A Case of Anatopic Phenomenon in Dapsone Hypersensitivity Syndrome.

We report a case of a 67-year-old woman on multidrug therapy for borderline lepromatous leprosy who developed dapsone hypersensitivity syndrome (DHS). She presented with fever and red pruritic rash over her face, neck, trunk and upper limbs, with distinct sparing of hypopigmented leprosy patches on her trunk. Laboratory findings showed anemia, elevated white blood cell count and liver function abnormalities. Upon discontinuation of dapsone and initiation of intravenous dexamethasone, the reaction subsided. This case report describes anatopic response, a phenomenon where a cutaneous infection modifies the inflammatory response of a secondary inflammatory dermatoses at the same location. We further elucidate the pathogenic mechanisms implicated in anatopic response, a phenomenon not commonly documented in the literature.

Deciphering the genetic impact of signal peptide missense CTLA-4 polymorphism with rheumatoid arthritis in the Indian population: A case-control and in silico studies.

Cytoplasmic T Lymphocyte Antigen-4 (CTLA-4) gene encodes for a glycoprotein, expressed on activated T-cells to transfer an inhibitory signal to control T-cell activation and proliferation. Techniques coupled with Real-time Polymerase Chain Reaction (PCR) and High-Resolution Melting Analysis (HRMA) were used to screen a missense signal peptide polymorphism (CTLA-4 + 49 A/G rs231775) in the Indian population to detect its association with Rheumatoid Arthritis (RA). Further, the resulting outcome was confirmed by Sanger's sequencing technique, and genotype frequencies were calculated. In eukaryotic cells, the M domain of the Signal Recognition Particle (SRP-54) recognizes the N-terminal region of the Signal Peptide (SP) sequence. SP directs the polypeptide chain into the Sec-61 translocon of the Endoplasmic Reticulum (ER) for further protein modification. As the Single Nucleotide Polymorphism (SNP) rs231775 lies in the signal peptide region of CTLA-4, an in-silico study was also performed to predict the mRNA stability and SP-SRP protein interaction. From the study, it was observed that the genotype frequency of rs231775 SNP G/G homozygous dominant was significantly higher in RA patients than G/A heterozygous dominant and A/A homozygous recessive conditions (Odd Ratio (OR) = 2.0862; 95 % Confidence Interval (C.I) = 1.2584 to 3.4584; Relative Risk (RR) = 1.8507; p = 0.0044). Moreover, the rs231775 SNP G allele frequency was higher in RA than the control group G = 0.407 (40.7 %) vs 0.32 (32 %). In silico approaches of Protein-Protein docking and Molecular Dynamics (MD) simulation reveal CTLA-4 rs231775 SNP (G allele) has destabilized the SP-SRP protein complex, which may affect the translocation of CTLA-4 nascent polypeptide chains into the ER via activating Regulation of Aberrant Protein Production (RAPP) pathway.

Optimized production of carboxymethyl cellulose/guar gum based durable hydrogel for in vitro performance assessment.

An important objective of researchers is to develop a perfect wound dressing that can effectively treat different kinds of wounds. Natural substances with beneficial qualities, such as plant extracts and biopolymers are an ideal aid for wound care. Hydrogels based on biopolymers offer a lot of promising applications for topical use and are biocompatible, hydrophilic and non-toxic. When employed alone or in conjunction with other active agents, herbal extracts have a great deal of use in the healing of wounds. This study comprises Ruellia tuberosa extract loaded with carboxymethyl cellulose and guar gum hydrogels that have potential anti-bacterial, antioxidant, anti-inflammatory and hemocompatibility. Using mouse fibroblast cells (L929), the MTT (3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) test was conducted to assess the biocompatibility. Furthermore, the scratch wound assay using the L929 fibroblast cell line of mouse was employed to assess the in vitro wound healing potential of the synthesised composite hydrogels.

Greater benefits of deep learning-based computer-aided detection systems for finding small signals in 3D volumetric medical images.

