Pathophysiological and pharmacological modulation of melatonergic system

Pineal gland once considered as rudimentary or vestigial, has become a principal endocrine gland that regulates the body’s internal environment, after the discovery of melatonin - a hormone produced by it. Melatonin is also synthesized from extra-pineal sites such as retina, skin, platelets, bone marrow, and gastrointestinal tract. The chronobiological property of this hormone in maintaining the circadian rhythm by synchronizing with the dark-light cycle is well-established. Melatonin also possesses anti-inflammatory, anti-depressant, anti-oxidant, oncostatic, immunomodulatory, antiepileptic, and glucose-regulating properties. These pleiotropic effects of melatonin on diverse organ systems either through a receptor or non-receptor mediated pathways are under investigation. This review highlights the pathophysiological and pharmacological actions of melatonin along with melatonergic agonists in “real life” clinical practice

Biomechanical analysis of the effect of ‘intermediate screws’ in short segment posterior fixation of unstable burst fractures of thoracolumbar spine in calf spine model

Background: Efforts in preserving motion levels in unstable thoracolumbar burst fractures steered to short segment fixation. However, short segment spanning fixation in clinical scenario reported high failure rates.  Augmentation of spanning fixation by inserting intermediate screws into the fracture level is proposed to enhance stability. An experimental comparative study was performed to assess the biomechanical role of the ‘intermediate screws.’ Methods: Five calf spine specimens were freshly prepared to record the biomechanical characteristics, range of motion (ROM), and stiffness. CT scan confirmed an unstable burst fracture in each specimen. Each specimen was instrumented with short-segment posterior fixation with an intermediate screw. The same test protocols were repeated with and without intermediate screws. Results: Intermediate screws contribute to 20.2%, 16.5%, 14.5% and 23% decrease in ROM and 15.4%, 25.6%, 48.3%, and 160.2% increase in construct stiffness. Conclusions: Intermediate screws significantly increase the construct stiffness and decrease the ROM. 

Antimicrobial Resistance in <em>Staphylococcus aureus</em>

Staphylococcus aureus is a Gram-Positive bacteria that are responsible to cause skin infections and also shows toxic shock syndrome. Several antibiotics were given against the S. aureus infections but eventually, the prevalence of multidrug resistance of Staphylococcus aureus started emerging. Since then Methicillin-resistant Staphylococcus aureus strains (MRSA)were very common which causes nosocomial infections. Microorganisms for the need of the survival undergoes mutational changes either in their chromosomal DNA/RNA which confers the resistance. One of the famous examples is the resistance against methicillin in Staphylococcus aureus. The evolution of S. aureus is successful in developing multiple resistant strains. Plasmids are capable of carrying the resistant genes and also several toxic genes. In a recent study, it has been observed that drug resistance genes are located in the R plasmids and they are also responsible in conferring multi drug resistance and induce less utilization of multiple antimicrobial therapy. MRSA was not only resistant to methicillin, studies proved MRSA strains were resistant to macrolides, tetracyclines, chloramphenicol. Resistance to vancomycin was very evidently observed, and its transfer among the population and rising of resistant strains was becoming a major threat globally. The resistance of all these antimicrobial agents against the pathogenic microorganisms are taking a rise in some patients due to prolong use of the antimicrobial agents by these patients. The multi drug resistance has enhanced the mortality and morbidity rate which referred to the infecting agents as the “Super Bugs”. Survival of the microorganisms has increased due to the gradual development of extensive resistance against varied antimicrobial drugs. Possible treatments with combinations are found to be the only hope for infections against S. aureus. Few drugs are in development such as Dalbavancin, Oritavancin, Tigecycline. These are the possible treatments upon which the work is going on to reduce the resistance against the invasive MRSA. This chapter highlights the profiles of Staphylococcus aureus and the resistance patterns along with transmission and the role of the plasmid in transmitting the resistance

Primary Laryngeal Aspergillosis in the Immunocompetent Patient

Introduction Fungal infections of the larynx are truly rare in immunocompetent people with only a handful of cases reported in the past five decades. Here we present a case series of 3 people (from 2019 to 2021), with no comorbid conditions, who presented with primary laryngeal aspergillosis. Materials and Methods Three patients with primary aspergillosis of the larynx were seen in the ENT outpatient department from 2019 to 2021, aged between 40-50 years of which two were females and one patient was a male. We describe the clinical presentation of each patient. Discussion Aspergillosis of the larynx usually occurs secondary to bronchopulmonary infections in the immunocompromised. The usual etiological factors include prolonged use of inhaled steroids, cytotoxic drugs, radiotherapy, smoking, mucosal injury, and antibiotic abuse. Persistent hoarseness of voice is the most common presenting symptom. Video laryngoscopy reveals erythema, oedema, hyperkeratosis, adherent white plaques, shallow ulcerations, and grey or white pseudo membrane formation over the vocal cords. Definitive diagnosis is done by the demonstration of hyphae either by KOH staining, culture in Sabouraud Dextrose Agar at 28 degrees Celsius, or tissue biopsy. Conclusion Primary aspergillosis of the larynx has occurred more frequently in recent times. Aspergillosis of the larynx can often mimic malignant or premalignant lesions. Persistent hoarseness of voice not responding to treatment should also raise a suspicion of fungal laryngitis, in the clinician and relatively simple treatment be done before significant morbidity occurs

