Revisiting acute retinal pigment epitheliitis (Krill disease).

We reevaluate acute retinal pigment epitheliitis (ARPE) first described by Krill and Deutman in 1972, integrating a meticulous literature review with advanced multimodal imaging analyses. Our review included 98 eyes from 86 published cases diagnosed with ARPE. We scrutinized ARPE's clinical presentations, variability, and imaging characteristics, revealing that a large majority (90 %) of cases previously diagnosed as ARPE align more closely with other retinal disorders based on modern diagnostic criteria and imaging techniques. Only a small fraction (5 eyes) did not fit into any known categories, casting doubt on ARPE's distinct existence. This underscores the critical role of multimodal imaging in redefining our understanding of macular diseases and challenges the historical classification of ARPE as a unique clinical entity.

Comprehensive Systematic Review of Breast Implant Illness: Symptoms, Management, and Long-Term Outcomes.

BACKGROUND: Breast augmentation using silicone implants is common, with over 300,000 annual US surgeries. It was initially approved in 1962, there were safety concerns with the use of silicone implants, leading to a 1992-2006 FDA moratorium. Recently, Breast Implant Illness (BII) was described as a cluster of symptoms associated with silicone implants, with a lack of diagnostic criteria, which increased the likelihood of implant removal and a variety of treatment options. This comprehensive review aims to shed light on the extent, symptoms, management, and outcomes of BII. METHODS: Multiple electronic databases were systematically searched in May 2023 for studies on Breast Implant Illness utilizing terms related to BII and its symptoms, diagnosis, and treatment. Out of 1204 studies, 20 met the inclusion criteria and were included in the systematic review. The Newcastle-Ottawa Scale for the included cohort prospective and retrospective studies, and the tool for evaluating the methodological quality of case reports and case series were utilized during quality assessment. RESULTS: There were 20 papers on Breast Implant Illness published between 1995 and 2022, including a peak of papers published in 2020 and 2022. The majority of the studies came from the USA, with a variety of research methods, including case reports. Reports of arthralgia and fatigue were common findings. These symptoms were frequently alleviated by surgical procedures such as en bloc explantation and capsulectomy, highlighting the intricacy of the problem and the need for individualized treatment plans. CONCLUSION: The review underscores the critical need for further research into BII, advocating for a multidisciplinary strategy that prioritizes patient safety, informed decision-making, and comprehensive care. As the medical community progresses in understanding and managing BII, emphasizing evidence-based practices and patient-provider communication will be essential in addressing this complex condition effectively. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Identification and prevalence of ticks infesting small ruminants of Fort Munro region in South Punjab, Pakistan.

Fort Munro is a hill station in Southern Punjab the residents of whom are heavily dependent upon livestock for their living but ticks are a big treat for the livestock. The purpose of this study was to ascertain the tick infestation among the small ruminants of Fort Munro. Ticks (N = 273) were collected from 333 animals (165 goats and 168 sheep) during August and September 2022. Two tick genera Hyalomma and Rhipicephalus were identified. Rhipicephalus was most abundant tick genera (78.02%) followed by Hyalomma (21.98%).Tick distribution significantly varied with the host: Rhipicephalus ticks were more frequently infesting goats while Hyalomma were more common on sheep. For both hosts, tick infestation varied with the sampling sites and male animals were significantly more infested than females. Five tick species were infesting goats with the following relative abundance: Rhipicephalus (R.) senegalensis (39.20%) > R. sanguineus (36.8%) > R. appendiculatus (10.40%) > R. turanicus (8%) > R. guilhoni (5.6%). Rhipicephalus senegalensis (41.22%) was also the most common tick species infesting sheep followed by Hyalomma (H.) marginatum (29.73%), R. guilhoni (18.24%), H. dromedarii (5.41%) and H. impeltatum (5.41%). Male ticks very more abundantly on both goats and sheep than female. Distribution of Hyalomma species also varied between the sampling sites. In conclusion, we are reporting the infestation of 3 Hyalomma and 5 Rhipicephalus in small ruminants of Fort Munro. The data generated through this study will help in developing appropriate tick control in the study area and will add to the existing knowledge regarding tick species that are infesting the small ruminants of Pakistan.

