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.

Right ventricular-arterial coupling - A new perspective for right ventricle evaluation in heart failure patients undergoing cardiac resynchronization therapy.

BACKGROUND: Right ventricular - arterial (RV-PA) coupling can be estimated by echocardiography using the ratio between (TAPSE) and pulmonary arterial systolic pressure (PASP). TAPSE/PASP ratio proved to be a prognostic parameter in patients with heart failure and reduced ejection fraction (HFrEF). OBJECTIVE: To evaluate the significance of RV-PA coupling in patients with HFrEF undergoing cardiac resynchronization therapy (CRT). METHODS: Patients undergoing CRT in our center between January 2017 and November 2019 were eligible. Response to CRT was defined by a reduction of more than 15% of left ventricle systolic volume (LVESV) one year after CRT. Primary endpoint was a composite of HF hospitalizations and death during follow-up. RESULTS: 54 patients (Age 64.0 ± 13.8 years; 58% male; left ventricular ejection fraction (LVEF) 28.4 ± 1.3%) were prospectively included. After a mean follow-up of 31 ± 12.9months, the primary endpoint had occurred in 18 (33.3%) patients. A lower TAPSE/PASP ratio was associated with baseline worse HF symptoms, lower LVEF and long-term less LV reverse remodeling (P < .05). After one year CRT improved RV systolic function (TAPSE, RV global longitudinal strain, P < .05), but not TAPSE/PASP ratio (P = .4). The ratio TAPSE/PASP (AUC=0.834) ≥ 0.58 mm/mm Hg showed good sensitivity (90%) and specificity (81.8%) for predicting response to CRT while a ratio <0.58 mm/mm Hg was associated with a higher risk of death and HF hospitalizations during the follow-up (HR 5.37 95%CI [1.6-18], P < .001). CONCLUSION: RV-PA coupling evaluation using TAPSE/PASP ratio predicts CRT response. A lower TAPSE/PASP ratio is associated with a higher risk of adverse cardiovascular events.

State of the Art in Fertility Preservation for Female Patients Prior to Oncologic Therapies.

Quality of life improvement stands as one of the main goals of the medical sciences. Increasing cancer survival rates associated with better early detection and extended therapeutic options led to the specific modeling of patients' choices, comprising aspects of reproductive life that correlated with the evolution of modern society, and requires better assessment. Of these, fertility preservation and ovarian function conservation for pre-menopause female oncologic patients pose a contemporary challenge due to procreation age advance in evolved societies and to the growing expectations regarding cancer treatment. Progress made in cell and tissue-freezing technologies brought hope and shed new light on the onco-fertility field. Additionally, crossing roads with general fertility and senescence studies proved highly beneficial due to the enlarged scope and better synergies and funding. We here strive to bring attention to this domain of care and to sensitize all medical specialties towards a more cohesive approach and to better communication among caregivers and patients.

Impact of early supplementation with low-dose aspirin on functional first trimester parameters in low-risk pregnancies.

INTRODUCTION: There is recent evidence that prophylaxis with 150 mg of aspirin given before 14-16 weeks significantly reduces preeclampsia rates and may improve pregnancy outcome. We conducted an observational study that investigates the effect of low-dose aspirin initiated early in pregnancy or in preconception on functional parameters assessed at 11-14 weeks. MATERIALS AND METHODS: We have retrospectively selected 128 pregnant women that presented for the first trimester screening for aneuploidies between 11+0 and 13+6 weeks of gestation and received low-dose aspirin before 14 weeks. We excluded cases with an estimated high risk for early preeclampsia (cut-off > 1:100). This group was matched to 1044 cases that did not receive aspirin in early pregnancy. We have selected for statistical analysis maternal parameters, ultrasound parameters (crown-rump length, nuchal translucency thickness, pulsatility index in uterine arteries - left, right, average and average uterine PI expressed in multiple of median (MoM)), first trimester maternal biochemical markers (free ß hCG and PAPP-A expressed in MoM), and the calculated risk for early onset and late onset preeclampsia. RESULTS: The most common dosages of aspirin were 75 mg (77 cases) and 100 mg (32 cases). The most significant results are within the aspirin group. In the subgroup that received aspirin before 11 weeks (110 cases), irrespective of the dosage, the uterine blood flow is significantly improved (average uterine PI 1.7 compared with 2.22, p < .05, (0.24-0.7) 95% CI) and the PAPP-A levels are higher (1.2 compared with 0.82, p > .05, [(-0.65) - 0.02] 95% CI). The estimated risk for both early and late onset preeclampsia in this group is reduced (1:2141 compared with 1:333 for early preeclampsia, p < .05, (1216-2398) 95% CI; 1:361 compared with 1:99 for late onset preeclampsia, p < .05, (173-351) 95% CI). CONCLUSION: Even though the results are not always statistically significant, they demonstrate that placentation parameters improve with higher doses of aspirin started before 11 weeks.

Morphological, imaging and surgical aspects in a complex case of uterine leiomyosarcoma - case report and review of the literature.

