Warfarin therapy provides extensive antithrombotic benefits and, thus, is widely used in the general population. However, as with most medications, there are also risks associated with warfarin use. Specifically, because of the narrow therapeutic window of this drug, patients taking it are at a much higher risk of accidental bleeding. Additionally, patients may also present with bleeding complications when infected with illnesses with coughing as a symptom, such as influenza or COVID-19. These patients have the potential to suffer hemorrhagic morbidities related to the increased intra-abdominal and intra-thoracic pressures that are generated from coughing. Moreover, a synergistic effect is seen when patients find themselves in a situation where they are taking anticoagulation therapy and become infected with illnesses such as influenza or COVID-19. We present a case in which an individual on warfarin therapy was infected with Influenza A. This combination of factors eventually led to massive hemorrhage and large abdominal wall hematoma formation. This case brings to light the importance of having a low threshold for considering the prospect of massive hemorrhage in any patient who is anticoagulated and develops a condition that is associated with increased abdominal pressure. Because these bleeding events can have devastating effects, raising awareness of this risk is increasingly important. Early detection of massive hemorrhage will lead to better outcomes and can ultimately be life-saving for these patients.
This meta-analysis aimed to evaluate the efficacy and safety of relamorelin, a synthetic ghrelin receptor agonist, for the treatment of gastroparesis and diabetic gastroparesis. A total of 1,033 participants from five randomized controlled trials were included. The primary outcome was the mean change in gastric emptying time from baseline. Relamorelin demonstrated a statistically significant improvement in gastric emptying time with a mean difference of -11.40 minutes compared to the placebo group. Furthermore, a significant improvement was observed specifically in diabetic gastroparesis patients, with a mean difference of -8.43 minutes. However, adverse effects, such as headaches, dizziness, and gastrointestinal symptoms, were more prevalent in the relamorelin group. Despite these adverse effects, the study concludes that relamorelin offers a promising avenue for gastroparesis treatment, especially given the limited existing therapeutic options. This comprehensive meta-analysis synthesizes existing evidence to inform clinical practice and guides future research in this domain.
Barrett's esophagus (BE) remains a significant precursor to esophageal adenocarcinoma, requiring accurate and efficient diagnosis and management. The increasing application of machine learning (ML) technologies presents a transformative opportunity for diagnosing and treating BE. This systematic review evaluates the effectiveness and accuracy of machine learning technologies in BE diagnosis and management by conducting a comprehensive search across PubMed, Scopus, and Web of Science databases up to the year 2023. The studies were organized into five categories: computer-aided systems, natural language processing and text-based systems, deep learning on histology and biopsy images, real-time and video analysis, and miscellaneous studies. Results indicate high sensitivity and specificity across machine learning applications. Specifically, computer-aided systems showed sensitivities ranging from 84% to 100% and specificities from 64% to 90.7%. Natural language processing and text-based systems achieved an accuracy as high as 98.7%. Deep learning techniques applied to histology and biopsy images displayed sensitivities up to greater than 90% and a specificity of 100%. Furthermore, real-time and video analysis technologies demonstrated high performance with assessment speeds of up to 48 frames per second (fps) and a mean average precision of 75.3%. Overall, the reviewed literature underscores the growing capability and efficiency of machine learning technologies in diagnosing and managing Barrett's esophagus, often outperforming traditional diagnostic methods. These findings highlight the promising future role of machine learning in enhancing clinical practice and improving patient care for Barrett's esophagus.
Acute urinary retention is a known complication of inguinal hernia repair. However, the development of severe agitation and delirium as a result of acute urinary retention following inguinal hernia repair is less commonly reported. Here, we present the case of a 40-year-old male with no relevant medical history who underwent open mesh hernia repair for an uncomplicated left-sided indirect inguinal hernia. Postoperatively, the patient became hypertensive, delirious, and violent. He was found to have urinary retention on a bladder scan. Urgent intervention with catheterization and bladder decompression resulted in the prompt resolution of the patient's symptoms. The patient regained his senses and did not remember the events that led to it. This case highlights the importance of recognizing and managing acute urinary retention to prevent the development of severe agitation and delirium following spinal anesthesia. Further research and awareness are necessary to better understand the underlying neurovisceral mechanisms and optimize preventive strategies.
