Journal of Medical Hypotheses and Ideas最新文献

In this study we examine the possibility of constructing metadata from Positron Emission Tomography images based on a Radial Basis Function neural network, which uses histological data extracted via the enzyme-linked immunosorbent assay abbreviation. The aim of constructing such metadata is to achieve a bringing between the binding potential receptor in vitro and in vivo Positron Emission Tomography procedures, which it is possible to calculate using a classic simplified reference tissue model. This knowledge representation procedure may then be transmitted in the Positron Emission Tomography using the testing neural network procedure. The latest satisfies the primary aim of this study, which was to avoid painful and risky biopsies of patients.

Traditionally, two divergent approaches are used to explain the mechanism of action of psychotropic drugs. The dominant “Disease-centred” view emphasises the biochemical imbalance caused by ‘illnesses’. In contrast the “Drug-centred” view emphasises the psychoactive properties of these drugs and their ability to induce an ‘altered-state’ of mind. In this article we propose a new paradigm for classifying the therapeutic uses of psychotropic drugs based on the relation between their psychoactive effects and symptoms of indicated mental illness; as well as their clinical responses e.g. emerging tolerance, paradoxical initial worsening and being recommended for long/short term use. Based on this premise, therapeutic uses of psychotropic drugs can be placed on a continuum between two distinguishable modes. We define these modes as “Psycho-antagonistic” and “Psycho-agonistic”. 105 therapeutic uses of 85 psychotropic drugs are placed on this continuum; 74% on the Psycho-agnostic spectrum and 25% on the Psycho-antagonistic side. Hypnotic agents used for insomnia are clear examples of Psycho-antagonistic mode of use. Citalopram for treatment of Panic disorder is a clear example of using a drug in Psycho-agonistic mode. Only the therapeutic use of Lithium for bipolar affective disorder could not be allocated to any mode and considered as borderline. The paradigm highlights the possibility of initial worsening in majority of therapeutic uses of psychotropic drugs and importance of using lower doses. Further studies and clinical trials are needed to explore the full extent of the clinical implications of this paradigm in psychiatry and perhaps in other branches of medicine.

Radiation induced injury is a limiting factor in radiation related approaches from earth to space. Inductions of a wide spectrum of damages in radiotherapy patients due to unwanted normal tissues irradiation and space radiation related diseases in astronauts have been caused many limitations in cancer treatment and space missions. There are many radiation protection/mitigation approaches including: physical, chemical, biological and physiological methods. Radiation protection using these methods is expensive and also has many problems including acute toxicities and difficulties in their targeting to normal tissues. Based on experimental and hypothetical data, showing that medical/biological gases have many protective effects such as antioxidant, anti-inflammatory, anti-apoptotic, and induction of radioresistance, we hypothesize that similar gases which have been produced by microorganisms (biogases) have those properties and may be used as radiation mitigators/protectors in radiation related approaches such as radiotherapy, radiation accidents and in space missions. Isolation microorganism in safe laboratory conditions in enough amounts, finding non-toxic dose of microorganisms that provide highest radioprotection percent, dose reduction factor (DRF) calculation to compare the radioprotective efficacy of the microorganisms, finding the best targeting techniques to deliver those microorganisms into normal tissues, genetically manipulations of microorganism to achieve the highest amount of biogases with lowest side effects can be done for testing the hypothesis.

Recent studies on stem cells differentiation into germ cells have changed scientists’ attitude to reproductive problems as well as infertility topics. It is supposed there are promising and new approaches in treatment of infertile couples and numerous advances will be made in reproductive medicine in near future. Application of embryonic stem cells for clinical trials is limited due to high potent of tumorogenicity and ethical issues. Therefore, pluripotent cells taken from adult tissues or organs, could be a good alternative for gamete production. Herein, we hypothesize to stimulate human endometrial stem cells (hEnSCs) differentiation into germ cell-like cells by culturing in retinoic acid (RA) as 2D medium and then in fibrin as 3D scaffold. Germ cell markers such as DAZL, DDX4 and Dppa3, will be assessed by immunofluorescence and real-time PCR. Fibrin mechanical properties will be examined by rheology analysis and cell viability will be determined by MTT assay. Specific markers expression and the cells’ integrity will be detected by immunofluorescence staining and SEM analysis respectively. We suggest differentiation of hEnSCs into germ cell-like cells in a medium containing 10⁻⁵ M RA in which the specific markers were expressed properly in both 2D and 3D medium cultures. Additionally, fibrin scaffold will offer a proper 3D scaffold for hEnSCs-derived germ cell-like cells.

Despite great advances in clarifying the pathogenesis of multiple sclerosis (MS), the exact underlying mechanism has not been definitely established. However, the responsibility of cross-reactive antibodies as the initiating factor in MS pathogenesis is a novel idea. Recently, an antibody against-α-gliadin 33-mer peptide which is found in most patients with gluten sensitivity have shown to cross-react significantly with various neural antigens including asialoganglioside, synapsin, and myelin basic protein (MBP). Furthermore, evidence indicates that IL-17, circulating immune complexes and even antibodies produced during gluten sensitivity can contribute to blood–brain barrier (BBB) permeability. Accordingly, extravasation of these anti-α-gliadin antibodies (AGA; especially IgG isotype) through the impaired BBB thought to target asialoganglioside, synapsin, and MBP in neurons. This opsonization may trigger a series of cascade pathways including complement activation, antibody-dependent microglial cytotoxicity against neurons, secretion of inflammatory mediators, myelin sheath damage, chemokine expression, CNS inflammation, BBB disruption and then leukocyte infiltration. The present hypothesis introduces a new antibody-dependent alternative pathway which may lead to multiple sclerosis (MS) during gluten sensitivity.