Leiomyosarcoma is a rare condition so there are relatively few and small case series and no prospective studies to provide clear guidelines regarding management. We report on a case that presents some particularities that further underline diagnostic and treatment difficulties posed by the affliction of such a rare tumor. This is the case of a 43-year-old woman who had a large tumor arising from the uterus, with a spectacular growth rate over a short period. The patient, with congenital spastic tetraparesis and hydrocephalus, came for belly enlargement with rapid increase in size over the previous two months. Physical exam and ultrasound lead to the conclusion of a large abdominal mass. A computed tomography scan showed a mass arising from the pelvis and a large amount of ascites. An exploratory laparotomy was performed and the histopathology report confirmed the diagnosis of uterine leiomyosarcoma. Leiomyosarcoma poses challenging problems regarding histological grading and, due to its rate of growth, real surgical difficulties. Final diagnosis is done by histopathological examination after surgical excision. Frequently, it is late diagnosed when complete removal of the tumor is often impossible.

New cardiovascular risk factors and their use for an accurate cardiovascular risk assessment in hypertensive patients.

OBJECTIVES: To analyze the predictive value of new cardiovascular (CV) risk factors for CV risk assessment in the adult Romanian hypertensive (HT) population. METHODS: Hypertensive adults aged between 40-65 years of age, identified in national representative SEPHAR II survey were evaluated by anthropometric, BP and arterial stiffness measurements: aortic pulse wave velocity (PWVao), aortic augmentation index (AIXao), revers time (RT) and central systolic blood pressure (SBPao), 12 lead ECGs and laboratory workup. Values above the 4th quartile of mean SBP' standard deviation (s.d.) defined increased BP variability. Log(TG/HDL-cholesterol) defined atherogenic index of plasma (AIP). Serum uric acid levels above 5.70 mg/dl for women and 7.0 mg/dl for males defined hyperuricemia (HUA). CV risk was assessed based on SCORE chart for high CV risk countries. Binary logistic regression using a stepwise likelihood ratio method (adjustments for major confounders and colliniarity analysis) was used in order to validate predictors of high and very high CV risk class. RESULTS: The mean SBP value of the study group was 148.46±19.61 mmHg. Over forty percent of hypertensives had a high and very high CV risk. Predictors of high/very high CV risk category validated by regression analysis were: increased visit-to-visit BP variability (OR: 2.49; 95%CI: 1.67-3.73), PWVao (OR: 1.12; 95%CI: 1.02-1.22), RT (OR: 0.95; 95% CI: 0.93-0.98), SBPao (OR: 1.01; 95%CI: 1.01-1.03) and AIP (OR: 7.08; 95%CI: 3.91-12.82). CONCLUSION: The results of our study suggests that the new CV risk factors such as increased BP variability, arterial stiffness indices and AIP are useful tools for a more accurate identification of hypertensives patients at high and very high CV risk.

KrF pulsed laser ablation of thin films made from fluorinated heterocyclic poly(naphthyl-imide)s.

Among the many aspects of laser ablation, development of conical structures induced by excimer laser radiation on polyimide surfaces has been thoroughly investigated. Because the mechanisms that produce these surface textures are not fully understood, two theories, photochemical bond breaking and thermal reaction, have been introduced. Here we present the first study of ultraviolet laser ablation behavior of thin films made from fluorinated poly(naphthyl-imide)s containing oxadiazole rings and the investigation of the mechanism of cone-like structure formation at two laser fluences, 57 and 240 mJ/cm(2). The morphology of thin films before and after laser ablation was studied by using various spectroscopy techniques such as Fourier transform infrared spectroscopy, time-resolved emission and X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle measurements. All of the data suggest impurities shielded at low fluence radiation (57 mJ/cm(2)) and a radiation hardening process at high value fluence (240 mJ/cm(2)), which are proposed as the main mechanisms for laser ablation of our polyimide films, and we bring evidence to support them.

Surgical therapy of an asymptomatic primary popliteal venous aneurysm.

Primary popliteal venous aneurysm is a rare condition. To date, approximately 150 cases have been reported. In the present article, we report a 59-year-old man who presented with a swelling of the left popliteal fossa. Duplex ultrasound scan revealed a saccular aneurysm of the popliteal vein, with a diameter of 2.5 × 2.5 cm. The distal part of the popliteal vein was dilated in a fusiform configuration up to 2.0 cm on both sides. The diagnosis was confirmed using magnetic resonance imaging and ascending phlebography. There was no sign of venous thrombosis. Our patient presented without any previous clinical evidence of pulmonary emboli. Surgery was deemed indicated. A traditional tangential aneurysmectomy and lateral venorrhaphy of the distal fusiform part of the popliteal lesion was performed as well as resection of the saccular part using a dorsal approach. Surgery and recovery were uneventful. The patient presented for follow-up after 6 and 12 weeks without any complaints. Duplex ultrasound scanning and ascending phlebography (only once after 12 weeks) were performed, which confirmed patency.