Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.

Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer's, Parkinson's, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin's mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as "metformin", "neuroprotection", and "neurodegenerative diseases", with data up to September 2023. Recent research on metformin's glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1-AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions.

Pharmacological Basis for Antispasmodic, Bronchodilator, and Antidiarrheal Potential of Dryopteris ramosa (Hope) C. via In Vitro, In Vivo, and In Silico Studies.

Background:Dryopteris ramosa is used as an old treatment for several diseases. D. ramose fronds are eaten to treat gastrointestinal (GIT) issues and as an antibiotic. However, there is a dearth of literature justifying its traditional use. Aims and objectives: the current work used biological and molecular docking studies to support traditional usage and elucidate D. ramosa's multitarget mechanism. Materials and methods: Bioactive compounds were docked in silico. Force displacement transducers coupled with a power lab data gathering system examined the effects of compounds on rabbit jejunum, trachea, and aorta tissues. Albino mice and rats were used for in vivo studies. Results: Bioactive compounds interacted with inflammation, asthma, and diarrhea genes, according to in silico studies. D. ramosa crude extract (Dr.Cr) calmed impulsive contractions and K+ (80 mM)-provoked contractions in the jejunum and tracheal tissue dose-dependently, showing the presence of the Ca++ channel-blocking (CCB) effect, further verified by the rightward parallel shift of CRCs equivalent to verapamil. Polarity-based fractionation showed spasmolytic activity in Dr.DCM and muscarinic receptors mediated spasmogenic activity in the Dr.Aq fraction. Dr.Cr vasoconstricted the aortic preparation, which was totally blocked by an angiotensin II receptor antagonist. This suggests that Dr. Cr's contractile effect is mediated through angiotensin receptors. In rats and mice, it showed anti-inflammatory and antidiarrheal action. Conclusion: This study supports the traditional medicinal uses of D. ramosa against GIT disorders and may be an important therapeutic agent in the future.

Physiotherapy Efficiency in Post-stroke Upper Extremity Spasticity: TENS vs. Ultrasound vs. Paraffin.

BACKGROUND/AIM: Post-stroke spasticity is a significant debilitating condition with negative consequences on individual functional independence and quality of life. This study aimed to identify the differences between transcutaneous electrical stimulation (TENS), ultrasound therapy and paraffin procedures on post-stroke upper extremity spasticity and dexterity. PATIENTS AND METHODS: Twenty-six patients were enrolled in the study, divided into three therapy groups: TENS (n=9), paraffin (n=10) and ultrasound therapy (n=7). For 10 days, the patients received specific group therapy and conventional physical therapy exercises for upper extremities. Modified Ashworth Scale, Functional Independence Measure, Functional Coefficient, Stroke Specific Quality of Life Scale, Activities of Daily Living score and ABILHAND questionnaire were used to assess the participants before and after therapy. RESULTS: The results of the group comparisons by analysis of variance showed no significant difference between outcomes by the applied treatments. In contrast, one-way analysis of variance suggested significant improvements in patients in all three groups after therapy. Step-wise regression results on functional independence measure and quality-of-life scales suggested that functional range of motion values for elbow and wrist influence individual independence and quality of life. CONCLUSION: TENS, ultrasound, and paraffin therapy bring equal benefits in the management of post-stroke spasticity.

Failure in Medical Practice: Human Error, System Failure, or Case Severity?

The success rate in medical practice will probably never reach 100%. Success rates depend on many factors. Defining the success rate is both a technical and a philosophical issue. In opposition to the concept of success, medical failure should also be discussed. Its causality is multifactorial and extremely complex. Its actual rate and its real impact are unknown. In medical practice, failure depends not only on the human factor but also on the medical system and has at its center a very important variable-the patient. To combat errors, capturing, tracking, and analyzing them at an institutional level are important. Barriers such as the fear of consequences or a specific work climate or culture can affect this process. Although important data regarding medical errors and their consequences can be extracted by analyzing patient outcomes or using quality indicators, patient stories (clinical cases) seem to have the greatest impact on our subconscious as medical doctors and nurses and these may generate the corresponding and necessary reactions. Every clinical case has its own story. In this study, three different cases are presented to illustrate how human error, the limits of the system, and the particularities of the patient's condition (severity of the disease), alone or in combination, may lead to tragic outcomes There is a need to talk openly and in a balanced way about failure, regardless of its cause, to look at things as they are, without hiding the inconvenient truth. The common goal is not to find culprits but to find solutions and create a culture of safety.

Outcomes in revision total knee arthroplasty (Review).

Revision total knee arthroplasty (TKA) is a challenging surgical procedure. Although good results are presented, the outcomes are worse in comparison with those of primary TKA, with a higher failure rate. The main reasons for the failure of revision TKA include: sepsis, loosening and instability. There are multiple variables linked to these results, and it is difficult to determinate the exact cause as it is often a multifactorial issue. These variables may be related to the quality of the index-procedure (TKA), to the revision procedure or to patient characteristics. The purpose of this review was to highlight the outcomes of revision knee arthroplasty and main factors that may influence the results. Considerable progress has been made during the last 30 years regarding infection treatment and prevention, complex revision prosthetic design and surgical technique development. Although the outcomes have improved over time, patients who undergo revision TKA may need further re-operations in the future.

[Contributions to the study of the chemical variability of some Galium album Mill. Populations harvested from wild flora in northern Moldavia]. / Contributii la studiul variabilitatii chimice a unor populatii de Galium album Mill. Recoltate din flora spontana din nordul Moldovei.

UNLABELLED: Within a complex research regarding the chemical intra- and inter-specific variability of some medicinal plants, we compared two species of Galium: Galium verum L. and Galium album Mill. AIM: In the present study, we quantified some secondary metabolites from 7 natural populations of Galium album Mill., harvested from Suceava and Neamt districts, during July 2008. MATERIAL AND METHODS: The chemical investigations used TLC, UV-VIS spectrophotometry and HPLC, in order to analyze the composition in iridoids, flavones and polyphenolic acids. RESULTS: Our study revealed the existence of important chemical variations between the different populations (Râsca, Crucea/ Borca, Runc, Târzial). Meanwhile the harvesting moment within the vegetative cycle plays a major role for the further quality of the product.