Medical hypotheses最新文献

There is an imperative need of an effective prophylactic strategy to contain or even end the SARS-CoV-2 pandemic, and to protect the human race from further such pandemics. We propose that NIoBReTH, a composite paradigm of Negative air Ions, virus Blockage, Respiratory Treatment with disinfectants, and Hand hygiene, may provide enough protection against infection by SARS-CoV-2 and perhaps other airborne pathogens, with acceptable safety and less restriction on social/economic activities. Compared to traditional paradigms like N95 respirators and strict social distancing or even large-scale lockdown, the new paradigm may be more easily practiced by individuals, and government adoption may be more robust to individual non-compliance.

Alzheimer’s disease (AD) is one of the most unanswered diseases in the world as its complicated pathological mechanism makes it a formidable challenge in modern healthcare with limited intervention options. Due to its chronic nature in neurodegeneration, leading to cognitive decline and brain damage, mitigating this disease is now of major concern globally. The revelation of certain key hallmarks of AD pathology such as cholinergic dysfunction and amyloid plaque toxicity has thrown some insight into identifying therapeutic targets. Only symptomatic relief has been achieved by a single-target therapeutic approach, thus, the development of multi-impediment drugs is urgently needed. The adverse effects of current AD medication and repeated failure of futuristic drugs led us to hunt for a natural compound with beneficial properties that can target multi-facets of AD pathology, and cure this devastating brain disorder. The hypothesis of targeting different pathways contributing to progressive neurodegeneration in AD pathophysiology can be considered a new-age intervention. Coptisine, a bioactive alkaloid with benzyl tetrahydroisoquinoline in structure possesses enormous pharmacological benefits including neuroprotective abilities. Together with the potential of coptisine to inhibit the major targets of AD pathogenesis namely acetylcholinesterase (AChE), beta-secretase (BACE1), and gamma-secretase, this alkaloid can emerge as a new-age multi-target therapeutic for AD. However, robust research on coptisine’s suitability against AD pathogenesis is pivotal considering its therapeutic promises and an unambiguous understanding of the coptisine’s future can be predicted by evaluating its efficacy and safety for ameliorating AD.

Triple negative breast cancer stands out as the most aggressive subtype within the spectrum of breast malignancies, characterized by increased risks of recurrence, metastasis, and dismal prognosis. Notably, TNBC cells exhibit extensive overexpression of folate receptors, particularly folate receptor alpha, which drives tumor cell proliferation and migration. Addressing TNBC remains a formidable challenge in oncology, necessitating innovative therapeutic strategies. While chemotherapy serves as the cornerstone of TNBC treatment, its efficacy is often compromised by systemic toxicity, resulting in suboptimal clinical outcomes. This hypothesis proposes a novel approach utilizing lignin nanoparticles functionalized with folic acid for targeted delivery to FRα-overexpressing TNBC cells. These nanoparticles will encapsulate both the chemopreventive agent Sulphoraphane and the chemotherapeutic agent Teriflunomide, offering advantages such as enhanced drug targeting, synergistic therapeutic effects, cost-effectiveness, and reduced off-target toxicity. Additionally, this hypothesis highlights the repurposing of Teriflunomide to overcome drug resistance and the antioxidant properties of lignin. Furthermore, the ease of nanoparticle fabrication via self-assembly presents a promising avenue for streamlined production and clinical translation.

Caffeine and theophylline use can lead to methylxanthine toxicity, resulting in life-threatening tachyarrhythmias and hypotension. Esmolol, a beta-adrenergic antagonist, is a suggested option for controlling associated tachyarrhythmias. However, esmolol is not universally available, and its hypotensive effects often deter its use. Digoxin, another rate control agent which is widely available, theoretically possesses the circulatory system effects needed to tackle both tachyarrhythmia and hypotension induced by methylxanthine toxicity. We propose digoxin as an alternative to esmolol, especially in regions where esmolol is unavailable and for individuals experiencing hypotension due to methylxanthine toxicity.

