Kinetic View of Enzyme Catalysis from Enhanced Sampling QM/MM Simulations.

The rate constants of enzyme-catalyzed reactions (kcat) are often approximated from the barrier height of the reactive step. We introduce an enhanced sampling QM/MM approach that directly calculates the kinetics of enzymatic reactions, without introducing the transition-state theory assumptions, and takes into account the dynamical equilibrium between the reactive and non-reactive conformations of the enzyme/substrate complex. Our computed kcat values are in order-of-magnitude agreement with the experimental data for two representative enzymatic reactions.

Biosorption of pb(II) from aqueous solution by citrus reticulate: adsorption studies, and modeling.

Removing toxic Pb(II) ions from aqueous solution by the peels of citrus reticulate (mandarin orange), a fruit industry waste, presents suitable scale-up possibilities. The Scanning Electron Microscope (SEM) and Brunauer-Emmett-Teller (BET) studies reflected that the mandarin orange peel powder had a porous surface area (32.46 m2g-1), average pore size and pore volume was 38.6 Å and 0.402 cm3g-1, respectively, favorable for binding Pb(II) ions. Fourier-transform infrared spectroscopy (FTIR) showed C-Br stretching, primary alcohol (C-O), phenolic O-H, and carbodimide N = C = N bands primarily helped to bind Pb(II) ions. The study evaluated and optimized the parametric influences of pH, adsorbate and biosorbent concentration, contact time and temperature on the removal efficiency of Pb(II) ions. A maximum of 97.08% Pb(II) was removed from 20 mg L-1 solution when 2.5 g L-1 adsorbent was present. The reaction obeyed the pseudo-second-order kinetic model. The intra-particle diffusion was involved in lead sorption. The Langmuir isotherm model resulted in an adsorption capacity of 23.04 mg g-1. 35.28% Pb(II) was removed in the 3rd adsorption-desorption cycle with 0.4 M HCl. The adsorption process was natural, impulsive and endothermic. The statistical investigation used Multiple Polynomial Regression (MPR) and Genetic Algorithm (GA). The analysis effectively forecasted the percentage removal at the optimized condition.

The results of toxic Pb(II) ion removal from aqueous solution by the peels of citrus reticulate (mandarin orange), a food industry waste, are reported. The maximum Pb(II) adsorption capacity of 23.04 mg/g. This work provides a new way to realize good adsorption capacity of Pb(II) by orange peel and accelerates to utilize for small and medium-sized industries in rural areas of 3^rd World Countries.

Effect of complex nutrients, amino acids, vitamins on Ni(II) biosorption from aqueous solution by Ni(II) resistant Saccharomyces cerevisiae AJ208.

The paper aims to establish and enhance the microorganism's successful growth, proper activity, and biosorption potency for Ni(II) biosorption from an aqueous solution using 5,000 mg/l Ni(II) resistant Saccharomyces cerevisiae AJ208. Complex nutrients, amino acids, and vitamins were added to the specifically optimized fermentation media as essential growth factors. Amino acids such as L-cysteine (0.0002 g/ml), L-Proline (0.0002 g/ml), L-Lysine (0.0002 g/ml), L-tryptophan (0.0001 g/ml) and L-Histidine (0.0003 g/ml) led to an increase of more than 87% biosorption. Vitamins such as, Ascorbic acids (0.01 × 10-8 g/ml), folic acids (0.01 × 10-8 g/ml), pyridoxine-HCl (0.01 × 10-8 g/ml),Thiamin-HCl (0.05 × 10-8 g/ml) promotes biosorption more than 91%. The Ni(II) bio-removal increased with complex nutrients like soybean meal, malt extract, and yeast extract at the concentration of 0.03, 0.4, 0.05 in g/ml, and nickel removal reached more than 85%. The multiple linear regression (MLR) and ANN application of the experimental data have predicted Ni(II) percentage removal well. This adsorption shows that the proposed Ni(II) removal process using complex nutrients is environmentally friendly and economically feasible.Novelty statement: This study evaluates a cost-effective approach to bioremediation of Ni(II) by using complex nutrients as a growth factor. Media enriched with complex nutrients is cheap than chemical media. Ni(II) Removal significant increased up to 87%, 88.34%, 96% with soybean meal, L-proline, and L-ascorbic acids at 3,000 mg/l initial Ni(II) concentration using newly developed 5,000 mg/l Ni(II) resistant Saccharomyces cerevisiae AJ208 and their NCBI accession number: MZ027228 (AJ208 ITS 1) and MZ027229 (AJ208 ITS 2).

