Sexually Transmitted Infections: Experience in a Multidisciplinary Clinic in a Tertiary Hospital (2010-2013).

INTRODUCTION: The number of consultations for sexually transmitted infections (STIs) is increasing in Spain. The aim of this study was to describe and analyze the epidemiological, behavioral, clinical, and microbiological characteristics of patients registered at the STI unit of a tertiary hospital. METHODS: This was a retrospective, single-center descriptive study carried out between 2010 and 2013 in a multidisciplinary unit specialized in STIs, situated in a tertiary hospital. Epidemiological, clinical, and behavioral data were gathered using a face-to-face interview and a standardized questionnaire. Samples were collected for microbiology analysis. RESULTS: The study included 546 patients: 96% were men, 41% had human immunodeficiency virus (HIV) infection, and 56% were men who have sex with men. The reasons for consultation were the following: urethritis; genital, anal, or perianal ulcers; proctitis; oral ulcers; sexual contact with a person with a known STI; and high-risk sexual contact. The most common microbiological diagnoses were Neisseria gonorrhoeae in urethritis, Treponema pallidum in genital and anal or perianal ulcers, and Chlamydia trachomatis lymphogranuloma venereum serovars in proctitis. The highest prevalences of the main STIs studied occurred in homosexual men with HIV infection. CONCLUSION: This study confirms the increase in the incidence of STIs in recent years and the epidemiological characteristics of the HIV/STI epidemic in Spain.

A multiscale orchestrated computational framework to reveal emergent phenomena in neuroblastoma.

Neuroblastoma is a complex and aggressive type of cancer that affects children. Current treatments involve a combination of surgery, chemotherapy, radiotherapy, and stem cell transplantation. However, treatment outcomes vary due to the heterogeneous nature of the disease. Computational models have been used to analyse data, simulate biological processes, and predict disease progression and treatment outcomes. While continuum cancer models capture the overall behaviour of tumours, and agent-based models represent the complex behaviour of individual cells, multiscale models represent interactions at different organisational levels, providing a more comprehensive understanding of the system. In 2018, the PRIMAGE consortium was formed to build a cloud-based decision support system for neuroblastoma, including a multi-scale model for patient-specific simulations of disease progression. In this work we have developed this multi-scale model that includes data such as patient's tumour geometry, cellularity, vascularization, genetics and type of chemotherapy treatment, and integrated it into an online platform that runs the simulations on a high-performance computation cluster using Onedata and Kubernetes technologies. This infrastructure will allow clinicians to optimise treatment regimens and reduce the number of costly and time-consuming clinical trials. This manuscript outlines the challenging framework's model architecture, data workflow, hypothesis, and resources employed in its development.

Evaluation of QSAR models for predicting mutagenicity: outcome of the Second Ames/QSAR international challenge project.

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.

Comparison of two methods for obtaining and transporting corneal samples in suspected infectious keratitis.

BACKGROUND AND PURPOSE: The purpose of this study is to compare two alternative methods of collecting and transporting media for the diagnosis of corneal ulcers, as not all clinical settings have conventional culture materials and transport media available. METHODS: In this open-label, prospective, comparative, and randomized study, patients with clinical suspicion of infectious keratitis with high risk of loss of vision had corneal specimens collected using two methods and transport media: Eswab scraping with Amies transport medium and 23-gauge needle scraping in BACTEC Peds broth. The order of each collection method was randomized. The samples were processed by standard methods, comparing the positivity frequencies for both by parametric and nonparametric tests, according to normality criteria. RESULTS: Corneal infiltrates from 40 eyes of 40 patients were analyzed. Culture positivity rate was 50% for Eswab and 35% for 23-gauge needle (P=0.258). The overall growth rate of the two methods combined was not higher than with the swab alone. The results obtained with a swab were not influenced by the collection sequence (P=0.112); however, the positivity rate was significantly higher when the sample taken with the needle was performed first (P=0.046). CONCLUSIONS: The single sample Eswab method of collection and transportation for the diagnosis of high risk corneal ulcers is a valid alternative and can be used in cases in which, for various reasons, there is no access to the full set of traditional culture materials.

