Patch Testing in Allergic Contact Dermatitis.

BACKGROUND: Allergic contact dermatitis is one of the most common forms of skin diseases that require medical intervention. Appropriate detection of allergens by patch test and accurate avoidance of them is the key to management. The objective of this study is to determine the types and frequency of allergens responsible for Allergic contact dermatitis in a tertiary hospital of Nepal. METHODS: Altogether 120 patients with Allergic contact dermatitis were enrolled in the study. Patch test was performed to find out the most common inciting allergen, utilizing the Indian Standard Series of allergens approved by The Contact and Occupational Dermatoses Forum of India. Results were read at 48 and 96 hours. Grading of the reactions was done based on the criteria of the International Contact Dermatitis Research Group. Pattern of reactivity of different allergens was assessed. RESULTS: Of all the patients, 63 (53%) showed positivity to at least one allergen. Nickel sulfate was the most frequent sensitizing agent in 22 (18%) cases, followed by Fragrance mix in 11(9%) and Paraphenylenediamine in 7 (6%) cases. Out of all positive results, Grade 1 positivity was seen in 44 (51%), Grade 2 positivity in 41(47%) and only 2 (2%) cases showed Grade 3 positivity. Mercaptobenzothiazole, Balsam of Peru, Nitrofurazone and Wool Alcohol did not show positive results in any of our patients. CONCLUSIONS: Patch testing helps in the treatment, long term remission, and patient counseling for prevention. Larger scale studies are required to know the sensitivity to allergens in Nepalese population.

Third Generation Solid Dispersion-Based Formulation of Novel Anti-Tubercular Agent Exhibited Improvement in Solubility, Dissolution and Biological Activity.

The long treatment period and development of drug resistance in tuberculosis (TB) necessitates the discovery of new anti-tubercular agents. The drug discovery program of the institute leads to the development of an anti-tubercular lead (IIIM-019), which is an analogue of nitrodihydroimidazooxazole and exhibited promising anti-tubercular action. However, IIIM-019 displays poor aqueous solubility (1.2 µg/mL), which demands suitable dosage form for its efficient oral administration. In the present study, third generation solid dispersion-based formulation was developed to increase the solubility and dissolution of IIIM-019. The solubility profile of IIIM-019 using various polymeric carriers was determined and subsequently, PVP K-30 and P-407 were selected for preparation of binary and ternary solid dispersion. The third-generation ternary solid dispersion comprising PVP K-30 and P-407 revealed a remarkable enhancement in the aqueous solubility of IIIM-019. Physicochemical characterization of the developed formulations was done by employing FTIR spectroscopy, scanning electron microscopy, X-ray diffraction analysis, differential scanning calorimetry, and dynamic light scattering analysis. The dissolution study indicated an impressive release profile with the optimized formulation. The optimized formulation was further examined for cytotoxicity, cellular uptake, and hemolytic activity. The results indicated that the formulation had no apparent cytotoxicity on Caco-2 cells and was non-hemolytic in nature. Moreover, the optimized formulation showed significantly improved anti-tubercular activity compared to the native molecule. These findings showed that the developed third generation ternary solid dispersion could be a promising option for the oral delivery of investigated anti-tubercular molecule.

Novel purification platform based on multimodal preparative scale separation of mAb fragments and aggregates.

Monoclonal antibodies (mAbs) continue to dominate the biopharmaceutical industry. Certain mAbs are prone to fragmentation and clipping and in these cases, adequate removal of these species is critical during manufacturing. Fragments can be generated during fermentation, purification, storage, formulation, and administration. Their addition to the acidic charge-variant of the purified mAb has been reported to decrease stability and potency of the final product. However, contrary to mAb aggregation, manufacturers have not given much attention to removal of fragments and clipped species and as a result most conventional mAb platforms offer at best limited capabilities for their removal. In this study, we propose a novel purification platform that uses multimodal chromatography and achieves complete removal of a range of mAb fragments and clipped products (25-120 kDa). The utility of the platform has been successfully demonstrated for 2 IgG1s and 2 IgG4s. Further, adequate removal of the various host cell impurities such as host cell proteins (<10 ppm) and host cell DNA (<5 ppb) has been achieved. Finally, the platform was able to deliver adequate removal of high molecular weight impurities (<1 %) and a 30 % clearance of the acidic charge variant. The proposed single step has been shown to deliver what the polishing chromatography and intermediate purification chromatography steps deliver in a traditional mAb platform.

