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Niemann-Pick disease type C1 (NPC1) is a fatal congenital neurodegenerative disorder caused by mutations in the NPC1 gene, which is involved in cholesterol transport in lysosomes. Broad clinical manifestations of NPC1 include liver failure, pulmonary disorder, neurological deficits, and psychiatric symptoms. The main cause of death in NPC1 patients involves central nervous system (CNS) dysfunction; there is no essential treatment. We generated a tyrosine-mutant adeno-associated virus (AAV) 9/3 vector that expresses human NPC1 under a cytomegalovirus (CMV) promoter (AAV-CMV-hNPC1) and injected it into the left lateral ventricle (5 μL) and cisterna magna (10 μL) of Npc1 homo-knockout (Npc1-/-) mice. Each mouse received total 1.35 × 1011 vector genome on days 4 or 5 of life. AAV-treated Npc1-/- mice (n = 11) had an average survival of &gt;28 weeks, while all saline-treated Npc1-/- mice (n = 11) and untreated Npc1-/- mice (n = 6) died within 16 weeks. Saline-treated and untreated Npc1-/- mice lost body weight from 7 weeks until death. However, the average body weight of AAV-treated Npc1-/- mice increased until 15 weeks. AAV-treated Npc1-/- mice also showed a significant improvement in the rotarod test performance. A pathological analysis at 11 weeks showed that cerebellar Purkinje cells were preserved in AAV-treated Npc1-/- mice. In contrast, untreated Npc1-/- mice showed an almost total loss of cerebellar Purkinje cells. Combined injection into both the lateral ventricle and cisterna magna achieved broader delivery of the vector to the CNS, leading to better outcomes than noted in previous reports, with injection into the lateral ventricles or veins alone. In AAV-treated Npc1-/- mice, vector genome DNA was detected widely in the CNS and liver. Human NPC1 RNA was detected in the brain, liver, lung, and heart. Accumulated unesterified cholesterol in the liver was reduced in the AAV-treated Npc1-/- mice. Our results suggest the feasibility of gene therapy for patients with NPC1.Recently, chemokine receptor CC chemokine receptor 5 (CCR5) was found to be a negative modulator of learning and memory. Its inhibition improved outcome after stroke and traumatic brain injury (TBI). To better understand its role after TBI and establish therapeutic strategies, we investigated the effect of reduced CCR5 signaling as a neuroprotective strategy and of the temporal changes of CCR5 expression after TBI in different brain cell types. To silence CCR5 expression, ccr5 short hairpin RNA (shRNA) or dsred shRNA (control) was injected into the cornu ammonis (CA) 1 and CA3 regions of the hippocampus 2 weeks before induction of closed-head injury in mice. Animals were then monitored for 32 days and euthanized at different time points to assess lesion area, inflammatory components of the glial response (immunohistochemistry; IHC), cytokine levels (enzyme-linked immunosorbent array), and extracellular signal-regulated kinase (ERK) phosphorylation (western blot). Fluorescence-activated cell sorting (FACS) analysis was performed to study post-injury temporal changes of CCR5 and C-X-C motif chemokine receptor 4 (CXCR4) expression in cortical and hippocampal cell populations (neurons, astrocytes, and microglia). Phosphorylation of the N-methyl-d-aspartate subunit 1 (NR1) subunit of N-methyl-d-aspartate (western blot) and cAMP-response-element-binding protein (CREB; IHC) were also assessed. The ccr5 shRNA mice displayed reduced lesion area, dynamic alterations in levels of inflammation-related CCR5 ligands and cytokines, and higher levels of phosphorylated ERK. The ccr5 shRNA also reduced astrocytosis in the lesioned and sublesioned cortex. FACS analysis revealed increased cortical CCR5 and CXCR4 expression in CD11b-positive cells, astrocytes, and neurons, which was most evident in cells expressing both receptors, at 3 and 11 days post-injury. The lowest levels of phosphorylated NR1 and phosphorylated CREB were found at day 3 post-injury, suggesting that this is the critical time point for therapeutic intervention.There is not a single pharmacological agent with demonstrated therapeutic efficacy for traumatic brain injury (TBI). [https://www.selleckchem.com/products/avacopan-ccx168-.html selleck products] With recent legalization efforts and the growing popularity of medical cannabis, patients with TBI will inevitably consider medical cannabis as a treatment option. Pre-clinical TBI research suggests that cannabinoids have neuroprotective and psychotherapeutic properties. In contrast, recreational cannabis use has consistently shown to have detrimental effects. Our review identified a paucity of high-quality studies examining the beneficial and adverse effects of medical cannabis on TBI, with only a single phase III randomized control trial. However, observational studies demonstrate that TBI patients are using medical and recreational cannabis to treat their symptoms, highlighting inconsistencies between public policy, perception of potential efficacy, and the dearth of empirical evidence. We conclude that randomized controlled trials and prospective studies with appropriate control groups are necessary to fully understand the efficacy and potential adverse effects of medical cannabis for TBI.<br /><br /> Preoperative planning is an important step before any joint replacement surgery. In developing countries standardised radiographs and planning tools might not be available but nevertheless hemiarthroplasties are performed in certain trauma cases. An equation should be devised to allow a preoperative estimation of the expected femoral head size dimensions in those situations.<br /><br /> 35 lower limbs of human cadavers were studied. The estimated femoral head (EFH) size of each femur was obtained by measuring the trochanteric length (TL) (in cm) and using the equation 'EFH = 16 + (0.7 × TL)'. The hip joint was dissected, and the actual size of the femoral head (AFH) was measured on the specimen.<br /><br /> There was a correlation between the EFH and AFH (<br /><br />  = 0.0001). Accepting a range of ±3 mm the femoral head size was predicted correctly in 31 hips (89%), for ±4 mm in 33 hips (94%) and for ±5 mm in 35 hips (100%), respectively.<br /><br /> A simple tape measurement and the equation Femoral head size = 16 + (0.7 × Trochanteric Length) ±5 mm gives a rather reliable guess for the expected femoral head size.