RATIONALE: Neuropsychiatric disorders encompass a broad category of medical conditions that include both neurology as well as psychiatry such as major depressive disorder, autism spectrum disorder, bipolar disorder, schizophrenia as well as psychosis. OBJECTIVE: NADPH-oxidase (NOX), which is the free radical generator, plays a substantial part in oxidative stress in neuropsychiatric disorders. It is thought that elevated oxidative stress as well as neuroinflammation plays a part in the emergence of neuropsychiatric disorders. Including two linked with membranes and four with subunits of cytosol, NOX is a complex of multiple subunits. NOX has been linked to a significant source of reactive oxygen species in the brain. NOX has been shown to control memory processing and neural signaling. However, excessive NOX production has been linked to cardiovascular disorders, CNS degeneration, and neurotoxicity. The increase in NOX leads to the progression of neuropsychiatric disorders. RESULT: Our review mainly emphasized the characteristics of NOX and its various mechanisms, the modulation of NOX in various neuropsychiatric disorders, and various studies supporting the fact that NOX might be the potential therapeutic target for neuropsychiatric disorders. CONCLUSION: Here, we summarizes various pharmacological studies involving NOX inhibitors in neuropsychiatric disorders.
Autism Spectrum Disorder , Depressive Disorder, Major , Humans , NADPH Oxidases/metabolism , Depressive Disorder, Major/drug therapy , Oxidative Stress , Reactive Oxygen Species
Hepatopulmonary syndrome (HPS) is a rare complication of liver disease characterized by intrapulmonary vascular dilatations leading to arterial hypoxemia. We present the case of a 59-year-old female with a past medical history of bilateral breast cancer status post mastectomy who presented with progressive dyspnea on exertion and fatigue. A comprehensive diagnostic workup was conducted to exclude other cardiac, pulmonary, and systemic etiologies. She was diagnosed with autoimmune hepatitis along with chronic hepatitis C. Echocardiography revealed characteristic findings of intrapulmonary shunting characteristic of HPS. The patient showed improvement in pulmonary symptoms and oxygenation status following the initiation of steroid therapy. Although corticosteroids are not the definitive treatment for HPS, they were considered a supportive measure in this case. However, it is important to note that liver transplantation remains the definitive treatment for HPS. This case underscores the importance of echocardiography and the potential role of supportive measures, like corticosteroids, in managing HPS-related symptoms, particularly in patients with autoimmune hepatitis, as a bridging therapy while awaiting liver transplantation.
This case report presents a rare and unique instance of a 70-year-old morbidly obese female with type 2 diabetes mellitus and bilateral lymphedema, who presented with fever and expressive aphasia, initially suspected to be a stroke. A negative CT scan prompted the performance of an MRI, which revealed suggestive imaging findings of herpes encephalitis. Following the MRI, the patient experienced seizures and required intubation in the intensive care unit. Subsequently, a lumbar puncture was performed, confirming the diagnosis of herpes simplex virus (HSV) meningoencephalitis. Prompt initiation of acyclovir therapy led to an improvement in aphasia, ultimately allowing for extubation and transfer to the general ward. The rarity of this case lies in the unusual manifestation of Broca's aphasia caused by HSV, which is not typically associated with this neurological deficit. This report highlights the importance of considering herpes encephalitis as a potential etiology in patients presenting with atypical neurological symptoms, even in the absence of typical radiological findings. Early diagnosis and appropriate management with acyclovir are crucial in improving outcomes in such cases.
HYPOTHESIS: This review article represents a brief layout of the risk factors and pathophysiology responsible for obesity, customary treatment strategies, and nanotechnology-based nutraceutical for the therapeutics of obesity. EXPERIMENTS: An exhaustive search of the literature was done for this purpose, using Google Scholar, PubMed, and ScienceDirect databases. A literature study was conducted using publications published in peer-reviewed journals between 2000 and 2022. FINDINGS: This was revealed that risk factors responsible for obesity were genetic abnormalities and environmental and socio-economic factors. Several research articles published between 2000 and 2022 were based on phytoconstituents-based nanoformulation for obesity therapeutics and, therefore, have been systematically compiled in this review. Various nutraceuticals like Garcinia cambogia, quercetin, resveratrol, capsaicin, Capsicum, Curcuma longa, Camella Sinensis, Zingiber officinalis, Citrus aurantium, Aegle marmelos, Coffea canephora, Asparagus officinalis, Gardenia jasminoides, Catha edulis, Clusia nemroisa, Rosmarinus officinalis, Cirsium setidens, Betula platyphylla, Tripterygium wilfordi possessing anti-obesity actions are discussed in this review along with their patents, clinical trials as well as their nanoformulation available. CONCLUSION: This review illustrates that nanotechnology has a great propensity to impart a promising role in delivering phytochemicals and nutraceuticals in managing obesity conditions and other related disorders.