Questions From Family Members During the Dying Process And Moral Distress Experienced by ICU Nurses.

BACKGROUND: For a hospitalized patient, transitioning to comfort measures only (CMO) involves discontinuation of life-prolonging interventions with a goal of allowing natural death. Nurses play a pivotal role during the provision of CMO, caring for both the dying patient and their family. OBJECTIVE: To examine the experiences of ICU nurses caring for patients receiving CMO. METHODS: Between October 2020 and June 2021, nurses in the neuro- and medical-cardiac intensive care units at Harborview Medical Center in Seattle, WA, completed surveys about their experiences providing CMO. Surveys addressed involvement in discussions about CMO and questions asked by family members of dying patients. We also assessed nurses' moral distress related to CMO and used ordinal logistic regression to examine predictors of moral distress. RESULTS: Surveys were completed by 82 nurses (response rate 44%), with 79 (96%) reporting experience providing CMO in the previous year. Most preferred to be present for discussions between physicians or advanced practice providers and family members about transitioning to CMO (89% most of the time or always); however, only 31% were present most of the time or always. Questions from family about time to death, changes in breathing, and medications to relieve symptoms were common. Most nurses reported moral distress at least some of the time when providing CMO (62%). Feeling well-prepared to answer specific questions from family was associated with less moral distress. CONCLUSION: There is discordance between nurses' preferences for inclusion in discussions about the transition to CMO and their actual presence. Moral distress is common for nurses when providing CMO and feeling prepared to answer questions from family members may attenuate distress.

A Halogen-Bond-Driven Artificial Chloride-Selective Channel Constructed from 5-Iodoisophthalamide-based Molecules.

Despite considerable emphasis on advancing artificial ion channels, progress is constrained by the limited availability of small molecules with the necessary attributes of self-assembly and ion selectivity. In this study, a library of small molecules based on 5-haloisophthalamide and a non-halogenated isophthalamide were examined for their ion transport properties across the lipid bilayer membranes, and the finding demonstrates that the di-hexyl-substituted 5-iodoisophthalamide derivative exhibits the highest level of activity. Furthermore, it was established that the highest active compound facilitates the selective chloride transport that occurs via an antiport-mediated mechanism. The crystal structure of the compound unveils a distinctive self-assembly of molecules, forming a zig-zag channel pore that is well-suited for the permeation of anions. Planar bilayer conductance measurements proved the formation of chloride selective channels. A molecular dynamics simulation study, relying on the self-assembled component derived from the crystal structure, affirmed the paramount significance of intermolecular hydrogen bonding in the formation of supramolecular barrel-rosette structures that span the bilayer. Furthermore, it was demonstrated that the transport of chloride across the lipid bilayer membrane is facilitated by the synergistic effects of halogen bonding and hydrogen bonding within the channel.

Role and Responsibilities of Various Stakeholders in Pharmacovigilance (PV).

