Beyond Lipids: Exploring Advances in Polymeric Gene Delivery in the Lipid Nanoparticles Era.

The recent success of gene therapy during the COVID-19 pandemic has underscored the importance of effective and safe delivery systems. Complementing lipid-based delivery systems, polymers present a promising alternative for gene delivery. Significant advances have been made in the recent past, with multiple clinical trials progressing beyond phase I and several companies actively working on polymeric delivery systems which provides assurance that polymeric carriers can soon achieve clinical translation. The massive advantage of structural tunability and vast chemical space of polymers is being actively leveraged to mitigate shortcomings of traditional polycationic polymers and improve the translatability of delivery systems. Tailored polymeric approaches for diverse nucleic acids and for specific subcellular targets are now being designed to improve therapeutic efficacy. This review describes the recent advances in polymer design for improved gene delivery by polyplexes and covalent polymer-nucleic acid conjugates. The review also offers a brief note on novel computational techniques for improved polymer design. The review concludes with an overview of the current state of polymeric gene therapies in the clinic as well as future directions on their translation to the clinic.

Role of Machine Learning and Artificial Intelligence in Arrhythmias and Electrophysiology.

Machine learning (ML), a subset of artificial intelligence (AI) centered on machines learning from extensive datasets, stands at the forefront of a technological revolution shaping various facets of society. Cardiovascular medicine has emerged as a key domain for ML applications, with considerable efforts to integrate these innovations into routine clinical practice. Within cardiac electrophysiology, ML applications, especially in the automated interpretation of electrocardiograms, have garnered substantial attention in existing literature. However, less recognized are the diverse applications of ML in cardiac electrophysiology and arrhythmias, spanning basic science research on arrhythmia mechanisms, both experimental and computational, as well as contributions to enhanced techniques for mapping cardiac electrical function and translational research related to arrhythmia management. This comprehensive review delves into various ML applications within the scope of this journal, organized into 3 parts. The first section provides a fundamental understanding of general ML principles and methodologies, serving as a foundational resource for readers interested in exploring ML applications in arrhythmia research. The second part offers an in-depth review of studies in arrhythmia and electrophysiology that leverage ML methodologies, showcasing the broad potential of ML approaches. Each subject is thoroughly outlined, accompanied by a review of notable ML research advancements. Finally, the review delves into the primary challenges and future perspectives surrounding ML-driven cardiac electrophysiology and arrhythmias research.

Assessment of Postoperative Swelling and Pain Following Alveolar Ridge Preservation with Different Biomaterials: A Randomized Controlled Trial.

Background: This randomized controlled trial aimed to assess and compare postoperative swelling and pain in patients undergoing alveolar ridge preservation using RidgeMax Pro and AlveoGraft Plus. Methods: A total of 20 patients requiring tooth extraction were enrolled in this study and randomly assigned to two groups: Group A received alveolar ridge preservation with RidgeMax Pro and Group B with AlveoGraft Plus. Postoperative swelling was evaluated by measuring facial dimensions using standardized facial photographs at baseline and at 24, 48, and 72 hours postoperatively. Pain was assessed using a visual analog scale (VAS) at the same time points. Statistical analysis was performed using t-tests and repeated measures ANOVA. Results: Both RidgeMax Pro and AlveoGraft Plus demonstrated effective alveolar ridge preservation without any reported complications. In terms of postoperative swelling, Group A (RidgeMax Pro) exhibited significantly lower facial swelling compared to Group B (AlveoGraft Plus) at all time points (P < 0.05). The mean pain scores on the VAS were consistently lower in Group A than in Group B across the assessment time points (P < 0.05). The trend of reduced swelling and pain in Group A persisted throughout the 72-hour follow-up period. Conclusion: Alveolar ridge preservation with RidgeMax Pro (Trade Name: RidgeMax Pro) resulted in significantly reduced postoperative swelling and pain compared to AlveoGraft Plus (Trade Name: AlveoGraft Plus).

Correction: Anwer et al. Molecular and Morphological Characterization of Exserohilum turcicum (Passerini) Leonard and Suggs Causing Northern Corn Leaf Blight of Maize in Bihar. Bioengineering 2022, 9, 403.

