Nasal cytology as a screening tool in formaldehyde-exposed workers.

Background: Workers in pathology and anatomy laboratories may be exposed to formaldehyde. An evaluation of the early effects of this substance is, therefore, paramount. This preliminary study was conducted to evaluate if nasal cytology could be used as a tool to detect changes in nasal mucosa in workers exposed to formaldehyde. Aims: To assess whether nasal cytology was able to reveal any alteration of nasal mucosa in workers exposed to formaldehyde compared to unexposed subjects, and to ascertain whether a specific pattern of alterations correlated with years of exposure in order to evaluate long-term occupational exposure effects. Methods: The study included a group of workers exposed to formaldehyde and a group of non-exposed workers. All subjects underwent clinical examination, followed by nasal cytology. Pathological indices from each rhinocytograms were compared between the two groups. Results: Nasal cytology revealed a chronic inflammatory non-allergic condition in the exposed group. Qualitative analysis of data distribution of neutrophils and mucous-secreting/ciliated cells ratio showed data clustering with a cut-off set at 15 years of exposure. The mean formaldehyde concentrations ranged from <0.04 to 0.15 parts per million (ppm). The maximum levels of formaldehyde concentrations ranged from 0.2 to 0.67 ppm. Conclusions: Our data indicate that nasal cytology may be a promising tool for the health surveillance of workers exposed to formaldehyde and may also represent a useful research tool for the study of the health effects of other chemicals irritants for the upper airways.

Pharmacogenetic comparison of CYP2D6 predictive and measured phenotypes in a South African cohort.

This corrects the article DOI: 10.1038/tpj.2015.76.

Emotional intelligence and coping strategies as determinants of quality of life in depressed patient-caregiver dyads: An actor-partner interdependence analysis.

OBJECTIVE: Patients with major depressive disorder (MDD) and their natural caregivers experience major lifestyle difficulties. Little is known concerning dyadic (i.e., patient and natural caregiver) characteristics' impact on quality of life. In a sample of depressed patient-caregiver dyads, we examined quality of life (QoL) levels compared with the general population and whether QoL is influenced by emotional intelligence (EI) and coping strategies using the actor-partner interdependence model (APIM). METHODS: This cross-sectional study involved 79 patient-caregiver dyads. The self-reported data, completed by patients and their primary caregivers, included QoL (SF-36), EI (TEIQue-SF) and coping strategies (BriefCope). The QoL of patients and caregivers was compared with 158 French age-sex-matched healthy controls. The dyadic interactions were analyzed using structural equation modeling. RESULTS: Patients and their caregivers experienced lower QoL levels than French age-sex-matched controls. The EI findings showed actor (degree to which the person's EI was associated with his/her own QoL) and partner (degree to which the person's EI was associated with QoL of the other member of the dyad) effects for patients and caregivers. The coping strategies (i.e., problem solving, positive thinking, avoidance and social support) revealed only actor effects. CONCLUSION: QoL is seriously impaired in depressed patients and their primary caregivers and is associated with EI and coping strategies. Targeted interventions focusing on EI and coping strategies could be offered to improve QoL in dyads.

Pharmacogenetic comparison of CYP2D6 predictive and measured phenotypes in a South African cohort.

The relationship between genetic variation in CYP2D6 and variable drug response represents a potentially powerful pharmacogenetic tool. However, little is known regarding this relationship in the genetically diverse South African population. The aim was therefore to evaluate the relationship between predicted and measured CYP2D6 phenotype. An XL-PCR+Sequencing approach was used to determine CYP2D6 genotype in 100 healthy volunteers and phenotype was predicted using activity scores. With dextromethorphan as the probe drug, metabolic ratios served as a surrogate measure of in vivo CYP2D6 activity. Three-hour plasma metabolic ratios of dextrorphan/dextromethorphan were measured simultaneously using semi-automated online solid phase extraction coupled with tandem mass spectrometry. Partial adaptation of the activity score system demonstrated a strong association between genotype and phenotype, as illustrated by a kappa value of 0.792, inter-rater discrepancy of 0.051 and sensitivity of 72.7%. Predicted phenotype frequencies using the modified activity score were 1.3% for poor metabolisers (PM), 7.6% for intermediate metabolisers (IM) and 87.3% for extensive metabolisers (EM). Measured phenotype frequencies were 1.3% for PM, 13.9% for IM and 84.8% for EM. Comprehensive CYP2D6 genotyping reliably predicts CYP2D6 activity in this South African cohort and can be utilised as a valuable pharmacogenetic tool.

