Miracle-dz/UniFAR-FTUs huggingface dataset:
Agomelatine potentiates anti-nociceptive effects of morphine in a mice model for diabetic neuropathy: involvement of NMDA receptor subtype NR1 within the raphe nucleus and periaqueductal grey

ABSTRACT Objectives Opioid analgesics have been used for a long time in the treatment of acute and chronic pain. However, they have many side effects including tolerance development to a significant extent. Agomelatine, an atypical antidepressant, has been demonstrated to be effective in experimental studies on pain. However, the effect of agomelatine on morphine tolerance development and its mechanism of action are unknown. The antinociceptive effects of agomelatine, morphine and their combination were assessed in a mice model for painful diabetic neuropathy. The roles of glutamate ionotropic receptor N-methyl-D-aspartate (NMDA) type subunit-1 (GluN1) in raphe nucleus and periaqueductal gray (PAG) in the effect of agomelatine on neuropathic pain were also investigated in diabetic mice. Methods Agomelatine (10 mg/kg), morphine (10 mg/kg) and agomelatine + morphine were administered intraperitoneally for 15 consecutive days (twice per day), and the analgesic responses were assessed at days 1, 3, 6, 9, 12 and 15 in healthy and diabetic mice. Real time polymerase chain reaction (RT-PCR) was used to determine the changes in GluN1 expression. Results The tolerance development for morphine was evident, started at 6th day and remained thereafter, but not for agomelatine. GluN1 in raphe nucleus and PAG was upregulated in morphine treated but not in agomelatine-treated groups. Discussion The combination of agomelatine with morphine alone causes outlasting analgesic effects of repeated treatment, which can be interpreted as attenuated tolerance. Moreover, we also pointed out for the first time the modulatory effects of agomelatine on GluN1 expression in raphe nucleus and PAG after chronic morphine treatment. Abbreviations Ca2+: Calcium; D2DR: Dopamine D2 receptor; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GluN1: Glutamate ionotropic receptor N-methyl-D-aspartate type subunit-1; 5-HT: 5-hydroxytryptamine; i.p.: intraperitoneal injection; MPE: Maximal possible effect; MT: Melatonin; NMDA: N-methyl-D-aspartate; NMDAR1: NMDA receptors-1; PAG: Periaqueductal grey; PKCγ: Protein kinase C gamma; RT-PCR: Real time polymerase chain reaction; STZ: Streptozotocin
Evaluation of ocular symptoms and tropism of SARS‐CoV‐2 in patients confirmed with COVID‐19

The SARS‐CoV‐2 RNA has been detected in tears and conjunctival samples from infected individuals. Conjunctivitis is also reported in a small number of cases. We evaluated ocular symptoms and ocular tropism of SARS‐CoV‐2 in a group of patients with COVID‐19.
Depression, functional disability, and accessing health care among older Ghanaians and South Africans: a comparative study based on WHO study on global ageing and adult health (SAGE)

Abstract Objectives The study explored the association and variabilities between mild depression, functional disability, and healthcare access among older Ghanaians and South Africans. Method The data used in this study was based on the Cross-sectional wave 1 (2007–2010) data from WHO's Study on Global Ageing and Adult Health (SAGE). Using multiple binary logistic regression, responses from a sample of 4558 Ghanaians and 3076 South Africans were analyzed to investigate hypothesized patterns. Results The proportion of mild depression (MD) is 6.0 % and 7.53% for older Ghanaians and older South Africans, respectively. At 95% Confidence Interval, increased severity (mild and high levels) of functional disability are associated with increased odds of MD in Ghanaian and South African older adults. Apart from South African older adults, older Ghanaians in the study who do not receive healthcare when needed have increased odds of MD than those who do. Sociodemographic and socioeconomic factors are also associated with MD. Discussion An untreated, persistent MD may lead to worse conditions with fatal outcomes. Since mental health care is lacking in both countries, this study may inform policies directed towards support for formal and informal long-term care, and healthcare access to reduce the risks of depression.
Attitude Toward Death From the Perspective of Erik Erikson’s Theory of Psychosocial Ego Development: An Unused Potential

