Earthworms improve the rhizosphere micro-environment to mitigate the toxicity of microplastics to tomato (Solanum lycopersicum).

Microplastics (MPs) are widespread in agricultural soil, potentially threatening soil environmental quality and plant growth. However, toxicological research on MPs has mainly been limited to individual components (such as plants, microbes, and animals), without considering their interactions. Here, we examined earthworm-mediated effects on tomato growth and the rhizosphere micro-environment under MPs contamination. Earthworms (Eisenia fetida) mitigated the growth-inhibiting effect of MPs on tomato plant. Particularly, when exposed to environmentally relevant concentrations (ERC, 0.02% w/w) of MPs, the addition of earthworms significantly (p < 0.05) increased shoot and root dry weight by 12-13% and 13-14%, respectively. MPs significantly reduced (p < 0.05) soil ammonium (NH4+-N) (0.55-0.69 mg/kg), nitrate nitrogen (NO3--N) (7.02-8.65 mg/kg) contents, and N cycle related enzyme activities (33.47-42.39 µg/h/g) by 37.7-50.9%, 22.6-37.2%, and 34.2-48.0%, respectively, while earthworms significantly enhanced (p < 0.05) inorganic N mineralization and bioavailability. Furthermore, earthworms increased bacterial network complexity, thereby enhancing the robustness of the bacterial system to resist soil MPs stress. Meanwhile, partial least squares modelling showed that earthworms significantly influenced (p < 0.01) soil nutrients, which in turn significantly affected (p < 0.01) plant growth. Therefore, the comprehensive consideration of soil ecological composition is important for assessing MPs ecological risk.

Molecular identification of Proteus mirabilis, Vibrio species leading to CRISPR-Cas9 modification of tcpA and UreC genes causing cholera and UTI.

Heavy metal accumulation increases rapidly in the environment due to anthropogenic activities and industrialization. The leather and surgical industry produces many contaminants containing heavy metals. Cadmium, a prominent contaminant, is linked to severe health risks, notably kidney and liver damage, especially among individuals exposed to contaminated wastewater. This study aims to leverage the natural cadmium resistance mechanisms in bacteria for bioaccumulation purposes. The industrial wastewater samples, characterized by an alarming cadmium concentration of 29.6 ppm, 52 ppm, and 76.4 ppm-far exceeding the recommended limit of 0.003 ppm-were subjected to screening for cadmium-resistant bacteria using cadmium-supplemented media with CdCl2. 16S rRNA characterization identified Vibrio cholerae and Proteus mirabilis as cadmium-resistant bacteria in the collected samples. Subsequently, the cadmium resistance-associated cadA gene was successfully amplified in Vibrio species and Proteus mirabilis, revealing a product size of 623 bp. Further analysis of the identified bacteria included the examination of virulent genes, specifically the tcpA gene (472 bp) associated with cholera and the UreC gene (317 bp) linked to urinary tract infections. To enhance the bioaccumulation of cadmium, the study proposes the potential suppression of virulent gene expression through in-silico gene-editing tools such as CRISPR-Cas9. A total of 27 gRNAs were generated for UreC, with five selected for expression. Similarly, 42 gRNA sequences were generated for tcpA, with eight chosen for expression analysis. The selected gRNAs were integrated into the lentiCRISPR v2 expression vector. This strategic approach aims to facilitate precise gene editing of disease-causing genes (tcpA and UreC) within the bacterial genome. In conclusion, this study underscores the potential utility of Vibrio species and Proteus mirabilis as effective candidates for the removal of cadmium from industrial wastewater, offering insights for future environmental remediation strategies.

The natural breakthrough: phytochemicals as potent therapeutic agents against spinocerebellar ataxia type 3.