Colorimetric nanofibers as optical sensors

Sensors play a major role in many applications today, ranging from biomedicine to safety equipment, where they detect and warn us about changes in the environment. Nanofibers, characterized by high porosity, flexibility, and a large specific surface area, are the ideal material for ultrasensitive, fastresponding, and user-friendly sensor design. Indeed, a large specific surface area increases the sensitivity and response time of the sensor as the contact area with the analyte is enlarged. Thanks to the flexibility of membranes, nanofibrous sensors cannot only be applied in high-end analyte detection, but also in personal, daily use. Many different nanofibrous sensors have already been designed; albeit, the most straightforward and easiest-to-interpret sensor response is a visual change in color, which is of particular interest in the case of warning signals. Recently, many researchers have focused on the design of so-called colorimetric nanofibers, which typically involve the incorporation of a colorimetric functionality into the nanofibrous matrix. Many different strategies have been used and explored for colorimetric nanofibrous sensor design, which are outlined in this feature article. The many examples and applications demonstrate the value of colorimetric nanofibers for advanced optical sensor design, and could provide directions for future research in this area

Amalgam Attribute Based Encryption Scheme over the Cloud Data for Secure Access in the Hybrid Cloud

Abstract In the emergence of cloud computing, data owners are aggravated to outsource their complex data management system from local site to commercial cloud for great flexibility and economic saving. But for protecting data privacy, sensitive data has to be encrypted before outsourcing to commercial public cloud. Encrypted cloud data search system remains a very challenging task because of inherent security and privacy obstacles. There are so many security issues over the hybrid cloud during migration of data from one site to public cloud and also we cannot handle group of receivers in case of SKE. For secure communication and also handle dynamic attributes with continuous values, we need a new technique called as Amalgam attribute based encryption techniques. It is amalgam, as it combines the cipher text -policy attribute-based encryption (CP-ABE) with location-based encryption (LBE) on the level of symmetric keys in the hybrid cloud

Selpercatinib: A narrative drug review

Rearranged during transfection (RET) alteration promotes oncogenesis in a few cancers. RET mutation positivity is seen in approximately 70% of medullary thyroid cancers, around 30% of differentiated papillary thyroid cancers, and 1-2% of non-small-cell lung cancers (NSCLC). To write this narrative drug review, we searched various websites like the United States Food and Drug Administration, PubMed, Google Scholar, UpToDate, and recently published papers in various international conferences using the search terms “RET,” “RET alteration,” “Retevmo,” “RET inhibitors,” and “selpercatinib.” We shortlisted 31 articles published between January 1980 and January 2024. We discuss the history, mechanism of action, resistance, pharmacodynamics, pharmacokinetics, dosing, toxicity, pivotal trials, and indications of selpercatinib. Selective RET inhibitors like selpercatinib are indicated in the treatment of RET-altered NSCLC and thyroid cancer

Genetic polymorphisms of multidrug and toxin extrusion proteins (MATE1 and MATE2) in South Indian population

Introduction: Drug transporters are key determinants of pharmacokinetic and pharmacodynamic profiles of certain drugs. SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin. Our study was proposed to determine the normative frequencies of the single nucleotide polymorphisms (SNPs) rs2289669 and rs12943590 in the SLC47A1 and SLC47A2 genes, respectively, in South Indian population and also to compare those with those of the HapMap populations. Methods: One hundred two unrelated healthy volunteers from South India were enrolled in the study. Genomic DNA was extracted by ‘phenol-chloroform extraction method’ from the peripheral blood leucocytes and genotyping was accomplished by real-time polymerase chain reaction using TaqMan SNP genotyping assay method. Results: In contrast to other populations, the minor allele in SLC47A1 gene was found to be "G" with a frequency of 46.6% in South Indian population. The populations of Hans Chinese in Beijing (HCB) [P = 0.017] and Japanese in Tokyo (JPT) [P < 0.001] had significantly different genotype and allele frequencies (SNP rs2289669) compared to those of South Indian population. Similarly, in the SNP rs12943590 of SLC47A2 gene, the genotype and allele frequencies of South Indian population differed significantly from those of Yoruba in Ibadan, Nigeria (YRI) [P < 0.001] and Utah residents with Northern and Western European ancestry (CEU) [P = 0.005] populations. Conclusion: Thus, the allele and genotype distributions of SLC47A1 and SLC47A2 gene polymorphisms were established in South Indian population and were found to be different from the frequencies of other ethnicities