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Herpes simplex virus type 1 (HSV-1) is highly prevalent in humans and can reach the brain without evident clinical symptoms. Once in the central nervous system (CNS), the virus can either reside in a quiescent latent state in this tissue, or eventually actively lead to severe acute necrotizing encephalitis, which is characterized by exacerbated neuroinflammation and prolonged neuroimmune activation producing a life-threatening disease. Although HSV-1 encephalitis can be treated with antivirals that limit virus replication, neurological sequelae are common and the virus will nevertheless remain for life in the neural tissue. Importantly, there is accumulating evidence that suggests that HSV-1 infection of the brain both, in symptomatic and asymptomatic individuals could lead to neuronal damage and eventually, neurodegenerative disorders. Here, we review and discuss acute and chronic infection of particular brain regions by HSV-1 and how this may affect neuron and cognitive functions in the host. We review potential cellular and molecular mechanisms leading to neurodegeneration, such as protein aggregation, dysregulation of autophagy, oxidative cell damage and apoptosis, among others. Furthermore, we discuss the impact of HSV-1 infection on brain inflammation and its potential relationship with neurodegenerative diseases.
Figure 1. Central nervous system (CNS) infection with herpes simplex virus type 1 (HSV-1). (A) HSV-1 CNS infection through the olfactory route: HSV-1 can infect the termini of olfactory neurons enervating the nasal epithelium and access the CNS by retrograde axonal transport through neurons until reaching the olfactory bulb in the brain. (B) HSV-1 can also infect the CNS because of HSV-1 peripheral reactivation. HSV-1 can reactivate from neurons in the trigeminal ganglia (TG) and reach either the skin or CNS through anterograde transport. (C) HSV-1 can also reach different regions of the CNS because of HSV-1 reactivation within the brain. Reactivation of latent virus within the CNS has been reported to reach the cerebellum, olfactory bulb, frontal cortex, or hippocampus. (D) Finally, HSV-1 can infect the CNS through a hematogenous route. HSV-1 can infect the CNS of fetuses because of HSV-1 infection in the mother, through the bloodstream by accessing the placenta. Once the fetus is infected, HSV-1 accesses the brain and has been reported to infect the hippocampus. Neural stem cells (NSCs) in the subventricular zone of the lateral ventricle and subgranular zone of the hippocampus have been shown to be infected by HSV-1, affecting the maturation and proliferation, as well as differentiation of these cells.
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Witnesses undergoing baptism are required to publicly confirm that they are associating themselves "with God's spirit-directed organization", thereby submitting themselves to its direction and judicial system. Watch Tower Society publications urge Witnesses to demonstrate loyalty to the organization without dissent, even at the cost of family ties. Loyalty to the organization is said to require full involvement in public preaching and regular meeting attendance.
The Watch Tower Bible and Tract Society used the Cross and Crown symbol on tombstones, and on its publications until 1931. Since 1936, Jehovah's Witnesses have rejected the idea that Jesus died on a cross, and instead teach that he died on a single wooden stake (crux simplex), asserting that the Koine Greek word "σταυρός" (stauros) refers to a single upright post. They consider the cross to be of pagan origins and an object of idol worship. According to the Watch Tower society, some Jehovah's Witnesses have been persecuted or killed for not venerating a cross.
Jehovah's Witnesses do not believe that Satan lives in Hell or that he has been given responsibility to punish the wicked. Satan and his demons are said to have been cast down from heaven to the earth in 1914, marking the beginning of the "last days". Witnesses believe that Satan and his demons influence individuals, organizations and nations, and that they are the cause of human suffering. At Armageddon, Satan is to be bound for 1,000 years, and then given a brief opportunity to mislead perfect humanity before being destroyed.
Writers including James Beckford and former members James Penton and Barbara Grizzuti Harrison have stated that Jehovah's Witnesses' have a fear of demons, which Penton says is "sometimes so extreme that it becomes quite superstitious". However, Penton also notes that avoidance of "demonistic practices" has released many people in Africa and Latin America from fear of spirits. Watch Tower Society publications state that Witnesses need not harbor dread or superstitious fear of demons, because their power over humans is limited.
Jehovah's Witnesses' believe that faith in Jesus' ransom sacrifice is essential for salvation. They reject the concept of universal salvation and the concept of predestination. They believe that all intelligent creatures are endowed with free will, and that salvation is dependent on God's "undeserved kindness", but also requires faith in God and in the "ransom sacrifice" of Jesus Christ, demonstrated by "zealous" preaching activity. According to Watch Tower Society theology, salvation requires Christ's mediation as part of God's purpose to grant humans everlasting life, either in heaven (for 144,000 "anointed" Christians, or the "little flock") or on earth (for the "other sheep", the remainder of faithful humanity).
Most of those who had died prior to God's intervention will gradually be resurrected to a "day of judgment" lasting for the thousand years referred to in Revelation 20. This judgment will be based on their actions after resurrection rather than past deeds. At the end of the thousand years, Christ will hand all authority back to God. Then Satan is released for a final opportunity to mislead perfect mankind; Satan, his demons, and any who fail the test will be destroyed, leaving a fully tested, perfect human race who will live forever.
More recently, however, critics had begun asking for proof that Theranos's technology actually works, and that its results are accurate. After all, the evidence on this wasn't public: The Food and Drug Administration (FDA) hadn't cleared Theranos's tests. And Holmes had never published her claims in peer-reviewed journals.
Since the Journal's story, other critics have come forward and claimed that their blood test results from Theranos didn't quite match those from standard labs. In a follow-up, the Wall Street Journal confirmed that the FDA had pressured Theranos to stop using its Edison technology on almost all of its blood tests save for one (a test for Type 1 herpes simplex) because of concerns about the machine's accuracy. Last week, Holmes admitted that Theranos had stopped taking pinprick blood samples for all but one of its tests.
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