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The loss of coulombic interaction part of a crucial hydrogen bond between the drug and the protease is likely to play a major role in reduced affinity and resistance towards nelfinavir. The decreased catalytic activity of D30N HIV-1 protease due to altered interaction with the substrates and reduced stability of folding core may be the reason for the reduced replicative capacity of the virus harboring mutant HIV-1 protease.Communicated by Ramaswamy H. Sarma.Citrus fruits are consumed in large quantities worldwide due to their attractive aromas and taste, as well as their high nutritional values and various health-promoting effects, which are due to their abundance of nutrients and bioactives. In addition to water, carbohydrates, vitamins, minerals, and dietary fibers are important nutrients in citrus, providing them with high nutritional values. Citrus fruits are also rich in various bioactives such as flavonoids, essential oils, carotenoids, limonoids, and synephrines, which protect from various ailments, including cancer and inflammatory, digestive, and cardiovascular diseases. The composition and content of nutrients and bioactives differ significantly among citrus varieties, fruit parts, and growth stages. To better understand the nutrient and bioactive profiles of citrus fruits and provide guidance for the utilization of high-value citrus resources, this review systematically summarizes the nutrients and bioactives in citrus fruit, including their contents, structural characteristics, and potential health benefits. We also explore the composition variation in different citrus varieties, fruits parts, and growth stages, as well as their health-promoting effects and applications.Brain aging is one of the unavoidable aspects of geriatric life. As one ages, changes such as the shrinking of certain parts (particularly the frontal cortex, which is vital to learning and other complex mental activities) of the brain may occur. Consequently, communications between neurons are less effective, and blood flow to the brain could also decrease. Efforts made at the biological level for repair become inadequate, leading to the accumulation of β-amyloid peptide in the brain faster than its probable degradation mechanism, resulting in cognitive malfunction. Subsequent clinical usage of drugs in battling related brain-aging ailments has been associated with several undesirable side effects. However, recent research has investigated the potential use of natural compounds from food in combating such occurrences. This review provides information about the use of Piper guineense (black pepper) as a possible agent in managing brain aging because of its implications for practical brain function. P. guineense contains an alkaloid (piperine) reported to be an antioxidant, anti-depressant, and central nervous system stimulant. This alkaloid and other related compounds are neuroprotective agents that reduce lipid oxidation and inhibit tangles in the brain tissues.Dendritic morphogenesis requires dynamic microtubules (MTs) to form a coordinated cytoskeletal network during development. Dynamic MTs are characterized by their number, polarity and speed of polymerization. Previous studies described a correlation between anterograde MT growth and terminal branch extension in Drosophila dendritic arborization (da) neurons, suggesting a model that anterograde MT polymerization provides a driving force for dendritic branching. We recently found that the Ste20-like kinase Tao specifically regulates dendritic branching by controlling the number of dynamic MTs in a kinase activity-dependent fashion, without affecting MT polarity or speed. This finding raises the interesting question of how MT dynamics affects dendritic morphogenesis, and if Tao kinase activity is developmentally regulated to coordinate MT dynamics and dendritic morphogenesis. We explored the possible correlation between MT dynamics and dendritic morphogenesis together with the activity changes of Tao kinase in C1da and C4da neurons during larval development. Our data show that spatiotemporal changes in the number of dynamic MTs, but not polarity or polymerization speed, correlate with dendritic branching and Tao kinase activity. Our findings suggest that Tao kinase limits dendritic branching by controlling the abundance of dynamic MTs and we propose a novel model on how regulation of MT dynamics might influence dendritic morphogenesis.Notch signalling is a well-conserved signalling pathway that regulates cell fate through cell-cell communication. A typical feature of Notch signalling is 'lateral inhibition', whereby two neighbouring cells of equivalent state of differentiation acquire different cell fates. Recently, mathematical and computational approaches have addressed the Notch dynamics in Drosophila neural development. Typical examples of lateral inhibition are observed in the specification of neural stem cells in the embryo and sensory organ precursors in the thorax. In eye disc development, Notch signalling cooperates with other signalling pathways to define the evenly spaced positioning of the photoreceptor cells. The interplay between Notch and epidermal growth factor receptor signalling regulates the timing of neural stem cell differentiation in the optic lobe. In this review, we summarize the theoretical studies that have been conducted to elucidate the Notch dynamics in these systems and discuss the advantages of combining mathematical models with biological experiments.Transcranial direct current stimulation (tDCS) has been shown to create neuroplasticity in healthy and diseased populations. The control of stimulation duration by providing real-time brain state feedback using neuroimaging is a topic of great interest. This study presents the feasibility of a closed-loop modulation for the targeted functional network in the prefrontal cortex. We hypothesize that we cannot improve the brain state further after reaching a specific state during a stimulation therapy session. Tivozanib A high-definition tDCS of 1[Formula see text]mA arranged in a ring configuration was applied at the targeted right prefrontal cortex of 15 healthy male subjects for 10[Formula see text]min. Functional near-infrared spectroscopy was used to monitor hemoglobin chromophores during the stimulation period continuously. The correlation matrices obtained from filtered oxyhemoglobin were binarized to form subnetworks of short- and long-range connections. The connectivity in all subnetworks was analyzed individually using a new quantification measure of connectivity percentage based on the correlation matrix. The short-range network in the stimulated hemisphere showed increased connectivity in the initial stimulation phase. However, the increase in connection density reduced significantly after 6[Formula see text]min of stimulation. The short-range network of the left hemisphere and the long-range network gradually increased throughout the stimulation period. The connectivity percentage measure showed a similar response with network theory parameters. The connectivity percentage and network theory metrics represent the brain state during the stimulation therapy. The results from the network theory metrics, including degree centrality, efficiency, and connection density, support our hypothesis and provide a guideline for feedback on the brain state. The proposed neuro-feedback scheme is feasible to control the stimulation duration to avoid overdosage.