In silico pharmacology for drug discovery: applications to targets and beyond.

Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediting the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets.

In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling.

Pharmacology over the past 100 years has had a rich tradition of scientists with the ability to form qualitative or semi-quantitative relations between molecular structure and activity in cerebro. To test these hypotheses they have consistently used traditional pharmacology tools such as in vivo and in vitro models. Increasingly over the last decade however we have seen that computational (in silico) methods have been developed and applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, pharmacophores, homology models and other molecular modeling approaches, machine learning, data mining, network analysis tools and data analysis tools that use a computer. In silico methods are primarily used alongside the generation of in vitro data both to create the model and to test it. Such models have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The aim of this review is to illustrate some of the in silico methods for pharmacology that are used in drug discovery. Further applications of these methods to specific targets and their limitations will be discussed in the second accompanying part of this review.

The "in vitro" percutaneous penetration of three antioxidant compounds.

Caffeic acid, chlorogenic acid and oraposide, a natural glycoside, are phenyl-propanoid compounds. These natural products have been reported to have antioxidant activities such as the scavenging of superoxide anions and hydroxyl radicals. These compounds could be used in the dermocosmetic field to protect the skin from oxidative stress induced by UV radiation. To this end, the permeation of caffeic acid, chlorogenic acid, and oraposide, through pig-ear skin was evaluated in vitro. The percutaneous permeation of these three compounds through pig skin was measured and compared using Franz diffusion cells. At appropriate intervals, up to 72 h, diffusion samples were analyzed using an HPLC assay. After 48 h of drug contact the permeation was also evaluated with a fluorescent microscope on vertical microtomed pig skin sections. In this study on excised pig skin, the flux value was found to be equal to 0.32 and 0.48 microgcm(-2)h(-1) for caffeic and chlorogenic acids, respectively; for oraposide the levels were below the limit of detection and the flux was not evaluated. These results were corroborated by fluorescent microscopy. Caffeic and chlorogenic acids were found in all skin sections, and these might represent a systemic activity, whereas oraposide remained in the upper superficial layer of the skin. This latter phenomenon seems to be interesting for dermocosmetic applications.

Effects of different antihypertensive medication groups on cognitive function in older patients: A systematic review.

BACKGROUND: Chronic hypertension has been associated with an increased risk of cognitive decline. Although a link between hypertension and cognitive decline has been established, there is less evidence supported by systematic reviews. The main aim was to compare different antihypertensive drug groups in relation to their effect on cognition in older patients without established dementia using a systematic review. METHOD: A systematic search in Medline and Embase through to January 2017 was used to identify randomized controlled clinical trials (RCTs) studying the impact of different antihypertensives on cognition in older patients without dementia. Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-Is), beta-blockers (BBs), diuretics, and calcium channel blockers (CCBs) were included in this review. RESULTS: The systematic search identified 358 studies. The full text of 31 RCTs was reviewed and a total of 15 RCTs were included in the review. Most studies reported an improvement in episodic memory in patients treated with ARBs versus placebo or other types of antihypertensive drugs. No study showed an improvement in cognition in patients who received diuretics, BBs, or CCBs. Heterogeneity was high in most trials (predominantly in the blinding of participants and investigators). CONCLUSION: This review suggests that ARBs can improve cognitive functions in the elderly, especially episodic memory. ACE-Is, diuretics, BBs and CCBs did not seem to improve cognitive function in the elderly but were similarly effective in blood pressure lowering as ARBs.

Defining the optimal sequence for the systemic treatment of metastatic breast cancer.

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.

Plasma kallikrein-kinin system in patients with uncomplicated sepsis and septic shock--comparison with cardiogenic shock.