In this review paper, we have analyzed the potential and issues associated with Pharmacovigilance (PV). The analysis is divided into four sections: background, stakeholders, data sources, and medicinal chemistry. Each section discusses the current state, the future trends, and the best practices of Pharmacovigilance (PV). The main purpose, methods, results, and implications of our analysis are summarized. BACKGROUND: Pharmacovigilance (PV) is the science and practice of monitoring, evaluating, understanding, and preventing adverse drug reactions. Pharmacovigilance (PV) was established by the World Health Organization in response to the thalidomide tragedy of 1961. The main purpose of Pharmacovigilance (PV) is to ensure the safety and efficacy of drugs in clinical practice. Stakeholders: Pharmacovigilance (PV) involves various stakeholders, such as patients, pharmacists, pharmaceutical companies, healthcare professionals, and regulatory authorities. Each stakeholder has a different role and responsibility in reporting, processing, analyzing, and communicating information about adverse drug reactions. Patient engagement is a key factor for enhancing Pharmacovigilance (PV) practices. DATA SOURCES: Pharmacovigilance (PV) relies on data from various sources, such as clinical trials, spontaneous reports, electronic medical records, biomedical literature, and patient-reported data in online health forums. These data sources can provide valuable insights into the real-world use and safety of drugs, as well as the preferences and needs of patients. However, these data sources also pose challenges in terms of quality, validity, reliability, and accessibility. Medicinal Chemistry: Medicinal chemistry is the branch of chemistry that deals with the design, synthesis, and evaluation of new drugs and their biological effects. Medicinal chemistry can enhance Pharmacovigilance (PV) practices by finding new therapeutic indications for existing drugs or compounds that have already been tested for safety and efficacy. Medicinal chemistry also requires careful design and evaluation of covalent inhibitors, bi-substrate inhibitors, stabilizers of protein non-effective conformations, and hydrophobic pocket modifiers to ensure their safety and efficacy. IMPLICATIONS: Pharmacovigilance (PV) is a dynamic and evolving discipline that requires collaboration, regulation, education, and innovation to improve patient safety and care. This review aims to provide a comprehensive overview of the potential and issues associated with Pharmacovigilance (PV) practices.

Unraveling Dilemmas and Lacunae in the Escalating Drug Resistance of Mycobacterium tuberculosis to Bedaquiline, Delamanid, and Pretomanid.

Delamanid, bedaquiline, and pretomanid have been recently added in the anti-tuberculosis (anti-TB) treatment regimens and have emerged as potential solutions for combating drug-resistant TB. These drugs have proven to be effective in treating drug-resistant TB when used in combination. However, concerns have been raised about the eventual loss of these drugs due to evolving resistance mechanisms and certain adverse effects such as prolonged QT period, gastrointestinal problems, hepatotoxicity, and renal disorders. This Perspective emphasizes the properties of these first-in-class drugs, including their mechanism of action, pharmacokinetics/pharmacodynamics profiles, clinical studies, adverse events, and underlying resistance mechanisms. A brief coverage of efforts toward the generation of best-in-class leads in each class is also provided. The ongoing clinical trials of new combinations of these drugs are discussed, thus providing a better insight into the use of these drugs while designing an effective treatment regimen for resistant TB cases.

An Electronic Teen Questionnaire, the eTeenQ, for Risk Behavior Screening During Adolescent Well Visits in an Integrated Health System: Development and Pilot Implementation.

