The Current Landscape in the Development of Small-molecule Modulators Targeting Sphingosine-1-phosphate Receptors to Treat Neurodegenerative Diseases.

Sphingosine 1-phosphate (S1P) is extensively researched as a lysophospholipid and is crucial in various physiological and pathological processes. It achieves this via signalling through five different subtypes of G protein-coupled receptors (GPCRs), namely S1PR1 to S1PR5. S1PR modulators possess the ability to traverse the blood-brain barrier, potentially leading to direct ac-tions within the Central Nervous System (CNS). S1PR modulators specifically bind to receptors located on the surface of naive and central memory lymphocytes, causing these cells to be trapped or confined within the lymph node. The investigation of the S1P pathway has resulted in the ap-proval of three S1PR modulators, namely fingolimod, siponimod, and ozanimod, as medications for the treatment of patients suffering from Multiple Sclerosis (MS). Additionally, new S1PR modulators, such as ponesimod and etrasimod, are currently being developed and tested in clini-cal trials. Research on the creation of S1P modulators in neurodegenerative illnesses is ongoing as scientists continue to explore novel possibilities for selective S1P modulators. This study provides a concise overview of sphingolipid metabolism, the mechanism by which S1P receptors are af-fected, and the structural characteristics of several small molecule S1P modulators, with a particu-lar focus on their structure-activity connections.

Shape Reconstruction Processes for Interventional Application Devices: State of the Art, Progress, and Future Directions.

Soft and continuum robots are transforming medical interventions thanks to their flexibility, miniaturization, and multidirectional movement abilities. Although flexibility enables reaching targets in unstructured and dynamic environments, it also creates challenges for control, especially due to interactions with the anatomy. Thus, in recent years lots of efforts have been devoted for the development of shape reconstruction methods, with the advancement of different kinematic models, sensors, and imaging techniques. These methods can increase the performance of the control action as well as provide the tip position of robotic manipulators relative to the anatomy. Each method, however, has its advantages and disadvantages and can be worthwhile in different situations. For example, electromagnetic (EM) and Fiber Bragg Grating (FBG) sensor-based shape reconstruction methods can be used in small-scale robots due to their advantages thanks to miniaturization, fast response, and high sensitivity. Yet, the problem of electromagnetic interference in the case of EM sensors, and poor response to high strains in the case of FBG sensors need to be considered. To help the reader make a suitable choice, this paper presents a review of recent progress on shape reconstruction methods, based on a systematic literature search, excluding pure kinematic models. Methods are classified into two categories. First, sensor-based techniques are presented that discuss the use of various sensors such as FBG, EM, and passive stretchable sensors for reconstructing the shape of the robots. Second, imaging-based methods are discussed that utilize images from different imaging systems such as fluoroscopy, endoscopy cameras, and ultrasound for the shape reconstruction process. The applicability, benefits, and limitations of each method are discussed. Finally, the paper draws some future promising directions for the enhancement of the shape reconstruction methods by discussing open questions and alternative methods.

Effect of discontinuation of ticagrelor and switching-over to other P2Y12 agents in patients with acute coronary syndrome: a single-center real-world experience from India.

BACKGROUND: Dual antiplatelet therapy is the current standard of care after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). We intended to study the pattern of use of ticagrelor in patients with acute coronary syndrome undergoing PCI and the effect of switching over to other P2Y12 receptor inhibition on clinical outcomes. RESULTS: All patients aged > 18 years who had been admitted with acute coronary syndrome and had been provided ticagrelor as the second antiplatelet agent were included as study participants. The primary outcome of the study was the composite outcome of death, recurrent myocardial infarctions, re-intervention, and major bleeding. We studied 321 patients (54 female patients, 16.82%). The mean age of the patients was 56.65 ± 11.01 years. Ticagrelor was stopped in 76.7% on follow-up. It was stopped in 6.3%, 13.5%, 13.1%, 21.9%, and 45.1% of patients during the first month but after discharge, between first and third months, between 3 and 6 months, between 6 and 12 months, and after 12 months, respectively. In the majority of patients, ticagrelor was replaced by clopidogrel (97.9%). It was stopped according to the physician's discretion in 79.3% of patients, whereas it was the cost of the drug that made the patient to get swapped to another agent in 18.6%. No difference in the primary composite outcome was observed between the groups where ticagrelor was continued post 12 months and ticagrelor was continued and ticagrelor was switched-over to another agent. Similarly, no difference in death, recurrent myocardial infarctions, re-interventions, or major bleeding manifestations was observed between the two groups. CONCLUSION: In patients with acute coronary syndrome who undergo PCI, we observed that early discontinuation of ticagrelor and switching over to other P2Y12 inhibitors after discharge did not affect clinical outcomes.

Evaluation of Anthelmintic Activity of Pistia stratiotes Linn.

The ethanolic extract of the plant Pistia stratiotes (Araceae) was investigated for activity against Indian earthworms Pheretima posthuma and nematode Ascardi galli. Various concentrations (10, 20, 50 mg/ml) of ethanolic extract were tested, which involved determination of time of paralysis and time of death of the worms. It was compared with Piperazine citrate (15 mg/ml) and Albendazole (20 mg/ml) as standard reference and normal saline as control. The study indicated the potential usefulness of Pistia stratiotes against earthworm infections.

Prediabetes and hypertension.

Prediabetes occurs due to two basic defects--insulin resistance and/or beta-cell failure. An observation suggested that insulin resistance may be associated with essential hypertension. There are some thoughts to favour the argument that insulin resistant Individuals are at a higher risk to develop hypertension as compared to insulin sensitive individuals. Some pathophysiological causes which have been commonly observed and hypothesised are narrated in this article. Management of hypertension in prediabetes should include antihypertensives and therapeutic lifestyle modification. To manage hypertension in prediabetes one should think for dietary modification, reduced salt intake, physical activity, smoking cessation, use of statins and antihypertensives.