The multipotent thidiazuron: A mechanistic overview of its roles in callogenesis and other plant cultures in vitro.

Thidiazuron (TDZ) is an active substituted phenyl urea compound that has found a significant role as a plant growth regulator. The most exciting aspect of its function is that it can mimic auxins and cytokinin but is chemically different from these two. Many theories have been put forward, and experiments performed to understand the mode of action of TDZ in callogenesis. One suggested mechanism presents that it works by inhibiting the cytokinin degrading enzymes that compete with cytokinin for an active site on the enzyme. An example is the TDZ-induced suppressed expression of gibberellic acid (GA) biosynthesis genes encoding GA3 and GA20 oxidases. This is entailed with a slightly increased expression of GA catabolism genes encoding GA20 oxidase. Similarly, one of the recommendations is that TDZ induces the expression of specific genes and transcription regulatory sequences that are either responsible directly for callus formation or in turn induce other auxins or cytokinin for callogenesis. There is no concise review available that discusses the details of TDZ-induced callus, specifically and other in vitro cultures in general. This review is an attempt to explore all these pathways and mechanisms involved in callogenesis in plants stimulated by TDZ.

Is metformin poised for a second career as an antimicrobial?

Metformin, a widely used antihyperglycaemic, has a good safety profile, reasonably manageable side-effects, is inexpensive, and causes a desirable amount of weight loss. In 4 studies of patients with tuberculosis (1 prospective and 3 retrospective), metformin administration resulted in better outcomes. In mice with several models of endotoxemia, metformin diminished levels of proinflammatory cytokines and improved survival. Laboratory studies showed effectiveness of the drug on multiple pathogens, including Trichinella spiralis, Staphylococcus aureus, Pseudomonas aeruginosa, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Metformin administration in humans and mice produced major changes in the composition of the gut microbiota. These recently discovered microbe-modulating properties of the drug have led investigators to predict wide therapeutic utility for metformin. The recent easing in United States Food and Drug Administration (FDA) guidelines regarding administration of metformin to patients with kidney disease, and reduced anxiety about patient safety in terms of lactic acidosis, increase the probability of broadening of metformin's usage as a treatment of infectious agents. In this text we review articles pertinent to metformin's effects on microorganisms, both pathogens and commensals. We highlight the possible role of metformin in a wide range of infectious diseases and a possible expansion of its therapeutic profile in this field. A systematic review was done of PubMed indexed articles that examined the effects of metformin on a wide range of pathogens. Metformin was found to have efficacy as an antimicrobial agent in patients with tuberculosis. Mice infected with Trypanosomiasis cruzi had higher survival when also treated with metformin. The drug in vitro was active against T. spiralis, S. aureus, P. aeruginosa, and hepatitis B virus. In addition there is emerging literature on its role in sepsis. We conclude that metformin may have a potential role in the therapy for multiple infectious diseases. Metformin, in addition to its traditional effects on glucose metabolism, provides anti-microbial benefits in patients with tuberculosis and in a very wide range of other infections encounters in vitro and in vivo.

Challenges for pathologists in implementing clinical microbiome diagnostic testing.

Recent research has established that the microbiome plays potential roles in the pathogenesis of numerous chronic diseases, including carcinomas. This discovery has led to significant interest in clinical microbiome testing among physicians, translational investigators, and the lay public. As novel, inexpensive methodologies to interrogate the microbiota become available, research labs and commercial vendors have offered microbial assays. However, these tests still have not infiltrated the clinical laboratory space. Here, we provide an overview of the challenges of implementing microbiome testing in clinical pathology. We discuss challenges associated with preanalytical and analytic sample handling and collection that can influence results, choosing the appropriate testing methodology for the clinical context, establishing reference ranges, interpreting the data generated by testing and its value in making patient care decisions, regulation, and cost considerations of testing. Additionally, we suggest potential solutions for these problems to expedite the establishment of microbiome testing in the clinical laboratory.

Knowledge, attitudes, and practices related to dietary salt among older adults in Abha, Saudi Arabia.

