Perimeter Intrusion Detection by Video Surveillance: A Survey.

In recent times, we have seen a massive rise in vision-based applications, such as video anomaly detection, motion detection, object tracking, people counting, etc. Most of these tasks are well defined, with a clear idea of the goal, along with proper datasets and evaluation procedures. However, perimeter intrusion detection (PID), which is one of the major tasks in visual surveillance, still needs to be formally defined. A perimeter intrusion detection system (PIDS) aims to detect the presence of an unauthorized object in a protected outdoor site during a certain time. Existing works vaguely define a PIDS, and this has a direct impact on the evaluation of methods. In this paper, we mathematically define it. We review the existing methods, datasets and evaluation protocols based on this definition. Furthermore, we provide a suitable evaluation protocol for real-life application. Finally, we evaluate the existing systems on available datasets using different evaluation schemes and metrics.

Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive leukemia for which knowledge on disease mechanisms and effective therapies are currently lacking. Only a handful of recurring genetic mutations have been identified and none is specific to BPDCN. In this study, through molecular cloning in an index case that presented a balanced t(3;5)(q21;q31) and molecular cytogenetic analyses in a further 46 cases, we identify monoallelic deletion of NR3C1 (5q31), encoding the glucocorticoid receptor (GCR), in 13 of 47 (28%) BPDCN patients. Targeted deep sequencing in 36 BPDCN cases, including 10 with NR3C1 deletion, did not reveal NR3C1 point mutations or indels. Haploinsufficiency for NR3C1 defined a subset of BPDCN with lowered GCR expression and extremely poor overall survival (P = .0006). Consistent with a role for GCR in tumor suppression, functional analyses coupled with gene expression profiling identified corticoresistance and loss-of-EZH2 function as major downstream consequences of NR3C1 deletion in BPDCN. Subsequently, more detailed analyses of the t(3;5)(q21;q31) revealed fusion of NR3C1 to a long noncoding RNA (lncRNA) gene (lincRNA-3q) that encodes a novel, nuclear, noncoding RNA involved in the regulation of leukemia stem cell programs and G1/S transition, via E2F. Overexpression of lincRNA-3q was a consistent feature of malignant cells and could be abrogated by bromodomain and extraterminal domain (BET) protein inhibition. Taken together, this work points to NR3C1 as a haploinsufficient tumor suppressor in a subset of BPDCN and identifies BET inhibition, acting at least partially via lncRNA blockade, as a novel treatment option in BPDCN.

Bromodomain-dependent stage-specific male genome programming by Brdt.

Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic and post-meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential genes and repressing a 'progenitor cells' gene expression program. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdt's first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome.

Synaptodendritic recovery following HIV Tat exposure: neurorestoration by phytoestrogens.

HIV-1 infects the brain and, despite antiretroviral therapy, many infected individuals suffer from HIV-1-associated neurocognitive disorders (HAND). HAND is associated with dendritic simplification and synaptic loss. Prevention of synaptodendritic damage may ameliorate or forestall neurocognitive decline in latent HIV-1 infections. The HIV-1 transactivating protein (Tat) is produced during viral latency in the brain and may cause synaptodendritic damage. This study examined the integrity of the dendritic network after exposure to HIV-1 Tat by labeling filamentous actin (F-actin)-rich structures (puncta) in primary neuronal cultures. After 24 h of treatment, HIV-1 Tat was associated with the dendritic arbor and produced a significant reduction of F-actin-labeled dendritic puncta as well as loss of dendrites. Pre-treatment with either of two plant-derived phytoestrogen compounds (daidzein and liquiritigenin), significantly reduced synaptodendritic damage following HIV-1 Tat treatment. In addition, 6 days after HIV-1 Tat treatment, treatment with either daidzein, or liquiritigenin enhanced recovery, via the estrogen receptor, from HIV-1 Tat-induced synaptodendritic damage. These results suggest that either liquiritigenin or daidzein may not only attenuate acute synaptodendritic injury in HIV-1 but may also promote recovery from synaptodendritic damage. The HIV-1 transactivating protein (Tat) is produced during viral latency in the brain. Treatment with either daidzein or liquiritigenin restored the loss of synaptic connectivity produced by HIV-1 Tat. This neurorestoration was mediated by estrogen receptors (ER). These results suggest that plant-derived phytoestrogens may promote recovery from HIV-1-induced synaptodendritic damage.