In the original publication [...].

Clinical spectrum of fusariosis from a tertiary care center in India- a retrospective study.

Background and Objectives: Fusarium spp. is an emerging pathogen that presents with varied clinical presentations but there are very few studies from India that elaborate on the spectrum of infection caused by the fungus. Hence, the present study was conducted in our institute to understand the clinical spectrum of fusariosis. Materials and Methods: The present study was a retrospective study conducted at a tertiary care institute, in Hyderabad, Telangana, India for four years from January 2018 to December 2022. All the patients with clinically significant isolation of Fusarium spp. from various samples were included in the study. Results: There were 25 cases of fusariosis diagnosed during the study period. Fusarium was isolated predominantly from debrided tissue following road traffic accidents in 12/25 (84%) of the cases, nails in 3/25 (12%) and superficial leg ulcer in 1/25 (4%) of the cases. Speciation was done for four patients. Three were Fusarium incarnatum and one was Fusarium solani. The patients were treated surgically and with/without antifungal therapy and were discharged in a stable condition. Conclusion: Traumatic injuries were the major cause of infections in the present study. As Fusarium is a virulent and highly resistant pathogen, an early suspicion and an appropriate diagnosis would lead to a better outcome in these patients.

Nuclear localization signal in nuclear receptor VDR facilitates the mitotic genome bookmarking by involving distinct amino acid residues.

Mitotic genome-bookmarking preserves epigenetic information, re-establishing progenitor's gene expression profile through transcription factors, chromatin remodelers, and histone modifiers, thereby regulating cell fate and lineage commitment post-mitotically in progeny cells. Our recent study revealed that the constitutive association of VDR with mitotic chromatin involves its DNA-binding domain. However, amino acid residues in this domain, crucial for genome bookmarking, remain elusive. This study demonstrates that nuclear localization signal (NLS) residues between 49 and 55 amino acids in VDR are essential for receptor-chromatin interaction during mitosis. Furthermore, it is revealed that both bipartite nature of VDR-NLS region and N-terminally located positively charged arginine residues are critical for its 'genome-bookmarking' property. Since mitotic chromatin association of heterodimeric partner RXR depends on VDR-chromatin association, interventions in VDR binding also abort RXR-chromatin interaction. Overall, this study documents the mechanistic details underlying VDR-chromatin interactions in genome-bookmarking behavior, potentially aiding in comprehending VDR-mediated diseases attributed to certain SNPs.

Limbal stem cell deficiency: Demography, aetiology, and clinical presentation in Eastern India.

Aims: To determine demographic details, clinical profile, and underlying causes of limbal stem cell deficiency. Settings and Design: Descriptive cross-sectional study. Methods and Material: Patients visiting tertiary referral hospitals between January 2019 and December 2022 who satisfy the criteria for labeling limbal stem cell deficiency (LSCD) were enrolled. Parameters such as age, gender, region, duration, aetiology, and clinical features were noted. Descriptive statistics was applied. The student t-test was used. Results: A total of 731 eyes of 489 patients with LSCD were included in our study, with age ranging from 5 to 85 years (35.0 ± 19.4 years). The most common presenting complaints were a decrease in vision 473 (96.7%), most of them 342 (69.7%) are having history of gradual progression (>3 months), and 245 (50.1%) have bilateral involvement of eyes. Average corneal clarity was found to be grade 1.6 ± 1.2 and average corneal superficial neovascularization was found to be 7.9 ± 4.3 quadrants. Clinically, we found LSCD of about up to 90° in 57 eyes, 90 to 180° in 71 eyes, 215 eyes with 180 to 270°, and the rest of 388 eyes were having more than 270° of LSCD involvement. Out of 489 patients, 142 (29.0%) patients were of chemical injury, 125 (25.6%) patients were of Steven Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), followed by 61 (12.5%) patients of vernal keratoconjunctivitis (VKC). Conclusions: The majority of patients were young males presented with more than 270° LSCD and vision <2/60. In our study, chemical injury was most common in unilateral LSCD and SJS/TEN in bilateral LSCD.