Background: Screening for risk behaviors is a routine and essential component of adolescent preventive health visits. Early identification of risks can inform targeted counseling and care. If stored in discrete fields in the electronic health record (EHR), adolescent screening data can also be used to understand risk behaviors across a clinic or health system or to support quality improvement projects. Objective: Goals of this pilot study were to adapt and implement an existing paper adolescent risk behavior screening tool for use as an electronic data capture tool (the eTeenQ), to evaluate acceptance of the eTeenQ, and to describe the prevalence of the selected risk behaviors reported through the eTeenQ. Methods: The multidisciplinary project team applied an iterative process to develop the 29-item eTeenQ. Two unique data entry forms were created with attention to (1) user interface and user experience, (2) the need to maintain patient privacy, and (3) the potential to transmit and store data for future use in clinical care and research. Three primary care clinics within a large health system piloted the eTeenQ from August 17, 2020, to August 27, 2021. During preventive health visits for adolescents aged 12 to 18 years, the eTeenQ was completed on tablets and responses were converted to a provider display for teens and providers to review together. Responses to the eTeenQ were stored in a REDCap (Research Electronic Data Capture; Vanderbilt University) database, and for patients who agreed, responses were transferred to an EHR flowsheet. Responses to selected eTeenQ questions are reported for those consenting to research. At the conclusion of the pilot, the study team conducted semistructured interviews with providers and staff regarding their experience using the eTeenQ. Results: Among 2816 adolescents with well visits, 2098 (74.5%) completed the eTeenQ. Of these, 1811 (86.3%) agreed to store responses in the EHR. Of 1632 adolescents (77.8% of those completing the eTeenQ) who consented for research and remained eligible, 1472 (90.2%) reported having an adult they can really talk to and 1510 (92.5%) reported feeling safe in their community, yet 401 (24.6%) reported someone they lived with had a gun and 172 (10.5%) reported having had a stressful or scary event that still bothered them. In addition, 157 (9.6%) adolescents reported they were or wondered if they were gay, lesbian, bisexual, pansexual, asexual, or other, and 43 (2.6%) reported they were or wondered if they were transgender or gender diverse. Of 11 staff and 7 providers completing interviews, all felt that the eTeenQ improved confidentiality and willingness among adolescents to answer sensitive questions. All 7 providers preferred the eTeenQ over the paper screening tool. Conclusions: Electronic capture of adolescent risk behaviors is feasible in a busy clinic setting and well accepted among staff and clinicians. Most adolescents agreed for their responses to risk behavior screening to be stored in the EHR.

Identification of Chemical Scaffolds Targeting Drug-Resistant and Latent Mycobacterium tuberculosis through High-Throughput Whole-Cell Screening.

Identification of structurally unique chemical entities targeting unexplored bacterial targets is a prerequisite to combat increasing drug resistance against Mycobacterium tuberculosis. This study employed a whole-cell screening approach as an initial filter to scrutinize a 10,000-compound chemical library, resulting in the discovery of seven potent compounds with MIC values ranging from 1.56 to 25 µM. These compounds were categorized into four distinct chemical groups. Remarkably, they demonstrated efficacy against drug-resistant and nonreplicating tuberculosis strains, highlighting their effectiveness across different infection states. With a favorable selectivity index (>10), these compounds showed a safe therapeutic range and exhibited potency in an intracellular model of Mtb infection, mimicking the in vivo setup. Combining these identified hits with established anti-TB drugs revealed additive effects with rifampicin, isoniazid, and bedaquiline. Notably, IIIM-IDD-01 exhibited synergy with isoniazid and bedaquiline, likely due to their complementary mechanisms of targeting Mtb. Most potent hits, IIIM-IDD-01 and IIIM-IDD-02, displayed time- and concentration-dependent killing of Mtb. Mechanistic insights were sought through SEM and docking studies, although comprehensive evaluation is ongoing to unravel the hits' specific targets and modes of action. The hits demonstrated favorable pharmacokinetic properties (ADME-Tox) and showed a low risk of adverse effects, along with a predicted high level of oral bioavailability. These promising hits can serve as an initial basis for subsequent medicinal chemistry endeavors aimed at developing a new series of anti-TB agents. Moreover, the study affirms the significance of high-throughput in vitro assays for the TB drug discovery. It also emphasizes the necessity of targeting diverse TB strains to address the heterogeneity of tuberculosis bacteria.

The significance of persisters in tuberculosis drug discovery: Exploring the potential of targeting the glyoxylate shunt pathway.