Although paracetamol is considered a safe medication during pregnancy at therapeutic doses, and despite animal studies showing no negative effects or reporting no adverse effects during pregnancy, there are no well-controlled clinical studies demonstrating the safety for both the mother and fetus. Therefore, its use in this situation depends on the physician’s discretion. Its mechanism involves the inhibition of the enzymes cyclooxygenase 2 and 3 (COX-2,3), which modulate pain and inflammation by reducing prostaglandins. However, COX-2 and prostaglandins are also part of the molecular cascade organizing the brain towards a male direction during the prenatal period, and potentially during other periods as well. Herein, we hypothesize that paracetamol, a common medication used to treat fever and pain, may have long-term effects as a neuroendocrine disruptor of the sexual brain when administered during critical periods of development such as pregnancy, and to a lesser extent, during the neonatal, infancy, and puberty periods. Throughout this manuscript, we discuss the effects of COX-2,3 inhibition on the organization of the brain and sexual partner preference, particularly affecting masculinization of the medial preoptic area. We argue how administration of paracetamol in critical periods of plasticity might have an enduring effect on sexual behavior and other motivated behaviors. Impairments in each of these processes can directly impact individuals’ sexual and mental health. We also discuss how sexual experience in adulthood ameliorated the impaired sexual preference of paracetamol-treated males, indicating an interaction between biological and environmental mechanisms. This manuscript is meant to warn professionals that although paracetamol is a very effective and safe drug, it is likely to disorganize the developing sexual brain, probably contributing to what we call iatrogenic sexual diversity.

Rheumatoid nodules (RNs) are an extra-articular manifestation of rheumatoid arthritis and are frequently observed in patients with autoimmune and inflammatory conditions. The development of RNs involves several stages, including inflammation of blood vessels, cell death triggered by medications, and infiltration of inflammatory cells leading to nodule formation. Recent studies highlight the importance of the IL-23/IL-17 axis and the migration of chronic inflammatory cells in this process, forming palisading granulomas. Current treatments often fail to manage RNs effectively because they tend to reoccur and appear in multiple locations. This study proposes a new therapeutic strategy combining corticosteroid treatment with gene silencing therapy using small interfering RNA (siRNA) targeting IL-23. Targeting these inflammatory pathways simultaneously aims to reduce both the size and number of nodules, potentially shortening the treatment duration. An innovative delivery system utilizing lipid-polymer hybrid nanoparticles (LPNs) and hyaluronic acid-based dissolving microneedles (MNs) is proposed to be developed. The LPNs will be designed with DOTAP (1,2-dioleoyl-3-trimethylammonium propane) and DSPE-PEG (distearoyl-phosphoethanolamine-polyethylene glycol) as the lipid core, along with poly-lactic-co-glycolic acid (PLGA) polymer. These MN patches would improve the skin’s permeability, allowing LPN carrying the siRNA and corticosteroid to penetrate effectively. This non-invasive approach is expected to enhance the diffusion of LPNs into the skin, thereby increasing the availability of the therapeutic payload. Therefore, we hypothesize that targeting the IL-23/IL-17 axis and granuloma formation with the synergistic combination of targeted therapy and advanced delivery technology will revolutionize the treatment of RNs.

Various types of nystagmus during vertigo attacks in Meniere’s disease (MD) include direction-changing and non-direction-changing nystagmus. The direction-changing and non-direction-changing nystagmus may be associated with how the inner ear balance organs are influenced spatially and temporally. We hypothesized that the density difference inside the endolymph elicits the stereocilia inclination of the inner ear balance organs even if the density difference area does not directly touch the stereocilia. The direction of the nystagmus could change if the density difference area spreads around the inner ear balance organs. Numerous records of the nystagmus direction with new devices from the beginning of the nystagmus during the vertigo attacks will contribute to understanding how vertigo attacks appear in MD. The influence of the density difference may be associated with the degree of endolymphatic hydrops. Under significant endolymphatic hydrops, the volume effect due to the density difference becomes more prominent. The trabecular meshwork located in the perilymph in the superior part of the inner ear may maintain the perilymphatic space and prevent the enlargement of the endolymphatic space.