Microbes as a tool for the bioremediation of fish waste from the environment and the production of value-added compounds: a review.

Fish are the most edible protein source worldwide and generate several remnants such as scales, viscera, head, bone, and skin. Fish wastes are not disposed of properly, which adversely affects the environment, especially the water bodies where fish processing industries dispose of their waste. Fish waste mainly contains nitrogen, oil, fat, salts, heavy metals, and organic compounds, which increase the biological oxygen demand and chemical oxygen demand. Fish waste can degrade in various ways, such as physicochemical or by enzymatic action, but using microbes is an environmentally friendly approach that can provide valuable compounds such as products such as collagen, chitin, minerals, and fish protein concentrates. This review is designed to focus on the suitability of microbes as tools for fish waste degradation and the production of certain associated. This study also provides insight into the production of other compounds such as protease, chitinase, and chitin applicability of these products. After processing, fish waste as a microbial growth media for enzyme production since microorganisms synthesize enzymes such as proteases, protein hydrolysates, lipids, and chitinase, which have broader applications in the pharmaceutical, cosmetic, biomedical material, and food processing industries.

Anesthetic management in a huge hydrocephalus.

The pediatric age group with massive hydrocephalus posted for ventriculoperitoneal (VP) shunt presents a lot of confrontation to anesthesiologists due to macrocephalus and associated congenital anomalies. Here, we presented a case report with massive hydrocephalus with aqueduct stenosis, posted for VP shunt placement, and retained a difficult airway.

RésumésLe grouped'âgepédiatrique avec unehydrocéphalie massive affichée pour un shunt ventriculopéritonéal (VP) présente beaucoup de confrontation à l'anesthésisteen raison de la macrocéphalieet des anomalies congénitalesassociées. Ici, nous avonsprésentéun rapport de casd'hydrocéphalie massive avec sténose de l'aqueduc, affiché pour la miseen place d'un shunt VP, et conservéunevoierespiratoire difficile. Mots-clés : Pédiatrique, Voiesrespiratoiresdifficiles, hydrocéphalie, dérivationventriculopéritonéale.

Sediment-associated microplastics in Chilika lake, India: Highlighting their prevalence, polymer types, possible sources, and ecological risks.

The primary objective of this research was to assess microplastics (MPs) in the sediments of Chilika lake. MPs were extracted from 22 sediment samples using the density separation method combined with vacuum pump filtration. A stereo-zoom microscope and Raman spectroscopy were employed to identify the sediment-associated MPs. The total MPs collected from all 22 sites was 440 ± 3.53 particles kg-1 wet sediments, with sizes ranging between 50 and 500 µm. In terms of morphology, fibers and fragments emerged as the dominant MP types, with counts of 210 ± 1.66 and 175 ± 1.76 particles kg-1 wet sediments, respectively. Raman spectroscopy verified the presence of various MP polymers in the sediments, predominantly HDPE (37 %), followed by PS (20 %), PET (18 %), PA (11 %), PP (7 %), and PC (7 %). A notable color variation was observed in MPs; black being the most prevalent (38.8 %), succeeded by blue (19.5 %), green (11.8 %), white (11.5 %), red (10.6 %), and transparent (7.5 %). ANOVA results indicated significant (p > 0.05) variations in MP abundance across the 22 sampling locations. However, principal component analysis (PCA) and multiple regression analysis indicated that water quality parameters did not significantly influence MP abundance, yet it was found that MP retention was higher in fine-grained sediments like clay and silt. The leading sources of MPs in Chilika lake were found to be aquafarming, trailed by river and sewage discharges, fishing activities, antifouling coatings and tourism. Additionally, the pollution load index (PLI) was employed to gauge the ecological risks, categorizing the lake under risk category 1, which implies a minimal level of MPs pollution. This research aims to serve as an early warning system for MPs pollution in productive brackish water habitats globally, including Chilika lake, guiding policymakers towards appropriate management strategies and preventive measures.

ACE Gene I/D Polymorphism and Cardiometabolic Risk Factors: A Cross Sectional Study of Rural Population.

