Difficulties implementing a mental health guideline: an exploratory investigation using psychological theory

Background

Monitoring and Messaging Devices (MMDs) are telehealth systems used by patients in their homes, and are designed to promote patient self-management, patient education, and clinical monitoring and follow-up activities. Although these systems have been widely promoted by health care systems, including the Veterans Health Administration, very little information is available on factors that facilitate use of the MMD system, or on barriers to use.

Methods

We conducted in-depth qualitative interviews with clinicians using MMD-based telehealth programs at two Veterans Affairs Medical Centers in the Midwestern United States.

Results

Findings suggest that MMD program enrollment is limited by both clinical and non-clinical factors, and that patients have varying levels of program participation and system use. Telehealth providers see MMDs as a useful tool for monitoring patients who are interested in working on management of their disease, but are concerned with technical challenges and the time commitment required to use MMDs.

Conclusion

Telehealth includes a rapidly evolving and potentially promising range of technologies for meeting the growing number of patients and clinicians who face the challenges of diabetes care, and future research should explore the most effective means of ensuring successful program implementation.     

"Shrink wrapping" lectures: teaching cell and molecular biology within the context of human pathologies

Students are most motivated and learn best when they are immersed in an environment that causes them to realize why they should learn. Perhaps nowhere is this truer than when teaching the biological sciences to engineers. Transitioning from a traditionally mathematics-based to a traditionally knowledge-based pedagogical style can challenge student learning and engagement. To address this, human pathologies were used as a problem-based context for teaching knowledge-based cell biological mechanisms. Lectures were divided into four modules. First, a disease was presented from clinical, economic, and etiological standpoints. Second, fundamental concepts of cell and molecular biology were taught that were directly relevant to that disease. Finally, we discussed the cellular and molecular basis of the disease based on these fundamental concepts, together with current clinical approaches to the disease. The basic science is thus presented within a "shrink wrap" of disease application. Evaluation of this contextual technique suggests that it is very useful in improving undergraduate student focus and motivation, and offers many advantages to the instructor as well.     

"Mind the trap": mindfulness practice reduces cognitive rigidity

Two experiments examined the relation between mindfulness practice and cognitive rigidity by using a variation of the Einstellung water jar task. Participants were required to use three hypothetical jars to obtain a specific amount of water. Initial problems were solvable by the same complex formula, but in later problems ("critical" or "trap" problems) solving was possible by an additional much simpler formula. A rigidity score was compiled through perseverance of the complex formula. In Experiment 1, experienced mindfulness meditators received significantly lower rigidity scores than non-meditators who had registered for their first meditation retreat. Similar results were obtained in randomized controlled Experiment 2 comparing non-meditators who underwent an eight meeting mindfulness program with a waiting list group. The authors conclude that mindfulness meditation reduces cognitive rigidity via the tendency to be "blinded" by experience. Results are discussed in light of the benefits of mindfulness practice regarding a reduced tendency to overlook novel and adaptive ways of responding due to past experience, both in and out of the clinical setting.     

Preventing falls in older adults: new interventions to promote more effective change-in-support balance reactions.

"Change-in-support" (CIS) balance-recovery reactions that involve rapid stepping or reaching movements play a critical role in preventing falls; however, age-related deficits in the neuro-musculoskeletal systems may impede ability to execute these reactions effectively. This review describes four new interventions aimed at reducing fall risk in older adults by promoting more effective CIS reactions: (1) balance training, (2) balance-enhancing footwear, (3) safer mobility aids, and (4) handrail cueing systems. The training program uses unpredictable support-surface perturbations to counter specific CIS control problems associated with aging and fall risk. Pilot testing has demonstrated that the program is well-tolerated by balance-impaired older adults, and a randomized controlled trial is now in progress. The balance-enhancing footwear insole improves control of stepping reactions by compensating for age-related loss of plantar cutaneous sensation. In a clinical trial, subjects wore the insole for 12 weeks with no serious problems and no habituation of the balance-enhancing benefits. The mobility-aid intervention involves changes to the design of pickup walkers so as to reduce impediments to lateral stepping. Finally, work is underway to investigate the effectiveness of handrail cueing in attracting attention to the rail and ensuring that the brain registers its location, thereby facilitating more rapid and accurate grasping.     

"Floating arm" injury in a child with fractures of the proximal and distal parts of the humerus: a case report

Introduction

Primary malignant pericardial mesothelioma is a very rare pericardial tumor of unknown etiology.