There is no FDA-approved drug for neurological disorders like spinocerebellar ataxia type 3. CAG repeats mutation in the ATXN3 gene, causing spinocerebellar ataxia type 3 disease. Symptoms include sleep cycle disturbance, neurophysiological abnormalities, autonomic dysfunctions, and depression. This research focuses on drug discovery against ATXN3 using phytochemicals of different plants. Three phytochemical compounds (flavonoids, diterpenoids, and alkaloids) were used as potential drug candidates and screened against the ATXN3 protein. The 3D structure of ATXN3 protein and phytochemicals were retrieved and validation of the protein was 98.1% Rama favored. The protein binding sites were identified for the interaction by CASTp. ADMET was utilized for the pre-clinical analysis, including solubility, permeability, drug likeliness and toxicity, and chamanetin passed all the ADMET properties to become a lead drug candidate. Boiled egg analysis attested that the ligand could cross the gastrointestinal tract. Pharmacophore analysis showed that chamanetin has many hydrogen acceptors and donors which can form interaction bonds with the receptor proteins. Chamanetin passed all the screening analyses, having good absorption, no violation of Lipinski's rule, nontoxic properties, and good pharmacophore properties. Chamanetin was one of the lead compounds with a - 7.2 kcal/mol binding affinity after screening the phytochemicals. The stimulation of ATXN3 showed stability after 20 ns of interaction in an overall 50 ns MD simulation. Chamanetin (Flavonoid) was predicted to be highly active against ATXN3 with good drug-like properties. In-silico active drug against ATXN3 from a plant source and good pharmacokinetics parameters would be excellent drug therapy for SC3, such as flavonoids (Chamanetin).

Effects of polystyrene, polyethylene, and polypropylene microplastics on the soil-rhizosphere-plant system: Phytotoxicity, enzyme activity, and microbial community.

The widespread presence of soil microplastics (MPs) has become a global environmental problem. MPs of different properties (i.e., types, sizes, and concentrations) are present in the environment, while studies about the impact of MPs having different properties are limited. Thus, this study investigated the effects of three common polymers (polystyrene, polyethylene, and polypropylene) with two concentrations (0.01% and 0.1% w/w) on growth and stress response of lettuce (Lactuca sativa L.), soil enzymes, and rhizosphere microbial community. Lettuce growth was inhibited under MPs treatments. Moreover, the antioxidant system, metabolism composition, and phyllosphere microbiome of lettuce leaves was also perturbed. MPs reduced phytase activity and significantly increased dehydrogenase activity. The diversity and structure of rhizosphere microbial community were disturbed by MPs and more sensitive to polystyrene microplastics (PSMPs) and polypropylene microplastics (PPMPs). In general, the results by partial least squares pathway models (PLS-PMs) showed that the presence of MPs influenced the soil-rhizosphere-plant system, which may have essential implications for assessing the environmental risk of MPs.

Uncovering the impact of SARS-CoV2 spike protein variants on human receptors: A molecular dynamics docking and simulation approach.

BACKGROUND: The SARS-CoV-2 pandemic, caused by the novel coronavirus, has posed a significant global health threat since its emergence in late 2019. The World Health Organization declared the outbreak a pandemic on March 11, 2020, due to its rapid global spread and impact on public health. New variants have raised concerns about their potential impact on the transmission of the virus and the effectiveness of current diagnostic tools, treatments, and vaccines. This study aims to investigate the effect of new variants in Pakistani virus strains on human receptors, specifically ACE2 and NRP1. In-silico analysis provides a powerful tool to analyze the potential impact of new variants on protein structure, function, and interactions. OBJECTIVES: The SARS-CoV-2 virus is evolving quickly. After being exposed in Wuhan, SARS-CoV-2 underwent numerous mutations, leading to several variants' emergence. These variants stabilize the interaction of spike protein with human receptors ACE2 and NRP1. The study aims to check the molecular effect of these variants on human receptors using the in-silico approach. MATERIAL AND METHODS: We use in-silico mutational tools to analyze new variants in SARS-CoV-2 and to check the molecular interaction of spike protein with human receptors (ACE2 and NRP1). Genomic sequences of 41 SARS-CoV-2 strains were sequenced using Ion Torrent (NGS) and submitted to the GISAID database. Spike protein of SARS-CoV-2 sequence trimmed and translated into a protein sequence using ExPasy. We used multiple sequence alignments to check for variants in the spike protein of strains. We utilized mutation tools such as Mupro, SIFT, SNAP2, and Mutpred2.3D structures of SARS-CoV-2 spike proteins (wild and mutated) to analyze further the mutations, ACE2 and NRP1 modelled by the ITASSER protein modelling server. Interactions of spike proteins (wild and mutant) analyzed by MD Docking, Simulation, and MMGBSA RESULTS: Variants I210T, V213G, S371F, S373P, T478K, F486V, Y505H, and D796Y were identified in SARS-CoV-2 Pakistani strains' spike protein. Variant Y505H were found to affect protein function. MD Docking, MMGBSA and MD simulation revealed that these variants increased spike protein's binding affinity with human receptors (ACE2 and NRP1). MD simulation revealed that mutated spike protein stabilized earlier than wild when interacting with ACE2 after 40 ns and interaction with NRP1 stabilized after 30 ns for mutated spike protein compared to wild. CONCLUSION: These variants in Pakistani strains of SARS-CoV-2 are increasing the stability of spike protein with human receptors. These findings provide insight into how the SARS-CoV-2 virus evolves and adapts to human hosts. This information may help develop strategies to control the virus's spread and develop effective treatments and vaccines in the future.