Clinical Study of Single-Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients With Chronic Hepatitis B.

BACKGROUND AND AIMS: RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded locked nucleic acid oligonucleotide complementary to HBV RNA. GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR). This two-part phase 1 study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO7062931 in healthy volunteers and patients with chronic hepatitis B (CHB) who were virologically suppressed. APPROACH AND RESULTS: Part 1 was a single ascending dose study in healthy volunteers randomized to receive a single RO7062931 dose (0.1-4.0 mg/kg), or placebo. Part 2 was a multiple ascending dose study in patients with CHB randomized to receive RO7062931 at 0.5, 1.5, or 3.0 mg/kg or placebo every month for a total of 2 doses (Part 2a) or RO7062931 at 3.0 mg/kg every 2 weeks, 3.0 mg/kg every week (QW), or 4.0 mg/kg QW or placebo for a total of 3-5 doses (Part 2b). Sixty healthy volunteers and 59 patients received RO7062931 or placebo. The majority of adverse events (AEs) reported were mild in intensity. Common AEs included self-limiting injection site reactions and influenza-like illness. Supradose-proportional increases in RO7062931 plasma exposure and urinary excretion occurred at doses ≥3.0 mg/kg. In patients with CHB, RO7062931 resulted in dose-dependent and time-dependent reduction in HBsAg versus placebo. The greatest HBsAg declines from baseline were achieved with the 3.0 mg/kg QW dose regimen (mean nadir ~0.5 log10  IU/mL) independent of HBeAg status. CONCLUSIONS: RO7062931 is safe and well tolerated at doses up to 4.0 mg/kg QW. Supradose-proportional exposure at doses of 3.0-4.0 mg/kg was indicative of partial saturation of the ASGPR-mediated liver uptake system. Dose-dependent declines in HBsAg demonstrated target engagement with RO7062931.

A Retrospective Comparative Study on the Outcome of Microscope-Assisted Technique and Supra-Auricular Approach in Preauricular Sinus Surgery in a Tertiary Care Hospital.

Context: Preauricular sinus (PAS) can lead to severe complications such as facial paralysis, and squamous cell carcinoma may develop from this sinus later in life. Asymptomatic sinus needs no intervention, but symptomatic sinus needs surgical interventions. Aims: This study compares the surgical outcome of microscope-assisted sinus tract excision technique with the supra-auricular sinectomy technique. Settings and Design: This was a retrospective, observational study conducted at a tertiary care hospital in Purulia District, West Bengal, India. Subjects and Methods: Records of patients operated on for PAS were included following the proper inclusion and exclusion criteria. These patients were categorized and followed up based on disease pathology and the type of intervention received. Statistical Analysis Used: Data were collected, tabulated, and analyzed using the standard statistical software. Results: Fifty-two patients were included in our study. About 48.07% of patients were found in the age group of 11-15 years. In the microscope-assisted sinectomy category, recurrence of the disease was seen in 2 out of 15 operated patients compared to 1 patient among 13 in the supra-auricular sinectomy approach for uncomplicated cases. In complicated cases, the supra-auricular sinectomy approach had a nil recurrence rate compared to three patients out of ten operated in microscope-assisted technique (Fisher's exact test - 0.0593). Both the outcomes are not statistically significant. Conclusion: Supra-auricular sinectomy technique has the lowest recurrence rate for preauricular sinus surgery.

Effect of dragon fruit peel powder on quality and acceptability of fish nuggets stored in a solar cooler (5 ± 1 °C).