Semi-automatic outlining of levator hiatus.

OBJECTIVE: To create a semi-automated outlining tool for the levator hiatus, to reduce interobserver variability and and speed up analysis. METHODS: The proposed automated hiatus segmentation (AHS) algorithm takes a C-plane image, in the plane of minimal hiatal dimensions, and manually defined vertical hiatal limits as input. The AHS then creates an initial outline by fitting predefined templates on an intensity-invariant edge map, which is further refined using the B-spline explicit active surfaces framework. The AHS was tested using 91 representative C-plane images. Reference hiatal outlines were obtained manually and compared with the AHS outlines by three independent observers. The mean absolute distance (MAD), Hausdorff distance and Dice and Jaccard coefficients were used to quantify segmentation accuracy. Each of these metrics was calculated both for computer-observer differences (COD) and for interobserver differences. The Williams index was used to test the null hypothesis that the automated method would agree with the operators at least as well as the operators agreed with each other. Agreement between the two methods was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: The AHS contours matched well with the manual ones (median COD, 2.10 (interquartile range (IQR), 1.54) mm for MAD). The Williams index was greater than or close to 1 for all quality metrics, indicating that the algorithm performed at least as well as did the manual references in terms of interrater variability. The interobserver differences using each of the metrics were significantly lower, and a higher ICC was achieved (0.93), when obtaining outlines using the AHS compared with manually. The Bland-Altman plots showed negligible bias between the two methods. Using the AHS took a median time of 7.07 (IQR, 3.49) s, while manual outlining took 21.31 (IQR, 5.43) s, thus being almost three-fold faster. Using the AHS, in general, the hiatus could be outlined completely using only three points, two for initialization and one for manual adjustment. CONCLUSIONS: We present a method for tracing the levator hiatal outline with minimal user input. The AHS is fast, robust and reliable and improves interrater agreement. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Intranasal administration of hyaluronan as a further resource in olfactory performance in multiple chemical sensitivity syndrome.

Multiple chemical sensitivity (MCS) is a relatively common clinical diagnosis in western populations and its symptoms (i.e. dysosmia) are mainly triggered by chemical compounds, such as common odorants. The aim of this study was to test the effect of intranasal administration of hyaluronic acid (HA) on odour threshold and related quality of life in MCS syndrome. Two randomized groups of MCS patients received 30 days’ administration of either a nasal spray (Ialumar®) containing HA [HA group (HAG); n=29] or only physiological solution[PS group (PG); n=30]. Both groups were investigated using the Sniffin’ Sticks test (SST) battery, Questionnaire of Olfactory Disorder (QOD) and Zung Anxiety Scale (SAS) before randomization and after treatment. Paired t-test analysis found a statistically significant reduction in odour threshold (OT) and an improvement in QOD and SAS between pre- and post-treatment results only in the HAG. Furthermore, positive correlations were found between the OT reduction, SAS and QOD improvement. Thus, intranasal administration of HA could be suggested as a further well-tolerated resource in alleviating MCS olfactory discomfort.

[Evaluating the efficacy of a new drug]. / Principes d'évaluation de l'efficacité d'un (nouveau) médicament.

AIM: To give a practical guide for phase III clinical trial reading in order to evaluate independently the efficacy of a (new) drug therapy. METHOD: Synthesis established by public health teachers and illustrated with examples in the field of urology. RESULTS: A structured and simplified critical review of clinical trial remains the main way to "have an idea" of a new drug efficacy. Efficacy in clinical trial may be far from patient satisfaction, willingness to pursue with this treatment or cost-effectiveness relevance. CONCLUSION: Knowledge of patient expectation, disease evolution and epidemiology have to be put side by side to raw efficacy data coming from phase III study in order to evaluate efficiency and effectiveness of new drugs therapy.

Changes in sleep performance and chronotype behaviour after vestibular rehabilitation in unilateral vestibular hypofunction.

