Treatment of Iron-Induced Cutaneous Hyperpigmentation With Energy-Based Devices.

OBJECTIVES: Iatrogenic cutaneous siderosis is a well-recognized dermatologic complication after parenteral iron infusion. The condition manifests as discrete, hyperpigmented patches near the site of injection. Most cases do not resolve spontaneously, leading to significant aesthetic and psychological distress to patients. A recent case of iatrogenic cutaneous siderosis at our institution prompted a systematic review of the efficacy of energy-based devices previously reported in the treatment of this condition. METHODS: PubMed and Cochrane databases were searched for all peer-reviewed articles published using the following search terms: "iron OR heme OR hemosiderosis OR siderosis" and "hyperpigmentation OR staining OR tattoo." Articles reporting on energy-based devices in the treatment of iron-induced hyperpigmentation were included. RESULTS: A total of seven articles and 54 total patients were included in this review. All patients, including the patient treated at our institution, were female, with an average age of 44 years. Hyperpigmentation was most commonly associated with intravenous iron infusion (48/54, 89%), on the arm or forearm (44/54, 81%), and used for the treatment of underlying iron deficiency anemia (54/54, 100%). The application of six different nanosecond or picosecond quality-switched laser systems was reported in the treatment of cutaneous siderosis, with wavelengths ranging from 532 to 1064 nm. Spot sizes varied between 2 and 7 mm, with energy fluences spanning 0.5-40 J/cm2 depending on both the device and spot size. Outcomes were measured after an average of 5.4 laser treatments and 10.4 months, with over half of all reported patients experiencing complete clearance (27/50, 54%). Our patient received treatment in three test areas with picosecond alexandrite 785 nm, nanosecond Nd:YAG 532 nm, and picosecond Nd:YAG 532 nm devices. The nanosecond Nd:YAG 532 nm treated area demonstrated the greatest improvement, and the entire arm was subsequently treated with this device. CONCLUSIONS: Despite the often intractable nature of iatrogenic cutaneous siderosis, laser surgery is a reasonable and safe treatment modality for patients seeking cosmetic improvement of this dyschromia. Dermatologists should be aware of this entity and the efficacy of the energy-based devices currently in our armamentarium. A combination approach may need to be utilized with different wavelengths and pulsed widths to target iron pigment in both dermal and subcutaneous layers.

Estimation of rice yield using multivariate analysis techniques based on meteorological parameters.

This study aims to develop predictive models for rice yield by applying multivariate techniques. It utilizes stepwise multiple regression, discriminant function analysis and logistic regression techniques to forecast crop yield in specific districts of Haryana. The time series data on rice crop have been divided into two and three classes based on crop yield. The yearly time series data of rice yield from 1980-81 to 2020-21 have been taken from various issues of Statistical Abstracts of Haryana. The study also utilized fortnightly meteorological data sourced from the Agrometeorology Department of CCS HAU, India. For comparing various predictive models' performance, evaluation of measures like Root Mean Square Error, Predicted Error Sum of Squares, Mean Absolute Deviation and Mean Absolute Percentage Error have been used. Results of the study indicated that discriminant function analysis emerged as the most effective to predict the rice yield accurately as compared to logistic regression. Importantly, the research highlighted that the optimum time for forecasting the rice yield is 1 month prior to the crops harvesting, offering valuable insight for agricultural planning and decision-making. This approach demonstrates the fusion of weather data and advanced statistical techniques, showcasing the potential for more precise and informed agricultural practices.

Developmental stage and level of submersion in water impact the viability of lone star and winter tick eggs during flooding.

Female ticks deposit large egg clusters that range in size from hundreds to thousands. These clusters are restricted to a deposition site, usually under leaf litter and other debris. These sites can be exposed to periodic flooding, where the cluster of tick eggs can float to the surface or remain underneath organic debris entirely underwater. Here, we examined the viability of egg clusters from winter ticks, Dermacentor albipictus , and lone star ticks, Amblyomma americanum , when partially submerged or fully submerged in water in relation to the developmental stages of the eggs. In general, egg clusters that were older and partially submerged had a higher viability than fully submerged, young eggs in water. A. americanum was much more resistant to water exposure between the two species. These studies highlight that egg clusters for specific tick species can remain viable when exposed to water for at least two weeks, where eggs float on the surface. These studies also suggest that water-based distribution of egg clusters could occur for some species, and flooding will differentially impact tick egg survival based on the specific developmental stage of exposure and species.

Fate of multi-residue insecticides and their metabolites in the process of vinification: Analytical method validation, dissipation kinetics, processing factor, and risk assessment.