Fish nuggets were prepared with dragon fruit peel powder (1.0, 1.5 and 2.0% w/w) to evaluate its quality and improvement in shelf-life during 15 days storage in a prefabricated solar cooler (5 ± 1 °C). Antioxidative and antimicrobial effects of dragon fruit peel powder in fish model system were also evaluated during storage. Results showed that dragon fruit peel is a good source of dietary fibre (59.8%) and phenolic compounds [65.7 mg Gallic Acid Equivalent (GAE)/100 g of sample] and contained 6.03% protein, 6.14% fat and 4.34% ash. Use of dragon fruit peel powder significantly (p < 0.05) improved the emulsion stability and cooking yield and nuggets with peel powder had lower pH value than control. Fish nuggets with peel powder showed gradual decrease (p < 0.05) in hardness, springiness, cohesiveness, gumminess and chewiness with advancement of storage period. Nuggets with 1.5% dragon fruit peel showed better sensory attributes compared to the others. Dragon fruit peel powder significantly inhibited (p < 0.05) the lipid oxidation and microbial load in fish nuggets during the storage period. So, it can be concluded that dragon fruit peel powder may be used as antioxidant dietary fibre for improved quality and acceptability of fish nuggets in prefabricated solar cooler. 1.5% level of incorporation showed better results in terms of antioxidant activity and better shelf-life of the fish nuggets.

Structural basis for the hyperthermostability of an archaeal enzyme induced by succinimide formation.

Stability of proteins from hyperthermophiles (organisms existing under boiling water conditions) enabled by a reduction of conformational flexibility is realized through various mechanisms. A succinimide (SNN) arising from the post-translational cyclization of the side chains of aspartyl/asparaginyl residues with the backbone amide -NH of the succeeding residue would restrain the torsion angle Ψ and can serve as a new route for hyperthermostability. However, such a succinimide is typically prone to hydrolysis, transforming to either an aspartyl or ß-isoaspartyl residue. Here, we present the crystal structure of Methanocaldococcus jannaschii glutamine amidotransferase and, using enhanced sampling molecular dynamics simulations, address the mechanism of its increased thermostability, up to 100°C, imparted by an unexpectedly stable succinimidyl residue at position 109. The stability of SNN109 to hydrolysis is seen to arise from its electrostatic shielding by the side-chain carboxylate group of its succeeding residue Asp110, as well as through n → π∗ interactions between SNN109 and its preceding residue Glu108, both of which prevent water access to SNN. The stable succinimidyl residue induces the formation of an α-turn structure involving 13-atom hydrogen bonding, which locks the local conformation, reducing protein flexibility. The destabilization of the protein upon replacement of SNN with a Φ-restricted prolyl residue highlights the specificity of the succinimidyl residue in imparting hyperthermostability to the enzyme. The conservation of the succinimide-forming tripeptide sequence (E(N/D)(E/D)) in several archaeal GATases strongly suggests an adaptation of this otherwise detrimental post-translational modification as a harbinger of thermostability.

Development of CD133 Targeting Multi-Drug Polymer Micellar Nanoparticles for Glioblastoma - In Vitro Evaluation in Glioblastoma Stem Cells.

PURPOSE: Glioblastoma (GBM) is a malignant brain tumor with a poor long-term prognosis due to recurrence from highly resistant GBM cancer stem cells (CSCs), for which the current standard of treatment with temozolomide (TMZ) alone will unlikely produce a viable cure. In addition, CSCs regenerate rapidly and overexpress methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to resistance. The objective of this research was to apply the concepts of nanotechnology to develop a multi-drug therapy, TMZ and idasanutlin (RG7388, a potent mouse double minute 2 (MDM2) antagonist), loaded in functionalized nanoparticles (NPs) that target the GBM CSC subpopulation, reduce the cell viability and provide possibility of in vivo preclinical imaging. METHODS: Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed by a double emulsion technique loading TMZ and/or RG7388. The NPs were covalently bound to a 15-nucleotide base-pair CD133 aptamer to target the CD133 antigen expressed on the surfaces of GBM CSCs. For diagnostic functionality, the NPs were labelled with radiotracer Zirconium-89 (89Zr). RESULTS: NPs maintained size range less than 100 nm, a low negative charge and exhibited the ability to target and kill the CSC subpopulation when TMZ and RG7388 were used in combination. The targeting function of CD133 aptamer promoted killing in GBM CSCs providing impetus for further development of targeted nanosystems for localized therapy in future in vivo models. CONCLUSIONS: This work has provided a potential clinical application for targeting GBM CSCs with simultaneous diagnostic imaging.

An atomistic view of solvent-free protein liquids: the case of Lipase A.