Endogenous amyloidogenesis in long-term rat hippocampal cell cultures.

BACKGROUND: Long-term primary neuronal cultures are a useful tool for the investigation of biochemical processes associated with neuronal senescence. Improvements in available technology make it possible to observe maturation of neural cells isolated from different regions of the rodent brain over a prolonged period in vitro. Existing experimental evidence suggests that cellular aging occurs in mature, long-term, primary neuronal cell cultures. However, detailed studies of neuronal development in vitro are needed to demonstrate the validity of long-term cell culture-based models for investigation of the biochemical mechanisms of in vitro neuronal development and senescence. RESULTS: In the current study, neuron-enriched hippocampal cell cultures were used to analyze the differentiation and degeneration of hippocampal neurons over a two month time period. The expression of different neuronal and astroglial biomarkers was used to determine the cytochemical characteristics of hippocampal cells in long-term cultures of varying ages. It was observed that the expression of the intermediate filament nestin was absent from cultures older than 21 days in vitro (DIV), and the expression of neuronal or astrocytic markers appeared to replace nestin. Additionally, morphological evaluations of neuronal integrity and Hoescht staining were used to assess the cellular conditions in the process of hippocampal culture development and aging. It was found that there was an increase in endogenous production of Aß(1-42) and an increase in the accumulation of Congo Red-binding amyloidal aggregates associated with the aging of neurons in primary culture. In vitro changes in the morphology of co-existing astrocytes and cell culture age-dependent degeneration of neurodendritic network resemble features of in vivo brain aging at the cellular level. CONCLUSION: In conclusion, this study suggests that long-term primary CNS culture is a viable model for the study of basic mechanisms and effective methods to decelerate the process of neuronal senescence.

Opiophobia in Emergency Department Healthcare Providers: A Survey in Western Switzerland.

Opiophobia contributes to oligoanalgesia in the emergency department (ED), but its definition varies, and its association to healthcare providers' personality traits has been scantly explored. Our purpose was to study the different definitions of opiophobia and their association with two personality traits of doctors and nurses working in EDs, namely the stress from uncertainty and risk-taking. We used three online questionnaires: the 'Attitude Towards Morphine Use' Score (ATMS), the Stress From Uncertainty Scale (SUS) and the Risk-Taking Scale (RTS). Doctors and nurses from nine hospital EDs in francophone Switzerland were invited to participate. The ATMS score was analyzed according to demographic characteristics, SUS, and RTS. The response rate was 56%, with 57% of respondents being nurses and 63% women. Doctors, less experienced and non-indigenous participants had a significantly higher ATMS (all p ≤ 0.01). The main contributors of the ATMS were the fear of side effects and of addiction. In multivariate analysis, being a doctor, less experience and non-indigenous status were predictive of the ATMS; each point of the SUS increased the ATMS by 0.24 point. The fear of side effects and of addiction were the major contributors of opiophobia among ED healthcare providers; opiophobia was also associated with their personality traits.

S-Equol mitigates motivational deficits and dysregulation associated with HIV-1.