Alterations of the kallikrein-kinin system consistent with activation and increased consumption have been reported in septic patients and it has been suggested that this activation could contribute to the development of septic shock. The aim of this work was to confirm these alterations in septic patients and to investigate the possible existence of similar changes in subjects developing cardiogenic shock secondary to myocardial infarction as a model of non septic shock. Patients with septic shock, especially in fatal cases, showed a highly significant decrease in levels of factor XII, prekallikrein, high molecular weight kininogen (HMW-kininogen), alpha 2-macroglobulin (alpha 2-M) and antithrombin III (AT-III). C1-esterase inhibitor (C1-INH) activity was increased in uncomplicated sepsis but came back to normal or was slightly decreased in septic shock. Components and inhibitors of the kallikrein-kinin system were within normal limits in patients with cardiogenic shock. Our findings support the idea of a contribution of the kallikrein-kinin system to the development of septic shock though this system does not seem to play a significant role in the pathogenesis of cardiogenic shock or seem to be altered as a consequence of it.

Simple schizophrenia revisited: a clinical, neuropsychological, and neuroimaging analysis of nine cases.

Simple schizophrenia is widely considered to be a controversial or even discredited entity. However, cases showing typical clinical features continue to be identified in surveys of schizophrenia patients. This article reports on nine patients who met proposed diagnostic criteria for simple schizophrenia. The patients all showed the classical features of social and occupational decline, as well as negative symptoms in the absence of clear-cut positive symptoms. A range of other symptoms, which were either nonspecific or fell short of psychotic phenomena, was also seen. Neuropsychological testing revealed evidence of general intellectual impairment plus deficits in executive function and memory. Computed tomography scans were normal or showed only minor abnormalities. All patients, however, showed abnormalities on single photon emission computerized tomography (SPECT), mainly affecting frontal and temporal regions. It is concluded that cases conforming to the original descriptions of simple schizophrenia continue to be seen and are still best understood as representing a form of schizophrenia.

A molecular field-based similarity approach to pharmacophoric pattern recognition.

The use of molecular field-based similarity approaches for obtaining quality molecular alignments and for identifying field-based patterns in bioactive molecules is described. In addition to pairwise similarities, computation of multimolecule similarities affords a means for determining consensus multimolecule alignments. These multimolecule alignments constitute the basis for developing models for the relative binding of bioactive molecules to common protein-binding sites and for the graphical portrayal of molecular field similarity surface plots that identify, visually, molecular regions possessing similar molecular field characteristics. The latter information can then be exploited in the design of molecules that mimic appropriate characteristics of these highly similar steric and electrostatic domains. Regions with low steric and electrostatic similarity in suitably aligned sets of bioactive molecules represent tolerant domains where new structural motifs can be incorporated without significant reductions in activity. To illustrate the potential applicability of the actual molecular field-based similarity approaches to the design of bioactive molecules, a study on a set of HIV-1 protease inhibitors is presented.

Comparing protein structures: a Gaussian-based approach to the three-dimensional structural similarity of proteins.

This study describes a new method for comparing three-dimensional protein structures based on an optimal alignment of their steric fields. The method is based upon the use of spherical Gaussian functions located on individual atoms. This representation generates a flexible description of the underlying fold geometry of proteins that can be adjusted by changing the 'width' of the Gaussians. Reducing the width sharpens the representation and leads to a more 'atomlike' description; increasing the width creates a fuzzier representation that preserves the general shape features of the chain fold but with a consequent loss in atomic resolution. The width used in this study is based upon the features of individual atoms and provides a representation that is quite robust with respect to the variety of geometric features typically encountered in the alignment process. In addition, a post-alignment analysis is performed that generates sequence alignments from the corresponding structure alignments. An example, based on five mammalian and fungal matrix metalloproteinase crystal structures (human fibroblast collagenase, neutrophil collagenase, stromelysin, astacin, and adamalysin), illustrates a number of features of the Gaussian-based approach.