Solvent-free enzymes hold the promise of being able to deliver higher activity at elevated temperatures by virtue of them being not limited by the boiling point of the solvent. They have been realized in the liquid phase through a polymer surfactant coating on the protein surface. However, a clear understanding of intermolecular interactions, structure, dynamics, and the behaviour of the minuscule amount of water present in the solvent-free protein liquid is essential to enhance the activity of these biofluids. Using atomistic molecular dynamics simulations, we demonstrate that the scaled spatial correlations between proteins in the hybrid liquid phase of Lipase A enzymes are comparable to the inter-particle correlations in a noble gas fluid. The hydrophilic region of the surfactants forms a coronal layer around each enzyme which percolates throughout the liquid, while the hydrophobic parts are present as disjointed clusters. Inter-surfactant interactions, determined to be attractive and in the range of -200 to -300 kcal mol-1, stabilize the liquid state. While the protein retains its native state conformational dynamics in the solvent-free form, the fluxionality of its side chains is much reduced; at 333 K, the latter is found to be equivalent to that of the enzyme in an aqueous solution at 249 K. Despite the sluggishness of the solvent-free enzyme, some water molecules exhibit high mobility and transit between enzymes primarily via the interspersed hydrophilic regions. These microscopic insights offer ideas to improve substrate diffusion in the liquid to enable the enhancement of catalytic activity.

Electrohydrodynamics of Vesicles and Capsules.

Giant unilamellar vesicles (GUVs) made up of phospholipid bilayer membranes (liposomes) and elastic capsules with a cross-linked, polymerized membrane, have emerged as biomimetic alternatives to investigating biological cells such as leukocytes and erythrocytes. This feature article looks at the similarities and differences in the electrohydrodynamics (EHD) of vesicles and capsules under electric fields that determines their electromechanical response. The physics of EHD is illustrated through several examples such as the electrodeformation of single and compound, spherical and cylindrical, and charged and uncharged vesicles in uniform and nonuniform electric fields, and the relevance and challenges are discussed. Both small and large deformation results are discussed. The use of EHD in understanding complex interfacial kinetics in capsules and the synthesis of nonspherical capsules using electric fields are also presented. Finally, the review looks at the large electrodeformation of water-in-water capsules and the relevance of constitutive laws in their response.

Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation.

Staphylococcus aureus is a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia-derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, nonhemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection.

Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes.

Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection.

Large deformation electrohydrodynamics of a Skalak elastic capsule in AC electric field.

The axisymmetric electrohydrodynamic deformation of an elastic capsule with a capacitive membrane obeying the Skalak law under a uniform AC electric field is investigated using analytical and boundary integral theory. The low capillary number (the ratio of destabilizing shear or electric force to the stabilizing elastic force) regime shows that time-averaged prolate and oblate spheroid deformations, and the time-periodic prolate-sphere, oblate-sphere breathing modes are commensurate with the time averaged-deformation. A novel prolate-oblate breathing mode is observed due to an interplay of finite membrane charging time and the field reversal of the AC field. The study, when extended to high capillary numbers, shows new breathing modes of cylinder-prolate, cylinder-oblate, and biconcave-prolate deformation. These are the results of highly compressive normal Maxwell stress at the poles and are aided by a weak compressive equatorial stress, characteristic of a capacitive membrane. The findings of this work should form the basis for the understanding of more complex biological cells and synthetic capsules for industrial applications.

Fluctuating magnetic field induced resonant activation.

In this paper, we have studied the properties of a Brownian particle at stationary state in the presence of a fluctuating magnetic field. Time dependence of the field makes the system thermodynamically open. As a signature of that the steady state distribution function becomes function of damping strength, intensity of fluctuations and constant parts of the applied magnetic field. It also depends on the correlation time of the fluctuating magnetic field. Our another observation is that the random magnetic field can induce the resonant activation phenomenon. Here correlation time is increased under the fixed variance of the fluctuating field. But if the correlation time (τ) increases under the fixed field strength then the mean first passage time rapidly grows at low τ and it almost converges at other limit. This is sharp contrast to the usual colored noise driven open system case where the mean first passage time diverges exponentially. We have also observed that a giant enhancement of barrier crossing rate occurs particularly at large strength of constant parts of the applied magnetic field even for very weak fluctuating magnetic field. Finally, break down of the Arrhenius result and disappearance of the Kramers' turn over phenomenon may occur in the presence of a fluctuating magnetic field.

A Clinico-Epidemiological Study of Fixed Drug Eruption with a Special Focus on the Causative Agent and the Clinical Patterns.