Structure based functional identification of an uncharacterized protein from Coxiella burnetii involved in adipogenesis.

Coxiella burnetii, the causative agent of Q fever, is an intracellular pathogen posing a significant global public health threat. There is a pressing need for dependable and effective treatments, alongside an urgency for further research into the molecular characterization of its genome. Within the genomic landscape of Coxiella burnetii, numerous hypothetical proteins remain unidentified, underscoring the necessity for in-depth study. In this study, we conducted comprehensive in silico analyses to identify and prioritize potential hypothetical protein of Coxiella burnetii, aiming to elucidate the structure and function of uncharacterized protein. Furthermore, we delved into the physicochemical properties, localization, and molecular dynamics and simulations, and assessed the primary, secondary, and tertiary structures employing a variety of bioinformatics tools. The in-silico analysis revealed that the uncharacterized protein contains a conserved Mth938-like domain, suggesting a role in preadipocyte differentiation and adipogenesis. Subcellular localization predictions indicated its presence in the cytoplasm, implicating a significant role in cellular processes. Virtual screening identified ligands with high binding affinities, suggesting the protein's potential as a drug target against Q fever. Molecular dynamics simulations confirmed the stability of these complexes, indicating their therapeutic relevance. The findings provide a structural and functional overview of an uncharacterized protein from C. burnetii, implicating it in adipogenesis. This study underscores the power of in-silico approaches in uncovering the biological roles of uncharacterized proteins and facilitating the discovery of new therapeutic strategies. The findings provide valuable preliminary data for further investigation into the protein's role in adipogenesis.

Optimizing fungal treatment of lignocellulosic agro-industrial by-products to enhance their nutritional value.

This study delves into the dynamic interaction between various fungal strains, substrates, and treatment durations to optimize the nutritional value of these by-products. Six fungi, including Penicillium chrysogenum, Fusarium sp., Fusarium oxysporum, Fusarium solani, Penicillium crustosum, and Cosmospora viridescens, were evaluated across three substrates: wheat straw (WS), cedar sawdust (CW), and olive pomace (OP) over treatment periods of 4, 8, and 12 weeks. The study discerned profound impacts of these fungi across multiple parameters, including cellulose variation (C.var), lignin variation (L.var), and in vitro true digestibility variation (IVTD.var). Our results demonstrated that the various fungi had a significant effect on all parameters (p < .001). Noteworthy, F. oxysporum and F. solani emerged as exemplars, displaying notable lignin degradation, cellulose liberation, and IVTD enhancement. Importantly, P. crustosum demonstrated substantial cellulose degradation, exhibiting optimal efficacy in just 4 weeks for all substrates. Notably, F. sp. excelled, yielding favorable results when treating WS. P. chrysogenum achieved optimal outcomes with 8-week treatment for WS. Both Fusarium sp. and P. chrysogenum exhibited slight cellulose release, with remarkable reduction of WS lignin compared to other substrates. Especially, WS and OP displayed superior digestibility enhancements relative to CW. It should be noted that the treatment duration further shaped these outcomes, as prolonged treatment (12 weeks) fostered greater benefits in lignin degradation and digestibility, albeit with concomitant cellulose degradation. These findings underscore the intricate balance between fungal strains, substrates, and treatment durations in optimizing the nutritional value of lignocellulosic agro-industrial by-products. The outcomes of this study lead to the enhancement in the overall value of by-products, promoting sustainable livestock feed and advancing agricultural sustainability.

Assessing the antioxidant properties of Naringin and Rutin and investigating their oxidative DNA damage effects in breast cancer.

This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness.

An evaluation of inflammatory and endothelial dysfunction markers as determinants of peripheral arterial disease in those with diabetes mellitus.

