Socio-demographic profile of Human Immunodeficiency Virus patients on second line antiretroviral therapy in a tertiary care centre of North-East India

Background: HIV/ AIDS is one of the major global health issue, resulting an epidemic. Understanding the socio-demographic profile with magnitude of risky behavior might include positive messages in the routine HIV/AIDS care and treatment. Objective of this study was to find out the socio-demographic, behavioural characteristics among patients receiving second line ART (Anti-Retroviral therapy) in a tertiary centre of North-East India.Methods: A cross sectional study was carried out among 90 PLWHA patients receiving second line ART in Regional Institute of Medical Sciences (RIMS), Imphal from March 2016 to August 2017. A predesigned and pretested schedule was used as study tool to collect required information.Results: Majority participants (43.3%) belonged to 30-40 years age group, mean age 39.96±8.021 years; 51.1% were female. Majority (58.9%) got infected with HIV through heterosexual route followed by IV drug use (31.1%). Nearly half (51.1%) were diagnosed with HIV for 11-15 years duration and majority (61.1%) were under 2nd line ART for 6-10 years duration. Here, 3.3% subjects had Hepatitis B and 7.8% were infected with hepatitis C.Conclusions: Young population were most affected group and heterosexual route being the commonest mode of transmission. Combination of socio-demographic, behavioural risk factor and unawareness are responsible for rapid spread of HIV/AIDS. So, people need to be educated for primary and secondary prevention

Monobodies and nanobodies: The era of diagnostic miniature antibodies

Monobodies, as the name suggests, are the simplest synthetic version of antibodies engineered to mimic antibodies (antibody mimetics) without their complexity. These are constructed using a fibronectin type III domain (FN3) as a molecular scaffold. With a molecular mass of not more than 20 kDA at max, monobodies are excellent tools for in-vivo diagnosis. Unlike the conventional Ab that needs particular treatment protocols to enable them to enter into cells, mono, and nano bodies can be expressed inside the cells with expression cassettes. With high affinity and selectivity, mono and nanobodies can be developed in the shortest possible time with ease that otherwise can't be done by conventional antibodies. Produced from combinatorial libraries and diversified using phage display techniques, monobodies can be generated that are highly specific for their intracellular targets, like monobodies to detect COVID antigens. Similarly, monobodies against KRAS mutants using protein engineering technologies can be sued to detect mutant KRAS in solid tumors. They have a strong tendency to bind to functional sites of specific intracellular target proteins and thus exhibits drug-like properties as well as specific `inhibitors. Monobodies are evolving with additional diverse functions and may soon be used as am indispensable tool in biology and medicine

Checkmate with checkpoint inhibitors: New paradigm in immunotherapy

Cancer immunotherapy is a form of biotherapy (also called biological response modifier therapy) that refers to a broad array of anti-cancer therapies targeted to activate and trigger the body’s immune system against cancer. This includes targeted antibodies to specific cell surface entities on cancer cells, anti-cancer vaccines like vaccines against HPV in cervical cancer, cytolytic virus, adoptive cell transfer, biologicals like cytokines and other small molecular agents, and the most explored immune checkpoint inhibitors. Immunotherapies use immune modulatory materials from the same organism to fight disease, while some immunotherapy treatments use genetic engineering-based gene editing approaches to enhance the host immune system in an effort to eradicate the cancer cells and boost its cancer-fighting capabilities. Used in combination with surgery, chemotherapy, and radiotherapy, cancer immunotherapy improves their overall effectiveness. WHAT IS AN IMMUNE CHECKPOINT T cell activation involves the engagement of a number of signaling cascades, originating from the interaction between T cell receptors (TCR) with antigen-presenting cells (APC) that ultimately determine cell fate through regulating cytokine production, cell survival, proliferation, and differentiation. TCR alone is not sufficient to generate an adequate response. It needs the participation of coreceptors. Primary T cell activation involves the integration of three distinct signals (1) antigen recognition in the presence of APC, (2) costimulation, and (3) cytokine-mediated differentiation and expansion. To make sure that these activated T cells do not cross-react with self-antigens, these are rendered inactive by immune checkpoints. PDL on T cells and PDL1 on host cells engage in bringing about this. Programmed Cell Death Protein 1 (PD-1) inhibits immune responses by fostering a state of self-tolerance. This is achieved by activating apoptosis, anergy, and avoidance of antigen-specific T cells. The functional counterpart of PD-1, the Programmed Cell Death Ligand 1 (PD-L1), is a trans-membrane protein that acts as a coinhibitory immune response factor. This is what the cancer cells hijack for their survival. PD-L1 expressed on cancer cells attenuates the host T cell response transmitting negative signals. Therefore, the PD-1/PD-L1 axis is the main driver of cancer immune evasion, which needs serious attention. WHAT IS IMMUNE CHECKPOINT INHIBITORS These classes of molecules are designed to block the cross-talks between cancer cells expressing PD-L1 with T cells expressing PD-1 receptors. When the interaction is blocked, inhibitory influence on T-cells is circumvented, and an attack may be launched. Checkpoint inhibitors are used in cancer immunotherapy, including a wide range of cancers, such as melanoma, skin cancer, and lung cancer. Different drug classes block checkpoint proteins like CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors. Commercially checkpoint inhibitors include pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo), and atezolizumab (Tecentriq). RAYS OF HOPE AND CAUTION Because checkpoint inhibitors stimulate the immune system and are immunomodulatory, their usage has significantly improved cancer treatment and management, extending the life span for numerous patients. However, we need to be cautious as they may cause immune cells to attack healthy cells, causing side effects such as fatigue, nausea, high fever, flu-like symptoms, and inflammation

