furthermore, the design and development of a mobile phone application for Type 1 Diabetes Mellitus (T1DM) self-management is presented. The technical evaluation of the application, which permits the management of blood glucose measurements, blood pressure measurements, insulin dosage, food/drink intake and physical activity, has shown that the use of the mobile phone technologies along with data analysis methods might improve the self-management of T1DM.

German validation of the Conners Adult ADHD Rating Scales–self-report (CAARS-S) I: Factor structure and normative data

Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. Instruments for diagnosing ADHD in childhood are well validated and reliable, but diagnosis of ADHD in adults remains problematic. Attempts have been made to develop criteria specific for adult ADHD, resulting in the development of self-report and observer-rated questionnaires. To date, the Conners Adult ADHD Rating Scales (CAARS) are the international standard for questionnaire assessment of ADHD. The current study evaluates a German version of the CAARS self-report (CAARS-S).

Transmission of Chlamydia trachomatis through sexual partnerships: a comparison between three individual-based models and empirical data

Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in many developed countries. The highest prevalence rates are found among young adults who have frequent partner change rates. Three published individual-based models have incorporated a detailed description of age-specific sexual behaviour in order to quantify the transmission of C. trachomatis in the population and to assess the impact of screening interventions. Owing to varying assumptions about sexual partnership formation and dissolution and the great uncertainty about critical parameters, such models show conflicting results about the impact of preventive interventions. Here, we perform a detailed evaluation of these models by comparing the partnership formation and dissolution dynamics with data from Natsal 2000, a population-based probability sample survey of sexual attitudes and lifestyles in Britain. The data also allow us to describe the dispersion of C. trachomatis infections as a function of sexual behaviour, using the Gini coefficient. We suggest that the Gini coefficient is a useful measure for calibrating infectious disease models that include risk structure and highlight the need to estimate this measure for other STIs.

Immediate restoration of nonsubmerged titanium implants with a sandblasted and acid-etched surface: five-year results of a prospective case series study using clinical and radiographic data

The aim of this study was to evaluate the survival and success rates of immediately restored implants with sandblasted, large-grit, acid-etched (SLA) surfaces over a period of 5 years. Twenty patients (mean age, 47.3 years) received a total of 21 SLA wide-neck implants in healed mandibular first molar sites after initial periodontal treatment. To be included in the study, the implants had to demonstrate primary stability with an insertion torque value of 35 Ncm. A provisional restoration was fabricated chairside and placed on the day of surgery. Definitive cemented restorations were inserted 8 weeks after surgery. Community Periodontal Index of Treatment Needs (CPITN) indices and the radiographic distance between the implant shoulder and the first visible bone-implant contact (DIB) were measured and compared over the study period. The initial mean CPITN was 3.24, and decreased over the study period to 1.43. At the postoperative radiographic examination, the mean DIB was 1.41 mm for the 21 implants, indicating that part of the machined neck of the implants was placed slightly below the osseous crest. The mean DIB value increased to 1.99 mm at the 5-year examination. This increase proved to be statistically significant (P < .0001). Between the baseline and 5-year examinations, the mean bone crest level loss was 0.58 mm. Success and survival rates of the 21 implants after 5 years of function were 100%. This 5-year study confirms that immediate restoration of mandibular molar wide-neck implants with good primary stability, as noted by insertion torque values of at least 35 Ncm, is a safe and predictable procedure.

Patients' awareness of the potential benefit of smoking cessation. A study evaluating self-reported and clinical data from patients referred to an oral medicine unit

The present study analyzed history of smoking and willingness to quit smoking in patients referred for diagnosis and treatment of different oral mucosal lesions. Prior to the initial clinical examination, patients filled in a standardized questionnaire regarding their current and former smoking habits and willingness to quit. Definitive diagnoses were classified into three groups (benign/reactive lesions, premalignant lesions and conditions, and malignant diseases) and correlated with the self-reported data in the questionnaires. Of the 980 patients included, 514 (52%) described themselves as never smokers, 202 (21%) as former smokers, and 264 (27%) as current smokers. In the group of current smokers, 23% thought their premalignant lesions/conditions were related to their smoking habit, but only 15% of the patients with malignant mucosal diseases saw that correlation. Only 14% of the smokers wanted to commence smoking cessation within the next 30 days. Patients with malignant diseases (31%) showed greater willingness to quit than patients diagnosed with benign/reactive lesions (11%). Future clinical studies should attempt (1) to enhance patients' awareness of the negative impact of smoking on the oral mucosa and (2) to increase willingness to quit in smokers referred to a dental/oral medicine setting.