The significant challenge in confronting TB eradication is the discursive treatment that results in the disease reactivation, patient non compliance and drug resistance. The presently available drug regimen for TB largely targets the active bacilli and thus remains inadequate against the dormant or persistent subpopulation of Mtb that results in latent TB affecting a quarter of the global population. The crucial pathways that are particularly essential for the survival of dormant Mtb demand better apprehension. Novel drugs are needed to specifically address these persisters in order to enhance treatment effectiveness. Among such pathways, the glyoxylate bypass plays a critical role in the persistence and latent infection of Mtb, making it a promising target for drug development in recent years. In this review, we have compiled the attributes of bacterial subpopulations liable for latent TB and the pathways indispensable for their survival. Specifically, we delve into the glyoxylate shunt pathway and its key enzymes as potential drug targets.

An Insight into the Promising Therapeutic Potential of Chicoric Acid.

The pharmacological treatments that are now recommended for the therapy of chronic illnesses are examined in a great number of studies to determine whether or not they are both safe and effective. Therefore, it is important to investigate various alternative therapeutic assistance, such as natural remedies derived from medicinal plants. In this context, chicoric acid, classified as a hydroxycinnamic acid, has been documented to exhibit a range of health advantages. These include antiviral, antioxidant, anti-inflammatory, obesity-preventing, and neuroprotective effects. Due to its considerable pharmacological properties, chicoric acid has found extensive applications in food, pharmaceuticals, animal husbandry, and various other commercial sectors. This article provides a comprehensive overview of in vitro and in vivo investigations on chicoric acid, highlighting its beneficial effects and therapeutic activity when used as a preventative and management aid for public health conditions, including diabetes, cardiovascular disease, and hepatic illnesses like non-alcoholic steatohepatitis. Moreover, further investigation of this compound can lead to its development as a potential phytopharmaceutical candidate.

Multiple ocean parameter-based potential fishing zone (PFZ) location generation and validation in the Western Bay of Bengal.

A new conceptual framework based on satellite data, including chlorophyll (CHL), sea surface temperature (SST) fronts, relative winds, current vectors, Ekman transport, and eddies, has been developed to identify potential fishing zones (PFZ) in the Bay of Bengal (BoB). The framework aims to provide persistent forecasts, even under cloudy conditions, based on feature propagation. The validation of the PFZ was carried out using fish catch data collected by the Fishery Survey of India (FSI) between 2016 and 2018. Hooking rates (HR) from longlines and catch per unit effort (CPUE) from trawl nets were used to analyse the data points in hook rate categories (1.0-3.0 and > 3.0) and CPUE categories (50-100 kg and > 100 kg) and interpret them with the PFZ maps. The analysis showed that the high fish catch locations were consistent with persisting features in the BoB, such as high chlorophyll patches, SST fronts, and cyclonic eddies. The high fish catch locations based on hook rate and high CPUE were found to be collocated with the high chlorophyll persisting features and thermal gradients in the BoB. The regression analysis shows that availability of the food (CHL) had the strongest correlation with fish catch, followed by the comfort condition (fronts and eddies).

Highly regioselective 6-exo-dig iodo/bromo cyclizations of functionalized 5-amino propargyl pyrimidinones: an efficient synthesis of functionalized pteridines.

The manuscript describes the highly regioselective 6-exo-dig iodo/bromo cyclization of functionalized N-propagyl-amino-pyrimidinones under ambient conditions. The cyclization afforded functionalized pteridines in excellent yields. The optimized procedures are mild, operationally simple and working successfully with different substrates. The synthesis of functionalized pteridines is of great significance because of their potential pharmacological profile.

Unveiling the ESR1 Conformational Stability and Screening Potent Inhibitors for Breast Cancer Treatment

BACKGROUND: The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses. METHOD: In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα. RESULTS: Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity. CONCLUSION: Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer.

Awareness Regarding Antimicrobial Resistance and Antibiotic Prescribing Behavior among Physicians: Results from a Nationwide Cross-Sectional Survey in India.