In viticulture, the use of synthetic chemical formulations introduces insecticide residues into harvested grapes and further into processed grape products, posing a safety concern to consumers. This study investigated the fate of ten insecticide residues and their metabolites from vine to wine. A rapid validated multi-residue approach using QuEChERS extraction and LC-MS/MS configuration was employed for targeted analysis in grape, pomace, and wine. The targeted insecticides showed satisfactory mean recoveries (76.03-111.95%) and precision (RSD = 0.75-7.90%) across the three matrices, with a matrix effect ranging from -16.88 to 35.18%, particularly higher in pomace. Preliminary grape washing effectively removed 15.52-61.31% of insecticide residues based on water solubility and systemic nature. Residue dissipation during fermentation ranged from 73.19% to 87.15% with a half-life spanning from 1 to 5.5 days. The mitigation rate was observed at 12.85-26.81% for wine and 17.76-51.55% for pomace, with the highest transfer rate for buprofezin (51.55%) to pomace and fipronil (25.72%) to wine. Calculated processing factors (PF) for final wine ranged from 0.16 to 0.44, correlating strongly with the octanol-water partition ratio of targeted insecticides. The reported PF, calculated hazard quotient (HQ) (0.003-5.800%), and chronic hazard index (cHI) (2.041-10.387%) indicate reduced residue concentrations in wine and no potential chronic risk to consumers, ensuring a lower dietary risk to wine consumers.

Oxidative Coupling and Self-Assembly of Polyphenols for the Development of Novel Biomaterials.

In recent years, the development of biomaterials from green organic sources with nontoxicity and hyposensitivity has been explored for a wide array of biotherapeutic applications. Polyphenolic compounds have unique structural features, and self-assembly by oxidative coupling allows molecular species to rearrange into complex biomaterial that can be used for multiple applications. Self-assembled polyphenolic structures, such as hollow spheres, can be designed to respond to various chemical and physical stimuli that can release therapeutic drugs smartly. The self-assembled metallic-phenol network (MPN) has been used for modulating interfacial properties and designing biomaterials, and there are several advantages and challenges associated with such biomaterials. This review comprehensively summarizes current challenges and prospects of self-assembled polyphenolic hollow spheres and MPN coatings and self-assembly for biomedical applications.

Impact of N-Glycosylation on Protein Structure and Dynamics Linked to Enzymatic C-H Activation in the M. oryzae Lipoxygenase.

Lipoxygenases (LOXs) from pathogenic fungi are potential therapeutic targets for defense against plant and select human diseases. In contrast to the canonical LOXs in plants and animals, fungal LOXs are unique in having appended N-linked glycans. Such important post-translational modifications (PTMs) endow proteins with altered structure, stability, and/or function. In this study, we present the structural and functional outcomes of removing or altering these surface carbohydrates on the LOX from the devastating rice blast fungus, M. oryzae, MoLOX. Alteration of the PTMs did notinfluence the active site enzyme-substrate ground state structures as visualized by electron-nuclear double resonance (ENDOR) spectroscopy. However, removal of the eight N-linked glycans by asparagine-to-glutamine mutagenesis nonetheless led to a change in substrate selectivity and an elevated activation energy for the reaction with substrate linoleic acid, as determined by kinetic measurements. Comparative hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis of wild-type and Asn-to-Gln MoLOX variants revealed a regionally defined impact on the dynamics of the arched helix that covers the active site. Guided by these HDX results, a single glycan sequon knockout was generated at position 72, and its comparative substrate selectivity from kinetics nearly matched that of the Asn-to-Gln variant. The cumulative data from model glyco-enzyme MoLOX showcase how the presence, alteration, or removal of even a single N-linked glycan can influence the structural integrity and dynamics of the protein that are linked to an enzyme's catalytic proficiency, while indicating that extensive glycosylation protects the enzyme during pathogenesis by protecting it from protease degradation.

Fission Yeast as a Platform for Antibacterial Drug Screens Targeting Bacterial Cytoskeleton Proteins.