Motivational deficits (e.g., apathy) and dysregulation (e.g., addiction) in HIV-1 seropositive individuals, despite treatment with combination antiretroviral therapy, necessitates the development of innovative adjunctive therapeutics. S-Equol (SE), a selective estrogen receptor ß agonist, has been implicated as a neuroprotective and/or neurorestorative therapeutic for HIV-1 associated neurocognitive disorders (HAND); its therapeutic utility for motivational alterations, however, has yet to be systematically evaluated. Thus, HIV-1 transgenic (Tg) and control animals were treated with either a daily oral dose of SE (0.2 mg) or vehicle and assessed in a series of tasks to evaluate goal-directed and drug-seeking behavior. First, at the genotypic level, motivational deficits in HIV-1 Tg rats treated with vehicle were characterized by a diminished reinforcing efficacy of, and sensitivity to, sucrose. Motivational dysregulation was evidenced by enhanced drug-seeking for cocaine relative to control animals treated with vehicle. Second, treatment with SE ameliorated both motivational deficits and dysregulation in HIV-1 Tg rats. Following a history of cocaine self-administration, HIV-1 Tg animals treated with vehicle exhibited lower levels of dendritic branching and a shift towards longer dendritic spines with decreased head diameter. Treatment with SE, however, led to long-term enhancements in dendritic spine morphology in HIV-1 Tg animals supporting a potential underlying basis by which SE exerts its therapeutic effects. Taken together, SE restored motivated behavior in the HIV-1 Tg rat, expanding the potential clinical utility of SE to include both neurocognitive and affective alterations.

Role of Ketamine in the Treatment of Psychiatric Disorders.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding the use of ketamine as a treatment for treatment-resistant depression (TRD). It covers the epidemiology, risk factors, pathophysiology, and current treatment modalities regarding Major Depressive Disorder (MDD) and TRD. It provides background on the mechanism of action of ketamine, its history, current approved and off-label indications in the field of psychiatry, and then provides an overview of the existing evidence for the use of ketamine in the treatment of TRD. RECENT FINDINGS: MDD is a mental illness that puts an enormous strain on the affected and a high socio-economic burden on society. The illness is complex and combines genetic, pathophysiologic, and environmental factors that combine to negatively affect neurotransmitter balance in the brain. Additional evidence suggests dysregulation of the hypothalamic-pituitary (HPA) axis, brain-derived neurotrophic factor (BDNF), vitamin D levels, and involvement of pro-inflammatory markers. Core symptoms include depressed mood or anhedonia, combined with neurovegetative symptoms such as sleep impairment, changes in appetite, feelings of worthlessness and guilt, and psychomotor retardation. Current first-line treatment options are antidepressants of the selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) class. Failure to respond to two adequate trials of treatment meets the criteria for TRD. Esketamine (Spravato) is an NMDA-receptor antagonist with additional AMPA-receptor agonist properties, which the FDA approved in 2019 to treat adult TRD in conjunction with an oral antidepressant. It can be administered intranasally, providing a rapid response and proven effective and safe. Additional research suggests that oral ketamine might be effective for PTSD and anxiety disorders. Intravenous administration of ketamine has also shown benefits for acute suicidal ideation and depression and substance use to reduce relapse rates. SUMMARY: TRD is associated with huge costs on individual and societal levels. Underlying disease processes are multifactorial and not well understood. Adjunctive therapies for TRD with proven benefits exist, but acutely depressed and suicidal patients often require prolonged inpatient stabilization. Intranasal esketamine is a new FDA-approved alternative with rapid benefit for TRD, which has also shown a rapid reduction in suicidal ideation while maintaining a favorable side-effect profile. Additional potential off-label uses for ketamine in psychiatric disorders have been studied, including PTSD, anxiety disorders, bipolar depression, and substance use disorders.

Transient neonatal sleep fragmentation results in long-term neuroinflammation and cognitive impairment in a rabbit model.

Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.

Asenapine Transdermal Patch for the Management of Schizophrenia.