Case presentation

A 61-year-old Caucasian woman was admitted to our hospital complaining of exertional dyspnea due to a large pericardial effusion. Intrapericardial fluid volume declined after repeated pericardiocentesis, but the patient progressively developed a hemodynamically relevant pericardial constriction. Pericardiectomy revealed a pericardial mesothelioma. Subsequently, four cycles of chemotherapy (dosage according to recently published trials) were administered. The patient remained asymptomatic, and there was no recurrence of the tumor after three years.

Conclusion

Pericardial mesothelioma should be considered and managed appropriately in non-responders to pericardiocentesis, and in patients who develop constrictive pericarditis late in their clinical course.     

Repairing quite swimmingly: advances in regenerative medicine using zebrafish

Regenerative medicine has the promise to alleviate morbidity and mortality caused by organ dysfunction, longstanding injury and trauma. Although regenerative approaches for a few diseases have been highly successful, some organs either do not regenerate well or have no current treatment approach to harness their intrinsic regenerative potential. In this Review, we describe the modeling of human disease and tissue repair in zebrafish, through the discovery of disease-causing genes using classical forward-genetic screens and by modulating clinically relevant phenotypes through chemical genetic screening approaches. Furthermore, we present an overview of those organ systems that regenerate well in zebrafish in contrast to mammalian tissue, as well as those organs in which the regenerative potential is conserved from fish to mammals, enabling drug discovery in preclinical disease-relevant models. We provide two examples from our own work in which the clinical translation of zebrafish findings is either imminent or has already proven successful. The promising results in multiple organs suggest that further insight into regenerative mechanisms and novel clinically relevant therapeutic approaches will emerge from zebrafish research in the future.KEY WORDS: Regeneration, Zebrafish, Disease model, Gastrointestinal, Hematovascular     

"Hairy cell" leukemia]

By means of individual observations the clinical, cytological and cytochemical marks of the so-called "hairy cell"leukemia are described. Peculiarities in the course of the disease and in prognosis justify this rare variant to be separated from reticular systems diseases. A diagnosis can also be made on the basis of cytomorphological characteristics.     

Fabry Disease – Underestimated in the Differential Diagnosis of Multiple Sclerosis?

Objective

Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.

Methods

Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.

Results

Four patients were identified as having a “possible” history of MS, and 7 patients as “definite” cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.

Conclusion

There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.     

In vivo therapeutic applications of cell spheroids

Spheroids are increasingly being employed to answer a wide range of clinical and biomedical inquiries ranging from pharmacology to disease pathophysiology, with the ultimate goal of using spheroids for tissue engineering and regeneration. When compared to traditional two-dimensional cell culture, spheroids have the advantage of better replicating the 3D extracellular microenvironment and its associated growth factors and signaling cascades. As knowledge about the preparation and maintenance of spheroids has improved, there has been a plethora of translational experiments investigating in vivo implantation of spheroids into various animal models studying tissue regeneration.We review methods for spheroid delivery and how they have been utilized in tissue engineering experiments. We break down efforts in this field by organ systems, discussing applications of spheroids to various animal models of disease processes and their potential clinical implications. These breakthroughs have been made possible by advancements in spheroid formation, in vivo delivery and assessment. There is unexplored potential and room for further research and development in spheroid-based tissue engineering approaches. Regenerative medicine and other clinical applications ensure this exciting area of research remains relevant for patient care.     

Biosynthesis of <Emphasis Type="Italic">Veratrum californicum</Emphasis> specialty chemicals in <Emphasis Type="Italic">Camelina sativa</Emphasis> seed

Economically feasible systems for heterologous production of complex secondary metabolites originating from difficult to cultivate species are in demand since Escherichia coli and Saccharomyces cerevisiae are not always suitable for expression of plant and animal genes. An emerging oilseed crop, Camelina sativa, has recently been engineered to produce novel oil profiles, jet fuel precursors, and small molecules of industrial interest. To establish C. sativa as a system for the production of medicinally relevant compounds, we introduced four genes from Veratrum californicum involved in steroid alkaloid biosynthesis. Together, these four genes produce verazine, the hypothesized precursor to cyclopamine, a medicinally relevant steroid alkaloid whose analogs are currently being tested for cancer therapy in clinical trials. The future supply of this potential cancer treatment is uncertain as V. californicum is slow-growing and not amendable to cultivation. Moreover, the complex stereochemistry of cyclopamine results in low-yield syntheses. Herein, we successfully engineered C. sativa to synthesize verazine, as well as other V. californicum secondary metabolites, in seed. In addition, we have clarified the stereochemistry of verazine and related V. californicum metabolites.     