Bacterial cytoskeletal proteins such as FtsZ and MreB perform essential functions such as cell division and cell shape maintenance. Further, FtsZ and MreB have emerged as important targets for novel antimicrobial discovery. Several assays have been developed to identify compounds targeting nucleotide binding and polymerization of these cytoskeletal proteins, primarily focused on FtsZ. Moreover, many of the assays are either laborious or cost-intensive, and ascertaining whether these proteins are the cellular target of the drug often requires multiple methods. Finally, the toxicity of the drugs to eukaryotic cells also poses a problem. Here, we describe a single-step cell-based assay to discover novel molecules targeting bacterial cytoskeleton and minimize hits that might be potentially toxic to eukaryotic cells. Fission yeast is amenable to high-throughput screens based on microscopy, and a visual screen can easily identify any molecule that alters the polymerization of FtsZ or MreB. Our assay utilizes the standard 96-well plate and relies on the ability of the bacterial cytoskeletal proteins to polymerize in a eukaryotic cell such as the fission yeast. While the protocols described here are for fission yeast and utilize FtsZ from Staphylococcus aureus and MreB from Escherichia coli, they are easily adaptable to other bacterial cytoskeletal proteins that readily assemble into polymers in any eukaryotic expression hosts. The method described here should help facilitate further discovery of novel antimicrobials targeting bacterial cytoskeletal proteins.

Familial Chiari malformation: a systematic review and illustrative cases.

OBJECTIVE: Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members. METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included. RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%). CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.

The effects of keratin-coated titanium on osteoblast function and bone regeneration.

Wool derived keratin, due to its demonstrated ability to promote bone formation, has been suggested as a potential bioactive material for implant surfaces. The aim of this study was to assess the effects of keratin-coated titanium on osteoblast functionin vitroand bone healingin vivo. Keratin-coated titanium surfaces were fabricated via solvent casting and molecular grafting. The effect of these surfaces on the attachment, osteogenic gene, and osteogenic protein expression of MG-63 osteoblast-like cells were quantifiedin vitro. The effect of these keratin-modified surfaces on bone healing over three weeks using an intraosseous calvaria defect was assessed in rodents. Keratin coating did not affect MG-63 proliferation or viability, but enhanced osteopontin, osteocalcin and bone morphogenetic expressionin vitro. Histological analysis of recovered calvaria specimens showed osseous defects covered with keratin-coated titanium had a higher percentage of new bone area two weeks after implantation compared to that in defects covered with titanium alone. The keratin-coated surfaces were biocompatible and stimulated osteogenic expression in adherent MG-63 osteoblasts. Furthermore, a pilot preclinical study in rodents suggested keratin may stimulate earlier intraosseous calvaria bone healing.

Residue behavior and consumer risk assessment of spirotetramat and chlorpyrifos on cabbage heads and cropped soil.

A field experiment following good agricultural practices was laid out to study the dissipation of spirotetramat (90 g a.i. ha-1 and 180 g a.i. ha-1) and chlorpyrifos (400 g a.i. ha-1 and 800 g a.i. ha-1) on cabbage heads and soil. Samples were processed using quick, easy, cheap, effective, rugged, and safe (QuEChERS) method for residue estimation of spirotetramat and chlorpyrifos, which were further detected using HPLC-PDA and GC-FPD respectively. The residues of spirotetramat on cabbage heads reached below detection limit (BDL) (< 0.05 mg kg-1) on 7th and 10th day and for chlorpyrifos, BDL (< 0.01 mg kg-1) was achieved on 10th and 15th day for X and 2X dose, respectively. On 20th day after second spray, residues in soil were found to be BDL for both the pesticides. Half-life of spirotetramat and chlorpyrifos was found to be 3 and 2 days, respectively while a safe pre-harvest interval (PHI) of 9 days for spirotetramat and 10 days for chlorpyrifos is suggested on cabbage. The dietary risk assessment studies for various age groups of Indian population, ascertained safety of treated cabbage heads for consumption, as current study revealed that hazard quotient (HQ) < 1 and theoretical maximum dietary intake (TMDI) < maximum permissible intake (MPI) for both the pesticides at respective PHI.

Computational and in vitro screening validates the repositioning potential of Coxibs as anti-fibrotic agents.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease with a survival rate of <5 years. The TGF-ß plays a significant role in the progression and severity of IPF. The TGF-ß receptor type1 TGFBR1 antagonists inhibit the process of fibrosis and may have a role in the treatment of IPF. The main objective of the study was to identify promising drug candidates against IPF using In-silico and In-vitro evaluation methods. An in-silico screening was carried out of the marketed Coxibs to find their TGFBR1 inhibitory potential considering their structural resemblance with the JZO-a co-crystalized ligand of the crystal structure of the TGFBR1. The virtual screening yielded rofecoxib as a TGFBR1 ligand with a significant docking score. To further validate the outcome of molecular docking studies, MD simulation of 200 ns was carried out followed by the determination of conformational stability, binding free energy calculation using MMPBSA/MMGBSA, and Free Energy Landscape (FEL). The therapeutic efficacy of rofecoxib was compared with that of nintedanib (a therapeutic agent used in the treatment of IPF) at equimolar concentrations (5 µM). The model of TGF-ß1 (1 ng/ml)-induced EMT of A549 was used to determine the effect of rofecoxib on the EMT markers like cellular morphology, cytokine expressions, fibrosis associated protein, E-cadherin, and α-smooth muscle actin. In vitro results indicated that rofecoxib significantly suppresses the TGF-ß1-induced EMT of A549 cells and validates the possible preventive/protective role of rofecoxib in pulmonary fibrosis. In conclusion, rofecoxib may be considered for repositioning as an anti-fibrotic agent.Communicated by Ramaswamy H. Sarma.

