Infectious atherosclerosis: Is the hypothesis still alive? A clinically based approach to the dilemma

Among the multiple factors involved in the pathophysiology of heart disease, infections have been proposed to play a role in atherosclerosis with most of the available evidence implicating Chlamydia pneumonia, influenza virus and Mycoplasma pneumoniae. Based on a model case presentation, we speculate that in the absence of traditional risk factors and in the context of an ongoing respiratory infection caused by a pro-inflammatory pathogen (M. pneumoniae) along with a past positive serologic history for potentially proven atherogenic microorganism (C. pneumoniae) and infection may elicit potentially pathogenic events on vascular wall cells and leukocytes of atheromatous lesions, supporting the hypothesis that such infections may potentiate atherosclerotic cardiovascular disease (CVD).     

A novel approach to describing the pancreas and submandibular gland: Can they be classified as primary and secondary tissue organs?

Our aim is to examine the relationship between the submandibular gland (SMG) and the pancreas by discussing similarities and differences in their embryology, histology, physiology, and pathology, and to introduce the question of classifying them as primary or secondary organs. From an embryonic standpoint, SMG and pancreas originate from different germ layers, yet they share a variety of similar elements in their morphogenesis, branching process, and mesenchymal molecular interaction. The histological and anatomical comparison between these two organs reveals parallels in the basic function of their exocrine physiology. With both the SMG and pancreas playing a significant role in digestive processes, there are also common aspects in their exocrine function. Furthermore, recent research has unraveled an intricate novel system of hormonal interaction between the salivary glands and pancreas which regulates pancreatic cellular differentiation and injury repair mechanism. Lastly, there are analogous features in the pathological mechanisms and inflammatory processes in the course of chronic disease in both organs. By defining this close relationship between the SMG and the pancreas, we aim to provide alternative insights for scholars and physicians in the shared characteristics of basic function of these organs, and possible pathological consequences of their dysregulation.     

Escaping the tyranny of the embryo? A new approach to ART regulation based on UK and Australian experiences

The early legislative responses to fertilization of human oocytes in vitro exaggerated the protection of the embryo at the expense of the interests of other parties. Although more recent legislative changes have lessened this embryonic grip, it nonetheless still distorts legal thinking and is fundamentally in conflict with biological understanding. Drawing largely on experiences in the UK and Australia, a proposal is explored that reframes the legislative approach to the regulation of assisted reproductive technology (ART) with the following objectives: (i) to align more closely the legal and biological understandings of the earliest stages of human development; (ii) to place the legislative focus on objective, intent and outcome; and in the process (iii) to disentangle legally and conceptually the status of the embryo from that of the potential child. Experiences in the UK and Australia are drawn on, because these two jurisdictions have a common legal heritage and were among the earliest players both scientifically and legally but have pursued very different legal routes to their current legislative practices.     

Is it a primary or metastatic melanocytic neoplasm of the central nervous system?: A molecular based approach

Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon and must be distinguished from metastatic lesions as patients with metastatic disease carry a worse prognosis. Therefore, tools to aid in the diagnosis of a primary CNS melanocytic neoplasm would be of clinical utility. Primary CNS melanocytic neoplasms, including uveal melanomas have frequent mutations in GNAQ and GNA11, but are rare in cutaneous and mucosal melanomas. Additionally, primary uveal melanomas often exhibit monosomy 3 conferring an elevated risk of metastasis. We present a 63 year‐old male with a melanocytic neoplasm in the thoracic spinal cord. Molecular studies revealed the tumor contained a GNAQ mutation and four‐color fluorescent in situ hybridization (FISH) composed of chromosome enumeration probes for 3, 7, 17 and a locus specific probe for 9p21/CDKN2A yielded a normal result (i.e. two copies per cell), favoring a primary versus metastatic melanocytic neoplasm of the CNS. We report a case in which the combination of mutational analysis and FISH aided in identifying the origin of the neoplasm.     

Oral-gut connection: one step closer to an integrated view of the gastrointestinal tract?

Although an enrichment of orally derived bacteria is reported in the gut microbiota of patients with several diseases, it is mostly unknown whether oral bacteria can colonize and induce intestinal inflammation. In a recent paper in Science, Atarashi et al.¹ from Kenya Honda's laboratory show that a subset of orally derived bacteria colonizes and persists in the gut, leading to activation of the intestinal immune system and subsequent chronic inflammation in a susceptible host. The impact of oral health status as a potential contributor to inflammatory diseases at distal sites of the body deserves consideration.     

Is the transtheoretical model and motivational interviewing approach applicable to the treatment of eating disorders? A review

Research in eating disorders is reviewed examining the (1) utility of the Transtheoretical Model in predicting outcome, and (2) efficacy of Motivational Interviewing (MI). There were promising results showing significant relationships between initial stage of change and treatment outcome related to eating pathology (not including purging), body mass index, and some aspects of psychopathology. Of those treatment studies utilising a control group, there was little indication that using MI conferred significant treatment benefit, with the exception of improving motivation and binge eating for people with binge eating disorder and bulimia nervosa. Overall the content of the studies varied greatly with relation to: stage of change and outcome measures, format of MI, diagnostic groupings, age of participants, utilisation of other adjunctive treatments, sample size, presence of follow-up assessments, and study design. Few of the 9 studies examining the efficacy of MI could be considered to have robust methodology. It is recommended that future research using the Transtheoretical Model to predict outcome adopt more uniform methodology so that we can more specifically determine its applicability, and that well-designed treatment studies in eating disorder populations be conducted so that we develop a stronger evidence base from which to decide whether MI confers benefit.     

