Global synergistic actions to improve brain health for human development.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Exposure to hydrocarbons and chlorpyrifos alters the expression of nuclear receptors and antioxidant, detoxifying, and immune response proteins in the liver of the rainbow trout, Oncorhynchus mykiss.

The development of oil and gas production together with the fruit production in nearby areas of North Patagonia, Argentina, suggests aquatic pollution scenarios which include permanent oil pollution combined with short events of pesticides application. It has been reported that oil hydrocarbons activate the aryl hydrocarbon receptor (AhR) pathway in the rainbow trout, Oncorhynchus mykiss, and that the insecticide Chlorpyrifos (CPF) interacts with these effects. Thus, it is interesting to investigate whether hydrocarbons and insecticides, applied by separate or combined, can affect fish health and reproductive signaling by acting on different nuclear receptors' regulatory pathways. To study this kind of interactions, we exposed juvenile rainbow trout to water accommodated fraction (WAF) of crude oil (62 µg L-1 TPH) for 48 h and subsequently exposed the livers ex vivo to the insecticide Chlorpyrifos (CPF) (20 µg L-1) for 1 h. We analyzed the mRNA expression of nuclear receptors and proteins involved in detoxifying, antioxidant, immune and apoptosis responses by qRT-PCR. We also performed histopathological analysis. WAF induced the expression of the androgen (AR) and the Liver X receptor (LXR) by 8- and 3-fold, respectively. AR induction was reversed by subsequent exposure to CPF. The progesterone receptor (PR) and glucocorticoid receptor (GR) were increased 2-fold and 3-fold by WAF respectively, while estrogen and mineralocorticoid receptors were not affected. GR was also induced by CPF with an additive effect in the WAF-CPF treatment. The antioxidant genes, gamma glutamyl transferase (GGT), superoxide dismutase (SOD1) were induced by WAF (2-3-fold). WAF upregulated the ATP Binding Cassette Subfamily C Member 2 (ABCC2, MRP2) (4-fold) and downregulated alkaline phosphatase. WAF also induced the inflammatory interleukins (IL) IL-8, and IL-6 and the anti-inflammatory IL-10, while CPF induced the inflammatory tumor necrosis factor (-α) and IL-6, and activated the intrinsic apoptotic pathway through the induction of caspases 3 and 9. Both, WAF and CPF downregulated the expression of the extrinsic apoptosis initiator caspase 8 and the inflammatory caspase 1. In conclusion, WAF hydrocarbons alter O. mykiss endocrine regulation by inducing AR, PR and GR. The subsequent exposure to CPF reverses AR, suggesting a complex interaction of different pollutants in contaminated environments, WAF hydrocarbons alter liver metabolism by inducing the expression of LXR, GR, antioxidant and detoxifying enzymes, and both inflammatory and anti-inflammatory cytokines, and causing mild hepatic steatosis. CPF activates inflammatory and stress responses associated with the induction of inflammatory cytokines together with apoptosis initiator and executioner caspases.

Gills CYP1A of Oncorhynchus mykiss as a sensitive biomarker of crude oil pollution in freshwater environments.

The induction of CYP1A activity (EROD) and protein expression was compared in liver and gills of rainbow trout from a stream polluted with crude oil, and through laboratory exposures to 1% and 5% of water accommodated fraction of the crude oil (WAF) for 1 and 4 days. Gills EROD increased 1.6-2.7-fold in fish from the polluted stream and during experiments, while liver EROD was induced only by 1% WAF at day 1 (1.5-fold). Contrastingly, crude oil pollution strongly induced both liver and gills CYP1A protein expression in the field (14-36-fold) and in experiments (4-25-fold). This highlights that crude oil induced CYP1A activity markedly in gills but only slightly or not at all in the liver, suggesting that differences between organ EROD activities are related to the modulation of CYP1A enzyme activity but not to the regulation at transcriptional or translational levels.

Effects of sequential exposure to water accommodated fraction of crude oil and chlorpyrifos on molecular and biochemical biomarkers in rainbow trout.