Functional Outcome of Lower Limb Long Bone Trauma Management in Pregnant Mothers: A Prospective Study of 30 Cases From a Tertiary Care Centre in North India.

INTRODUCTION: The occurrence of orthopedic injuries during pregnancy carries considerable morbidity and mortality for both the mother and fetus. Successful care of lower limb fractures during pregnancy requires a multidisciplinary approach. Both operative and non-operative treatments must be taken into account by the treating orthopedic physician. There is limited literature available on the management of these lower limb fractures in pregnancy, and peri-operative management of this obstetric and orthopedic trauma is largely unclear. Trauma during pregnancy is a common cause of non-obstetrical maternal death, having a significant public health burden to both the mother and child. The aims and objectives of this study were to review the common causes of lower limb long bone trauma during pregnancy and their functional outcome in terms of morbidity and mortality. This study evaluates various operative and conservative methods of treatment to provide a comprehensive management approach to pregnant patients with lower limb trauma. MATERIALS AND METHODS: A prospective study on functional outcomes of 30 pregnant females who were admitted with lower limb long bone fractures from 2017 to 2021 was done. The patients were randomly selected intra-operatively for various procedures based on the surgeon's preference. All patients were followed for two years or till union occurred, and the radiographic union score for tibial (RUST) and modified radiographic union score for tibial (mRUST) fracture criteria were used to assess bony union clinico-radiologically.  Results: During this study, the mean age of patients was 27 years (range 19-38), having right-side (53.33%) predominance with road traffic accidents (n=22) and falls (n=6) as the most common causes of injury. Two cases of domestic violence were also reported. In our study, the maximum number of cases was 17-25 weeks of their gestation; 12 (40%) patients had tibial fractures, and 18 (60%) had femoral fractures. Six tibial fractures were handled conservatively, while all femoral fractures required surgical intervention. Out of 18 femoral fractures, which were treated surgically, dynamic compression plating was done in 15 (83.33%) patients, while interlock nailing was done in three patients. Six tibial fractures have been operated upon, two (66.66%) with dynamic compression plating and four (33.33%) with an interlocking nail. CONCLUSION: A multidisciplinary approach in terms of both operative and non-operative methods must be taken into account for treating pregnant mothers by the orthopedic physician while carefully weighing the benefits and risks of both procedures. Based on the pattern and displacement of the fracture, many prenatal fractures can be treated conservatively. Another alternative that is frequently safe is to postpone the surgical procedure until childbirth. The physiologic changes associated with pregnancy and any potential dangers to the fetus must be taken into account by the orthopedic surgeon when fractures necessitate surgical intervention. The surgeon is responsible for the patient's correct placement, the C-arm's use, the radiation dose, and the intra-operative fetal monitoring, as well as the danger brought on by anesthetics, antibiotics, analgesics, and anticoagulants.

Advances in the polymeric nanoparticulate delivery systems for RNA therapeutics.

RNA therapeutics have emerged as potential treatments for genetic disorders, infectious diseases, and cancer. RNA delivery to target cells for efficient therapeutic applications remains challenging due to instability and poor uptake. Polymeric nanoparticulate delivery systems offer stability, protection, and controlled release. These systems shield RNA from degradation, enabling efficient uptake and extended circulation. Various polymeric nanoparticle platforms have been explored, including lipid-based nanoparticles, polymeric micelles, dendrimers, and polymer-drug conjugates. This review outlines recent breakthroughs of recent advances, design principles, characterization techniques, and performance evaluation of these delivery systems. It highlights their potential in translating preclinical studies into clinical applications. Additionally, the review discusses the application of polymeric nanoparticles in ophthalmic drug delivery, particularly for medications that dissolve poorly in water, and the progress made in siRNA-based therapies for viral infections, autoimmune diseases, and cancers. SiRNA holds great promise for precision medicine and therapeutic intervention, with the ability to target specific genes and modulate disease-associated pathways. The versatility and potency of siRNA-based drugs offer a broader scope for therapeutic intervention compared to traditional biological drugs. As research in RNA therapeutics continues to advance, these technologies hold tremendous potential to revolutionize the treatment of various diseases and improve patient outcomes.