Major depressive disorder (MDD) is characterized by symptoms such as low mood and anhedonia related to altered dopamine transmission in the reward system. In addition, approximately one-third of patients with MDD develop treatment-resistance to the pharmaceutical treatment, necessitating alternative therapeutic strategies. While non-invasive brain stimulation (NIBS) holds promise for improving treatment-resistant MDD, remission rates are still relatively modest. It has been demonstrated that NIBS effects not only depend of the stimulation properties but are also “state-dependent”, meaning that when patients engage in specific tasks or states that involve similar neural networks targeted by NIBS, a synergistic and additive therapeutic effect may occur. Therefore, a recent strategy to improve treatment outcomes is to combine NIBS with other types of interventions targeting the same network.

Numerous studies have demonstrated a clinically meaningful antidepressant effects when NIBS are combined with psychotherapy, cognitive-behavioral approaches, or cognitive remediation programs for patients with MDD. However, widespread use of this combination may be hindered by barriers such as cost and accessibility for both clinicians and patients. Alternatively, sensory-based interventions alone (such as music therapy or exposure to specific odors) represent a promising, easy-to-implement, cost-effective and innovative therapeutic approach for MDD. These interventions are known to activate the meso-cortico-limbic system, triggering dopamine release, or modulating dopaminergic tone in various brain structures, similar to what is observed with NIBS. In this paper, the hypothesis that combining sensory-based interventions with NIBS is a compelling approach to alleviating MDD symptoms is tested. Specifically, it is hypothesized that the dual activation of the reward system induced by sensory-based interventions, combined with the concurrent application of NIBS, will result in a synergistic effect, ultimately leading to enhanced alleviation of MDD symptoms.

Carotid artery intima media thickness (CIMT) is increased in cardiovascular (CRVD) and cerebrovascular diseases (CBVD) as well as in post cancer therapy. CIMT represents primarily the thickness of cholesterol on arterial wall. It gets increased in atherosclerotic impairment. A switch to hypocholesterolemia in the pathogenicity of carcinogenesis maintains CIMT at the thinner side. Cancer therapy increases the CIMT of carotid artery. Thus, CIMT may be used to differentiate the severity of atherosclerotic flare in post-cancer-therapy. We thus herein describe the diagnostic benefits of CIMT in the outcome of cardiovascular (CRVD), cerebrovascular (CBVD) and carcinogenesis type of disorders. We hypothesize that CIMT can be used as a common diagnostic index for joint venture viz the differentiation of atherosclerosis and carcinogenesis, both biochemically and clinically on a single template.

Pelvic organ prolapse (POP) is a globally prevalent condition effecting over half of post-menopausal women. It is caused by a weakening of the soft tissue of the pelvic floor so that it is no longer able to support the organs of the pelvis. This results in a descent of the pelvic organs down the vagina, including bladder, rectum, small bowel, uterus, or vaginal vault (post-hysterectomy). Symptoms can include discomfort and pain, urinary incontinence, faecal incontinence, and dyspareunia, depending on the organ effected. This can have a significant impact on mental, social, and sexual wellbeing.

Current conservative management options include lifestyle changes or the insertion of a temporary silicone pessary. The silicone pessary requires regular maintenance and replacement and can thus result in secondary pain and discomfort. Surgical options include native tissue repair or surgical augmentation with the use of a polypropylene (PP) mesh adjunct. However, the PP mesh implants have now been banned in several countries – including UK, USA, Canada and Australia, due to concerns over the safety of the material. Complications of the PP mesh included mesh exposure; chronic infection; chronic pain; and dyspareunia. These complications are thought to have occurred due to a mismatch of the biomechanical/viscoelastic properties of the PP mesh and native tissue, at the site of implantation. The alternative of native tissue repair has a high recurrence rate for POP and does not provide an effective cure to the condition. Therefore, POP is a condition with an unmet clinical need.

Scientists across the globe consider graphene to be a ‘wonder material’ with superior physicochemical properties that will revolutionise every field and all industries. Graphene is a 2D single layer of carbon atoms arranged in a honeycomb lattice structure. Its properties include being 200× stronger than steel but at the same time incredibly lightweight and elastic. We developed a graphene-based nanocomposite (GBN) material that harnesses the superior properties of graphene. The material is non-toxic and biocompatible and suitable for surgical application. It is currently under development for heart valves, breast implants, and tendons, amongst other applications. The objective of this research is to use this GBN material for the development of a surgical membrane for the treatment of POP.