Temporomandibular joint (TMJ) ankylosis can restrict the mandibular movement, followed by resulting in numerous problems. To understand the mechanism of TMJ ankylosis (TMJA) and prevent the generation of TMJA is urgent necessary. Although many factors contribute to it, trauma is the most common cause of TMJA. The mechanisms of TMJA are still unclear, and the distraction osteogenesis of the lateral pterygoid muscle (LPM) may play an important role. Injection of very small amounts of botulinum toxin type A (BTA) can temporarily block the muscle’s impulse and has been revealed to be an effective treatment method for many temporomandibular disorders. In this article, we make a hypothesis that LPM injection of BTA as a novel method for immobilization of mandible, followed by preventing the traumatic TMJA. Furthermore, the side effects of local injection of BTA also are minimal, temporary, reversible and self-limiting. If this strategy is validated, LPM injection of BTA will be a cost effective way to be administrated to prevent the traumatic TMJA.

This article reflects the comparison of downloads, readership and citation data for the Journal of Medical Hypotheses and Ideas. A brief analysis of the journal’s recent performance indicates that the journal articles appear to have a high rate of downloads around the world. Its published articles are from a variety of countries and the odds of accepted articles for publication is surprisingly even across regions. However, the rate of received citations to the published articles indicated a lack of considerable impact in scholarly publications. This approach has double value as it shows the overall impact of the journal in social web as well as scholarly publications and also provides future directions for the journal’s editorial boards. Altmetrics was also proposed as an alternative to the widely used citation and usage indicators in tracking the impact of individual articles.

Osteoradionecrosis of jaws (ORNJ) is a serious complication of radiotherapy for patients with head and neck cancer. As of yet, no universally accepted treatment exists for this chronic pathologic condition. It has been shown that ultrasound is an effective, noninvasive adjunctive therapy in ORNJ, as ultrasound can result in the increase of angiogenesis and bone production, which are essential for ORNJ healing. Recently, low-frequency ultrasound has been demonstrated to enhance the transdermal delivery of macromolecules and hydrophilic drugs (low-frequency sonophoresis, LFS). As a biological macromolecule, basic fibroblast growth factor (bFGF) also has potential osteoinductive and angiogenic properties. Herein, we present a hypothesis that LFS-mediated transdermal bFGF delivery is capable of improving the healing of ORNJ and will be a new effective adjunctive therapy to surgery. This treatment combines low-frequency ultrasound with bFGF to respectively promote vascularly compromised bone and soft tissue wound healing, and is expected to be more effective than ultrasound therapy alone.

Total hip arthroplasty (THA) has progressed to be one of the most cost-effective surgical procedures to relieve pain and restore function to the pathological hip. Official retrospective statistics revealed over 500,000 cases of THA were performed per annum in the US alone, but failure cases brought about more than 40,000 revision procedures among them. The revision surgery is usually hard to manipulate due to the formidable difficulty of repairing the critical bone defect. Plenty of attempts aiming at tackling this problem have been dedicated by both tissue engineering and clinical investigators. Despite of the initial success, it is still a great challenge to overcome atypical intertrochanteric and diaphyseal defects of proximal femur to reach a satisfied therapeutic outcome in terms of long-term survivorship of the prosthesis. Given the interdisciplinary integration of biomaterial fabrication, bone tissue engineering, rapid prototyping, and biomacromolecule/drug delivery, we propose a hypothesis to construct a biphasic articular spacer to reach the dual goal of infection control and bone regeneration in this study. To be specific, this complex is consisted by a geometry-specific calcium phosphate sheath, derived from computer aided design and low temperature 3D printing, and an axial bone cement pillar delivering antibiotics. Theoretically, this modularized spacer possesses the potency of enhanced osteogenesis, controlled release of specific drugs, and co-delivery of growth factors. If this strategy is validated, further effort can be made to strengthen the printability of calcium phosphate using the 3D printing technique, and to accelerate its translation from lab to clinics.

Hodgkin’s Lymphoma (HL) as a prevalent hematolymphoid malignancy begins in cells of immune system and is characterized by the specific histologic, clinical properties. Abnormality in apoptosis has been recognized as a crucial pathway in its progression. Nowadays, 35–40% of patients in stages III and IV show disease relapse or symptoms of refractory to first-line chemotherapy; therefore, novel treatment strategies are required. As apoptosis inducing is an important mechanism in cancer treatments, novel anticancer molecules to induce programmed cell death are required. The authors present a novel therapeutic approach for HL, with regard to anti-tumoral and immunomodulatory effects of the mda-7/IL-24. This gene, located in human chromosome 1q32-33, has shown tumor suppressor activity in various human malignant cells in, in vitro, in vivo, and even in clinical trial studies. Our hypothesis was designed to evaluate anti- tumoral effects of mda-7/IL-24 in SCID mice model using the adenovirus-based vector. mda-7/IL-24 interestingly has antiangiogenic, immunomodulatory, and bystander antitumoral activities. mda-7/IL-24 can suppress anti-apoptotic Bcl-2 family proteins, and induces GADD family, Bak, Bax, and other pro-apoptosis proteins. This hypothesis suggests that adenovirus vectors expressing mda-7/IL-24 may help for effective immunotherapies of HL.