The purpose of this study was to assess and compare neurological soft signs in patients of cannabis use disorder (CUD) with and without co-occurring psychosis in a treatment-seeking sample.

We included 30 right-handed male subjects aged 18-65 years diagnosed with CUD (as per DSM-5) without any co-occurring psychiatric disorder in group I and those with co-occurring non-affective psychosis in group II. Group III consisted of 30 age and sex-matched, right-handed, healthy subjects with no psychiatric or medical conditions. Neurological Evaluation Scale (NES) was applied to measure neurological soft signs across the groups. We also used the Severity of Dependence Scale (in CUD with or without co-occurring non-affective psychosis groups) and Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Barnes Akathisia Rating Scale, Abnormal Involuntary Movements Scale, and Simpson Angus Scale (in CUD with co-occurring non-affective psychosis group).

Our data suggested highetween cannabis use disorder with or without co-occurring non-affective psychosis groups. The mean of subdomain scores of motor incoordination, sequencing of complex motor tasks, sensory integration, and others was significantly higher in CUD with or without co-occurring non-affective psychosis groups compared to healthy controls. Conclusion Impairment in neurological soft signs is present in patients with CUD regardless of a co-occurring psychosis. Cannabinoids might be interacting with the brain circuits known to be involved in schizophrenia.Background Norway and Sweden are similar countries in terms of socioeconomics and health care. Norway implemented extensive COVID-19 measures, such as school closures and lockdowns, whereas Sweden did not. Aims To compare mortality in Norway and Sweden, two similar countries with very different mitigation measures against COVID-19. Methods Using real-world data from national registries, we compared all-cause and COVID-19-related mortality rates with 95% confidence intervals (CI) per 100,000 person-weeks and mortality rate ratios (MRR) comparing the five preceding years (2015-2019) with the pandemic year (2020) in Norway and Sweden. Results In Norway, all-cause mortality was stable from 2015 to 2019 (mortality rate 14.6-15.1 per 100,000 person-weeks; mean mortality rate 14.9) and was lower in 2020 than from 2015 to 2019 (mortality rate 14.4; MRR 0.97; 95% CI 0.96-0.98). In Sweden, all-cause mortality was stable from 2015 to 2018 (mortality rate 17.0-17.8; mean mortality rate 17.1) and similar to that in 2020 (mortality rate 17.6), but lower in 2019 (mortality rate 16.2). Compared with the years 2015-2019, all-cause mortality in the pandemic year was 3% higher due to the lower rate in 2019 (MRR 1.03; 95% CI 1.02-1.04). Excess mortality was confined to people aged ⩾70 years in Sweden compared with previous years. The COVID-19-associated mortality rates per 100,000 person-weeks during the first wave of the pandemic were 0.3 in Norway and 2.9 in Sweden. Conclusions All-cause mortality in 2020 decreased in Norway and increased in Sweden compared with previous years. The observed excess deaths in Sweden during the pandemic may, in part, be explained by mortality displacement due to the low all-cause mortality in the previous year.Aims To provide an overview of published research on migration and health conducted in Norway and identify gaps in the research field. Methods Applying a scoping review methodology, we searched Medline for articles on migration health in Norway published between 2008 and 2020, and assessed them according to research topic, methodology, user-involvement and characteristics of the populations studied (country or area of origin, type of migrant/immigrant status). Results Of the 707 articles retrieved, 303 met the inclusion criteria. Most studies (77%) were within the clinical disciplines reproductive health, mental health, infectious diseases and cardiovascular diseases, or on socio-cultural aspects and the use of healthcare services. One third of the papers (36%) pulled participants from various geographic backgrounds together or did not specify the geographic background. Among those who did so, participants were mostly from The Middle East, South and Southeast Asia and sub-Saharan Africa. Only 14% of the articles specified the type of migrant/immigrant status and those included refugees, asylum seekers and undocumented migrants.

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