A nomenclature and classification for the congenital myasthenic syndromes: preparing for FAIR data in the genomic era

Background

Congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited neuromuscular disorders sharing the common feature of fatigable weakness due to defective neuromuscular transmission. Despite rapidly increasing knowledge about the genetic origins, specific features and potential treatments for the known CMS entities, the lack of standardized classification at the most granular level has hindered the implementation of computer-based systems for knowledge capture and reuse. Where individual clinical or genetic entities do not exist in disease coding systems, they are often invisible in clinical records and inadequately annotated in information systems, and features that apply to one disease but not another cannot be adequately differentiated.

Results

We created a detailed classification of all CMS disease entities suitable for use in clinical and genetic databases and decision support systems. To avoid conflict with existing coding systems as well as with expert-defined group-level classifications, we developed a collaboration with the Orphanet nomenclature for rare diseases, creating a clinically understandable name for each entity and placing it within a logical hierarchy that paves the way towards computer-aided clinical systems and improved knowledge bases for CMS that can adequately differentiate between types and ascribe relevant expert knowledge to each.

Conclusions

We suggest that data science approaches can be used effectively in the clinical domain in a way that does not disrupt preexisting expert classification and that enhances the utility of existing coding systems. Our classification provides a comprehensive view of the individual CMS entities in a manner that supports differential diagnosis and understanding of the range and heterogeneity of the disease but that also enables robust computational coding and hierarchy for machine-readability. It can be extended as required in the light of future scientific advances, but already provides the starting point for the creation of FAIR (Findable, Accessible, Interoperable and Reusable) knowledge bases of data on the congenital myasthenic syndromes.

     

Highly aligned lipid membrane systems in the physiologically relevant "excess water" condition

The "excess water" condition in biologically relevant systems is met when a membrane mesophase coexists with excess bulk water. Further addition of water to such a system results in no change to any of the system's physical properties (e.g., transition temperature, repeat spacing, and structural mesophases). Moreover, because biological membranes are anisotropic systems, many of their properties are best studied using aligned samples. Although model membrane systems are routinely aligned, they have traditionally been hydrated with water vapor. It is well known that membranes exposed to water vapor at 100% humidity do not imbibe the same quantity of water as a sample in contact with liquid water. As such, membranes that have been hydrated with water vapor have physical properties different from those of membranes dispersed in water. Because of this shortcoming, aligned membranes have not been utilized to their full potential. Here we present a novel and simple method of aligning model membrane systems under conditions of excess water, which will make possible, for the first time, a variety of techniques (e.g., neutron and x-ray diffraction, nuclear magnetic resonance, electron spin resonance, attenuated total reflection infrared spectroscopy, etc.) for studying such systems under physiologically relevant conditions. In addition, when dealing with samples of limited availability, the system allows for the conditions (buffer pH and ionic strength) to be altered without any effect on the sample's alignment.     

False "false-positive" results in diagnostic cytology

With the introduction of transbronchial brushings and fine needle aspiration biopsy, which enable us to obtain samples directly from lesions, the diagnostic potential of cytology for the detection of malignancy, including early cancer, has been greatly enhanced. From 1976 to 1982, five positive cytology reports were initially considered to be "false positives" on the basis of negative gross findings, benign operative biopsies or negative histologic findings in the resected surgical specimens. However, these proved to be false "false positives," based upon the clinical follow-up or further examination of the surgical specimens. Presentation is made of three of these cases with positive cytologic findings and initially negative histologic diagnoses, with an analysis of the causes of the latter. From our experience, four types of cancerous lesions seem prone to being missed during gross examination, namely: any small cancer with a consistency similar to that of the parenchyma of the organ in which the tumor is located, superficially invasive carcinoma, scar cancer and a radiologically occult lung cancer in the presence of a coexisting radiologically demonstrable lesion. With more clinical application of these cytologic methods, false "false positives" are expected to occur more often.     

