SPR

Bimatoprost Ophthalmic Solution (BOS) 0.3 mg w/v for 1 Open Trial of Long-term Preventive Therapy of Migraine in 3 patients with Pathophysiologic Shift from Brain to Eye

Published on: 9th November, 2023

Known since antiquity, migraine is a complex primary disorder, an episodic painful Autonomic Nervous System (ANS) storm, generally following the stress/post-stress phase. Despite exhaustive study of neuropeptides, neurochemicals, molecules, neurogenetics, neuroimaging along with animal and human experiments over the last 50 years, the scientific basis of migraine remains unknown. Straddling eight decades from Cortical Spreading Depression (CSD) to Calcitonin-Gene Related Peptide (CGRP) and its antagonists, exponentially increasing data have failed to create a gestalt synthesis. This article lays cohesive and robust fundamental principles for the comprehension and management of migraine. The continuum between migraine and non-congestive Primary Open-Angle Glaucoma (POAG), Normal Tension Glaucoma (NTG), or Low-Tension Glaucoma (LTG) is advancing. The case of sustained remission of migraine attacks (> 75%) over 3 years - 5 years with ocular hypotensive topical Bimatoprost Ophthalmic Solution (BOS) 0.3% in an N-of-1 trial in 3 patients with refractory migraine is presented. A cause-effect-adaptive process underlies the ANS-stress/post-stress-linked biology of migraine. Vasopressin-serotonin-norepinephrine ‘homeostatic-adaptive system’ Lowers Intraocular Pressure (IOP), while enhancing anti-stress, antinociception, vasomotor, and behaviour control functions, thereby selectively decreasing algogenic neural traffic in the ophthalmic division of trigeminal nerve (V1), and, raising the threshold to develop migraine. Striking migraine headache-aborting feature of vomiting is also likely linked to a several hundred-fold increase in arginine-vasopressin secretion. Eye-cover tests and self-ocular digital displacement are essential to studying the visual aura. Real-time physical displacement of Scintillating Scotoma (SS) and floating ‘stars’ is reported. The basis of spontaneous onset and offset, self-limited duration of migraine attacks, as well as female preponderance, and age/menopause decline in prevalence, are elucidated. Intraocular implants with long-term ocular hypotensive effects, including bimatoprost, are the future of migraine management. Controlled trials are required to establish the migraine-preventive effect of topical bimatoprost, a revolutionary advance in neuroscience.
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Case Series of Metastatic Cutaneous Malignant Melanoma to the Gallbladder and the First Reported Case of Metachronous Adenocarcinoma of the Colon

Published on: 18th January, 2024

Two female patients in their fifties with a previous history of cutaneous malignant melanoma were found during follow-up to have a 'hot' lesion in the gallbladder on a Positron Emission Tomography scan. Imaging showed a gallbladder polyp. Histology revealed infiltration of the polyp mucosa by metastatic malignant melanoma. One case had a BRAF mutation. A male in his 70s was found on a staging computed tomography scan to have a suspicious intraluminal lesion in the gallbladder and thickening of the sigmoid colon. Subsequent histology confirmed metastatic malignant melanoma in the chest wall and to the gallbladder and adenocarcinoma in the colon. Molecular testing showed BRAF mutation. The metachronous adenocarcinoma in the colon was mismatch repair protein proficient and had no KRAS mutation. Histology from all cases showed that metastatic malignant melanoma to the gallbladder is superficial.Discussion: Reports from autopsy examinations revealed that metastasis from malignant melanoma to the gallbladder can be up to 15% - 20%. Most patients have mild symptoms or are asymptomatic which explains the paucity of cases reported in living patients within the published literature. Most of the previous reports showed the metastatic malignant melanoma to the gallbladder presented macroscopically as a polyploidal lesion. Conclusion: Our histological observation and previous reports showed that metastatic malignant melanoma in the gallbladder tends to be superficial. All our cases show no lymphatic or vascular invasion in the histological examination as previously published reports, however, the hematological spread is the most commonly suggested mechanism of spread.
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Schizoaffective Disorder in an Individual with Mowat-Wilson Syndrome (MWS)