Citrus , Dietary Supplements , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Obesity/drug therapy , Nanotechnology
Several experimental studies have linked adenosine's neuroprotective role in cerebral ischemia. During ischemia, adenosine is formed due to intracellular ATP breakdown into ADP, further when phosphate is released from ADP, the adenosine monophosphate is formed. It acts via A1, A2, and A3 receptors found on neurons, blood vessels, glial cells, platelets, and leukocytes. It is related to various effector systems such as adenyl cyclase and membrane ion channels via G-proteins. Pharmacological manipulation of adenosine receptors by agonists (CCPA, ADAC, IB-MECA) increases ischemic brain damage in various in vivo and in vitro models of cerebral ischemia whereas, agonist can also be neuroprotective. Mainly, receptor antagonists (CGS15943, MRS1706) indicated neuroprotection. Later, various studies also revealed that the downregulation or upregulation of specific adenosine receptors is necessary during the recovery of cerebral ischemia by activating several downstream signaling pathways. In the current review, we elaborate on the dual roles of adenosine and its receptor subtypes A1, A2, and A3 and their involvement in the pathobiology of cerebral ischemic injury. Adenosine-based therapies have the potential to improve the outcomes of cerebral injury patients, thereby providing them with a more optimistic future.
Adenosine , Brain Ischemia , Humans , Adenosine/pharmacology , Receptors, Purinergic P1 , Brain Ischemia/drug therapy , Ischemia/drug therapy , Adenosine Diphosphate
Glycosylphosphatidylinositol (GPI) functions to anchor certain proteins to the cell surface. Although defects in GPI biosynthesis can result in a wide range of phenotypes, most affected patients present with neurological abnormalities and their diseases are grouped as inherited-GPI deficiency disorders. We present two siblings with global developmental delay, brain anomalies, hypotonia, and contractures. Exome sequencing revealed a homozygous variant, NM_001035005.4:c.90dupC (p.Phe31Leufs*3) in C18orf32, a gene not previously associated with any disease in humans. The encoded protein is known to be important for GPI-inositol deacylation. Knockout of C18orf32 in HEK293 cells followed by a transfection rescue assay revealed that the PIPLC (Phosphatidylinositol-Specific Phospholipase C) sensitivity of GPI-APs (GPI-anchored proteins) was restored only by the wild type and not the mutant C18orf32. Immunofluorescence revealed that the mutant C18orf32 was localized to the endoplasmic reticulum and was also found as aggregates in the nucleus. In conclusion, we identified a pathogenic variant in C18orf32 as the cause of a novel autosomal recessive neurodevelopmental disorder with hypotonia and contractures. Our results demonstrate the importance of C18orf32 in the biosynthesis of GPI-anchors, the molecular impact of the variant on the protein function, and add a novel candidate gene to the existing repertoire of genes implicated in neurodevelopmental disorders.
Contracture , Muscle Hypotonia , Nervous System Malformations , Neurodevelopmental Disorders , Contracture/genetics , Contracture/metabolism , Glycosylphosphatidylinositols/metabolism , HEK293 Cells , Humans , Muscle Hypotonia/genetics , Nervous System Malformations/genetics , Nervous System Malformations/metabolism , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/metabolism
The Kennedy pathways catalyse the de novo synthesis of phosphatidylcholine and phosphatidylethanolamine, the most abundant components of eukaryotic cell membranes. In recent years, these pathways have moved into clinical focus because four of ten genes involved have been associated with a range of autosomal recessive rare diseases such as a neurodevelopmental disorder with muscular dystrophy (CHKB), bone abnormalities and cone-rod dystrophy (PCYT1A) and spastic paraplegia (PCYT2, SELENOI). We identified six individuals from five families with bi-allelic variants in CHKA presenting with severe global developmental delay, epilepsy, movement disorders and microcephaly. Using structural molecular modelling and functional testing of the variants in a cell-based Saccharomyces cerevisiae model, we determined that these variants reduce the enzymatic activity of CHKA and confer a significant impairment of the first enzymatic step of the Kennedy pathway. In summary, we present CHKA as a novel autosomal recessive gene for a neurodevelopmental disorder with epilepsy and microcephaly.
