Comprehensive Analysis and Assessment of the Role of Major Bioactive Compounds Isolated from Justicia Adhatoda Leaves as Potent Antimycobacterial Agents

Tuberculosis (TB) continues to be one of the world's leading causes of death by the infectious pathogen Mycobacterium tuberculosis, which infects one-third of the global population. The emergence of the COVID-19 pandemic made its spread rapid and the treatment task more daunting. With the havoc of infectious disease expansion, traditional medicines have triggered tremendous interest worldwide. However, less availability of scientific evidence still hinders its practical use. In the present study, we evaluated the potential of the traditional medicinal plant, Justicia adhatoda, which has been used to treat respiratory ailments since ancient times. We have successfully isolated and characterized several bioactive compounds viz- Vasicoline, Vasicolinone, Adhatodine, Adhavasine, Aniflorine, and Vasicinone from J. adhatoda plant leaves, including Vasicine as the principal compound, and showed their anti-tubercular activity on nutrient-starved Mycobacterium smegmatis and Mycobacterium bovis. The study also directs their in-vitro and ex-vivo antimycobacterial potential on THP1 macrophages with internalized Mycobacterium. Our study is one of its first kind, where we assessed the synergistic antimycobacterial effect of the isolated compounds with the first-line drug Isoniazid (INH). Their potential role in promoting phagolysosome fusion and apoptosis of M. bovis infected THP1 macrophages is further evaluated.

Steroid-Responsive Post-Traumatic Persistent Neutrophilic Meningitis

Post-traumatic meningitis is a potentially fatal condition that presents as a diagnostic and therapeutic challenge. The vast majority of post-traumatic meningitides are caused by infectious pathogens, most commonly multi-drug-resistant (MDR) bacterial pathogens. However, aseptic meningitis occurs less frequently due to tissue response to injury or stimulation by noninfectious agents, such as blood breakdown products or chemicals. Here, we present a case of post-traumatic persistent neutrophilic meningitis who was found to be steroid responsive. Diagnostic evaluation in our patient did not reveal any infectious pathogen, and the patient did not respond to broad-spectrum antimicrobial treatment. We suggest that physicians who treat patients with post-traumatic meningitis should consider steroid-responsive post-traumatic persistent neutrophilic meningitis (SPNM) in the list of differential diagnosis particularly when no infectious etiology is found and the patient does not respond to empirical antimicrobial treatment. Brain injury-induced immune dysregulation causing exaggerated inflammatory reaction might play a role in the pathogenesis of SPNM; however, further neuropathological studies are absolutely necessary to evaluate and characterize trauma-induced immune dysregulation.

Surgical Site Infections in Gynaecological Surgeries

Surgical contaminations are one of the utmost familiar medical management related contamination within the economically developing nations. Gynecologic tactics constitute a completely distinctive venture within which the infectious pathogen arising out of pores and the underlying skin or the vagina and endo-cervix can also relocate up to the area of surgery and may bring about vaginal cuff cellulitis, cellulitis of the pelvis, and abscesses of the pelvis. Numerous organisms along with operation threat elements were recognized as dangers that grow infectious sequelae after pelvic surgical treatment. The full-size use of antibiotic prophylaxis has decreased however now no longer removed severe postoperative infections; the common anticipated SSIs price being three–15% after c-section. Those costs are multiplied by the existence of various threat elements like surgical infection, which is compounded by untimely rupture of membranes, obstructed labour, chorioamnionitis, large obesity, extended duration of surgery, emergency surgeries, and immunodeficiency, all of that are not uncommon within aid-deficient nations. Other factors linked to physician ability, such as poor operation skills, insufficient hemostasis, and the presence of a useless region, lead to increased injury contamination. Working at the pinnacle, such as those medical conditions that occur during pregnancy and malnutrition, also contribute significantly to the problem. SSIs as the most common motive concerning hospital-acquired contamination in obstetrics, although the present contemporary era, remains as chief residence fitness hassle within growing nations. We may even evaluate the definitions, microbiology, pathogenesis, diagnosis, and control of pelvic SSIs after gynecologic surgical procedures.

Quarantine

<p>This thesis is set in a world similar to many pieces of science fiction literature and film. The world is fighting against the outbreak of a lethal and highly infectious pathogen that threatens to decimate the global population. The virus spreads quickly and has no current known cures or vaccines. Whilst the backdrop for this thesis is fictional, it addresses a very real concern that could face society. The research and outcomes of this thesis were based on a detailed study of quarantine solutions with the intention to quickly control and treat a virus pandemic. The focus was given to the architecture of emergency quarantine hospitals but also to a specific pathogen that this proposal is based upon, the H5N1 virus, more commonly known as Bird Flu. This thesis proposes to investigate a movable architecture dedicated to quarantine which can transport itself between cities and set up where it is most needed, be that in a busy city or a cluster of small villages. This allows for ease of access for those infected as well as quick integration back into society should those who are isolated respond well to treatment. The thesis will propose a potential direction for the further development of modern human quarantine, a system that will be ready and waiting for the day that it is desperately required.</p>

Quarantine

<p>This thesis is set in a world similar to many pieces of science fiction literature and film. The world is fighting against the outbreak of a lethal and highly infectious pathogen that threatens to decimate the global population. The virus spreads quickly and has no current known cures or vaccines. Whilst the backdrop for this thesis is fictional, it addresses a very real concern that could face society. The research and outcomes of this thesis were based on a detailed study of quarantine solutions with the intention to quickly control and treat a virus pandemic. The focus was given to the architecture of emergency quarantine hospitals but also to a specific pathogen that this proposal is based upon, the H5N1 virus, more commonly known as Bird Flu. This thesis proposes to investigate a movable architecture dedicated to quarantine which can transport itself between cities and set up where it is most needed, be that in a busy city or a cluster of small villages. This allows for ease of access for those infected as well as quick integration back into society should those who are isolated respond well to treatment. The thesis will propose a potential direction for the further development of modern human quarantine, a system that will be ready and waiting for the day that it is desperately required.</p>