Survey of knowledge and attitude towards fibromyalgia among physicians in Karachi, Pakistan.

Objectives: Our study aims to assess knowledge and understanding of FM among doctors employed at a tertiary care hospital in Karachi, Pakistan with a focus on its diagnostic criteria, treatment modalities, and general knowledge of symptoms. Study Design: Cross-sectional Study. Methods: Our cross-sectional study recruited participants through convenience sampling. A total of 104 participants responded, which included (a) House Officers, (b) Medical Officers, and (c) Residents. A structured questionnaire was used, and an electronic form was generated which was then emailed to the participants to acquire their responses. Results: The majority (66.3%) of our respondents were female and the median age was 26 years. A majority (93.3%) accepted FM as a separate and distinct clinical identity, and 79.8% were confident in recognizing its general symptoms. Widespread pain (95.2%) and fatigue (80.8%) were correctly identified as most commonly observed symptoms. Moreover, 68.3% of respondents possessed no knowledge of both ACR 1990 and 2010 diagnostic criteria for FM. Of those aware, majority favored using the most recent ACR 2010 criteria (72.7%). Majority of our respondents (75%) preferred using pharmaceutical and non-pharmaceutical interventions simultaneously in the treatment. Conclusions: Our study indicates that while physicians have satisfactory knowledge of the symptoms and treatment modalities of FM, a knowledge gap concerning its diagnostic criteria exists. Proper treatment can only be successful when physicians successfully diagnose FM, therefore, future training programs should use this fact as a stepping stone for advances in its healthcare.

Prevalence, determinants of chronic rhinosinusitis and its impact on quality of life among students in Karachi, Pakistan.

Background: Chronic rhinosinusitis (CRS) is a common public health issue among students. Methodology:  A total of 300 undergraduate students were selected through multistage cluster sampling from three public-sector universities. Sino-nasal Outcome Test (SNOT-22) and Rhinosinusitis Disability Index (RSDI) were used for determining the quality of life. Chi-square and independent t-test were used. Results: About 46% and 54% (p = 0.001) of social science and health science students were suffering from CRS, respectively. Around 7% and 9% of CRS patients had poor quality of life according to SNOT-22 and RSDI, respectively (p = 0.042 and p = 0.032, respectively). Conclusion: Quality of life was affected in all domains of SNOT-22 and RSDI.

Rhinosinusitis is a common problem in society. Students are affected commonly because of exposure and low awareness. This study determines the burden of flu among medical and nonmedical students. We conducted the survey in public-sector universities. Results of study found that medical students were more suffering from chronic flu. This flu affected the social and family life. Common symptoms are pain in the face, pain in the eye and continuous headache. There is need to increase awareness among students regarding flu.

Design of a novel multiple epitope-based vaccine: An immunoinformatics approach to combat SARS-CoV-2 strains.

