Quantitative analysis of the bioenergetics of Mycobacterium tuberculosis along with Glyoxylate cycle as a drug target under inhibition of enzymes using Petri net.

The bacteria Mycobacterium tuberculosis is responsible for the infectious disease Tuberculosis. Targeting the tubercule bacteria is an important challenge in developing the antimycobacterials. The glyoxylate cycle is considered as a potential target for the development of anti-tuberculosis agents, due to its absence in the humans. Humans only possess tricarboxylic acid cycle, while this cycle gets connected to glyoxylate cycle in microbes. Glyoxylate cycle is essential to the Mycobacterium for its growth and survival. Due to this reason, it is considered as a potential therapeutic target for the development of anti-tuberculosis agents. Here, we explore the effect on the behavior of the tricarboxylic acid cycle, glyoxylate cycle and their integrated pathway with the bioenergetics of the Mycobacterium, under the inhibition of key glyoxylate cycle enzymes using Continuous Petri net. Continuous Petri net is a special Petri net used to perform the quantitative analysis of the networks. We first study the tricarboxylic acid cycle and glyoxylate cycle of the tubercule bacteria by simulating its Continuous Petri net model under different scenarios. Both the cycles are then integrated with the bioenergetics of the bacteria and the integrated pathway is again simulated under different conditions. The simulation graphs show the metabolic consequences of inhibiting the key glyoxylate cycle enzymes and adding the uncouplers on the individual as well as integrated pathway. The uncouplers that inhibit the synthesis of adenosine triphosphate, play an important role as anti-mycobacterials. The simulation study done here validates the proposed Continuous Petri net model as compared with the experimental outcomes and also explains the consequences of the enzyme inhibition on the biochemical reactions involved in the metabolic pathways of the mycobacterium.

Hospital at home: emergence of a high-value model of care delivery.

Background: With increasing healthcare demands for acute illness in patients especially in the times of pandemic, healthcare organizations require modern solutions. Hospital at home (HaH) is one such tool that has the potential to solve these problems without compromising the care of the patients. Main body: Hospitals have been the conventional setting for managing acute sickness patients; however, it could be a very challenging environment for a few patients, especially for the older population who are highly susceptible to hospital-acquired infections. Health care in a hospital setting can also be very expensive, as it often involves a lot of healthcare professionals providing care. HaH service can provide the same quality of care expected in traditional settings. Conclusions: The median length of stay and the rate of readmissions were lower in people under HaH care. Compared with patients in a hospital setting, patients in HaH had better clinical outcomes. HaH unit provides an integrated, flexible, easy-to-scale platform that can be cost-effectively adapted to high-demand situations.

Migraine and heart: A reality check.

Migraine is a common neurological disorder affecting 12% of the global population. The common risk factors are adolescent age, genetics, and female sex, and are triggered by hormonal fluctuations, emotional stress, sensory overload, weather changes, alcohol consumption, fasting, cheese, chocolate, smoked fish, yeast extract, cured meats, artificial sweeteners, food preservatives containing nitrates and nitrites, and sleep disturbances. Migraine with aura is associated with an increased risk of cardiovascular disease events, such as myocardial infarction, angina pectoris, and cardiac arrhythmias, and has recently been added to the QRISK3 cardiovascular disease prediction score. Population-based cohort studies have shown a significant association of migraine with aura and cardiac arrhythmias, most importantly atrial fibrillation. Patients suffering from migraine with aura are at an increased risk for cardiac arrhythmias; thus, it is essential to screen these patients for undiagnosed cardiovascular disorders.

Study of the bioenergetics to identify the novel pathways as a drug target against Mycobacterium tuberculosis using Petri net.

Tuberculosis is one of the life-threatening diseases globally, caused by the bacteria Mycobacterium tuberculosis. In order to control this epidemic globally, there is an urgent need to discover new drugs with novel mechanism of action that can help in shortening the duration of treatment for both drug resistant and drug sensitive tuberculosis. Mycobacterium essentially depends on oxidative phosphorylation for its growth and establishment of pathogenesis. This pathway is unique in Mycobacterium tuberculosis as compared to host due to the differences in some of the enzyme complexes carrying electron transfer. Hence, it serves as an important drug target area. The uncouplers which inhibit adenosine triphosphate synthesis, could play a vital role in serving as antimycobacterial agents and thus could help in eradicating this deadly disease. In this article, the bioenergetics of Mycobacterium tuberculosis are studied with and without uncouplers using Petri net. Petri net is among the most widely used mathematical and computational tools to model and study the complex biochemical networks. We first represented the bioenergetic pathway as a Petri net which is then validated and analyzed using invariant analysis techniques of Petri net. The valid mathematical models presented here are capable to explain the molecular mechanism of uncouplers and the processes occurring within the electron transport chain of Mycobacterium tuberculosis. The results explained the net behavior in agreement with the biological results and also suggested some possible processes and pathways to be studied as a drug target for developing antimycobacterials.