Fish can be simultaneously or sequentially exposed to various kinds of pollutants, resulting in combined effects. Polycyclic aromatic hydrocarbons induce cytochrome P450 monooxygenase 1A (CYP1A) expression, which catalyzes the conversion of the organophosphorus insecticide chlorpyrifos (CPF) into its most active derivative, CPF-oxon. CPF-oxon inhibits CYP1A and other enzymes, including carboxylesterases (CEs) and acetylcholinesterase (AChE). We studied the effects of an in vivo exposure to crude oil water accommodated fraction (WAF) followed by an ex vivo exposure of liver tissue to CPF on the expression of Cyp1a, AhR and ARNT mRNA, CYP1A protein and on the activity of biomarker enzymes in the rainbow trout (Oncorhynchus mykiss). Juvenile rainbow trout were exposed to WAF (62 µg L-1 TPH) for 48 h. Then, liver was dissected out, sliced and exposed to 20 µg L-1 CPF ex vivo for 1 h. Liver tissue was analyzed for mRNA and protein expression and for CEs, AChE, glutathione S-transferase (GST) and CYP1A (EROD) activity. WAF induced Cyp1a mRNA and CYP1A protein expression by 10-fold and 2.5-8.3-fold, respectively, with no effect of CPF. WAF induced AhR expression significantly (4-fold) in control but not in CPF treated liver tissue. ARNT mRNA expression was significantly lowered (5-fold) by WAF. CPF significantly reduced liver EROD activity, independently of WAF pre-treatment. CEs activity was significantly inhibited in an additive manner following in vivo exposure to WAF (42%) and ex vivo exposure to CPF (19%). CPF exposure inhibited AChE activity (37%) and increased GST activity (42%).

Endovenous 808-nm diode laser occlusion of perforating veins and varicose collaterals: a prospective study of 482 limbs.

BACKGROUND: Endovenous laser ablation (EVLA) was performed in the treatment of great and small saphenous veins (GSVs, SSVs), perforating veins (PVs), and varicose collaterals (VCs). OBJECTIVE To verify the outcome in PVs and VCs. MATERIALS AND METHODS: Four hundred eighty-two limbs of 306 patients were studied. EVLA was performed on 167 GSVs, 52 SSVs, and 534 PVs of 303 limbs and on VCs of 467 limbs; 133 GSVs were stripped, 300 of saphenofemoral junctions (SFJs) and 45 saphenopopliteal junctions (SPJs) were interrupted. Limbs were selected using duplex ultrasound examination and photographs; PVs-VCs diameter (<4 mm) and VC length were measured. EVLA was performed using a 808-nm diode laser, 0.6-mm fibers, continuous emission, 4 to 10 W, and 10 to 20 J/cm. Follow-up on 467 limbs occurred over a mean 27.5 months (range 3 months to 6 years); 98 limbs were followed up for longer than 4 years. RESULTS: Operating time range from 10 to 30 minutes per limb. Blood vaporization, thrombosis, fibrosis, and atrophy prevailed in PVs and in the large VCs (>4 mm) and massive coagulation in the smaller (<4 mm). High rate of occlusion was seen, with different rates of patent PV-VC mainly in diameter >6 mm. Thirty-nine out of 511 patent PVs (7.6%) and 96 out of 778 VCs (12-13%) were re-treated using EVLA or foam sclerotherapy. Minor complications occurred in 88 of the 778 (11%). CONCLUSIONS: EVLA of PVs and VCs is effective and faster than surgery in 2- to 6-mm PVs and VCs using an 808-nm diode laser.

Reparative surgery of valves in the treatment of superficial venous insufficiency. External banding valvuloplasty versus high ligation or disconnection. A prospective multicentric trial.

OBJECTIVE: A prospective study was performed in order to compare results obtained in the treatment of early and/or limited primary varicose veins of the lower limbs using two different procedures: external valvuloplasty and high ligation or disconnection of the sapheno-femoral junction. MATERIALS AND METHODS: 116 limbs (113 patients) were selected. 57 with normal cusps in dilated valves were subjected to external valvuloplasty with Silicone prosthesis under Doppler control (intraoperative angioscopy in 16 cases); 59 limbs were subjected to high ligation or disconnection of the junction; 57 limbs out of 116 were subjected to complementary procedures. Duplex and photoplethysmographic examinations were performed before and after the surgical procedures in all patients. Doppler venous pressures were measured in 36 limbs and invasive pressures in 40 limbs. Patients were postoperatively followed up every 4 months until the 12th month. RESULTS: Indications for valvuloplasty were found in 8.2% of cases and in 66.3% of the early varices. Clinical results were slightly superior in the reparative surgery group. Thrombotic occlusion of the proximal long saphenous vein was significantly higher in the ligation-disconnection group. Results from photoplethysmography and venous pressure measurements indicated that both operations are equally effective in the elimination of reflux in the junction.