(1) Background: Understanding the physicians' knowledge, attitudes, and antimicrobial prescribing behavior is a crucial step towards designing strategies for the optimal use of these agents. (2) Methods: A cross-sectional online survey was conducted among clinicians across India between May and July 2022 using a self-administered questionnaire in English comprising 35 questions pertaining to demographic characteristics, knowledge, attitude, and practices domains. (3) Results: A total of 544 responses were received from 710 physicians contacted. Sixty percent of participants were males, with mean age of 34.7 years. Mean ± Standard Deviation scores for knowledge, attitude, and practices domains were 8 ± 1.6, 20.2 ± 3.5, and 15.3 ± 2.1, respectively. Higher scores were associated with basic [odds ratio (95% Confidence Interval), p value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03], and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe (access, watch, and reserve) classification of antibiotics, and the role of infection prevention and control (IPC) measures in the containment of antimicrobial resistance (AMR). (4) Conclusions: There is a need to sensitize and educate clinicians on various issues related to antimicrobial use, such as antibiograms, double anaerobic cover, IPC practices, and guideline-based recommendations, to curb the AMR pandemic.

Supportive care decision-making processes of persons with dementia and their caregivers.

Little is known about the decision-making processes around seeking more supportive care for dementia. Persons with dementia are often left out of decision-making regarding seeking more supportive care as their dementia progresses. This paper provides a description of findings from the Decision-making in Alzheimer's Research project (DMAR) investigating the process of decision-making about transitions to more supportive care. We conducted 61 qualitative interviews with two stakeholder groups: 24 persons with dementia, and 37 informal caregivers to explore supportive care decisions and associated decision-making factors from the perspectives of persons with dementia and their caregivers. We identified four main decisions that persons with dementia and their informal caregivers played a role in: (1) sharing household responsibilities; (2) limiting routine daily activities; (3) bringing in formal support; and (4) moving to a care facility. Based on our findings we developed a schematized roadmap of decision-making that we used to guide the discussion of our findings. Four crosscutting themes emerged from our analysis: unknowns and uncertainties, maintaining life as you know it, there's no place like home and resource constraints. These results will be incorporated into the development of instruments whose goal is to identify preferences of persons with dementia and their caregivers, in order to include persons with dementia in care decisions even as their dementia progresses.

Supramolecular Barrel-Rosette Ion Channel Based on 3,5-Diaminobenzoic Acid for Cation-Anion Symport.

The structural tropology and functions of natural cation-anion symporting channels have been continuously investigated due to their crucial role in regulating various physiological functions. To understand the physiological functions of the natural symporter channels, it is vital to develop small-molecule-based biomimicking systems that can provide mechanistic insights into the ion-binding sites and the ion-translocation pathways. Herein, we report a series of bis((R)-(-)-mandelic acid)-linked 3,5-diaminobenzoic acid based self-assembled ion channels with distinctive ion transport ability. Ion transport experiment across the lipid bilayer membrane revealed that compound 1 b exhibits the highest transport activity among the series, and it has interesting selective co-transporting functions, i.e., facilitates K+ /ClO4 - symport. Electrophysiology experiments confirmed the formation of supramolecular ion channels with an average diameter of 6.2±1 Šand single channel conductance of 57.3±1.9 pS. Selectivity studies of channel 1 b in a bilayer lipid membrane demonstrated a permeability ratio of P C l - / P K + = 0 . 053 ± 0 . 02 ${{P}_{{Cl}^{-}}/{P}_{{K}^{+}}=0.053\pm 0.02}$ , P C l O 4 - / P C l - = 2 . 1 ± 0 . 5 ${{P}_{{ClO}_{4}^{-}}/{P}_{{Cl}^{-}}=2.1\pm 0.5}$ , and P K + / P N a + = 1 . 5 ± 1 , ${{P}_{{K}^{+}}/{P}_{{Na}^{+}}=1.5\pm 1,}$ indicating the higher selectivity of the channel towards KClO4 over KCl salt. A hexameric assembly of a trimeric rosette of 1 b was subjected to molecular dynamics simulations with different salts to understand the supramolecular channel formation and ion selectivity pattern.