Purpose of Review: This is a comprehensive review of the literature regarding the use of asenapine for the treatment of schizophrenia (SZ) in adults. It covers an introduction, epidemiology, risk factors, pathophysiology, and current treatment modalities regarding SZ, provides a background on the mechanism of action of asenapine, and then reviews the existing evidence for use of asenapine in both its sublingual and transdermal formulation in the treatment of SZ. Recent Findings: SZ is a complex and multifactorial mental disorder which is thought to combine several genetic, epigenetic, and environmental factors causing abnormalities in the dopaminergic system. Symptoms are categorized in delusions, hallucinations, disorganization, and negative presentations like affective flattening and apathy. Current treatment focuses on antipsychotic medications by means of oral administration or long-acting injection. Asenapine is a second-generation antipsychotic with 5HT-2A antagonist and 5HT-1A/1B partial agonist properties, which provides a favorable profile in targeting schizophrenic symptoms, while reducing motor side effects and improving mood and cognition. Asenapine in its sublingual formulation was FDA approved for treatment of SZ and bipolar I disorder in adults in August of 2009 and has been proven to be both effective and safe. Transdermal patch of asenapine (Secuado) was FDA approved in October of 2019, the first and only FDA approved patch for SZ in adults, which offers another strategy for treatment to improve compliance and ease of administration. Summary: SZ is a chronic and debilitating disease which is still not well understood and comes at great cost with regards to the quality of life for patients. Medication side-effects and compliance are enormous issues which take a toll on health care systems in industrialized nations and keep patients from achieving stability with their disease. Transdermal asenapine is a new first-in-class dosage form and provides a novel modality of administration. It has been shown to be effective in reducing positive, as well as negative symptoms, while still maintaining a favorable side-effect profile.

HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

Genetic Basis of Chronotype in Humans: Insights From Three Landmark GWAS.

Study Objectives: Chronotype, or diurnal preference, refers to behavioral manifestations of the endogenous circadian system that governs preferred timing of sleep and wake. As variations in circadian timing and system perturbations are linked to disease development, the fundamental biology of chronotype has received attention for its role in the regulation and dysregulation of sleep and related illnesses. Family studies indicate that chronotype is a heritable trait, thus directing attention toward its genetic basis. Although discoveries from molecular studies of candidate genes have shed light onto its genetic architecture, the contribution of genetic variation to chronotype has remained unclear with few related variants identified. In the advent of large-scale genome-wide association studies (GWAS), scientists now have the ability to discover novel common genetic variants associated with complex phenotypes. Three recent large-scale GWASs of chronotype were conducted on subjects of European ancestry from the 23andMe cohort and the UK Biobank. This review discusses the findings of these landmark GWASs in the context of prior research. Methods: We systematically reviewed and compared methodological and analytical approaches and results across the three GWASs of chronotype. Results: A good deal of consistency was observed across studies with 9 genes identified in 2 of the 3 GWASs. Several genes previously unknown to influence chronotype were identified. Conclusions: GWAS is an important tool in identifying common variants associated with the complex chronotype phenotype, the findings of which can supplement and guide molecular science. Future directions in model systems and discovery of rare variants are discussed.

Complete Genome Sequences of Mycobacteriophages Clautastrophe, Kingsolomon, Krypton555, and Nicholas.

We report here the complete genome sequences of four subcluster L3 mycobacteriophages newly isolated from soil samples, using Mycobacterium smegmatis mc2155 as the host. Comparative genomic analyses with four previously described subcluster L3 phages reveal strong nucleotide similarity and gene conservation, with several large insertions/deletions near their right genome ends.

Quantification of Filamentous Actin (F-actin) Puncta in Rat Cortical Neurons.

Filamentous actin protein (F-actin) plays a major role in spinogenesis, synaptic plasticity, and synaptic stability. Changes in dendritic F-actin rich structures suggest alterations in synaptic integrity and connectivity. Here we provide a detailed protocol for culturing primary rat cortical neurons, Phalloidin staining for F-actin puncta, and subsequent quantification techniques. First, the frontal cortex of E18 rat embryos are dissociated into low-density cell culture, then the neurons grown in vitro for at least 12-14 days. Following experimental treatment, the cortical neurons are stained with AlexaFluor 488 Phalloidin (to label the dendritic F-actin puncta) and microtubule-associated protein 2 (MAP2; to validate the neuronal cells and dendritic integrity). Finally, specialized software is used to analyze and quantify randomly selected neuronal dendrites. F-actin rich structures are identified on second order dendritic branches (length range 25-75 µm) with continuous MAP2 immunofluorescence. The protocol presented here will be a useful method for investigating changes in dendritic synapse structures subsequent to experimental treatments.

HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol.

Illicit drugs, such as cocaine, are known to increase the likelihood and severity of HIV-1 associated neurocognitive disorders (HAND). In the current studies synaptic integrity was assessed following exposure to low concentrations of the HIV-1 viral protein Tat 1-86B, with or without cocaine, by quantifying filamentous actin (F-actin) rich structures (i.e., puncta and dendritic spines) on neuronal dendrites in vitro. In addition, the synapse-protective effects of either R-Equol (RE) or S-Equol (SE; derivatives of the soy isoflavone, daidzein) were determined. Individually, neither low concentrations of HIV-1 Tat (10 nM) nor low concentrations of cocaine (1.6 µM) had any significant effect on F-actin puncta number; however, the same low concentrations of HIV-1 Tat + cocaine in combination significantly reduced dendritic synapses. This synaptic reduction was prevented by pre-treatment with either RE or SE, in an estrogen receptor beta dependent manner. In sum, targeted therapeutic intervention with SE may prevent HIV-1 + drug abuse synaptopathy, and thereby potentially influence the development of HAND.

HIV-1 Tat protein variants: critical role for the cysteine region in synaptodendritic injury.

HIV-1 enters the central nervous system early in infection; although HIV-1 does not directly infect neurons, HIV-1 may cause a variety of neurological disorders. Neuronal loss has been found in HIV-1, but synaptodendritic injury is more closely associated with the neurocognitive disorders of HIV-1. The HIV-1 transactivator of transcription (Tat) protein causes direct and indirect damage to neurons. The cysteine rich domain (residues 22-37) of Tat is important for producing neuronal death; however, little is known about the effects of the Tat protein functional domains on the dendritic network. The ability of HIV-1 Tat 1-101 Clades B and C, Tat 1-86 and Tat 1-72 proteins, as well as novel peptides (truncated 47-57, 1-72δ31-61, and 1-86 with a mutation at Cys22) to produce early synaptodendritic injury (24h), relative to later cell death (48h), was examined using cell culture. Treatment of primary hippocampal neurons with Tat proteins 1-72, 1-86 and 1-101B produced a significant early reduction in F-actin labeled puncta, implicating that these peptides play a role in synaptodendritic injury. Variants with a mutation, deletion, or lack of a cysteine rich region (1-86[Cys22], 1-101C, 1-72δ31-61, or 47-57) did not cause a significant reduction in F-actin rich puncta. Tat 1-72, 1-86, and 1-101B proteins did not significantly differ from one another, indicating that the second exon (73-86 or 73-101) does not play a significant role in the reduction of F-actin puncta. Conversely, peptides with a mutation, deletion, or lack of the cysteine rich domain (22-37) failed to produce a loss of F-actin puncta, indicating that the cysteine rich domain plays a key role in synaptodendritic injury. Collectively, these results suggest that for Tat proteins, 1) synaptodendritic injury occurs early, relative to cell death, and 2) the cysteine rich domain of the first exon is key for synaptic loss. Preventing such early synaptic loss may attenuate HIV-1 associated neurocognitive disorders.

Parallel solution-phase synthesis of 2-alkylthio-5-arylidene-3,5-dihydro-4H-imidazol-4-one by one-pot three-component domino reaction.

A practical protocol for the preparation of a parallel solution-phase library of 5-arylidene imidazolone is reported. Target compounds were obtained in good yield, stereoselectively, and purity by one-pot domino reaction from various thiohydantoines, arylaldimines, and halogenoalkanes. Purification of the final products by recrystallization with a mixture of pentane/ethanol allowed simple isolation of the 17 components of the array.