Published on: 31st January, 2024

Mowat-Wilson Syndrome (MWS) is an autosomal dominant genetic syndrome caused by mutations in the ZEB2 gene. It is characterized by distinctive facial appearance, intellectual disability (ID), epilepsy, Hirschsprung disease (HSCR), and other congenital anomalies. The psychiatric symptoms, associated with MWS have rarely been reported. The following report highlights a case of schizoaffective disorder in a 24-year-old male with MWS and the challenges he encountered over his treatment course.After considering numerous diagnoses including bipolar disorder and psychosis secondary to a general medical condition, the patient was diagnosed with schizoaffective disorder. Various trials consisting of atypical antipsychotics and mood stabilizers were unsuccessful in managing his symptoms. Eventually, the patient stabilized on a medication regimen consisting of clozapine 300 mg once daily, topiramate 75 mg twice per day, and lithium 1800 mg once daily. This case report documents co-occurrence of MWS and Schizoaffective disorder.
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Strengthening Healthcare Delivery in the Democratic Republic of Congo through Adequate Nursing Workforce

Published on: 19th February, 2024

The Democratic Republic of Congo (DRC) grapples with a critical shortage of nurses, exacerbating disparities in healthcare access and outcomes. This mini-review examines the factors impacting the nursing workforce in the DRC and presents potential solutions to strengthen it. Decades-long regional conflicts have endangered the nursing workforce, resulting in an imbalanced distribution that disproportionately favors urban areas over rural regions. Inadequate healthcare funding, compounded by mismanagement, has led to resource scarcity and inequitable distribution, further hampering nursing efforts. Additionally, stagnant policy reforms and ineffective advocacy have hindered improvements in nurse employment, wages, education, and working conditions. Infrastructure deficiencies and medical supply shortages have also contributed to reduced incentives for nursing professionals. Therefore, we undertook a mini-review aimed at offering a succinct and targeted overview of nursing care in the DRC. This involved analyzing available literature and data concerning the nursing workforce with a particular focus on the DRC. We believe that addressing these interlinked challenges necessitates comprehensive strategies that prioritize establishing regional stability, responsibly allocating and increasing healthcare funding, incentivizing nurse recruitment and retention through policy adjustments, enhancing healthcare infrastructure and nursing education, and fostering both local and global collaboration. Investing in nursing is paramount for transforming healthcare delivery in the DRC, particularly considering nurses' pivotal roles in delivering preventive, therapeutic, and palliative care services. Strengthening nursing capacity and addressing systemic challenges are essential steps toward mitigating healthcare disparities and enhancing population health, aligning with the objectives outlined in the United Nations Sustainable Development Goals.
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Evaluation of the Anti-inflammatory Activity of Equisetum arvense and Baccharis trimera Fractions

Published on: 19th March, 2024

Inflammation is a natural response of the body to defend itself against potential threats and can be reduced through physical activity, proper nutrition, and the use of herbal medicines, which are medicinal plants. In the study, we aim to examine the anti-inflammatory effects of the volatile and ethanolic fractions of two commonly used medicinal plants, Equisetum arvense, and Baccharis trimera. The essential oils were obtained by hydrodistillation of the fresh leaves of the plants, while the ethanolic extracts were obtained using classical methodologies. All fractions were tested for anti-inflammatory activity, evaluating their ability to stabilize the red blood cell membrane and inhibit the spreading, and phagocytosis by macrophages, at concentrations varying from 200 to 600 µg mL-1. The results of the experiments suggest that the ethanolic fraction of B. trimera shows promising results compared to the positive controls. Our investigations thus contribute to the specialized literature on the use of herbal medicines around nutrition, providing guidance for future studies on these fractions.
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Laws of Pathophysiology of Migraine in the Third Millennium