OBJECTIVE: This study aimed to investigate changes in sleep parameters and self-perceived sleep quality in unilateral vestibular hypofunction participants after vestibular rehabilitation. METHOD: Forty-six unilateral vestibular hypofunction participants (before and after vestibular rehabilitation) along with a control group of 60 healthy patients underwent otoneurological examination, a one-week actigraphy sleep analysis and a series of self-report and performance measures. RESULTS: After vestibular rehabilitation, unilateral vestibular hypofunction participants showed a significant score decrease in the Pittsburgh Sleep Quality Index, a self-rated reliable questionnaire depicting sleep quality during the last month, as well as a reduction in sleep onset latency and an increase in total sleep time, indicating an objective improvement in sleep quality as measured by actigraphy analysis. However, after vestibular rehabilitation, unilateral vestibular hypofunction participants still showed statistically significant differences with respect to the control group in both self-rated and objective measurements of sleep quality. CONCLUSION: Vestibular rehabilitation may impact on sleep performance and chronotype behaviour, possibly by opposing long-term structural changes along neural pathways entangled in sleep activity because of the deafferentation of the vestibular nuclei.

Unusual case of oral chronic lymphocytic leukemia presenting as recurrent epistaxis and asymptomatic intraoral swelling.

INTRODUCTION: Usually, oral manifestations of chronic lymphocytic leukemia CLL are related to an advanced stage of a diagnosed disease, and rarely may lead to diagnosis. CLL can also present as bleeding, rarely isolated. We report a rare case of CLL the first symptoms of which were recurrent epistaxis and asymptomatic intraoral swelling. CASE PRESENTATION: A 74-year-old woman consulted for recurrent epistaxis. She presented with a small asymptomatic swelling in the left superior vestibule. Computed tomography revealed a tissular-like mass without invasion of surrounding tissues. The hemogram revealed thrombocytopenia and leukocytosis with 51% of lymphocytes. The immuno-histochemical analysis of the lesion and of the bone marrow allowed diagnosing stage IV CLL. DISCUSSION: CLL may present as unusual symptoms. It should be suspected in elderly patients presenting with atypical clinical signs such as oral swelling or signs of bone marrow involvement.

A grapevine leaves dataset for early detection and classification of esca disease in vineyards through machine learning.

Esca is one of the most common disease that can severely damage grapevine. This disease, if not properly treated in time, is the cause of vegetative stress or death of the attacked plant, with the consequence of losses in production as well as a rising risk of propagation to the closer grapevines. Nowadays, the detection of Esca is carried out manually through visual surveys usually done by agronomists, requiring enormous amount of time. Recently, image processing, computer vision and machine learning methods have been widely adopted for plant diseases classification. These methods can minimize the time spent for anomaly detection ensuring an early detection of Esca disease in grapevine plants that helps in preventing it to spread in the vineyards and in minimizing the financial loss to the wine producers. In this article, an image dataset of grapevine leaves is presented. The dataset holds grapevine leaves images belonging to two classes: unhealthy leaves acquired from plants affected by Esca disease and healthy leaves. The data presented has been collected to be used in a research project jointly developed by the Department of Information Engineering, Polytechnic University of Marche, Ancona, Italy and the STMicroelectronics, Italy, under the cooperation of the Umani Ronchi SPA winery, Osimo, Ancona, Marche, Italy. The dataset could be helpful to researchers who use machine learning and computer vision algorithms to develop applications that help agronomists in early detection of grapevine plant diseases. The dataset is freely available at http://dx.doi.org/10.17632/89cnxc58kj.1.

Explant-derived human dental pulp stem cells enhance differentiation and proliferation potentials.

Numerous stem cell niches are present in the different tissues and organs of the adult human body. Among these tissues, dental pulp, entrapped within the 'sealed niche' of the pulp chamber, is an extremely rich site for collecting stem cells. In this study, we demonstrate that the isolation of human dental pulp stem cells by the explants culture method (hD-DPSCs) allows the recovery of a population of dental mesenchymal stem cells that exhibit an elevated proliferation potential. Moreover, we highlight that hD-DPSCs are not only capable of differentiating into osteoblasts and chondrocytes but are also able to switch their genetic programme when co-cultured with murine myoblasts. High levels of MyoD expression were detected, indicating that muscle-specific genes in dental pulp cells can be turned on through myogenic fusion, confirming thus their multipotency. A perivascular niche may be the potential source of hD-DPSCs, as suggested by the consistent Ca(2+) release from these cells in response to endothelin-1 (ET-1) treatment, which is also able to significantly increase cell proliferation. Moreover, response to ET-1 has been found to be superior in hD-DPSCs than in DPSCs, probably due to the isolation method that promotes release of stem/progenitor cells from perivascular structures. The ability to isolate, expand and direct the differentiation of hD-DPSCs into several lineages, mainly towards myogenesis, offers an opportunity for the study of events associated with cell commitment and differentiation. Therefore, hD-DPSCs display enhanced differentiation abilities when compared to DPSCs, and this might be of relevance for their use in therapy.