Purpose: Radiologists are tasked with visually scrutinizing large amounts of data produced by 3D volumetric imaging modalities. Small signals can go unnoticed during the 3D search because they are hard to detect in the visual periphery. Recent advances in machine learning and computer vision have led to effective computer-aided detection (CADe) support systems with the potential to mitigate perceptual errors. Approach: Sixteen nonexpert observers searched through digital breast tomosynthesis (DBT) phantoms and single cross-sectional slices of the DBT phantoms. The 3D/2D searches occurred with and without a convolutional neural network (CNN)-based CADe support system. The model provided observers with bounding boxes superimposed on the image stimuli while they looked for a small microcalcification signal and a large mass signal. Eye gaze positions were recorded and correlated with changes in the area under the ROC curve (AUC). Results: The CNN-CADe improved the 3D search for the small microcalcification signal ( Δ AUC = 0.098 , p = 0.0002 ) and the 2D search for the large mass signal ( Δ AUC = 0.076 , p = 0.002 ). The CNN-CADe benefit in 3D for the small signal was markedly greater than in 2D ( Δ Δ AUC = 0.066 , p = 0.035 ). Analysis of individual differences suggests that those who explored the least with eye movements benefited the most from the CNN-CADe ( r = - 0.528 , p = 0.036 ). However, for the large signal, the 2D benefit was not significantly greater than the 3D benefit ( Δ Δ AUC = 0.033 , p = 0.133 ). Conclusion: The CNN-CADe brings unique performance benefits to the 3D (versus 2D) search of small signals by reducing errors caused by the underexploration of the volumetric data.

Experimental assessment of biostimulants on mung bean growth on a soilless culture system using superabsorbent pectin based hydrogel.

Sustainable agriculture initiatives are needed to ensure the food security of the people all over the world. Soilless cultivation methods using hydrogels may give a revolutionary response as well as a more ecological and productive alternative to conventional farming. This study attempted extraction of pectin from the rind of albedo yellow passion fruit (Passiflora edulis var. flavicarpa Degener)and hydrogels from pectin and activated carbon was compared with pure pectin hydrogel; Pectin- Activated Carbon hydrogels (PAC) showed a microporous structure with excellent hydrophilicity and showed superior water holding capacity. Then the prepared hydrogels were examined with various instrumental techniques like FTIR, SEM, XRD, Raman, BET and rheological properties. In the BET analysis, PAC3 shows the highest surface area of 28.771 m2/g when compared to PAC0 at 15.063 m2/g. The germination experiments were performed using mung beans. This study provides an opportunity for the application of pectin hydrogels in agriculture field specifically for home garden or rooftop cultivation.

An In Vitro Study to Compare the Shear Bond Strength of Metal and Ceramic Brackets Using Conventional Acid Etch and Self-Etch Primer.

Aim: In this, in vitro study's objective is to assess the shear bond strength (SBS) of metal and ceramic orthodontic brackets that have been adhered to enamel using a conventional acid etch/primer and self-etching primer (SEP) adhesive method. Materials and Methods: One hundred excised human premolars were bonded on brackets and were divided into group 1 -Metal brackets were bonded on teeth and group 2 -Ceramic brackets were bonded on teeth. These two groups were further subdivided: subgroup 1a - 25 metal brackets bonded using conventional acid etch/primer adhesive system, subgroup 1b - 25 metal brackets bonded using SEP, subgroup 2a - 25 ceramic brackets bonded using conventional acid etch/primer adhesive system, and subgroup 2b - 25 ceramic brackets bonded using SEP; brackets were debonded using a computerized Instron universal testing machine. Results: The mean value of SBS of metal and ceramic brackets bonded using conventional acid etch/primer adhesive systems had higher SBS than those bonded using SEP. SBS ranged from 7.95 to 12.24 MPa which was in the acceptable clinical range. Conclusion: SBS values of all four subgroups exceeded the range of 6-8 MPa observed to be acceptable for routine clinical use.

Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape.