Choline Kinase , Epilepsy , Microcephaly , Nervous System Malformations , Neurodevelopmental Disorders , Alleles , Choline Kinase/genetics , Epilepsy/genetics , Humans , Microcephaly/complications , Microcephaly/genetics , Nervous System Malformations/genetics , Neurodevelopmental Disorders/genetics
Free radical or oxidative stress may be a fundamental mechanism underlying several human neurologic diseases. Therapy using free radical scavengers (antioxidants) has the potential to prevent, delay, or ameliorate many neurologic disorders. However, the biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases. In vitro and animal model studies support the potential beneficial role of various antioxidant compounds in neurological disease. Antioxidants generally play an important role in reducing or preventing the cell damage and other changes which occur in the cells like mitochondrial dysfunction, DNA mutations, and lipid peroxidation in the cell membrane. Based on their mechanism of action, antioxidants can be used to treat various neurological disorders like Huntington's disease, Alzheimer's disease, and Parkinson's disease. Vitamin E has a scavenging action for reactive oxygen species (ROS) and also prevents the lipid peroxidation. Creatine generally reduces the mitochondrial dysfunction in Parkinson's disease (PD) patients. Various metal chelators are used in PD for the prevention of accumulation of the metals. Superoxidase dismutase (SOD), lipases, and proteases act as repair enzymes in patients with AD. Accordingly, the antioxidant defense system is found to be most useful for treating various neurological disorders.
Neurodegenerative Diseases , Parkinson Disease , Animals , Antioxidants/metabolism , Humans , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Oxidative Stress , Parkinson Disease/drug therapy , Reactive Oxygen Species/metabolism
The first case of coronavirus illness was discovered in Wuhan, China, in January 2020 and quickly spread worldwide within the next couple of months. The condition was initially only linked with respiratory disorders. After the evolution of various variants of the SARS-CoV-2, the critical impact of the virus spread to multiple organs and soon, neurological disorder manifestations started to appear in the infected patients. The review is focused on the manifestation of various neurological disorders linked with both the central nervous system and peripheral nervous system. Disorders such as cytokine release syndrome, encephalitis, acute stroke, and Bell's palsy are given specific attention and psychological manifestations are also investigated. For a clear conclusion, cognitive impairment, drug addiction disorders, mood and anxiety disorders, and post-traumatic stress disorder are all fully examined. The association of the SARS-CoV-2 with neurological disorders and pathway is yet to be clear. For better understanding, the explanation of the possible mechanism of viral infection influencing the nervous system is also attempted in the review. While several vaccines and drugs are already involved in treating the SARS-CoV-2 condition, the disease is still considered fatal and more likely to leave permanent neurological damage, which leads to an essential requirement for more research to explore the neurological toll of the COVID-19 disease.
COVID-19 , Nervous System Diseases , Stroke , Central Nervous System , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , SARS-CoV-2
The COVID-19 lockdown has led all the citizens (mobile subscribers) of India to stay at home and rather work from home. The people have started consuming more channel utilization (in mobile communication) through a continuous long duration conversations and more internet data through more streaming content as well as logging on to work from home. It was also reflected in how data demand from residential areas rose as compared to commercial areas. Consequently the bandwidth and channel saturation has evolved out to be a severe problem thereby affecting the work performance of all online offices and multi-national companies. This research paper proposes the simulation based experimental study of DITMC technique for mitigating this effect with a special concern in North Western Rajasthan part of India. The simulation results show that significant enhancement of 60.52% in channel utilization and bandwidth optimization is possible with negligible overhead of 0.23%. This technique also enables the telecom operators to ponder research in this field that will promisingly lead to manage augmented number of mobile subscribers (independent of any lockdown period) in limited bandwidth thereby using the spectrum efficiently.
TRAPPC4-related neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (MIM# 618741) is a recently described TRAPPopathy with clinical findings of developmental delay, seizures, postnatal microcephaly, spasticity, facial dysmorphism, and cerebral and cerebellar atrophy. Muscle involvement, a frequent finding in TRAPPopathies, was observed in one individual with TRAPPC4-related disorder previously. Only a single variant, an in-frame deletion in one family has been reported outside a recurrent disease-causing variant. We report three individuals from two Indian families harboring novel bi-allelic missense variants c.191T>C and c.278C>T (NM_016146.6) in TRAPPC4 with classic clinical presentation in one and milder and later onset in the other family. We provide further evidence for muscle involvement and review the detailed phenotypic findings in individuals reported with this disorder till date.
Epilepsy , Intellectual Disability , Neurodevelopmental Disorders , Atrophy/pathology , Brain , Epilepsy/genetics , Epilepsy/pathology , Humans , Intellectual Disability/pathology , Muscles , Neurodevelopmental Disorders/pathology
Neutral sphingomyelinases have an important role in generation of ceramide and phosphorylcholine from sphingomyelins which then act as secondary messengers in various signaling pathways of the cellular machinery. They function ubiquitously with a predominant role in the central nervous system. Neutral sphingomyelinase type 3, encoded by SMPD4 gene has recently been reported to cause a severe autosomal recessive neurodevelopmental disorder with congenital arthrogryposis and microcephaly. We report a 22-month-old girl having characteristic features of neurodevelopmental delay, prenatal onset growth failure, arthrogryposis, microcephaly and brain anomalies including severe hypomyelination, simplified gyral pattern and hypoplasia of corpus callosum and brain stem. In addition, she was noted to have nystagmus and visual impairment secondary to macular dystrophy and retinal pigment epithelial stippling at posterior pole. Copy number variant analysis from trio whole exome sequencing (ES) enabled identification of a homozygous 11 kb deletion encompassing exons 18-20 of SMPD 4 gene, confirming the diagnosis of SMPD4-related disorder in her.