Acinetobacter baumannii isolates from pets and horses in Switzerland: molecular characterization and clinical data

OBJECTIVES: We investigated whether Acinetobacter baumannii isolates of veterinary origin shared common molecular characteristics with those described in humans. METHODS: Nineteen A. baumannii isolates collected in pets and horses were analysed. Clonality was studied using repetitive extragenic palindromic PCR (rep-PCR) and multilocus sequence typing (MLST). PCR and DNA sequencing for various beta-lactamase, aminoglycoside-modifying enzyme, gyrA and parC, ISAba1 and IS1133, adeR and adeS of the AdeABC efflux pump, carO porin and class 1/2/3 integron genes were performed. RESULTS: Two main clones [A (n = 8) and B (n = 9)] were observed by rep-PCR. MLST indicated that clone A contained isolates of sequence type (ST) ST12 (international clone II) and clone B contained isolates of ST15 (international clone I). Two isolates of ST10 and ST20 were also noted. Seventeen isolates were resistant to gentamicin, 12 to ciprofloxacin and 3 to carbapenems. Isolates of ST12 carried bla(OXA-66), bla(ADC-25), bla(TEM-1), aacC2 and IS1133. Strains of ST15 possessed bla(OXA-69), bla(ADC-11), bla(TEM-1) and a class 1 integron carrying aacC1 and aadA1. ISAba1 was found upstream of bla(ADC) (one ST10 and one ST12) and/or bla(OXA-66) (seven ST12). Twelve isolates of different STs contained the substitutions Ser83Leu in GyrA and Ser80Leu or Glu84Lys in ParC. Significant disruptions of CarO porin and overexpressed efflux pumps were not observed. The majority of infections were hospital acquired and in animals with predisposing conditions for infection. CONCLUSIONS: STs and the molecular background of resistance observed in our collection have been frequently described in A. baumannii detected in human patients. Animals should be considered as a potential reservoir of multidrug-resistant A. baumannii.

Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using Ingenuity Pathway Analysis(R)

BACKGROUND: Recurrent airway obstruction (RAO) is a severe chronic respiratory disease affecting horses worldwide, though mostly in the Northern hemisphere. Environmental as well as genetic factors strongly influence the course and prognosis of the disease. Research has been focused on characterization of immunologic factors contributing to inflammatory responses, on genetic linkage analysis, and, more recently, on proteomic analysis of airway secretions from affected horses. The goal of this study was to investigate the interactions between eight candidate genes previously identified in a genetic linkage study and proteins expressed in bronchoalveolar lavage fluid (BALF) collected from healthy and RAO-affected horses. The analysis was carried out with Ingenuity Pathway Analysis(R) bioinformatics software. RESULTS: The gene with the greatest number of indirect interactions with the set of proteins identified is Interleukin 4 Receptor (IL-4R), whose protein has also been detected in BALF. Interleukin 21 receptor and chemokine (C-C motif) ligand 24 also showed a large number of interactions with the group of detected proteins. Protein products of other genes like that of SOCS5, revealed direct interactions with the IL-4R protein. The interacting proteins NOD2, RPS6KA5 and FOXP3 found in several pathways are reported regulators of the NFkappaB pathway. CONCLUSIONS: The pathways generated with IL-4R highlight possible important intracellular signaling cascades implicating, for instance, NFkappaB. Furthermore, the proposed interaction between SOCS5 and IL-4R could explain how different genes can lead to identical clinical RAO phenotypes, as observed in two Swiss Warmblood half sibling families because these proteins interact upstream of an important cascade where they may act as a functional unit.