The D allele has been identified as being linked to cardiovascular disease since the discovery of an insertion/deletion (I/D) polymorphism in the ACE gene, this polymorphism has been found to have significant associations with a variety of cardiovascular risk factors. Recent findings indicate a rising prevalence of metabolic disorders among rural populations in developing nations. Research on health matters has been predominantly focused on urban populations, with relatively less attention given to their rural counterparts Hence, the present study attempts to estimate the prevalence of ACE gene I/D polymorphism and explore its association with various cardiovascular risk factors among Rural Yadav population from India. In the present study, 207 (Male 47, Female 160) members of the Yadav community participated in the cross-sectional study. All the socio-demographic factors, somatometric (anthropometric) variables, and the intravenous blood was collected and Physiological (blood pressure), and biochemical (fasting glucose and lipid profile) parameters were measured as recommended by the American Heart Association, allele-specific PCR of the ACE gene I/D polymorphism was carried out, the PCR products were genotyped on 2% agarose gel Electrophoresis and ACE gene polymorphism was analysed for its association with various cardiovascular risk factors. Among the analysed individuals, 34 (16.4%) were found to have the II genotype, 58 (28.0%) had the ID genotype, and 115 (55.6%) had the DD genotype. The allele frequency of the I allele was found to be 0.31, and the frequency of the D allele was 0.69. The frequency of the DD genotype was found to be significantly higher among individuals with high TC, high TG, and low non-HDL levels (p value < 0.05). When considered collectively, the findings of this study are consistent with the hypothesis that the DD genotype of ACE polymorphism represents a correlation with cardiovascular disease risk factors in this population.

MCC950 reduces autophagy and improves cognitive function by inhibiting NLRP3-dependent neuroinflammation in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the seventh most common cause of mortality and one of the major causes of disability and vulnerability in the elderly. AD is characterized by gradual cognitive deterioration, the buildup of misfolded amyloid beta (Aß) peptide, and the generation of neurofibrillary tangles. Despite enormous scientific progress, there is no effective cure for AD. Thus, exploring new treatment options to stop AD or at least slow down its progress is important. In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in AD. Rats treated with streptozotocin (STZ) exhibited simultaneous activation of the NLRP3 inflammasome and autophagy, as confirmed by Western blot, immunofluorescence, and co-immunoprecipitation analyses. MCC950, a specific NLRP3 inhibitor, was intraperitoneally administered (50 mg/kg body weight) to rats with AD-like symptoms induced by intracerebroventricular STZ injections (3 mg/kg body weight). MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome inhibition.

Impacts of ultraviolet and photosynthetically active radiations on photosynthetic efficiency and antioxidant systems of the cyanobacterium Spirulina subsalsa HKAR-19.

This study summarizes the response of cyanobacterium Spirulina subsalsa HKAR-19 under simulated light conditions of photosynthetically active radiation (PAR), PAR+UV-A (PA), and PAR+UV-A+UV-B (PAB). Exposure to UV radiation caused a significant (P < 0.05) decrease in chlorophyll a, phycocyanin, and total protein. In contrast, total carotene content increased significantly (P < 0.05) under PA and PAB with increasing irradiation time. The photosynthetic efficiency of photosystem II also decreased significantly in PA and PAB radiation. We have also recorded a decrease in the fluorescence emission intensity of phycocyanin under PA and PAB exposure. The phycocyanin fluorescence shifted towards shorter wavelengths (blue-shift) after 72 h of PA and PAB exposure. Intracellular reactive oxygen species (ROS) levels increased significantly in PA and PAB. Fluorescence microscopic images showed an increase in green fluorescence, indicating ROS generation in UV radiation. We have also quantified ROS generation using green and red fluorescence ratio represented as G/R ratio. A 2-6-fold increase in antioxidative enzymes activity was observed to overcome the damaging effects caused by UV stress as compared to untreated control cultures. The lipid peroxidation was assessed in terms of malondialdehyde content which increases significantly (P < 0.05) as the duration of exposure increases. These results suggest that a combined effect of PAR, UV-A, and UV-B was more deleterious than an individual one.