Background: Fixed drug reaction (FDE) is characterized by the development of well-circumscribed, round, erythematous macules and plaques on cutaneous or mucosal surface following ingestion of the offending drug. Aim and Objectives: To study the etiological agents responsible for FDE and to study the clinical patterns of FDE due to different drugs. Materials and Methods: It was a hospital-based observational cross-sectional clinical study. The study period was 24 months. Fifty patients were included. The study was done after a literature search, hypothesis generation, protocol write-up, ethical submission, ethical clearance, patient enrollment, data collection, data analysis, and research. The patients were selected on the basis of the Naranjo scoring system. The patients with a history of combination drug intake were not included in the study. Results: A total of 0.11% patients presented with FDE in the study period. Out of them, 52% of the patients belonged to 20-39 years age group, having sex ratio of 1.6:1. About 64% of the patients presented with multiple lesions, whereas 36% had a single lesion. A total of 46% patients presented with first episode and 54% had recurrent episodes. The mean time intervals of first and subsequent episodes were 6.5 days and 4.3 hours, respectively. Also, 16% patients had a history of herpes infection. Extremities were more affected followed by trunk and mucosa. Fluoroquinolones were the most common etiological agent found in 56% patients having cutaneous (48%) and mucosal lesions (14%). The most common drug was norfloxacin (36%) followed by both paracetamol (12%) and metronidazole (12%). Fluoroquinolones were the most common drugs implicated in bullous lesions and generalized bullous FDE. Limitations: The study population was small and the study was for a limited period of time. Conclusion: The patient should be aware of the offending drug and opt for any alternative agent after visiting the physician.

The role of nicotinamide adenine dinucleotide salvage enzymes in cardioprotection.

The increasing trend of cardiac diseases is becoming a major threat globally. Cardiac activities are based on integrated action potential through electronic flux changes within intra- and extracellular molecular activities. Nicotinamide adenine dinucleotide (NAD) is a major electron carrier present in almost all living cells and creates gated potential by electron exchange from one chemical to another in terms of oxidation (NAD+) and reduction (NADH) reactions. NAD+ plays an important role directly or indirectly in protecting against various cardiovascular diseases, including heart failure, occlusion, ischemia-reperfusion (IR) injury, arrhythmia, myocardial infarction (MI), rhythmic disorder, and a higher order of cardiovascular complexity. Nicotinamide phosphoribosyl transferase (NAMPT) is well known as a rate-limiting enzyme in this pathway except for de-novo NAD synthesis and directly involved in the cardioprotective activity. There are two more enzymes - nicotinate phosphoribosyl transferase (NAPRT) and nicotinamide riboside kinase (NRK) - which also work as rate-limiting factors in the NAD+ synthesis pathway. This study concentrated on the role of NAMPT, NAPRT, and NRK in cardioprotective activity and prospective cardiac health.

Oral Lichen Planus: An Updated Review of Etiopathogenesis, Clinical Presentation, and Management.

Lichen planus (LP) is a chronic idiopathic immune-mediated inflammatory condition. LP is a heterogeneous disease with varied clinical presentations having different natural history, prognosis, sequelae, and outcomes. It can affect skin, hair, nails, and mucosae. Mucosal LP (including oral LP) tends to be persistent and resistant to treatment, compared to cutaneous LP. Oral LP (OLP) is broadly divided into two main categories: hyperkeratotic (usually asymptomatic) and erosive (commonly symptomatic). It can present with symptoms including odynophagia, dysphagia, dysgeusia, and sensitivity to hot spicy foods. Apart from the superficial epidermal changes, which vary with the type of clinical presentation, histopathologically oral LP shows a unifying similar and consistent feature of a lichenoid interface dermatitis. Recently, researchers have highlighted the critical role played by IL-17 in the pathogenesis of OLP. World Health Organization has categorized oral LP as one of the oral potentially malignant disorders (OPMD), albeit with a low risk of malignant transformation. Also, in the last couple of years there have been various reports on the usage of newer drugs like anti-IL17, anti-IL12/23, anti-IL 23, PDE4 inhibitors, and JAK inhibitors in the management of refractory OLP. The principal aim of treatment still remains to resolve the symptoms, prolong the symptoms free period, and reduce the risk of potential malignant transformation. We have described many new revelations made in recent times regarding the etiopathogenesis, associated conditions as well as management of OLP. Thus, the objective of this review is to present a comprehensive up-to-date knowledge including the recent advances made regarding OLP.