BACKGROUND: Since the SARS-CoV-2 outbreak in December 2019 in Wuhan, China, the virus has infected more than 153 million individuals across the world due to its human-to-human transmission. The USA is the most affected country having more than 32-million cases till date. Sudden high fever, pneumonia and organ failure have been observed in infected individuals. OBJECTIVES: In the current situation of emerging viral disease, there is no specific vaccine, or any therapeutics available for SARS-CoV-2, thus there is a dire need to design a potential vaccine to combat the virus by developing immunity in the population. The purpose of present study was to develop a potential vaccine by targeting B and T-cell epitopes using bioinformatics approaches. METHODS: B- and T-cell epitopes are predicted from novel M protein-SARS-CoV-2 for the development of a unique multiple epitope vaccine by applying bioinformatics approaches. These epitopes were analyzed and selected for their immunogenicity, antigenicity scores, and toxicity in correspondence to their ability to trigger immune response. In combination to epitopes, best multi-epitope of potential immunogenic property was constructed. The epitopes were joined using EAAAK, AAY and GPGPG linkers. RESULTS: The constructed vaccine showed good results of worldwide population coverage and promising immune response. This constructed vaccine was subjected to in-silico immune simulations by C-ImmSim. Chimeric protein construct was cloned into PET28a (+) vector for expression study in Escherichia coli using snapgene. CONCLUSION: This vaccine design proved effective in various computer-based immune response analysis as well as showed good population coverage. This study is solely dependent on developing M protein-based vaccine, and these in silico findings would be a breakthrough in the development of an effective vaccine to eradicate SARS-CoV-2 globally.

Detection of glaucoma using retinal fundus images: A comprehensive review.

Content-based image analysis and computer vision techniques are used in various health-care systems to detect the diseases. The abnormalities in a human eye are detected through fundus images captured through a fundus camera. Among eye diseases, glaucoma is considered as the second leading case that can result in neurodegeneration illness. The inappropriate intraocular pressure within the human eye is reported as the main cause of this disease. There are no symptoms of glaucoma at earlier stages and if the disease remains unrectified then it can lead to complete blindness. The early diagnosis of glaucoma can prevent permanent loss of vision. Manual examination of human eye is a possible solution however it is dependant on human efforts. The automatic detection of glaucoma by using a combination of image processing, artificial intelligence and computer vision can help to prevent and detect this disease. In this review article, we aim to present a comprehensive review about the various types of glaucoma, causes of glaucoma, the details about the possible treatment, details about the publicly available image benchmarks, performance metrics, and various approaches based on digital image processing, computer vision, and deep learning. The review article presents a detailed study of various published research models that aim to detect glaucoma from low-level feature extraction to recent trends based on deep learning. The pros and cons of each approach are discussed in detail and tabular representations are used to summarize the results of each category. We report our findings and provide possible future research directions to detect glaucoma in conclusion.

Modeling global geometric spatial information for rotation invariant classification of satellite images.

The classification of high-resolution satellite images is an open research problem for computer vision research community. In last few decades, the Bag of Visual Word (BoVW) model has been used for the classification of satellite images. In BoVW model, an orderless histogram of visual words without any spatial information is used as image signature. The performance of BoVW model suffers due to this orderless nature and addition of spatial clues are reported beneficial for scene and geographical classification of images. Most of the image representations that can compute image spatial information as are not invariant to rotations. A rotation invariant image representation is considered as one of the main requirement for satellite image classification. This paper presents a novel approach that computes the spatial clues for the histograms of BoVW model that is robust to the image rotations. The spatial clues are calculated by computing the histograms of orthogonal vectors. This is achieved by calculating the magnitude of orthogonal vectors between Pairs of Identical Visual Words (PIVW) relative to the geometric center of an image. The comparative analysis is performed with recently proposed research to obtain the best spatial feature representation for the satellite imagery. We evaluated the proposed research for image classification using three standard image benchmarks of remote sensing. The results and comparisons conducted to evaluate this research show that the proposed approach performs better in terms of classification accuracy for a variety of datasets based on satellite images.

Retraction: Neurogenic Stunned Myocardium: A Literature Review.

[This retracts the article DOI: 10.7759/cureus.3129.].

Retraction: An Overview of the Pathology and Emerging Treatment Approaches for Interstitial Cystitis/Bladder Pain Syndrome.

[This retracts the article DOI: 10.7759/cureus.3321.].