The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature.

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.

The role of cholesterol levels in mood disorders and suicide.

The individuation of sensitive and specific biochemical markers, easily assessable on large samples of subjects and usefully employable as predictors of severe psychiatric disorders, such as mood disorders, could help clinicians to improve the diagnostic and therapeutic processes facilitating the long-term follow-up. In particular, serum cholesterol levels may potentially be optimal markers due to their relative easy sampling and low cost. The involvement of cholesterol in affective disorders such as Major Depression (MD), Seasonal Affective Disorder (SAD) and Bipolar Disorders (BD) is a debated issue in current research. However, current literature is controversial and, to date, it is still not possible to reach an agreement on its possible usefulness of cholesterol as a biological marker of affective disorders. Despite the controversial results on the relationships between cholesterol levels and affective disorders, the majority of literature seems to show a more consistent relationship between cholesterol levels and suicidal behaviour, with few studies that have found no relationships. The aim of this review is to elucidate current facts and views about the role of cholesterol levels in mood disorders as well as its involvement in suicidal behaviour.

Influenza vaccine effectiveness for the elderly: a cohort study involving general practitioners from Abruzzo, Italy.

INTRODUCTION: In all Italian regions influenza vaccine is routinely administered to the elderly population. However, vaccination impact has been rarely evaluated because of the high costs of conventional cohort investigations. A promising low-cost alternative approach uses administrative discharge data to derive vaccine effectiveness indicators (hospitalizations and/or deaths) and involves General Practitioners (GPs) to document the exposure. We conducted a cohort analysis using such approach to assess influenza vaccine effectiveness and to investigate the feasibility and validity of that methodology for routine vaccine evaluation. METHODS: During October 2006, all GPs from two Local Health Units (LHUs) were requested to indicate immunization status of all their patients in a specific form containing patient's demographic records. Immunization status information were also collected from Prevention Departments. Main outcomes were hospitalizations for influenza and/or pneumonia. Analyses were based upon random-effect logistic regression. RESULTS: Of a total of 414 GPs assisting 103,162 elderly, 116 GPs (28%) provided data on 32,457 individuals (31.5%). The sample was representative and had an overall 66.2% vaccina-tion rate. During the first semester 2007, the hospitalization rate was low in the sample, with only 7 elderly patients admitted for influenza and 135 for pneumonia. At either bivariate or multivariate analysis, vaccination did not significantly reduce the risk of in-hospital death, influenza or pneumonia admission. DISCUSSION: The study had minimal costs, recruited a large and representative sample size, and had no evidence of a substantial selection bias. Administrative and GP's data may be successively pooled to provide routine assessment of vaccination effectiveness.

Transplantation of gene-modified haematopoietic stem cells: Application and clinical considerations.

Autologous and allogeneic haematopoietic stem cell (HSC) transplantation has been performed in patients with various malignant and non-malignant haematological disorders for more than 50 years. Ex vivo gene modification of HSCs for autologous transplantation opens up new therapeutic avenues for genetic and infectious diseases. Major advances have been made over the last three decades with respect to gene modification of HSCs and transplantation strategies, ultimately culminating in the approval of two such therapies in Europe (Strimvelis for a rare primary immune deficiency, and LentiGlobin for beta-thalassaemia). Newer gene-modifying technologies and treatment regimens have also recently come to the fore, which hold great promise for the development of safer and more effective treatments. We provide an overview of the current state of gene-modified HSC therapies, highlighting success stories, limitations and important considerations for achieving successful translation of these therapies to the clinic.

Stem cell therapy for neurological disorders.

Neurological disease encompasses a diverse group of disorders of the central and peripheral nervous systems, which collectively are the leading cause of disease burden globally. The scope of treatment options for neurological disease is limited, and drug approval rates for improved treatments remain poor when compared with other therapeutic areas. Stem cell therapy provides hope for many patients, but should be tempered with the realisation that the scientific and medical communities are still to fully unravel the complexities of stem cell biology, and to provide satisfactory data that support the rational, evidence-based application of these cells from a therapeutic perspective. We provide an overview of the application of stem cells in neurological disease, starting with basic principles, and extending these to describe the clinical trial landscape and progress made over the last decade. Many forms of stem cell therapy exist, including the use of neural, haematopoietic and mesenchymal stem cells. Cell therapies derived from differentiated embryonic stem cells and induced pluripotent stem cells are also starting to feature prominently. Over 200 clinical studies applying various stem cell approaches to treat neurological disease have been registered to date (Clinicaltrials.gov), the majority of which are for multiple sclerosis, stroke and spinal cord injuries. In total, we identified 17 neurological indications in clinical stage development. Few studies have progressed into large, pivotal investigations with randomised clinical trial designs. Results from such studies will be essential for approval and application as mainstream treatments in the future.