Arthrogryposis , Microcephaly , Nervous System Malformations , Neurodevelopmental Disorders , Arthrogryposis/genetics , Brain/diagnostic imaging , Female , Humans , Infant , Microcephaly/diagnosis , Microcephaly/genetics , Nervous System Malformations/genetics , Pregnancy
The demand for novel and renewable sources of energy has increased as a result of rapid population growth, limited sources of bioenergy, and environmental pollution, caused by excessive use of fossil fuels. The need to meet future energy demands have motivated researchers to search for alternative and sustainable sources of energy. The bioconversion of lignocellulosic waste (agricultural and food waste) into biofuels shows competitive promises. Lignocellulosic waste is easily accessible and has a large enzyme system that can be immobilised onto nano-matrices. Consequently, resulting in higher biofuel production and process efficiency. However, the excessive production cost of the current procedures, which involve physical, chemical, and enzymatic reactions, is limited. The use of nanomaterials has recently been shown to concentrate lignocellulosic waste, therefore, reviewing the quest for efficient production of sustainable and cost-effective development of bioenergy from lignocellulosic wastes. This review paper explores the advanced strategies of using nanobiotechnology to combine enzyme-conjugated nanosystems for the cost-effective production of sustainable bioenergy solutions. This research will help to develop an inexpensive, eco-friendly technology for biofuels production and also help overcome the environmental burden of lignocellulosic waste worldwide.
Studies from past years have observed various enzymes that are artificial, which are issued to mimic naturally occurring enzymes based on their function and structure. The nanozymes possess nanomaterials that resemble natural enzymes and are considered an innovative class. This innovative class has achieved a brilliant response from various developments and researchers owing to this unique property. In this regard, numerous nanomaterials are inspected as natural enzyme mimics for multiple types of applications, such as imaging, water treatment, therapeutics, and sensing. Nanozymes have nanomaterial properties occurring with an inheritance that provides a single substitute and multiple platforms. Nanozymes can be controlled remotely via stimuli including heat, light, magnetic field, and ultrasound. Collectively, these all can be used to increase the therapeutic as well as diagnostic efficacies. These nanozymes have major biomedical applications including cancer therapy and diagnosis, medical diagnostics, and bio sensing. We summarized and emphasized the latest progress of nanozymes, including their biomedical mechanisms and applications involving synergistic and remote control nanozymes. Finally, we cover the challenges and limitations of further improving therapeutic applications and provide a future direction for using engineered nanozymes with enhanced biomedical and diagnostic applications.
The polyhydroxyalkanoate was discovered almost around a century ago. Still, all the efforts to replace the traditional non-biodegradable plastic with much more environmentally friendly alternative are not enough. While the petroleum-based plastic is like a parasite, taking over the planet rapidly and without any feasible cure, its perennial presence has made the ocean a floating island of life-threatening debris and has flooded the landfills with toxic towering mountains. It demands for an immediate solution; most resembling answer would be the polyhydroxyalkanoates. The production cost is yet one of the significant challenges that various corporate is facing to replace the petroleum-based plastic. To deal with the economic constrain better strain, better practices, and a better market can be adopted for superior results. It demands for systems for polyhydroxyalkanoate production namely bacteria, yeast, microalgae, and transgenic plants. Solely strains affect more than 40% of overall production cost, playing a significant role in both upstream and downstream processes. The highly modifiable nature of the biopolymer provides the opportunity to replace the petroleum plastic in almost all sectors from food packaging to medical industry. The review will highlight the recent advancements and techno-economic analysis of current commercial models of polyhydroxyalkanoate production. Bio-compatibility and the biodegradability perks to be utilized highly efficient in the medical applications gives ample reason to tilt the scale in the favor of the polyhydroxyalkanoate as the new conventional and sustainable plastic.
Bacteria/metabolism , Polyhydroxyalkanoates , Biodegradation, Environmental , Polyhydroxyalkanoates/biosynthesis , Polyhydroxyalkanoates/chemistry