Symptomatic involvement of the stomach and duodenum as initial presentation of AL amyloidosis.

Primary systemic or amyloid light chain (AL) amyloidosis is a multisystem disorder with myriad presentations. Although it can involve the upper gastrointestinal tract in 8% of cases, symptomatic involvement is exceedingly rare. We chronicle here a case of postprandial epigastric pain associated with AL amyloidosis involving the stomach and duodenum. Pathological examination of endoscopic biopsy using Congo red staining confirmed the diagnosis. In order to establish the underlying aetiology of AL amyloidosis, the patient underwent extensive workup. Eventually, she was diagnosed with multiple myeloma based on the standard set of investigations. This paper underscores the importance of clinical suspicion of amyloidosis in patients presenting with non-specific gastrointestinal symptoms and highlights the role of endoscopic biopsy to confirm the amyloid deposition. Since gastrointestinal amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are particularly warranted.

Hepatitis B virus reactivation following imatinib therapy: A comparative review of 9 cases.

Patients undergoing cytotoxic or immunosuppressive therapy for cancer have an established predilection for hepatitis B virus reactivation; however, the risk associated with newer molecularly targeted agents has not been well investigated. Imatinib, a small molecule tyrosine kinase inhibitor, induces rapid and sustained clinical benefit by inhibiting a number of signaling pathways, including BCR-ABL and c-KIT. We report the case of a patient who developed hepatitis B virus reactivation while receiving imatinib therapy for gastrointestinal stromal tumor. Furthermore, a structured literature search of the medical databases consisting of MEDLINE and PubMed was performed using the terms "hepatitis B", "reactivation", and "imatinib". The search identified nine case reports only. The data on patients' characteristics, epidemiology, clinical features, comorbid conditions, diagnosis, and management are summarized. Imatinib-associated hepatitis B virus reactivation was reported in seven patients with chronic myeloid leukemia, one with desmoid tumor, and one with gastrointestinal stromal tumor. This review serves to outline our current understanding of the epidemiology, risk factors, and pathophysiology of chronic hepatitis B virus reactivation secondary to imatinib therapy as well as the current approaches to diagnosis and management of this condition. We aim to increase awareness about this possible association and advocate for hepatitis B virus screening prior to imatinib therapy, especially in patients who are at increased risk for chronic hepatitis B virus infection.

Lafora Disease Masquerading as Hepatic Dysfunction.

Lafora disease is fatal intractable progressive myoclonic epilepsy. It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. We chronicle here an unusual case of an asymptomatic young male soccer player who presented with elevated liver enzymes. Neurological examination was unremarkable. The diagnostic workup for hepatitis, infectious etiologies, autoimmune disorders, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and other related diseases was inconclusive. He subsequently underwent an uneventful percutaneous liver biopsy. Based on the pathognomonic histopathological findings, Lafora disease was considered the likely etiology. The present study is a unique illustration of this rare disorder initially manifesting with abnormal liver enzymes. It underscores the importance of clinical suspicion of Lafora disease in cases with unexplained hepatic dysfunction. Prompt liver biopsy and genetic testing should be performed to antedate the onset of symptoms in these patients.

The risky side of weight-loss dietary supplements: disrupting arrhythmias causing sudden cardiac arrest.

The worldwide increasing prevalence of obesity has led to a corresponding increase in consumption of weight-loss dietary supplements. The limited de novo regulatory oversight and under-reported toxicity profile of these products reflect as a constellation of newer adverse events. We chronicle here the case of an otherwise healthy woman who developed ventricular fibrillation-related cardiac arrest secondary to the use of Hydroxycut and Metaboost preparations. Published medical literature has a handful of case reports associating these products with potentially life-threatening cardiac arrhythmias. The proposed hypothesis implicates ingredients of these diet aids to have proarrhythmogenic effects. Physicians should remain vigilant for possible cardiotoxicity associated with the use of dietary supplements. Individuals who are at risk of developing cardiac arrhythmias should avoid herbal weight-loss formulas, given the serious clinical implications. Additionally, this paper highlights the need for a proper framework to delineate the magnitude and scope of this association.

Small Bowel Perforation Secondary to Esophageal Stent Migration: A Comparative Review of Six Cases.