Neo-endocrinochemotherapy: A novel approach for enhancing chemotherapeutic efficacy in clinic?

Chemosensitization means enhancing the sensitivity of tumor cells to chemotherapy with certain methods for better efficacy. Tumor progression depends on stimulation of multiple hormones, decrease in hormones during chemotherapy induces G₀/G₁ arrest of tumor cells, which may be the main cause for chemoresistance. Some of the choriocarcinoma and testicular tumors are curable with chemotherapy only, underlying mechanism may refer high level of human chorionic gonadotropin, which has thyroid stimulating hormone like effect and even induce hyperthyroidism in these patients. Some of these patients usually have high levels of thyroid hormones or suffer thyroid crisis during chemotherapy. Possibly owning to the proliferative or metabolic promotion effect of thyroid hormones and/or other endocrine hormones, which can promote tumor cells in G₀ phase metabolizing actively or stepping into division cycle again, tumors are more sensitive to chemotherapy. Both endocrinotherapy and chemotherapy are major therapies for tumor, traditional endocrinotherapy suppresses tumor progression through decreasing tumor-dependent hormones or competitively combining and blocking hormone receptors. While, chemotherapy mostly killed tumor cells that proliferate actively, because tumor cells retardant in G₀ phase by endocrinotherapy are no more sensitive to chemotherapy, endocrinotherapy cannot be concurrently used with chemotherapy. Nevertheless, decrease in hormones during chemotherapy is similar to concurrently using endocrinotherapy and chemotherapy. It has been found in some basic researches that some chemotherapeutics concurrently combined with endocrine hormones can achieve better efficacy compared with chemotherapy only. It is therefore hypothesized in this article that decrease in hormones during chemotherapy causes cell cycle arrest and renders tumor cells insensitive to chemotherapy; addition of endocrine hormones to mimic the hormones and microenvironment changes during chemotherapy for patients with choriocarcinoma or testicular tumor-curable with chemotherapy only, will rescue tumor cells from cell cycle arrest rendering them sensitive to chemotherapy. This new combinative therapy of concurrently using endocrine hormones and chemotherapy is defined as choriocarcinoma-mimic chemotherapy or neo-endocrinochemotherapy to distinguish the routine term of endocrinochemotherapy and is expected to be a novel approach to enhance chemotherapeutic efficacy in clinic.     

Use of gene-modified regulatory T-cells to control autoimmune and alloimmune pathology: Is now the right time?

Adoptive immunotherapy using genetically targeted T-cells has recently begun to achieve impressive clinical impact in selected tumor types. Furthermore, long-term follow-up studies indicate thus far that integrating viral vectors do not elicit clinically evident genotoxicity in T-cells, unlike hematopoietic stem cells. The optimism engendered by this clinical experience provides a platform for consideration of the extended use of this technology in other disease types. One area of particular interest entails the harnessing of regulatory T-cells (Tregs) in order to down-regulate unwanted immune responses. Increasing evidence supports the efficacy of this approach in pre-clinical models of autoimmune disease and allograft rejection. Nonetheless, questions remain about optimal host cell, transgene cargo, phenotypic stability of engineered cells in vivo and potential for toxicity. Here, we review the evidence that genetically engineered Tregs can effectively dampen pathogenic immune responses and critically evaluate the prospects for clinical development of this approach.     

Introduction of calpain inhibitors in traumatic brain injury: A novel approach?

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world. In recent years, researchers focused on the pathological significance of calcium accumulation in the brain after TBI. Neuronal calcium homeostasis disturbances may result in the activation of calpain a ubiquitous calcium-sensitive protease. The calpain family has a well-established causal role in neuronal cell death following acute brain injury: their activation has been observed to progressively increase after either contusive or diffuse brain trauma in animals, suggesting calpain to be a mediator of early neuronal damage. We hypothesize that pretreatment with the calpain inhibitors in population at objective risk (military soldiers' pre combat) in appropriate dose would open therapeutic time window expected to prevent and reduce extensive brain damage by providing optimal TBI neuroprotection. Additional therapeutic strategy for TBI, based on calpain modulating actions such as pretreatment with calpain inhibitors has been proposed. Since calpain overexpression has been well established in acute neuronal injury and further subsequent neurodegeneration, from a clinical viewpoint, we speculate that if this hypothesis proves correct pretreatment inhibitors introduction may become a therapeutic option for different brain pathologies to be approached and treated with.     