Published on: 20th March, 2024

Science is the art of systematic and reproducible measurements, ultimately leading to knowledge supported by a holistic logic. Besides serendipity, there are 6 ways in general to obtain knowledge: authoritarianism; mysticism; rationalism, empiricism; pragmatism; and scepticism. Over the last 100 years, a canonical mythology – cortical spreading depression (CSD) – has prevailed in migraine pathophysiology. Conversely, a well-defined adaptive/protective role has evolved for CSD in locusts, Drosophila, and mammals. Additionally, an elaborate but entirely symptomatic nosologic system has arbitrarily evolved in migraine / primary headache. While the so-called systematic but symptomatic classification system of migraine / primary headache keeps on advancing the data-bank exponentially, the cause-effect nexus continues to obscure the most important systematic and insightful components of the knowledge of primary headache. The first step in advancing the cause-effect mystery of migraine / primary headache is to create a conceptual, consistent, and important adaptive-pathogenetic divide in the massive and disparate data-linked pathophysiology of the disorder. Once certain definitive principles (not laboratory/neuroimaging / genetic/epidemiologic data) emerge in the science of migraine / primary headache, we become empowered to understand the complex but key phenotypic blueprint as well as the neuro-pathophysiology / neuropsychiatry of the entity, including the visual (nasal visual-field sparing digitally-displaceable and eyeball-movement-synchronous scintillating scotomata), the lateralizing fronto-temporal-nuchal headache exclusively involving the ophthalmic division of the trigeminal nerve, and the associated features such as ‘stress’, ‘post-stress’, ‘autonomic storm’, ‘protean’ and ‘spontaneous’ onset and offset, and headache-aborting nausea-vomiting. In this manner, we have also evolved principles to begin to understand the most complex female predominance of migraine patients in adults [F:M=3:1] as well as the decline of prevalence in migraine attacks following menopause and advancing age. The Laws of the Pathophysiology of Migraine encompass the invaluable neurological / neuro-ophthalmological shift in pathophysiology from the brain to the eye.
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Management and Therapeutic Strategies for Spinal Muscular Atrophy

Published on: 29th March, 2024

Spinal muscular atrophy is an autosomal recessive neuromuscular disorder characterized by progressive muscle weakness and atrophy. It is one of the most common single-gene disorders with an incidence rate of approximately 1 in 10,000 live births. The clinical manifestations are progressive hypotonia and muscle weakness due to the degeneration of alpha neurons in the anterior horn cells of the spinal cord and motor nuclei in the lower brain stem. Depending on the severity of the symptoms, SMA has five subtypes. Supportive measures can be offered for respiratory, gastrointestinal, and musculoskeletal complications. Carrier testing for all couples is recommended and this can be done by Multiplex Ligation-dependent Probe Amplification (MLPA). Prenatal diagnosis can be offered to carrier couples. Therapies must be given within the newborn period for maximum benefit and before the loss of motor neurons. It is achieved by identifying the SMA babies through Newborn screening. Several new FDA-approved drugs can reduce the progression of symptoms in SMA. However, they cannot offer a definite cure. Clinical follow-up and Neurological assessment demonstrate that SMA children can attain developmental milestones after receiving treatment, which is never normally attained in untreated cases. In utero SMA treatment with Zolgensma would enhance the survival rate and favorable neurological outcomes in the future. Base editing and Gene editing with CRISPR-Cas technologies to target the mutations and restore functional and stable SMN protein levels are the future hopes for a permanent cure of SMA.
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Unlocking the Transformative Power of Synthetic Biology

Published on: 18th April, 2024

Artificial Intelligence (AI) combined with Synthetic Biology has the potential to change the way we approach medicine, agriculture, and manufacturing. AI automates tasks, optimizes experimental designs, and predicts biological behaviours, resulting in more efficient design and engineering of biological systems. However, there are challenges such as data limitations, interpretability issues, and ethical considerations like biosafety and biosecurity concerns that need to be addressed. AI can be used to analyze vast amounts of data and identify patterns. This has led to successful applications of AI in high-throughput screening and biomanufacturing, which can drive innovation and address critical challenges. AI-powered closed-loop systems for real-time monitoring and control of biological processes also show promise in providing real-time feedback and optimizing systems on the fly. Despite these advancements, it's important to consider ethical implications to ensure the responsible development and application of AI in synthetic biology. Proper consideration of challenges and ethical considerations can help leverage the power of AI to drive innovation and tackle pressing societal challenges. Overall, the potential of AI in synthetic biology is significant. By addressing challenges and ethical considerations, we can use them effectively to solve pressing problems.
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