Cystic fibrosis in South Africa: A changing diagnostic paradigm.

Cystic fibrosis (CF), one of the most commonly observed and diagnosed fatal monogenic disorders globally, was initially thought to affect individuals of Caucasian/European descent almost exclusively. It is increasingly appreciated, however, that non-Caucasian populations are also affected by this condition. Although this has been known in South Africa (SA) for over two decades, a large disparity still exists in data pertaining to the different population groups in the country. This article seeks to highlight existing published data on CF in SA populations and reflects on the means through which these have been generated over the years. Additionally, the article briefly discusses the consequences of incomplete data and how this could potentially be addressed in the future through innovative and collaborative approaches.

Cell and gene therapies at the forefront of innovative medical care: Implications for South Africa.

The fields of cell and gene therapy are moving rapidly towards providing innovative cures for incurable diseases. A current and highly topical example is immunotherapies involving T-cells that express chimeric antigen receptors (CAR T-cells), which have shown promise in the treatment of leukaemia and lymphoma. These new medicines are indicative of the changes we can anticipate in the practice of medicine in the near future. Despite their promise, they pose challenges for introduction into the healthcare sector in South Africa (SA), including: (i) that they are technologically demanding and their manufacture is resource intensive; (ii) that the regulatory system is underdeveloped and likely to be challenged by ethical, legal and social requirements that accompany these new therapies; and (iii) that costs are likely to be prohibitive, at least initially, and before economies of scale take effect. Investment should be made into finding novel and innovative ways to introduce these therapies into SA sooner rather than later to ensure that SA patients are not excluded from these exciting new opportunities.

Ethical considerations in the application of cell and gene therapies in children.

Rapidly evolving fields such as cell and gene therapies that involve state-of-the-art technology hold out possibilities that may be ahead of what ethics, guidelines and the law have considered. This results in a regulatory lag. Furthermore, ethical and legal considerations are often debated in real time as issues pertaining to these technologies that were previously not considered begin to come to the fore. Finding the appropriate balance between facilitating potential therapeutic gains and ensuring the safety interests of recipients of the new treatments requires close attention, especially for minors. This vulnerable population frequently has off-label treatment prescribed on the basis of extrapolation of clinical trial data derived from adults, which is ethically and scientifically questionable. In this article we discuss how best to maintain ethical integrity while introducing innovative cell and gene therapies to minors. We advocate that clinical trials of promising innovative therapies should be designed so that testing in adults is followed as soon as possible by testing in minors, given the impressive gains that have recently been reported.

Lack of functional remission in Cushing's syndrome.

INTRODUCTION: Hypercortisolism leads to severe clinical consequences persisting after the onset of remission. These physical sequelae of cortisol exposure are known to profoundly impact the patient's quality of life. As psychological factors may be correlated with this quality of life, our objective was to determine the specific weight of psychological determinants of quality of life in patients in remission from hypercortisolism. PATIENTS AND METHODS: In an observational study, 63 patients with hypercortisolism in remission were asked to complete exhaustive self-administered questionnaires including quality of life (WHOQoL-BREF and Cushing QoL), depression, anxiety, self-esteem, body image, and coping scales. Multivariate analyses were performed. Psychological variables relevant to the model were: anxiety, depression, self-esteem, body image, and positive thinking dimension of the Brief-COPE. Cortisol deficiency was defined as a potential confounder. RESULTS: The median time since remission was 3 years. Patients had significantly lower quality of life and body satisfaction score than the French population and patients with chronic diseases. Depression significantly impaired all WHOQoL and Cushing QoL domains. A low body satisfaction score significantly impaired social relationships quality of life score. In total, 42.9% of patients still needed working arrangements, 19% had disability or cessation of work. CONCLUSION: Patients in biological remission of hypercortisolism can rarely be considered as functionally cured: this is evidenced by altered quality of life, working arrangements, and chronic depression. A multidisciplinary management of these patients is thus mandatory on a long-term basis.