A six stage approach for the diagnosis of the Alzheimer’s disease based on fMRI data

The aim of this work is to present an automated method that assists in the diagnosis of Alzheimer’s disease and also supports the monitoring of the progression of the disease. The method is based on features extracted from the data acquired during an fMRI experiment. It consists of six stages: (a) preprocessing of fMRI data, (b) modeling of fMRI voxel time series using a Generalized Linear Model, (c) feature extraction from the fMRI data, (d) feature selection, (e) classification using classical and improved variations of the Random Forests algorithm and Support Vector Machines, and (f) conversion of the trees, of the Random Forest, to rules which have physical meaning. The method is evaluated using a dataset of 41 subjects. The results of the proposed method indicate the validity of the method in the diagnosis (accuracy 94%) and monitoring of the Alzheimer’s disease (accuracy 97% and 99%).     

A clinical and molecular review of inverted papilloma of the urinary tract: how to handle?

Inverted papilloma (IP) of the urinary tract is classified by the World Health Organisation as a non‐invasive urothelial tumour with normal to minimal cytological atypia of the neoplastic cells. During the 1980s, it came under suspicion of having a premalignant or malignant potential and of being concurrent with urothelial cell carcinoma (UCC). This quandary has been proven difficult to solve, due to the fact that IP is very rare and literature mostly consists of case reports with varying levels of information, making strong meta‐analyses problematic. New immunohistochemical techniques and genetic approaches are more frequently being used in the attempt to achieve better classifications, prognosis and treatment of lesions hereunder IP. This review will, in our awareness, be the first to combine the knowledge from retrospective studies with these new approaches for determining a possible premalignant potential and concurrency with UCC and subsequently outline a recommendation for follow‐up.     

Is the callus shape an optimal response to a mechanobiological stimulus?

After bone trauma, the natural response to restore bone function is the formation of a callus around the fracture. Although several bone healing models have been developed, none have effectively perceived early callus formation and shape as the result of an optimal response to a mechanobiological stimulus.In this paper, we investigate which stimulus regulates early callus formation. An optimal design problem is formulated, and several objective functions are defined, each using a different mechanobiological stimulus. The following stimuli were analysed: the interfragmentary strain, the second invariant of the deviatoric strain tensor and a generic inflammatory factor. Different regions for callus formation were also evaluated, such as the gap region, the periosteum and the periosteum border. Each stimulus was computed using the finite element method, and the callus shape was optimised using the steepest descent method.The results demonstrated that the inflammatory factor approach, the interfragmentary strain and the second invariant of the deviatoric strain tensor over the inner gap provided the best results when compared with histological callus shapes. Therefore, this work suggests that callus growth can be an optimal mechanobiological response to either local mechanical instability and/or local inflammatory reaction.     

Gene therapy: A novel way to treat respiratory failure?

Respiratory failure leads to tissue hypoxia and subsequent organ damage. The crocodile hemoglobin affinity for oxygen is significantly reduced in the presence of CO₂, allowing crocodiles to stay under water for more than 1 h. The crocodile bicarbonate effect can possibly be transplanted into the human hemoglobin by replacing only five and seven amino acid residues in the β-globin and α-globin chains, respectively. The resulting hybrid formed by these modified chains has been named Scuba hemoglobin. The in vitro production of Scuba hemoglobin by human hematopoietic stem cells and their reintroduction into the blood could be an interesting tool to improve tissue oxygenation in patients suffering from respiratory failure.     

Can we enhance the training of clinical supervisors? A national pilot study of an evidence‐based approach

Clinical supervision plays an essential part in maintaining professional standards and in achieving the National Health Service's objective of a modern workforce. Paradoxically, little is known about how supervisors themselves acquire competence, leading to lament that ‘something does not compute’. To contribute to a solution, a supervisor training manual that guided trainers in delivering continuing professional development to supervisors in an evidence‐based approach to clinical supervision was piloted nationally, in terms of the reactions of trainers (N = 25 tutors from clinical psychology courses) and their workshop delegates (N = 256 clinical psychology supervisors). Trainers were allocated randomly to either manual‐alone or to a manual‐plus consultancy group. The trainers all rated the manual favourably (mean rating of 78%), but there was no significant difference between the two groups. However, the supervisors within the consultancy group rated the sessions significantly more highly than their counterparts. It is concluded that brief training in an evidence‐based approach appears feasible and acceptable, making more rigorous evaluations appropriate. Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message:

• Clinical supervision is now recognised as essential, yet supervisors tend to receive little or no training, which tends not to be evidence based.
• A training guide in evidence‐based clinical supervision has been disseminated and evaluated, in terms of the acceptability of the approach taken to supervision.
• The reactions of trainers and supervisors (all associated with clinical psychology training programmes) to this guide were positive, indicating that it merits further development and more rigorous evaluation.

     

Is the high submandibular transmasseteric approach to the mandibular condyle safe for the inferior buccal branch?

Purpose  

There are basically 3 main approaches for extra-articular mandibular condyle fractures: low cervical, retromandibular and preauricular. These include a risk of facial palsy affecting the marginal mandibular branch. We use a high submandibular transmasseteric approach featuring masseter section 10–20 mm above the mandibular basilar edge. Our null hypothesis was that both the marginal mandibular and the inferior buccal branches are not more at risk than in other surgical approaches.