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy. Immune checkpoint inhibitors' anticancer properties have drawn considerable attention in recent studies in the cancer research domain. Programmed Cell Death Protein-1 (PD-1) and its ligand (PD-L1) checkpoint pathway are key regulators of the interactions between activated T-cells and cancer cells, protecting the latter from immune destruction. When the ligand PD-L1 attaches to the receptor PD-1, T-cells are prevented from destroying cells that contain PD-L1, including cancer cells. The PD-1/PD-L1 checkpoint inhibitors block them, boosting the immune response and strengthening the body's defenses against tumors. Recent years have seen incredible progress and tremendous advancement in developing anticancer therapies using PD-1/PD-L1 targeting antibodies. While immune-related adverse effects and low response rates significantly limit these therapies, there is a need for research on methods that raise their efficacy and lower their toxicity. This review discusses various recent innovative nanomedicine strategies such as PLGA nanoparticles, carbon nanotubes and drug loaded liposomes to treat cancer targeting PD-1/PD-L1 axis. The biological implications of PD-1/PD-L1 in cancer treatment and the fundamentals of nanotechnology, focusing on the novel strategies used in nanomedicine, are widely discussed along with the corresponding guidelines, clinical trial status, and the patent landscape of such formulations.

The role of beat-by-beat cardiac features in machine learning classification of ischemic heart disease (IHD) in magnetocardiogram (MCG).

Cardiac electrical changes associated with ischemic heart disease (IHD) are subtle and could be detected even in rest condition in magnetocardiography (MCG) which measures weak cardiac magnetic fields. Cardiac features that are derived from MCG recorded from multiple locations on the chest of subjects and some conventional time domain indices are widely used in Machine learning (ML) classifiers to objectively distinguish IHD and control subjects. Most of the earlier studies have employed features that are derived from signal-averaged cardiac beats and have ignored inter-beat information. The present study demonstrates the utility of beat-by-beat features to be useful in classifying IHD subjects (n = 23) and healthy controls (n = 75) in 37-channel MCG data taken under rest condition of subjects. The study reveals the importance of three features (out of eight measured features) namely, the field map angle (FMA) computed from magnetic field map, beat-by-beat variations of alpha angle in the ST-T region and T wave magnitude variations in yielding a better classification accuracy (92.7 %) against that achieved by conventional features (81 %). Further, beat-by-beat features are also found to augment the accuracy in classifying myocardial infarction (MI) Versus control subjects in two public ECG databases (92 % from 88 % and 94 % from 77 %). These demonstrations summarily suggest the importance of beat-by-beat features in clinical diagnosis of ischemia.

Knockout of ecdysis triggering hormone receptor (ETHr) gene adversely affects the nymphal molting and adult reproduction in Bemisia tabaci.

Bemisia tabaci (Gennadius) is one of the most dangerous polyphagous pests in the world causing damage to various crops by sucking sap during the nymphal and adult stages. Chemical management of whiteflies is challenging because of the emergence of pesticide resistance. RNA interference has been well established in whitefly to study the functions of various genes. G-protein coupled receptors (GPCRs) are important targets for development of new generation insecticides. In this study, Ecdysis triggering hormone receptor (ETHr) gene expression was recorded in different stages of whitefly and its function has been studied through RNAi. The expression of ETHr is highest in third-instar nymphs followed by other nymphal instars, pupae and newly emerged adults. Silencing of ETHr resulted in significantly higher adult mortality (68.88%), reduced fecundity (4.46 eggs /female), reduced longevity of male and female (1.05 and 1.40 days, respectively) when adults were fed with dsETHr @ 1.0 µg/µl. Silencing of ETHr in nymphs lead to significantly higher mortality (81.35%) as compared to control. This study confirms that ETHr gene is essential for growth and development of whitefly nymphs and adults. Hence, it can be future target for developing dsRNA based insecticides for management of whitefly.

Organic Remobilization of zinc and phosphorus availability to plants by application of mineral solubilizing bacteria Pseudomonas aeruginosa.