Therapeutic siRNAs: small molecules with bigger function

In the realm of molecular medicine, therapeutic small-interfering RNA (siRNA) is a promising class of molecules with exciting new opportunities in healthcare. An essential component of RNA interference (RNAi) is siRNA. In clinical setup, siRNA may be engineered to specifically target genes linked to certain diseases, providing a focused and accurate method of modulating gene expression. Many important factors characterize the use of therapeutic siRNA. Target gene expression is selectively silenced by therapeutic siRNA through the use of the RNAi pathway. Guided by corresponding messenger RNA (mRNA) sequences, the double-stranded siRNA molecule is integrated into the RNA-induced silencing complex (RISC). This mechanism causes translational repression or mRNA cleavage, which in turn causes the relevant protein to be downregulated. Therapeutic siRNA is a promising avenue in several areas. siRNA can be used in oncology to target oncogenes or other important regulators, inhibiting cancer cell proliferation. Furthermore, by modifying the expression of genes linked to disease, siRNA may be used to treat viral infections, neurological conditions, and other rare and hereditary diseases. The selectivity of therapeutic siRNA is one of its main advantages. siRNA sequences can be engineered and customized to target specific genes linked to different diseases like cancer or genetic disorders. This focused strategy improves the accuracy of the therapeutic intervention and reduces off-target effects. In a recent article by Nissen et al., siRNA targeting LP(a) in a trial with 48 participants without cardiovascular disease and with lipoprotein(a) concentrations of 75 nmol/L or greater (or ≥30 mg/dL), was used to evaluate its tolerability and efficacy to reduce LP(a). Results showed that Lepodisiran was found to be well tolerated and resulted in dose-dependent, long-lasting reduction in serum lipoprotein(a) concentrations in phase 1 trial with elevated lipoprotein(a) levels. Therapeutic siRNA-based diagnosis is rapidly advancing, and several siRNA-based medications are now entering clinical trials. These trials aim to assess the pharmacokinetics, safety, and effectiveness of siRNA therapeutics in human subjects, offering crucial new information about their potential as a treatment option. Despite the therapeutic potential of siRNA, clinical translation of siRNA faces a challenge in its effective delivery. Naked siRNA molecules are more likely to degrade with a poor half-life and poor cellular uptake. Therefore, to increase the stability and delivery of therapeutic siRNA to target cells, a variety of delivery systems, such as lipid nanoparticles, viral vectors, and polymer-based carriers, are being investigated