The need to foster successful aging has intensified with the aging of the global population. This study aimed to assess the knowledge, attitudes, and practices (KAP) concerning dietary salt consumption and to investigate the correlations between sociodemographic variables and salt-related KAP. A structured interview was administered to a cohort of 200 older adults in Abha City, Saudi Arabia, recruited through a convenience sampling approach. The evaluation of salt-related KAP revealed widespread low knowledge (91.5%) as participants scored less than 3, negative attitudes (85.5%) scored less than 12, and predominantly unsatisfactory practices (69.5%) with scores less than 26. Noteworthy differences emerged between participants with poor overall KAP (81.5%) and those with good KAP (18.5%). Significantly weak negative correlations were found between age (r=-0.212), marital status (-0.236), and body mass index (-0.243) with overall KAP. Further examination revealed a significantly weak positive correlation between attitude and practice (r = 0.141). KAP scores show a highly significant positive correlation with overall KAP scores (r = 0.169, 0.352, 0.969). The uncovered correlations contribute to a valuable understanding of the complex dynamics surrounding salt-related KAP. This understanding guides the design of targeted interventions, such as health education programs, promoting successful aging and public health outcomes.

Simulation Training to Interrupt Microaggressions.

ABSTRACT: Microaggressions in health care occur frequently and negatively impact the well-being of trainees. High-realism simulation can effectively train health care providers to communicate in emotionally difficult situations. In 2023, we developed and piloted 4 simulation scenarios for pediatric residents centered on addressing microaggressions in the clinical environment that built on an existing didactic curriculum. These scenarios included single and intersecting forms of oppression including racism, sexism, ableism, ethnocentrism, and weight bias. We also trained faculty, who had no prior simulation debriefing experience, to facilitate and debrief the simulation sessions. Thirty-three residents participated and reported an increase in confidence immediately following the simulation training; this increase was sustained at 3 months. Faculty participants reported increased empathy for residents, recognition of microaggressions, and confidence facilitating conversation after microaggressions that occur both in the simulated setting and in real life. High-realism simulation holds promise as a way to bridge the gap between classroom and real-life interruption of microaggressions, a necessary skill to improve the health care environment for learners and patients.

Exploring the most promising anti - Depressant drug targeting Microtubule Affinity Receptor Kinase 4 involved in Alzheimer's Disease through molecular docking and molecular dynamics simulation.

Alzheimer's Disease (AD) is the prevailing type of neurodegenerative illness, characterised by the accumulation of amyloid beta plaques. The symptoms associated with AD are memory loss, emotional variability, and a decline in cognitive functioning. To date, the pharmaceuticals currently accessible in the marketplace are limited to symptom management. According to several research, antidepressants have demonstrated potential efficacy in the management of AD. In this particular investigation, a total of 24 anti-depressant medications were selected as ligands, while the Microtubule Affinity Receptor Kinase 4 (MARK4) protein was chosen as the focal point of our study. The selection of MARK4 was based on its known involvement in the advancement of AD and other types of malignancies, rendering it a highly prospective target for therapeutic interventions. The initial step involved doing ADMET analysis, which was subsequently followed by molecular docking of 24 drugs. This was succeeded by molecular dynamics simulation and molecular mechanics generalised Born surface area (MMGBSA) calculations. Upon conducting molecular docking experiments, it has been determined that the binding affinities observed fall within the range of -5.5 kcal/mol to -9.0 kcal/mol. In this study, we selected six anti-depressant compounds (CID ID - 4184, 2771, 4205, 5533, 4543, and 2160) based on their binding affinities, which were determined to be -9.0, -8.7, -8.4, -8.3, -8.2, and -8.2, respectively. Molecular dynamics simulations were conducted for all six drugs, with donepezil serving as the control drug. Various analyses were performed, including basic analysis and post-trajectory analysis such as free energy landscape (FEL), polarizable continuum model (PCM), and MMGBSA calculations. Based on the findings from molecular dynamics simulations and the MMGBSA analysis, it can be inferred that citalopram and mirtazapine exhibit considerable potential as anti-depressant agents. Consequently, these compounds warrant further investigation through in vitro and in vivo investigations in the context of treating AD.