Incessant utilization of chemical fertilizers leads to the accumulation of minerals in the soil, rendering them unavailable to plants. Unaware of the mineral reserves present in the soil, farming communities employ chemical fertilizers once during each cultivation, a practice that causes elevated levels of insoluble minerals within the soil. The use of biofertilizers on the other hand, reduces the impact of chemical fertilizers through the action of microorganisms in the product, which dissolves minerals and makes them readily available for plant uptake, helping to create a sustainable environment for continuous agricultural production. In the current investigation, a field trial employing Arachis hypogaea L was conducted to evaluate the ability of Pseudomonas aeruginosa to enhance plant growth and development by solubilizing minerals present in the soil (such as zinc and phosphorus). A Randomized Complete Block Design (RCBD) included five different treatments as T1: Un inoculated Control; T2: Seeds treated with a liquid formulation of P. aeruginosa; T3: Seeds treated with a liquid formulation of P. aeruginosa and the soil amended with organic manure (farmyard); T4: Soil amended with organic manure (farmyard) alone; T5: Seeds treated with lignite (solid) based formulation of P. aeruginosa were used for the study. Efficacy was determined based on the plant's morphological characters and mineral contents (Zn and P) of plants and soil. Survival of P. aeruginosa in the field was validated using Antibiotic Intrinsic patterns (AIP). The results indicated that the combination treatment of P. aeruginosa liquid formulation and organic fertilizer (farmyard) (T3) produced the highest biometric parameters and mineral (Zn and P) content of the groundnut plants and the soil. This outcome is likely attributed to the mineral solubilizing capability of P. aeruginosa. Furthermore, the presence of farmyard manure increased the metabolic activity of P. aeruginosa by inducing its heterotrophic activity, leading to higher mineral content in T3 soil compared to other soil treatments. The AIP data confirmed the presence of the applied liquid inoculant by exhibiting a similar intrinsic pattern between the in vitro isolate and the isolate obtained from the fields. In summary, the Zn and P solubilization ability of P. aeruginosa facilitates the conversion of soil-unavailable mineral form into a form accessible to plants. It further proposes the utilization of the liquid formulation of P. aeruginosa as a viable solution to mitigate the challenges linked to solid-based biofertilizers and the reliance on mineral-based chemical fertilizers.

Cardiac arrest in the setting of probable catastrophic antiphospholipid syndrome in young patient with a history of COVID infection and polyglandular disorder-Case report.

Antiphospholipid syndrome is an autoimmune disorder characterized by arterial and venous thrombosis and recurrent spontaneous abortions due to the persistent presence of antiphospholipid antibodies. Probable Catastrophic antiphospholipid (Catastrophic antiphospholipid-like syndrome) is a life-threatening presentation of antiphospholipid syndrome which manifests as intravascular thrombosis, leading to rapid onset of symptoms and involvement of multiple organ systems. We present a case of a 28-year-old woman with a history of polyglandular autoimmune syndrome, systemic lupus erythematosus, provoked bilateral deep vein thrombosis in the setting of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection 2 years prior, and hypothyroidism who presents with a cardiac arrest in the setting of an acute ST-elevation myocardial infarction with thromboembolic occlusion of two coronary arteries simultaneously in the setting of noncompliance with anticoagulation for the past 1 week. Her presentation was further complicated by acute hypoxic respiratory failure due to diffuse alveolar hemorrhage during the hospital course with progressive multiorgan failure and eventual death. Catastrophic antiphospholipid is associated with high morbidity and mortality, thus a timely diagnosis and multidisciplinary approach to management is needed for evaluation and management.

Understanding immune checkpoints and PD-1/PD-L1-mediated immune resistance towards tumour immunotherapy.

Immunotherapy has emerged as a transformative approach in the treatment of various cancers, offering new hope for patients previously faced with limited treatment options. A cornerstone of cancer immunotherapy lies in targeting immune checkpoints, particularly the programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway. Immune checkpoints serve as crucial regulators of the immune response, preventing excessive immune activity and maintaining self-tolerance. PD-1, expressed on the surface of T cells, and its ligand PD-L1, expressed on various cell types, including cancer cells and immune cells, play a central role in this regulatory process. Although the success rate associated with these immunotherapies is very promising, most patients still show intrinsic or acquired resistance. Since the mechanisms related to PD-1/PD-L1 resistance are not well understood, an in-depth analysis is necessary to improve the success rate of anti-PD-1/PD-L1 therapy. Hence, here we provide an overview of PD-1, its ligand PD-L1, and the resistance mechanism towards PD-1/PD-L1. Furthermore, we have discussed the plausible solution to increase efficacy and clinical response. For the following research, joint endeavours of clinicians and basic scientists are essential to address the limitation of resistance towards immunotherapy.