Tree elements: Branching hopes after tissue injury in regenerative medicine

Humans are poor model systems for studying tissue regeneration. Unlike their amphibians or rodent counterparts, humans are deficient in this quality, making the repair process following a tissue injury infrequent and limited. Most human tissues or organs, except the liver, lack in their regenerative potential. This tends to be a serious problem in organ damage until recently with the identification of enhancer regulatory elements that engage in regenerating tissue. Tissue regeneration enhancer elements (TREEs) trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs. TREE orchestrates selective gene expression at the injury sites, thereby modulating the regenerative activities and potential of vertebrate organs. Using a genetic screen of a zebrafish-based tissue injury model, Kang et al., identified the gene expression signature associated with regeneration. This concept is being tried and tested to see its possibility in regenerating injured myocardium following myocardium infraction leading to ischemia and tissue damage. TREEs displayed specificity and efficacy in a systemically delivered recombinant AAV vector system in mice and can be used as a gene-therapy module to repair damaged tissue. A team of researchers at the Duke School of Medicine, USA, headed by Ken Poss, reported their findings in cell stem cell, 2022. These researchers further took a step ahead to actually orchestrate a damaged myocardium repair and the growth of new muscles to restore normal cardiac function. Even more spectacular is that tissue growth is selective only at injury sites and becomes quiescent once the damage is repaired. HOW THIS MAY IMPACT REGENERATIVE MEDICINE Using a TREE-based system, one can attempt to use gene therapy with viral vectors to enhance heart tissue cell proliferation and growth, thus improving cardiac regeneration. This system will further strengthen by incorporating better gene payloads, thereby opening new possibilities to rescue scar tissue and restore function. According to the World Health Organization, MI-related death in India accounts for one-fifth of deaths worldwide, which is alarmingly higher in the younger population. The age-standardized cardiovascular disease (CVD) death rate of 272/100,000 in India is much higher than the global average of 235. Under these circumstances, these findings seem extremely relevant. Although we may not fix a broken heart, engineered TREE elements might at least fix a damaged myocardium branching hopes for numerous suffering from CVD

Maternal dietary habit influences fetal life

Diet and nutrition have a tremendous influence on health and disease. Dietary constituents can affect health and have been known to supplement with essential nutrients, minerals, and calories for physiological homeostasis. However, diet can also affect gene expression through epigenetic reprogramming or by altering the level of micronutrients. While a nutrigenomics study has delineated this causal link, a recent study published in EMBO Molecular Medicine by Grant et al. went a step further to establish that maternal intake of dietary fibers can alter the fetal gut microbiome, influencing the diversity of the intestinal bacterial flora, thereby affecting the gut-brain axis. Although the relationship between diet and fertility in males and females has been reported, the effect on postnatal life is not well documented. In this study by Grant et al. at the (Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg), the authors reported that selected feeding of fiber-free diets to pregnant mice alters the gut microbiome composition of their neonate pups depriving them of protective and beneficial commensal, Akkermansia muciniphila, a mucin-foraging bacterium. Further, these animals exhibited heightened immune activity by enriching defense response pathways and IL-22 expression. Therefore, the protective role of A. muciniphila is associated with its protection against chronic inflammation through TLR4 signaling. The author’s study has far-reaching conclusions on improving human health outcomes by the rational choice of food, drugs, and lifestyle to prevent gut dysbiosis and colonization of the right microbiome