The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P < 0.05) different from each other. Therefore, it was concluded that the change in IL-6, IL-8, ICAM and VCAM can serve as an accurate diagnostic indicator and successful treatment.

The Effects of Sociodemographic Factors and BMI on Weight Stigma Among Adults With Obesity in Madinah Region, Saudi Arabia: A Cross-Sectional Analytical Study.

Introduction Weight stigma (WS), characterized by discrimination and stereotyping based on a person's weight, remains understudied in Saudi Arabia despite the country's high obesity rates. Particularly, limited research has been conducted on WS in Madinah. Understanding the factors contributing to WS in this region is crucial for developing targeted interventions to effectively address it. Hence, this study aimed to explore the effects of sociodemographic characteristics and body mass index (BMI) on WS among adults with obesity in Madinah. Methods Individuals with obesity who were seeking care at primary healthcare centers were included in this study. This research was an analytical cross-sectional study; Madinah City was divided into four areas. One primary health center from each area was randomly selected. Subsequently, a consecutive sampling technique was used to collect questionnaires from participants during the period of December 2023 to March 2024. The participants completed a self-administered electronic questionnaire, which included the Arabic-translated and validated version of the Weight Self-Stigma Questionnaire (WSSQ). Data analysis included descriptive, simple logistic regression and multiple logistic regression with forward stepwise analysis. Results A total of 383 participants completed the questionnaire, of which 225 (58.7%) were men and 158 (41.3%) were women. The analysis showed that individuals without a family history of obesity experienced higher WS levels than those with a family history [adjusted odds ratio (AOR) = 1.853, 95% confidence interval (CI): 1.010-2.844]. Moreover, individuals with obesity demonstrated the lowest WS levels than those without obesity (AOR = 0.027, 95% CI: 0.009-0.08). These findings provide insights into the association among sociodemographic factors, BMI, and WS in adults with obesity residing in Madinah, Saudi Arabia. Conclusion This study provides evidence that WS is a complex issue that is not solely determined by an individual's obesity status; rather, it is influenced by a lack of family history of obesity, which establishes the impact of social factors on WS. Therefore, comprehending the role of family dynamics and societal norms in shaping an individual's weight status is crucial in managing WS.

Facile Synthesis of 5-Bromo-N-Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo-ß-Lactamase Producing Klebsiella pneumoniae ST147.

Introduction: New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species. Methods: In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides (3a-c) by reacting 5-bromothiophene-2-sulfonamide (1) with various alkyl bromides (2) using LiH. We also synthesized a series of compounds (4a-g) from compound (3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56-72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I. Results: The compound (3b) with favourable drug candidate status, MIC of 0.39 µg/mL, and MBC of 0.78 µg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions. Conclusion: The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option.

Characterization of a thermostable protease from Bacillus subtilis BSP strain.

This study used conservative one variable-at-a-time study and statistical surface response methods to increase the yields of an extracellular thermostable protease secreted by a newly identified thermophilic Bacillus subtilis BSP strain. Using conventional optimization techniques, physical parameters in submerged fermentation were adjusted at the shake flask level to reach 184 U/mL. These physicochemical parameters were further optimized by statistical surface response methodology using Box Behnken design, and the protease yield increased to 295 U/mL. The protease was purified and characterized biochemically. Both Ca2+ and Fe2+ increased the activity of the 36 kDa protease enzyme. Based on its strong inhibition by ethylenediaminetetracetate (EDTA), the enzyme was confirmed to be a metalloprotease. The protease was also resistant to various organic solvents (benzene, ethanol, methanol), surfactants (Triton X-100), sodium dodecyl sulfate (SDS), Tween 20, Tween-80 and oxidants hydrogen per oxide (H2O2). Characteristics, such as tolerance to high SDS and H2O2 concentrations, indicate that this protease has potential applications in the pharmaceutical and detergent industries.

Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes.