Vosoritide, a miracle drug, covering unmet need in achondroplasia: A regulatory update.

Dwarfism is a rare condition characterized by small stature. Achondroplasia is predominantly considered the leading cause of dwarfism. Although the condition is not life-threatening, it dramatically impacts the social life of the patient. The United States Food and Drug Administration (US FDA) first approved the drug Voxzogo (vosoritide) for achondroplasia. The drug also received approval from the European Medicines Agency (EMA) via the centralized procedure. The drug is associated with a decrease in blood pressure, a severe adverse event. However, this adverse event/risk has been overcome by benefits, i.e. fulfilling of unmet medical need. In the United States, the drug received accelerated approval as it satisfied the criteria of rare pediatric disease. This review includes a detailed orphan drug approval process with particular reference to vosoritide, which is considered a milestone for the treatment of achondroplasia.

Public Health Dentistry as a Career Choice - Attitude of Dental Undergraduate Students in Puducherry.

Background: To pursue further education in a particular specialty of dentistry, it is important for dental students to be aware of the "expectation" associated with any specific specialty in dentistry. Therefore students 'attitudes' towards 'expectations' of various specialties, to a large extent enables a meaningful understanding that facilitates appropriate planning in the dental sector for the community. Materials and Methods: A cross-sectional questionnaire based survey was conducted, which included, final year and dental interns studying in two dental institutions, in the State of Puducherry. It consisted of 27 questions that were graded using 5-point Likert scale. The responses for the attitude questions toward selecting Public Health Dentistry for post-graduation were categorized into three factors, negative attitude (includes score 0-21), neutral attitude (score 22-44), and positive attitude (score 45-64). Differences between groups were examined using t-test for proportions. The level of statistical significance was set at p < 0.05. Results: Among 221 respondents, 73 (33.0) were males and 148 (67.0) females. About (52.2%) of the respondents had positive attitude toward selecting Public Health Dentistry as their future career and (76.7%) had neutral attitude, around (5 %) had negative attitude towards the speciality for pursuing post-graduation in both the two institutions. Conclusion: Our study could highlight many factors namely gender, year of study etc which influence the attitude of students for selecting PHD as career choice. These specific factors could be kept in mind while course planning for government or private institutions so that maximum interest can be fetched among students.

A method for noninvasive beat-by-beat visualization of His bundle signals.

BACKGROUND: Invasive recording of His bundle signals (HBS) in electrophysiological study (EPS) is important in determining HV interval, the time taken to activate the ventricles from the His bundle. Noninvasive surface measurements of HBS are attempted by averaging typically 100-200 cardiac cycles of ECG time series in body surface potential mapping (BSPM) and in magnetocardiography (MCG) which records weak cardiac magnetic fields by highly sensitive detectors. However, noninvasive beat-by-beat extraction of HBS is challenged by ramp-like atrial signals and noise in PR segment of the cardiac cycle. METHODS: By making use of a signal-averaged trace showing prominent HBS as a guide trace, we developed a method combining interval-dependent wavelet thresholding (IDWT) and signal space projection (SSP) technique to eliminate artifacts from single beats. The method was applied on MCG recorded on 21 subjects with known HV intervals based on EPS and noninvasive signal-averaging, including five subjects with BSPM recorded subsequently. The method was also applied on stress-MCG of a subject featuring autonomic dynamics. RESULTS: HBS could be extracted from 19 out of 21 subjects by signal-averaging whose timing differed from EPS between -8 and 11 ms as tested by 2 observers. HBS in single beats were seen as aligned patterns in inter-beat contours and were appreciable in stress-MCG and conspicuous than BSPM. The performance of the method was evaluated on simulated and measured MCG to be adequate if the signal-to-noise ratio was at least 20 dB. CONCLUSIONS: These results suggest the use of this method for noninvasive assessments on HBS.