Harnessing host-pathogen interactions for innovative drug discovery and host-directed therapeutics to tackle tuberculosis.

Tuberculosis (TB) is a highly contagious bacterial infection caused by Mycobacterium tuberculosis (Mtb), which has been ranked as the second leading cause of death worldwide from a single infectious agent. As an intracellular pathogen, Mtb has well adapted to the phagocytic host microenvironment, influencing diverse host processes such as gene expression, trafficking, metabolism, and signaling pathways of the host to its advantage. These responses are the result of dynamic interactions of the bacteria with the host cell signaling pathways, whereby the bacteria attenuate the host cellular processes for their survival. Specific host genes and the mechanisms involved in the entry and subsequent stabilization of M. tuberculosis intracellularly have been identified in various genetic and chemical screens recently. The present understanding of the co-evolution of Mtb and macrophage system presented us the new possibilities for exploring host-directed therapeutics (HDT). Here, we discuss the host-pathogen interaction for Mtb, including the pathways adapted by Mtb to escape immunity. The review sheds light on different host-directed therapies (HDTs) such as repurposed drugs and vitamins, along with their targets such as granuloma, autophagy, extracellular matrix, lipids, and cytokines, among others. The article also examines the available clinical data on these drug molecules. In conclusion, the review presents a perspective on the current knowledge in the field of HDTs and the need for additional research to overcome the challenges associated HDTs.

Evaluation of Thyroid Lesions by Fine Needle Aspiration Cytology According to Bethesda System.

Aim To study cytology of various Thyroid lesions based on Bethesda system and to evaluate diagnostic accuracy of cytology by comparing it with histomorphological diagnosis whenever available. Materials and method In this study Fine needle aspiration cytology of 330 patients of clinically palpable thyroid were evaluated from June 2019 to December 2021 and categorised according to TBSRTC. 38 patients underwent surgical management in our hospital. Sensitivity, specificity, positive predictive value, negative predictive value reported under bethesda system were obtained by comparing the cytological and histopathological diagnosis where ever possible. Result The distribution of various categories from 330 evaluated thyroid nodules was as follows: 2.73% Non Diagnostic, 83.03% Benign, 0% Atypia of undetermined significance, 9.70% FN, 0.61% Suspicious for malignancy and 3.94% malignant. Sensitivity, specificity, positive predictive value, negative predictive value was 100, 60, 94.29 and 100% respectively. The diagnostic accuracy was calculated to be 94.73%. Conclusion There is a clearcut distinction between the two ends of the spectrum of non-neoplastic and neoplastic lesions of thyroid. Diagnostic accuracy of Bethesda system for reporting cytopathology for better clinical management is proven by the present study.

Evolution of tuberculosis diagnostics: From molecular strategies to nanodiagnostics.

Tuberculosis has remained a global concern for public health affecting the lives of people for ages. Approximately 10 million people are affected by the disease and 1.5 million succumb to the disease worldwide annually. The COVID-19 pandemic has highlighted the role of early diagnosis to win the battle against such infectious diseases. Thus, advancement in the diagnostic approaches to provide early detection forms the foundation to eradicate and manage contagious diseases like tuberculosis. The conventional diagnostic strategies include microscopic examination, chest X-ray and tuberculin skin test. The limitations associated with sensitivity and specificity of these tests demands for exploring new techniques like probe-based assays, CRISPR-Cas and microRNA detection. The aim of the current review is to envisage the correlation between both the conventional and the newer approaches to enhance the specificity and sensitivity. A significant emphasis has been placed upon nanodiagnostic approaches manipulating quantum dots, magnetic nanoparticles, and biosensors for accurate diagnosis of latent, active and drug-resistant TB. Additionally, we would like to ponder upon a reliable method that is cost-effective, reproducible, require minimal infrastructure and provide point-of-care to the patients.