Esophageal stent placement is used to treat benign strictures, esophageal perforations, fistulas and for palliative therapy of esophageal cancer. Although it is a safe and effective method, complications are increasing the morbidity and mortality rate. Small bowel perforation as a result of esophageal stent migration is a remarkably rare occurrence. We report one case from our clinical experience and undertake a review of the previously reported cases retrieved from the PubMed. A total of six cases were found accessible. Abdominal pain was the common clinical presentation. The mean time from stent placement to perforation was 3.4 months (range, two weeks to 12 months). The jejunum was the frequently perforated portion of the small bowel. Surgical intervention was the mainstay of treatment. This comparative review illustrates that clinicians should remain vigilant for small bowel perforation in patients with esophageal stent placement. Further studies are required to delineate the magnitude and scope of this association.

An Overview of the Pathology and Emerging Treatment Approaches for Interstitial Cystitis/Bladder Pain Syndrome.

Our article will discuss bladder pain syndrome (BPS), which is the presence of chronic suprapubic pain to bladder filling accompanied by other urinary symptoms, such as frequency, urgency, discomfort with filling, and relief with emptying of the bladder in the absence of infections or other pathology. It is mostly seen in females and occurs in 0.06%-30% of the population. Some of the proposed mechanisms causing BPS include damage to the bladder lining, a problem manifesting in the pelvic musculature, endocrine, neurological, allergic, autoimmune system, and inflammatory system; however, a definite cause has not been yet identified. Two types of this syndrome have been identified, ulcerative and non-ulcerative. In the ulcerative disease, areas of reddened mucosa associated with small vessels radiating towards a central scar (at times, covered by a small clot or fibrin) can be seen. In the non-ulcerative type, a normal bladder mucosa can be observed initially, and the subsequent development of glomerulations after hydrodistension is considered a definite sign of its diagnosis. The diagnosis of BPS is primarily clinical; however, cystoscopy and biopsy can also be performed, if needed. Finally, we will discuss in detail the treatment of BPS, which constitutes three different guidelines (The European Association of Urology (EAU) Guidelines 2017, the American Urology Association (AUA) Guidelines 2014, and The Royal College of Obstetricians and Gynecologists (RCOG) in conjunction with the British Society of Urogynaecologists (BSUG) Guidelines 2016). All are proposing different types of therapy, including conservative, medical, and surgical treatment.

American Heart Association High Blood Pressure Protocol 2017: A Literature Review.

Hypertension is the most prevalent clinical symptom arising from various cardiovascular disorders. Likewise, it is considered a precursor or sequelae to the development of acute coronary artery disease and congestive heath failure (CHF). Hypertension has been considered a cardinal criterion to determine cardiovascular function. According to the World Health Organization (WHO) global observatory data, hypertension causes more than 7.5 million deaths a year, about 12.8% of the total human mortality. Similarly, the Center for Disease Control (CDC) states that 35% of the American adults have been estimated to have a persistently high blood pressure, which makes it about one in every three adults. Hypertension is a modifiable symptom that can be managed through pharmacological and non-pharmacological methods and standard protocols set forth by the American Heart Association (AHA). With new findings from various clinical trials related to the management of hypertension, new developments and recommendations have been made to update the previously established protocols for hypertension. This article aims to discuss and dissect the modern updates of hypertension management as comprehensively elaborated in the 2017 Hypertension Clinical Practice Guidelines.

Management of Orthostatic Hypotension: A Literature Review.

In the older population, especially the hospitalized patients who are prone to dehydration and hypovolemia, orthostatic hypotension (OH) presents as a debilitating disease. How different pharmacological and non-pharmacological interventions affect the incapacitating symptoms (falls and episodes of syncope), morbidity, and mortality related to OH has become a topic of debate. OH can predispose to ischemic heart disease (IHD). A non-pharmacological approach consisting of mobilization, early lifestyle changes, and therapeutic maneuvers is the first choice in the management of these patients. Individuals with persistent symptoms require pharmaceutical therapy to increase blood volume and peripheral vascular resistance. This article summarizes the management of OH that is vital to cope with the needs of the growing geriatric populations.