Deciphering the Enigma of Neuron-Glial Interactions in Neurological Disorders.

Innate lymphocytes, including microglial cells, astrocytes, and oligodendrocytes, play a crucial role in initiating neuroinflammatory reactions inside the central nervous system (CNS). The prime focus of this paper is on the involvement and interplay of neurons and glial cells in neurological disorders such as Alzheimer's Disease (AD), Autism Spectrum Disorder (ASD), epilepsy, and multiple sclerosis (MS). In this review, we explore the specific contributions of microglia and astrocytes and analyzes multiple pathways implicated in neuroinflammation and disturbances in excitatory and inhibitory processes. Firstly, we elucidate the mechanisms through which toxic protein accumulation in AD results in synaptic dysfunction and deregulation of the immune system and examines the roles of microglia, astrocytes, and hereditary factors in the pathogenesis of the disease. Secondly, we focus on ASD and the involvement of glial cells in the development of the nervous system and the formation of connections between neurons and investigates the genetic connections associated with these processes. Lastly, we also address the participation of glial cells in epilepsy and MS, providing insights into their pivotal functions in both conditions. We also tried to give an overview of seven different pathways like toll-like receptor signalling pathway, MyD88-dependent and independent pathway, etc and its relevance in the context with these neurological disorders. In this review, we also explore the role of activated glial cells in AD, ASD, epilepsy, and MS which lead to neuroinflammation. Even we focus on excitatory and inhibitory imbalance in all four neurological disorders as imbalance affect the proper functioning of neuronal circuits. Finally, this review concludes that there is necessity for additional investigation on glial cells and their involvement in neurological illnesses.

Reactive oxygen species induced oxidative damage to DNA, lipids, and proteins of antibiotic-resistant bacteria by plant-based silver nanoparticles.

This study assesses the mechanism of action of plant-based silver nanoparticles (AgNPs) against antibiotic-resistant bacteria. We compared AgNPs synthesized through Salvia moorcroftiana and Origanum vulgare extracts and their conjugates with the antibiotic Ceftriaxone for their capacity to cause oxidative damage through reactive oxygen species (ROS). We quantified ROS in the cells of two bacterial strains after treating them with all AgNP types and observed that AgNPs were most effective in K. pneumoniae as they resulted in the highest ChS1 count (44,675), while in P. aeruginosa, Cfx-AgNPs induced the highest levels of ROS with ChS1 count of 56,865. DNA analysis showed that both plant-based AgNPs (O-AgNPs = 0.192 and S-AgNPs = 0.152) were most effective in K. pneumoniae and S-AgNPs (abs = 0.174) and O-Cfx-AgNPs (abs = 0.261) in P. aeruginosa. We observed a significant increase in the levels of conjugated dienes (86.4 µM) and malondialdehyde (172.25 nM) in the bacterial strains after treatment with AgNPs, compared to the control (71.65 µM and 18.064 nM, respectively, in K. pneumoniae and P. aeruginosa). These results indicate lipid peroxidation. AgNPs also increased the levels of protein thiols (0.672 nM) compared to the control (0.441 nM) in K. pneumoniae, except for Chem-AgNPs (0.21 nM). These results suggest that plant-based AgNPs are more effective in oxidizing bacterial DNA, protein, and lipids than Chem-AgNPs. Furthermore, protein oxidation varied between AgNPs alone and AgNPs-antibiotic conjugates. The highest levels of protein thiols were found in the samples treated with O-Cfx-AgNPs (0.672 nM and 0.525 nM in K. pneumoniae and P. aeruginosa, respectively). The results demonstrated that AgNPs kill bacteria by altering bacterial macromolecules such as DNA, lipids, and proteins.