MASC Gets UNMASKED: Visiting a Rare Tumor with Emphasis on Cytomorphological Features.

Background: Secretory carcinoma (SC) is a newly described entity which has been often misdiagnosed earlier as acinic cell carcinoma on cytology. Diagnosing SC was initially based upon identifying the ETV6:NTRK3 fusion gene with the help of fluorescence in situ hybridization (FISH). Lately, with more knowledge of the reliable histomorphology, cytology, and immunohistochemistry features, definitive diagnosis can be confidently made without the help of FISH in almost every case. Materials and Methods: Six histologically confirmed cases of SC were studied. The cytology slides of all the six cases were retrieved and reviewed to identify the characteristic features which could have helped in raising the possibility of SC on fine needle aspiration cytology itself. Cell blocks were also studied, wherever available. Results: Patients were all male with average age of 35.2 years. The six cases in the current study demonstrated at least focal cytoplasmic vacuolization of varying sizes, papillae formations, and bland nuclear features on fine needle aspirate smears. It was also seen that S-100 and mammaglobin immunohistochemistry (IHC) are very helpful in confirming the diagnosis. Conclusions: The results of the current study highlight the cytomorphological features which may help in clinching the diagnosis SC on cytology itself. They also highlight certain cytological features which help to rule out the other differential diagnoses.

Superior functionality of niobium pentoxide nano-rod/tripod photocatalyst synthesized using polyethyleneimine as a soft template for the abatement of methylene blue under UV and visible irradiation.

Polyethyleneimine (PEI) capping agent-cum-template-mediated synthesis of niobium oxide nanoparticles is reported to explore its impact on the resultant morphology, porosity, crystallinity, phase complexation, and thus on the photocatalytic activity. The resultant niobium oxides calcined at 800°C and 1000°C crystallized into highly ordered nano-rod/tripod nanostructure with inter-rod angle <120° having orthorhombic phase and heavily agglomerated rod-like nanostructures having monoclinic crystal phase, respectively. Contrary to the expectations, the nano-rod/tripods showed superior photocatalytic degradation kinetics and high adsorption of methylene blue dye in the hydrocolloid than formerly reported monoclinic nanoparticles. The best adsorption capability and photocatalytic activity are observed for the sample calcined at 800°C, resulting in a combined degradation efficiency of 98.8% of methylene blue dye. The adsorption characteristics, stability of the hydrocolloid system, the existence of oxygen vacancies, and the distinct morphology of the photocatalytic nano-rod/tripods are mainly responsible for this behavior. The process and the performance of unique nanostructure over others presents a superior alternative.

Epidemiological and microbiological profiles of microbial keratitis in a tertiary eye center in Eastern India (Bihar).

Purpose: To determine the demography, risk factors, and causative organisms of microbial keratitis (MK) in Bihar, an eastern state of India. Design: Retrospective study. Methods: We reviewed the demographic, clinical, and microbiological data of 2303 patients with MK (non-viral) presenting between January 2019 and December 2022. Results: This study revealed a predominance of males (65.0%) compared to females (34.9%), with a mean age of 48.4 ± 16.5 years. The majority of patients (63.1%) presented after 2 weeks from the onset of symptoms. The most common risk factor observed was corneal injury (58.1%), followed by ocular surface diseases (13.6%) and diabetes mellitus (13.3%). The majority of patients (73.16%) were involved in agriculture. Prior to presentation, almost all patients (92%) had received topical antibiotics. Unsupervised use of topical corticosteroids was observed in 29.2% of the patients for the median duration of 3 days (odds ratio, 0.17). At presentation, the median size of corneal ulcers was 5 mm, the best-corrected visual acuity was less than 20/400 in 51.4% of patients, and corneal perforation was in 14% of patients. The smear and culture positivity rate were 75.4% and 47.9%, respectively. The common causative organism was fungus (48.8%), followed by bacteria (17.4%). Aspergillus spp. and Staphylococcus spp. were the most commonly identified organisms; a quarter of the patients (24.5%) remained unidentified. All bacteria showed good sensitivity to vancomycin. Conclusion: MK is a significant cause of ocular morbidity in Bihar. The knowledge of epidemiology, risk factors, and microbiological profiles of MK can provide a valuable approach to disease prevention, diagnosis, and management.

Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3'-oxindoles] under Microwave Irradiation and Their Anticancer Activity.

A novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins 1a-b, a number of α-amino acids 2a-e and (E)-2-aryl-1-nitroethenes 3a-e in a chemo/regio-selective manner using [3+2] cycloaddition (Huisgen) reaction under microwave irradiation conditions. The structure elucidation of all the synthesized spirooxindoles were done using 1H and 13C NMR and HRMS spectral analysis. The single crystal X-ray crystallographic study of compound 4l was used to assign the stereochemical arrangements of the groups around the pyrrolidine ring in spiro[pyrrolidine-2,3'-oxindoles] skeleton. The in vitro anticancer activity of spiro[pyrrolidine-2,3'-oxindoles] analogs 4a-w against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines shows promising results. Out of the 23 synthesized spiro[pyrrolidine-2,3'-oxindoles], while five compounds (4c, 4f, 4m, 4q, 4t) (IC50 = 34.99-47.92 µM; SI = 0.96-2.43) displayed significant in vitro anticancer activity against human lung (A549) cancer cell lines, six compounds (4c, 4f, 4k, 4m, 4q, 4t) (IC50 = 41.56-86.53 µM; SI = 0.49-0.99) displayed promising in vitro anticancer activity against human liver (HepG2) cancer cell lines. In the case of lung (A549) cancer cell lines, these compounds were recognized to be more efficient and selective than standard reference artemisinin (IC50 = 100 µM) and chloroquine (IC50 = 100 µM; SI: 0.03). However, none of them were found to be active as compared to artesunic acid [IC50 = 9.85 µM; SI = 0.76 against lung (A549) cancer cell line and IC50 = 4.09 µM; SI = 2.01 against liver (HepG2) cancer cell line].

Correlation of the Stature with Arch and Chord Dimensions in Young Subjects using Carrea's Index- An Anthropometric Study.

Background: Forensic identifications have utilized the height or stature of an individual in their field. Teeth and dentition can act as reliable tools to estimate the stature in cases where the only skull is presented as evidence. The Carrea's index assesses the stature in a subject from the lower anterior teeth dimensions. Aim: The present study was aimed to judge the reliability of Carrea's index in Indian subjects. Materials and Methods: From 80 subjects who were undergraduate students, plaster models were made and each was assessed individually making 160 hemiarches. These hemiarches were divided based on the teeth alignment into normal, diastema, and crowded forms. This was followed by measurement with a vernier caliper into chord and arch. Results: In both genders, the difference seen was statistically significant between dental arch types concerning various alignments with 95.23% and 83.75% success for males and females in normal dentition and 92.30% and 85.71% in crowded dentition. Also, a significant difference was seen for the type of arch with P ≤ 0.001 and 0.003, respectively. Lesser success was seen for spacing in both the genders and arches. Conclusion: The present study concludes that Carrea's index is a dependable and efficient tool for estimating height in subjects having arches with crowded and normal dentition which is functional for both the gender on the left and right side of the dental arches. However, in hemiarches with diastema, this method is not reliable.

In vitro Evaluation of Shear Bond Strength of Orthodontic Brackets Bonded with Different Adhesives.

Background: To endure the orthodontic forces used throughout treatment, the bond strength of bonded orthodontic brackets must be enough with assessment of shear bond strength when bonding orthodontic brackets with various adhesives. Materials and Methods: Overall, forty extracted premolars due to orthodontic treatment were included. They were split into four equal cohorts with various primers. With both adhesives, shear bond strength had been assessed with and without salivary contamination. SPSS software was used to assess the outcomes. Consideration was given to statistical significance of P value of less than 0.05. Results: Several groups' average bond strengths in MPa were assessed in both dry and contaminated saliva conditions. When it was dry, Transbond Plus demonstrated greater shear bond strength. Conclusion: Hydrophilic Transbond Plus resin outperformed hydrophobic Transbond XT resin in terms of shear bond strength under both situations.