Laser and Lights in Psoriasis.

Psoriasis is a chronic inflammatory skin condition affecting millions of individuals worldwide. Over the years, various treatment modalities have been explored to alleviate the symptoms and improve the quality of life for patients with psoriasis. Among these treatment options, lasers and lights have emerged as promising non-invasive approaches with significant efficacy. This review aims to provide an overview of the current understanding and clinical applications of lasers and lights in the management of psoriasis. We have discussed the mechanisms of action behind different laser and light therapies and their impact on psoriatic plaques. Additionally, we discuss the various types of lasers and lights utilized, including excimer lasers, pulsed dye lasers, and narrowband ultraviolet B (NB-UVB) phototherapy, highlighting their unique properties and clinical outcomes. Moreover, we have addressed important considerations related to patient selection, treatment protocols, and potential side effects associated with lasers and lights. We emphasize the need for proper evaluation, monitoring, and customization of treatment plans to ensure optimal outcomes and minimize adverse events.

An Observational Study to Correlate the Histopathological and Dermoscopic Features in Leprosy Patients in a Tertiary Care Hospital.

Introduction: Leprosy is a chronic granulomatous infection with varied clinical presentations. Dermoscopy is a noninvasive technique widely used in the diagnosis of various skin diseases. Objective: To see the correlation between the clinical and dermoscopic features with the histopathological findings in leprosy. Materials and Methods: A prospective observational study was conducted on clinically suspected leprosy patients attending the dermatology outpatient department (OPD) for 18 months. Representative lesions were observed by dermoscopy, and a biopsy was performed, followed by histopathology for final diagnosis. Patients were categorized by Ridley-Jopling classification. Results: A total of 70 clinically suspected leprosy patients were included in the study. Amongst 70 cases, 56 cases were diagnosed as leprosy by dermoscopy, and 53 cases were confirmed as leprosy by histopathology (hematoxylin and eosin [H and E] staining and Fite-Faraco staining). The other six cases were diagnosed as other nonspecific dermatitis by histopathological findings. Eleven cases that were dermoscopically negative were also confirmed by histopathology to be truly negative. There are three inconclusive cases of dermoscopic findings, which were diagnosed as mid-borderline leprosy by histopathology. Dermoscopic and histopathological correlation was found above 87% in all types of leprosy except mid-borderline leprosy, which showed only a 25% correlation. Conclusion: Dermoscopy is a useful noninvasive tool to assess lesions of leprosy, requires less time for diagnosis, skin features are magnified several times and may become evident before clinical presentation. It definitely helps to reduce the number of biopsies in case of diagnosis of leprosy. However, in doubtful cases, histopathology is required for definitive diagnosis as it is the gold standard to date.

Fabrication, evaluation, and enhanced penetration of vinyl and cellulose-engineered transdermal patch of nifedipine using essential oil as penetration enhancer.

The aim of this study was to develop and evaluate the transdermal patch formulations of nifedipine. The patch formulations containing nifedipine were prepared and optimized with different ratios of vinyl and cellulose-derived polymers, drug contents, and permeation enhancers. Among the various formulations, the patch formulation containing a 1:5 ratio of ethyl cellulose and polyvinyl pyrrolidone was selected for ex vivo pharmacokinetic study based on in vitro permeation studies using stratum corneum of the pig's skin. The cumulative percentage release after the transdermal administration of the optimized patch formulation was 71.43%, and the plasma concentration of nifedipine was maintained for 16 hrs. The physicochemical evaluation study including flatness, thickness, moisture content and uptake, drug content in vitro release, and ex vivo permeation indicated satisfactory results. The formulation batch with clove oil as a penetration enhancer has shown better ex vivo permeation as compared to the formulations without enhancers and another synthetic enhancer. These results suggest that the optimized patch formulation Q3 could be further developed for clinical applications, providing the therapeutic plasma level of nifedipine over an extended period. Hence analyzing the results of the evaluation tests, in vitro and ex vivo data on the preparation and optimization of nifedipine-loaded transdermal patch, it can be concluded that the formulation shows its feasibility as an effective transdermal delivery system for nifedipine.