Smart wearable devices for real-time health monitoring

Smartwatches have emerged as powerful tools for health monitoring in recent years. These wearable devices combine advanced technology with portability, enabling individuals to track various aspects of their health and well-being conveniently. Heart rate monitoring has several advantages. Many smartwatches are equipped with optical heart rate sensors that continuously monitor a user’s heart rate. This feature provides real-time data on heart rate variations, which can be crucial for identifying irregularities and assessing overall cardiovascular health. Activity tracking: Smartwatches often include accelerometers and gyroscopes that track physical activities such as steps taken, distance traveled, and calories burned. This information can aid in setting and achieving fitness goals. Sleep tracking:Some smartwatches offer sleep tracking features, recording sleep duration, quality, and patterns. These data help users understand their sleep habits and make improvements for better rest. Global positioning system (GPS) and location tracking: Integrated GPS allows users to track their outdoor activities accurately, including running and cycling. This feature not only measures performance but also enhances safety during workouts. Stress monitoring: Certain smartwatches include tools that measure stress levels through heart rate variability analysis. Users can learn to manage stress more effectively based on these data. Electrocardiogram (ECG) and blood pressure monitoring:High-end smartwatches may include ECG and blood pressure monitoring capabilities. These features are particularly useful for individuals with heart conditions or hypertension. Notifications and alerts: Smartwatches can deliver notifications and alerts related to health goals, reminders to move, medication schedules, and emergencies. This functionality enhances user engagement and timely interventions. BENEFITS OF SMARTWATCHES IN HEALTH MONITORING Unlike periodic doctor visits, smartwatches enable continuous health monitoring. Users can track their vital signs and activities throughout the day, providing a more comprehensive picture of their health. Smartwatches empower individuals to take control of their health. Users can make informed decisions about their lifestyle, exercise, and diet by providing real-time data. Smartwatches equipped with ECG and heart rate monitoring can detect irregularities and abnormalities early on. This early detection can be lifesaving for individuals at risk of heart-related conditions. Activity tracking and goal-setting features motivate users to engage in physical activities and maintain a healthier lifestyle. Achieving fitness goals can lead to increased motivation and adherence to healthier habits. Health data collected by smartwatches can be used to tailor fitness and wellness plans to an individual’s specific needs. This personalized approach can lead to more effective health improvements. LIMITATIONS AND CONSIDERATIONS Accuracy: While smartwatches offer valuable health data, their accuracy may vary. Factors such as skin type,device placement, and motion can affect the precision of measurements. Battery life: Continuous health monitoring can drain a smartwatch’s battery quickly. Users may need to recharge their devices frequently, potentially limiting the monitoring duration. Privacy and data security: Storing sensitive health data on a smartwatch raise concerns about privacy and data security. Manufacturers must implement robust security measures to protect users’ information. User reliance: There is a risk of over-reliance on smartwatches for health information. Users should be encouraged to consult health-care professionals for a comprehensive health assessment. CONCLUSION Smartwatches have become versatile tools for health monitoring, offering a range of features that empower users to track and improve their well-being. While they have numerous benefits, users should know their limitations and use them as complementary tools in their health-care journey. Manufacturers and health-care providers play a critical role in ensuring the accuracy and security of the health data collected by these devices

Indian twin registry: A gold mine for genetic studies

Twins are a source of curiosity, both for the family and the scientific community. Genetic similarities between twins have been the preferred choice to study the heritability of traits. The fact that nature and nurture play a significant role in shaping one’s phenotype has prompted Geneticists to use twins as a proxy to address this fact. Based on the similarities, twins are of two types, monozygotic twins (MZ) and Dizygotic twins (DZ). Identical or monozygotic twins are formed when one fertilized egg (ovum), fertilized by one sperm, splits and develops into two embryos with precisely the same genetic information. The combined ratio of MZ and DZ to singleton delivery is approx 1: 100. On the other hand, fraternal or dizygotic twins are formed when two eggs (ova) are fertilized by two sperm and produce two genetically unique children in the same pregnancy. Monochorionic twins are genetically identical, sharing the same placenta. If more than two twins share the placenta, these are monochorionic multiples. Monochorionic twins occur in 0.3% of all pregnancies. Monozygotic (identical) twins share all their genes, while dizygotic (fraternal) twins only share about 50%. Hence, any similarity seen between identical twins when comparing the similarity between sets of fraternal twins for a trait or condition is most probably due to genes rather than environment. TWIN REGISTRIES Progress in twin research worldwide is carried out by establishing Twin registries or consortia based on collaborations of several twin families. These registries are a rich source of materials for Twin research. It is much needed to establish such Twin registries in India. With its 1.5 Billion population, Indian Twin registries can be a source of materials for Twin Research for the whole world

JN.1: The new COVID-19 variant of concern?

Emergence of new variants of COVID-19 is nothing new. Different variants evolved with additional mutations of the virus as part of the viral replication cycle have different infectious properties. JN.1 is the latest COVID-19 variant that seems to circulate the globe contributing to many infections and hospitalizations labeling it a variant of interest by the WHO. The scientific community has yet to understand its full lethal potential if any. In this mini-review, we summarized the facts known so far about this variant and its possible consequences if any for humanity

Airway Management in Full Stomach Conditions

Pulmonary aspiration in the perioperative period is one of the well-known complications under anesthesia and procedural sedation. A full stomach condition either due to non-adherence to fasting guidelines or due to various other factors that delay gastric emptying are the most common causes. Following aspiration, a patient may develop a wide spectrum of clinical sequelae. The key factors in preventing aspiration include proper pre-operative assessment, appropriate premedication and operating room preparations. Rapid sequence induction and intubation is the recommended technique for securing the airway in cases of full stomach. Management of aspiration depends on the nature of the aspirate. Pre-operative fasting guidelines have been established by various medical societies which may be modified in special circumstances of high risk of aspiration. Prediction of difficult airway in certain cases of full stomach necessitates clinical expertise in airway management