Impaired survival of neural progenitor cells in dentate gyrus of adult mice lacking fMRP.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability in humans. Individuals affected with the disorder exhibit a deficiency of the fragile X mental retardation protein (FMRP), due to transcriptional silencing of the Fmr1 gene. It is widely accepted that learning deficits in FXS result from impaired synaptic function and/or plasticity in the brain. Interestingly, recent evidence suggests that conditional knockout of Fmr1 in neural progenitor cells in mice impairs hippocampal neurogenesis, which in turn contributes to learning impairments. To examine the nature of the neurogenic impairments and determine whether they impact the morphology of the dentate gyrus, we assessed the extent of neural progenitor cell proliferation, survival, and differentiation in older adult Fmr1 knockout mice. Here, we show that the number of fast-proliferating cells in the subgranular layer of the dentate gyrus, as well as the subsequent survival of these cells, are dramatically reduced in Fmr1 knockout mice. In addition, the number of mature neurons in the granule layer of the dentate gyrus of these mice is significantly smaller than in wild type littermate controls, suggesting that impaired proliferation and survival of neural progenitor cells compromises the structure of the dentate gyrus. Impaired adult neurogenesis may underlie, at least in part, the learning deficits that characterize fragile X syndrome.

Current understanding of treatment and management protocol for adult diabetic in-patients at a tertiary care hospital.

OBJECTIVE: To assess the current understanding of treatment and management protocols for adult diabetic inpatients at a tertiary care hospital. METHODS: This cross-sectional study, conducted at the Civil Hospital Karachi from July to September 2009, involved 450 participants, who were interviewed through a well-structured questionnaire regarding the patient's demography, clinical features, past medical history, type of diabetes mellitus, duration, associated complications, and also involved patient notes for laboratory tests and management. SPSSv15.0 was used for descriptive analysis. RESULTS: The study population of 450 diabetics had 144 (32%) males and 306 (68%) females. Of the total, 435 (96.7%) patients had type 2 diabetes. There were 231 (51%) patients using insulin, 168 (37.3%) oral hypoglycaemic drugs, and 51 (11.3%) using both. Among patients using insulin, regular insulin usage stood at 30% followed by a combination of regular insulin and NPH (26.7%) and NPH alone at 6%. The most popular drug used was metformin (27.3%) and the least used drug was glitazones (4%). In the study population, 73.3% patients controlled their diabetes with diet, and 24.7% with regular exercise. CONCLUSION: Majority of the study population had type 2 diabetes with a female preponderance. Insulin was prescribed for half the patients. Metformin was the most frequently used oral hypoglycaemic drug.

Household use of iodized salt in rural area.

BACKGROUND: Iodine deficiency is the world's single greatest cause of preventable mental retardation. In developing countries, only 69% of households are consuming iodized salt. OBJECTIVE: To assess knowledge and practices with respect to the current use of iodized salt, and to estimate its uptake at the household level. MATERIALS AND METHODS: This cross-sectional survey was conducted in six villages under Rural Health Training Center. A total number of households surveyed were 253. The data collectors obtained verbal consent from the Family, and Pretested Standardized Questionnaire was administered in every selected household. The respondents were asked questions regarding salt purchasing and consumption habits, salt storage, awareness of iodized salt, and iodine deficiency diseases. Rapid iodized salt test kit (MBI kit) was used in the survey to assess iodine content in salt used in households. RESULTS: In this study, 93.7% households were using packet salt. The most common source of information was a television (31.1%). More than half (53.8%) of the households were unaware of the benefits of iodine. About 62.5% of households were consuming adequately iodized salt. Significant association was found between the practice of storing salt in closed containers and use of packaged iodized salt (Chi-square value -37.6, P < 0.001), awareness about the benefits of iodine and type of salt used (P = 0.02) while no association was observed between the socioeconomic status and type of salt used in the household. CONCLUSIONS: Though the use of packet salt was more than 90%, adequately iodized salt was consumed only in 62.5%, and more than half of the subjects lacked the knowledge about iodine deficiency diseases.