[Medical counseling, nursing counseling, and nicotine chewing gum for smoking cessation in primary care]. / Consejo médico, consejo de enfermería y chicle de nicotina para dejar de fumar en atención primaria.

The 2-month results of a study designed to compare the effectiveness of three methods to encourage giving up smoking in primary health care are reported: individualized medical counseling (minimal intervention), counseling plus follow-up option by the nurse, and medical counseling plus nicotine chewing gum. Overall 425 smokers between 15 and 65 years of age were included in the study. In 349 of them (82%), short term follow-up was carried out by phone interview. The proportion who declared to have given up smoking, after adjustment for the estimated validity of the phone report of smoking status, was 10, 9%, 10.8% and 11.1%, respectively, without significant differences between the three groups. In the logistic regression analysis, only the existence of concomitant disease and the anticipated difficulty in giving up smoking appeared as predictive variables of abstention. The implications of the results for the strategies to control smoking are discussed.

[Medical treatment of Alzheimer's disease]. / Tratamiento médico de la enfermedad de Alzheimer.

OBJECTIVE: To review the drugs commercially available at present and in the near future in relation to the evolution of Alzheimer disease, bearing in mind the possible psychiatric disorders which may be associated with the disease. DEVELOPMENT: The therapeutic approach is planned according to the different phases of the disease. In the preclinical phase, anti-inflammatory drugs and estrogens in post-menopausal women have been effective. In the initial phase current recognition therapy is directed basically towards correcting the break-down of acetylcholine (tacrine, donepezil, SB202026, SDZ ENA 713). For depressive symptoms serotonin levels are corrected using selective inhibitors of serotonin uptake. CONCLUSIONS: Drug treatment should be considered with the association of drugs which activate the malfunctioning circuits and/or pathways. It would also be useful to design clinical studies using pharmacological combinations of cholinergic agonists, estrogens, anti-inflammatory drugs, seligiline and/or new anti-cholinesterase drugs amongst others.

[Integrated program of psychogeriatric care]. / Programa integral de atención psicogeriátrica.

INTRODUCTION: At the present time there is considerable controversy over the course to follow in attention to patients with psychogeriatric disorders. Rapid diagnosis and maintaining the patients in their homes are the basic objectives of the policy of sharing responsibility among those involved. DEVELOPMENT: We review the bibliography and suggest a form of attention based on experience acquired in the dementia evaluation unit of the Programme Vida als Anys of the Generalitat de Catalunya. The model described is based on making the diagnosis in the patient's home, giving support to the family and integrating the patient into a follow-up unit, with a person responsible for evaluating and resolving the needs of both patient and family as they arise. In order to carry out this programme, the attention must be given by multidiscliplinary units with the necessary resources.

[Effect of peripheral parenteral nutrition on the immediate postoperative period in surgery of the aortic sector]. / Efecto de la nutrición parenteral periférica en el postoperatorio inmediato de la cirugía del sector aórtico.

There is not an extensive literature about nutritional value in Vascular Surgery. In this study, efficacy and cost/benefit relation in the application of Peripheric Parenteral Nutrition (PPN) in postoperative of aortic surgery, are investigated through two randomized groups, in patients with aortoiliac obstructive arteriopathy and who needed an aortobifemoral bypass.

Drug repurposing: far beyond new targets for old drugs.

Repurposing drugs requires finding novel therapeutic indications compared to the ones for which they were already approved. This is an increasingly utilized strategy for finding novel medicines, one that capitalizes on previous investments while derisking clinical activities. This approach is of interest primarily because we continue to face significant gaps in the drug-target interactions matrix and to accumulate safety and efficacy data during clinical studies. Collecting and making publicly available as much data as possible on the target profile of drugs offer opportunities for drug repurposing, but may limit the commercial applications by patent applications. Certain clinical applications may be more feasible for repurposing than others because of marked differences in side effect tolerance. Other factors that ought to be considered when assessing drug repurposing opportunities include relevance to the disease in question and the intellectual property landscape. These activities go far beyond the identification of new targets for old drugs.