Better understanding of organ dysfunction requires proteomic involvement

Organ dysfunction is defined as a systemic consequence of acute and chronic diseases, a critical and important phase of disease development. The mortality of patients with severe illness is highly correlated with the number and duration of dysfunctional organs. There is still not an efficient and specific therapy to improve the prognosis of patients with organ dysfunction, due to the complexity and severity of the disease. There is a great need to understand molecular mechanisms of the disease, identify disease-related biomarkers, and validate therapeutic effects. Thus, it is important to have a special attention from proteomic scientists to explore the combination between advanced proteomic biotechnology, clinical proteomics, tissue imaging and profiling, and organ dysfunction score systems, to improve the clinical outcomes of these patients.     

Illness Perception and Clinical Treatment Experiences in Patients with M. Maroteaux-Lamy (Mucopolysaccharidosis Type VI) and a Turkish Migration Background in Germany

Introduction

Mucopolysaccharidosis VI (MPS VI) is an inherited lysosomal storage disease caused by a mutation of the gene for arylsulfatase B (ASB). Of the thirty-one patients registered in Germany, almost fifty percent have a Turkish migration background. MPS VI is treated by enzyme replacement therapy (ERT), which is time-consuming and expensive.

Methods

This interdisciplinary study explored the illness perceptions and clinical treatment experiences among ten MPS VI patients with a Turkish migration background in two centers for metabolic diseases (Berlin and Mainz, Germany). The clinical treatment situation was observed and semi-structured interviews were conducted with patients and health care personnel, in addition to participatory observation in four patients'' everyday environments in Berlin. The data from the interviews, patient records, and personal field notes were encoded, cross-related, and analyzed.

Results

Patients'' acknowledgement of the disease and coping strategies are influenced predominantly by the perception of their individual health status and the handling of the disease within their family. Patients'' willingness to cooperate with treatment strategies is further modified by their knowledge of the disease and the relationships with their health care providers. In this analysis, cultural factors turned out to be marginally relevant.

Conclusion

As with other chronic and debilitating diseases, effective treatment strategies have to reach beyond delivering medication. Health care providers need to strengthen the support for patients with a migration background. In this regard, they should respect the patients'' cultural and social background and their personal perception of the disease and the therapy. Yet structural and social aspects (clinical setting, family and educational background) may be more crucial here than “cultural barriers.”     

TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis

Background

TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place.

Methods

In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects.

Results

Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1.

Conclusions

These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.     

Conjectures on some curious connections among social status, calorie restriction, hunger, fatness, and longevity

Since the original publication of the article "Development of the IL-12/23 antagonist ustekinumab in psoriasis: Past, present and future perspectives" in March 2011 (see Appendix),(1) there have been several new publications and developments of note. A number of new reports from the ustekinumab psoriasis clinical development program have been published. The analysis of efficacy and safety in the PHOENIX 1 long-term extension demonstrated that continuous stable maintenance dosing of ustekinumab was generally well tolerated and sustained durable efficacy through up to three years of treatment.(2) Pooled safety data from the phase 2 and phase 3 global trials showed that the safety profile of long-term continuous ustekinumab treatment through up to three years(3,4) and four years(5) of follow-up was favorable and comparable to what has been reported previously in the shorter-term ustekinumab psoriasis studies.(6-8) This represents the greatest exposure and longest follow-up of psoriasis patients treated with a biologic published to date. Additional phase 3 trials in Asian populations demonstrated similar high levels of efficacy and favorable safety profiles in Japanese,(9,10) Korean,(11,12) and Taiwanese(11,12) patients as those observed in trials conducted in mostly White populations in North America and Europe.(6-8) These data support the positive benefit:risk profile and consistency of response to ustekinumab over years of usage, and in multiple ethnic groups. Results from up to five years of treatment with ustekinumab in the long-term extensions of the phase 3 trials, and the efficacy, safety, and effect on quality of life in Chinese patients will be available in 2012. In addition to clinical trials of ustekinumab for the treatment of psoriasis, 24-week data from one phase 3 study of ustekinumab for the treatment of psoriatic arthritis has recently been presented(13) and another study is ongoing. A Phase 2b trial in Crohn's disease has also been presented,(14) and three phase 3 studies in Crohn's disease are currently in progress.     

Opportunity Cost for Early Treatment of Chagas Disease in Mexico

Background

Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations.

Methodology/Principal Findings

A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment.

Conclusions/Significance

In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient''s quality of life.