A 2D Synthesized Image Improves the 3D Search for Foveated Visual Systems.

Current medical imaging increasingly relies on 3D volumetric data making it difficult for radiologists to thoroughly search all regions of the volume. In some applications (e.g., Digital Breast Tomosynthesis), the volumetric data is typically paired with a synthesized 2D image (2D-S) generated from the corresponding 3D volume. We investigate how this image pairing affects the search for spatially large and small signals. Observers searched for these signals in 3D volumes, 2D-S images, and while viewing both. We hypothesize that lower spatial acuity in the observers' visual periphery hinders the search for the small signals in the 3D images. However, the inclusion of the 2D-S guides eye movements to suspicious locations, improving the observer's ability to find the signals in 3D. Behavioral results show that the 2D-S, used as an adjunct to the volumetric data, improves the localization and detection of the small (but not large) signal compared to 3D alone. There is a concomitant reduction in search errors as well. To understand this process at a computational level, we implement a Foveated Search Model (FSM) that executes human eye movements and then processes points in the image with varying spatial detail based on their eccentricity from fixations. The FSM predicts human performance for both signals and captures the reduction in search errors when the 2D-S supplements the 3D search. Our experimental and modeling results delineate the utility of 2D-S in 3D search-reduce the detrimental impact of low-resolution peripheral processing by guiding attention to regions of interest, effectively reducing errors.

RARE PRESENTATION OF BILATERAL CAROTID-CAVERNOUS FISTULA AS SUPRACHOROIDAL HEMORRHAGE DURING CATARACT SURGERY.

OBJECTIVE: To report a rare case of suprachoroidal hemorrhage during phacoemulsification in a patient with bilateral carotid-cavernous fistula. METHOD: Case report. RESULT: A 76-year-old woman with underlying hypertension presented left eye poor vision due to an underlying dense cataract. Her initial preoperative assessment was uneventful, and she underwent phacoemulsification. During epinucleus removal, there was sudden, unexpected anterior chamber shallowing, resulting in posterior capsule rupture. While the surgeon extended the wound to facilitate epinucleus removal, there was a further decrease of red reflex, followed by hardening of the globe, indicating a suprachoroidal hemorrhage. The corneal wound was opposed swiftly without an intraocular lens. Further evaluation after that revealed the patient had a chronic headache for several years, and ocular examination showed bilateral esophoria. A computed tomography demonstrated features suggestive of bilateral carotid-cavernous fistula, which was confirmed with computed tomography angiography later. CONCLUSION: Patients with carotid-cavernous fistula have elevated episcleral venous pressure and vortex venous pressure. Sudden decompression of the globe in these patients predisposes them to higher suprachoroidal hemorrhage risk, although this condition is generally rare in phacoemulsification.

Molecular docking study on vitamin D supplements to understand their interaction with VDR-RXRα heterodimer and VDRE of TAGAP gene.

The expression level of T cell activation Rho GTPase activating protein (TAGAP) gene is higher in rheumatoid arthritis (RA) patients compared to healthy individuals. Vitamin D receptor element (VDRE) sequences present in the regulatory region of TAGAP gene are targeted by vitamin D dependent Vitamin D receptor (VDR) - retinoic acid X receptor (RXR) heterodimer complex to regulate the TAGAP gene expression. Reduction in the expression of the TAGAP gene can prevent different severity of RA disease conditions. Calcitriol is a proven vitamin D supplement prescribed to patients with RA. However, it is involved in causing hypercalcemia. Maxacalcitol, an analog of vitamin D, is shown to have less hypercalcemic activity when compared to calcitriol. This study was done to analyze and compare the binding modes of calcitriol and maxacalcitol with VDR. We also studied the interactions of these compounds with the VDR-RXRα heterodimer complex. In addition, the binding of the ligand-activated heterodimer complexes with VDREs of the TAGAP gene was also analyzed to comprehend the binding affinities of calcitriol and maxacalcitol to the gene. The current work utilizes in silico molecular docking and simulation analysis to understand the mechanism in each complex formation.Communicated by Ramaswamy H. Sarma.