This study aimed to provide an understanding of the influence of eugenol on CYP1A2, 2C9, 2D6, and 3A4 in human liver microsomes (HLM). Specific substrate for CYP1A2, 2C9, 2D6, and 3A4 were incubated in HLM with or without eugenol. The formation of their respective metabolites was assessed with HPLC analytical methods. Eugenol at 1, 10 and 100 µM levels inhibited the activity of CYP1A2 and CYP2C9 by 23.38 %, 23.57 %, 39.80 % and 62.82 %, 63.27 %, 67.70 % respectively. While, CYP2D6 and CYP3A4 activity was decreased by 40.70 %, 45.88 %, 62.68 % and 37.41 %, 42.58 % and 67.86 % at 1, 10 and 100 µM eugenol level respectively. The IC50 value of eugenol for CYP2D6 and CYP3A4 was calculated as 11.09 ± 3.49 µM and 13.48 ± 3.86 µM respectively. Potential herb-drug interactions was noted when eugenol is administered simultaneously with medications metabolized by these enzymes, most notably CYP2C9, CYP2D6 and CYP3A4.

HPLC, NMR Based Characterization, Antioxidant and Anticancer Activities of Chemical Constituents from Therapeutically Active Fungal Endophytes.

Fungi generate different metabolites some of which are intrinsically bioactive and could therefore serve as templates for drug development. In the current study, six endophytic fungi namely Aspergillus flavus, Aspergillus tubigenesis, Aspergillus oryzae, Penicillium oxalicum, Aspergillus niger and Aspergillus brasiliensis were isolated and identified from the medicinal plant, Silybum marianum. These endophytic fungi were identified through intra transcribed sequence (ITS) gene sequencing. The bioactive potentials of fungal extracts were investigated using several bioassays such as antibacterial activity by well-diffusion, MIC, MBC, anti-biofilm, antioxidant, and haemolysis. The Pseudomonas aeruginosa strain PAO1 was used to determine the antibiofilm activity. The ethyl acetate extract of Aspergillus flavus showed strong to moderate efficacy against Staphylococcus aureus, Escherichia coli, P. aeruginosa, and Bacillus spizizenii. Aspergillus flavus and Aspergillus brasiliensis exhibited significant antibiofilm activity with IC50 at 4.02 and 3.63 mg/ml while A. flavus exhibited maximum antioxidant activity of 50.8%. Based on, HPLC, LC-MS and NMR experiments kojic acid (1) and carbamic acid (methylene-4, 1-phenylene) bis-dimethyl ester (2) were identified from A. flavus. Kojic acid exhibited DPPH free radical scavenging activity with an IC50 value of 99.3 µg/ml and moderate activity against ovarian teratocarcinoma (CH1), colon carcinoma (SW480), and non-small cell lung cancer (A549) cell lines. These findings suggest that endophytic fungi are able produce promising bioactive compounds which deserve further investigation.

In silico design of peptide inhibitors for Dengue virus to treat Dengue virus-associated infections.

Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven non-structural proteins (NS1, NS2A, NS2B, NS3A, NS3B, NS4, and NS5). Dengue is a viral infection caused by the dengue virus (DENV). DENV infections are asymptomatic or produce only mild illness. However, DENV can occasionally cause more severe cases and even death. There is no specific treatment for dengue virus infections. Therapeutic peptides have several important advantages over proteins or antibodies: they are small in size, easy to synthesize, and have the ability to penetrate the cell membranes. They also have high activity, specificity, affinity, and less toxicity. Based on the known peptide inhibitor, the current study designs peptide inhibitors for dengue virus envelope protein using an alanine and residue scanning technique. By replacing I21 with Q21, L14 with H14, and V28 with K28, the binding affinity of the peptide inhibitors was increased. The newly designed peptide inhibitors with single residue mutation improved the binding affinity of the peptide inhibitors. The inhibitory capability of the new promising peptide inhibitors was further confirmed by the utilization of MD simulation and free binding energy calculations. The molecular dynamics simulation demonstrated that the newly engineered peptide inhibitors exhibited greater stability compared to the wild-type peptide inhibitors. According to the binding free energies MM(GB)SA of these developed peptides, the first peptide inhibitor was the most effective against the dengue virus envelope protein. All peptide derivatives had higher binding affinities for the envelope protein and have the potential to treat dengue virus-associated infections. In this study, new peptide inhibitors were developed for the dengue virus envelope protein based on the already reported peptide inhibitor.