Comprehensive Analysis and Assessment of the Role of Major Bioactive Compounds Isolated from Justicia Adhatoda Leaves as Potent Antimycobacterial Agents

Tuberculosis (TB) continues to be one of the world's leading causes of death by the infectious pathogen Mycobacterium tuberculosis, which infects one-third of the global population. The emergence of the COVID-19 pandemic made its spread rapid and the treatment task more daunting. With the havoc of infectious disease expansion, traditional medicines have triggered tremendous interest worldwide. However, less availability of scientific evidence still hinders its practical use. In the present study, we evaluated the potential of the traditional medicinal plant, Justicia adhatoda, which has been used to treat respiratory ailments since ancient times. We have successfully isolated and characterized several bioactive compounds viz- Vasicoline, Vasicolinone, Adhatodine, Adhavasine, Aniflorine, and Vasicinone from J. adhatoda plant leaves, including Vasicine as the principal compound, and showed their anti-tubercular activity on nutrient-starved Mycobacterium smegmatis and Mycobacterium bovis. The study also directs their in-vitro and ex-vivo antimycobacterial potential on THP1 macrophages with internalized Mycobacterium. Our study is one of its first kind, where we assessed the synergistic antimycobacterial effect of the isolated compounds with the first-line drug Isoniazid (INH). Their potential role in promoting phagolysosome fusion and apoptosis of M. bovis infected THP1 macrophages is further evaluated.

Potential Adjuvant Therapeutic Effect of Lactobacillus plantarum Probio-88 Postbiotics against SARS-COV-2

In response to the ongoing COVID-19 pandemic, the global effort to develop high efficacy countermeasures to control the infection are being conducted at full swing. While the efficacy of vaccines and coronavirus drugs are being tested, the microbiome approach represents an alternative pathophysiology-based approach to prevent the severity of the infection. In the current study, we evaluated the action of a novel probiotic Lactobacillus plantarum Probio-88 against SARS-COV-2 replication and immune regulation using an in vitro and in silico study. The results showed that extract from this strain (P88-CFS) significantly inhibited the replication of SARS-COV-2 and the production of reactive oxygen species (ROS) levels. Furthermore, compared with infected cells, P88-CFS treated cells showed a significant reduction in inflammatory markers such as IFN-α, IFN-β, and IL-6. Using an in silico molecular docking approach, it was postulated that the antiviral activity of L. plantarum Probio-88 was derived from plantaricin E (PlnE) and F (PlnF). The high binding affinity and formation of hydrogen bonding indicated that the association of PlnE and PlnF on SARS-COV-2 helicase might serve as a blocker by preventing the binding of ss-RNA during the replication of the virus. In conclusion, our study substantiated that P88-CFS could be used as an integrative therapeutic approach along with vaccine to contain the spread of the highly infectious pathogen and possibly its variants.

Integrated Microfluidic-Based Platforms for On-Site Detection and Quantification of Infectious Pathogens: Towards On-Site Medical Translation of SARS-CoV-2 Diagnostic Platforms

The rapid detection and quantification of infectious pathogens is an essential component to the control of potentially lethal outbreaks among human populations worldwide. Several of these highly infectious pathogens, such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been cemented in human history as causing epidemics or pandemics due to their lethality and contagiousness. SARS-CoV-2 is an example of these highly infectious pathogens that have recently become one of the leading causes of globally reported deaths, creating one of the worst economic downturns and health crises in the last century. As a result, the necessity for highly accurate and increasingly rapid on-site diagnostic platforms for highly infectious pathogens, such as SARS-CoV-2, has grown dramatically over the last two years. Current conventional non-microfluidic diagnostic techniques have limitations in their effectiveness as on-site devices due to their large turnaround times, operational costs and the need for laboratory equipment. In this review, we first present criteria, both novel and previously determined, as a foundation for the development of effective and viable on-site microfluidic diagnostic platforms for several notable pathogens, including SARS-CoV-2. This list of criteria includes standards that were set out by the WHO, as well as our own “seven pillars” for effective microfluidic integration. We then evaluate the use of microfluidic integration to improve upon currently, and previously, existing platforms for the detection of infectious pathogens. Finally, we discuss a stage-wise means to translate our findings into a fundamental framework towards the development of more effective on-site SARS-CoV-2 microfluidic-integrated platforms that may facilitate future pandemic diagnostic and research endeavors. Through microfluidic integration, many limitations in currently existing infectious pathogen diagnostic platforms can be eliminated or improved upon.

Adjusting for time of infection or positive test when estimating the risk of a post-infection outcome in an epidemic

When comparing the risk of a post-infection binary outcome, e.g. hospitalisation, for two variants of an infectious pathogen, it is important to adjust for calendar time of infection to avoid the confounding that would occur if the relative incidence of the two variants and the variant-specific risks of the outcome both change over time. Infection time is typically unknown and time of positive test used instead. Likewise, time of positive test may be used instead of infection time when assessing how the risk of the binary outcome changes over calendar time. Here we show that if mean time from infection to positive test is correlated with the outcome, the risk conditional on positive test time depends on whether incidence of infection is increasing or decreasing over calendar time. This complicates interpretation of risk ratios adjusted for positive test time. We also propose a simple sensitivity analysis that indicates how these risk ratios may differ from the risk ratios adjusted for infection time.