An electrochemical, and surface studies of synthesized Gemini ionic liquid as corrosion inhibitor for carbon steel in petroleum field.

In this work, we study the efficiency of N1, N3-dibenzyl-N1, N1, N3, N3-tetramethylpropane-1,3-diaminium chloride, as anticorrosion. This compound exhibits potential as a prospective remedy to stop the deterioration of carbon steel caused by corrosion in 1.0 M HCl. The synthesis of this compound is described in a comprehensive manner, and its composition is supported by a range of precise analytical approaches such as elemental analysis, and mass spectroscopy. Based on the findings of the investigation, the synthesized Gemini ionic liquid demonstrates a robust capacity to slow down the rate at which the metal corrodes. The Prepared compound was evaluation by electrochemical and morphology study. Our results revealed that elevating the inhibitor concentration led to an augmentation in inhibition effectiveness, reaching up to 94.8% at 200 ppm of the synthesized compound at 298 K. It is crucial to emphasize that the recently prepared Gemini ionic liquid is consistent with the Langmuir adsorption model and function as a mixed inhibitor, participating in the physio-chemisorption process of adsorption.

Spectroscopic, biochemical and computational studies of bioactive DNA minor groove binders targeting 5'-WGWWCW-3' motif.

Spectroscopic, biochemical, and computational modelling studies have been used to assess the binding capability of a set of minor groove binding (MGB) ligands against the self-complementary DNA sequences 5'-d(CGCACTAGTGCG)-3' and 5'-d(CGCAGTACTGCG)-3'. The ligands were carefully designed to target the DNA response element, 5'-WGWWCW-3', the binding site for several nuclear receptors. Basic 1D 1H NMR spectra of the DNA samples prepared with three MGB ligands show subtle variations suggestive of how each ligand associates with the double helical structure of both DNA sequences. The variations among the investigated ligands were reflected in the line shape and intensity of 1D 1H and 31P-{1H} NMR spectra. Rapid visual inspection of these 1D NMR spectra proves to be beneficial in providing valuable insights on MGB binding molecules. The NMR results were consistent with the findings from both UV DNA denaturation and molecular modelling studies. Both the NMR spectroscopic and computational analyses indicate that the investigated ligands bind to the minor grooves as antiparallel side-by-side dimers in a head-to-tail fashion. Moreover, comparisons with results from biochemical studies offered valuable insights into the mechanism of action, and antitumor activity of MGBs in relation to their structures, essential pre-requisites for future optimization of MGBs as therapeutic agents.

Aptamer biosensor design for the detection of endocrine-disrupting chemicals small organic molecules using novel bioinformatics methods.

Endocrine-disrupting chemicals (EDCs) are substances that can disrupt the normal functioning of hormones.Using aptamers, which are biological recognition elements, biosensors can quickly and accurately detect EDCs in environmental samples. However, the elucidation of aptamer structures by conventional methods is highly challenging due to their complexity. This has led to the development of three-dimensional aptamer structures based on different models and techniques. To do this, we developed a way to predict the 3D structures of the SS DNA needed for this sequence by starting with an aptamer sequence that has biosensor properties specific to bisphenol-A (BPA), one of the chemicals found in water samples that can interfere with hormones. In addition, we will elucidate the intermolecular mechanisms and binding affinity between aptamers and endocrine disruptors using bioinformatics techniques such as molecular docking, molecular dynamics simulation, and binding energies. The outcomes of our study are to compare modeling programs and force fields to see how reliable they are and how well they agree with results found in the existing literature, to understand the intermolecular mechanisms and affinity of aptamer-based biosensors, and to find a new way to make aptamers that takes less time and costs less.