The aim of the article is to design a conceptual framework within the theory of psychosocial ego development that will allow for a better understanding and explanation of attitude toward death in the life cycle. The main weaknesses of previous studies on death attitude were examined; Erikson’s concept may help exceed these limitations. The use of the model of hierarchy of defense mechanisms to study death attitude within Erikson’s theory was proposed. The concept of the death complex was mentioned to better conceptualize the problem of attitude toward death as a part of the psychosocial theory. Finally, the evolution of attitude toward death in the consecutive phases of psychosocial development was discussed in the light of the concept of syntonic and dystonic ego features, as well as death complex, defense mechanisms, and psychosexual modes.
WOOD ANATOMY OF WOLLEMI PINE (WOLLEMIA NOBILIS, ARAUCARIACEAE)

The wood anatomy of the recently-discovered conifer Wollemia nobilis (Wollemi pine) is described for the first time. Its mature heartwood is light brown in colour and has an air dry density of 0.57 g /cm3. Growth ring boundaries are distinct and the transition from earlywood to latewood is gradual. Average tracheid length is ~ 3.4 mm. Bordered pits are one-, two- or three-seriate and the double and triple rows of pits are ‘alternate’. In the bordered pits there is a flat transition from torus to margo. A warty layer lines tracheid walls and pit cavity surfaces. Resin plugs are common in tracheids that are adjacent to rays. Helical thickenings and crassulae are absent. Rays are uniseriate, low, and are composed entirely of parenchyma cells whose walls are thin and unpitted. Cross-field pitting is ‘araucaroid’ and the number of pits per cross-field ranges from 3–11 (av. 7). Resin canals and axial parenchyma cells are absent. The differences between normal mature wood compared to compression and juvenile wood are consistent with those of most other conifer genera. The anatomical features of wood of W. nobilis strongly support its classification as a member of the Araucariaceae, but show no major differences that distinguish it as a monotypic genus. On the basis of its wood anatomy, it is not possible to state whether W. nobilis is more closely related to Agathis or to Araucaria.
IGE PRODUCTION REGULATION VIA CD23 STALK ENGAGEMENT AND CELL CYCLE STIMULATION

IGE PRODUCTION REGULATION VIA CD23 STALK ENGAGEMENT AND CELL CYCLE STIMULATION By Timothy Hays Caven A dissertation in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Medical College of Virginia, Virginia Commonwealth University Virginia Commonwealth University, May, 2006 Director: Daniel H. Conrad, Ph.D. Professor, Department of Microbiology and Immunology CD23, the low affinity receptor for IgE, is expressed mainly on B cells and has been shown to regulate IgE production. Previously, recombinant mouse and human CD23 were constructed with a trimerizing isoleucine zipper motif attached in frame to the Nterminus of the entire extracellular CD23 (lz-ECCD23). The goal was to examine the role of the necessity of the CD23 stalk for binding IgE. Using PCR-based mutagenesis to delete the majority of the stalk, binding to IgE was lost. Further studies examined the effect of lz-ECCD23 in preventing IgE from binding FcεRI and therefore acting as a therapeutic agent. It was determined that the lz-ECCD23 construct was capable of doing
Landscape impacts of 3D‐seismic surveys in the Arctic National Wildlife Refuge, Alaska

Abstract Although three‐dimensional (3D) seismic surveys have improved the success rate of exploratory drilling for oil and gas, the impacts have received little scientific scrutiny, despite affecting more area than any other oil and gas activity. To aid policy‐makers and scientists, we reviewed studies of the landscape impacts of 3D‐seismic surveys in the Arctic. We analyzed a proposed 3D‐seismic program in northeast Alaska, in the northern Arctic National Wildlife Refuge, which includes a grid 63,000 km of seismic trails and additional camp‐move trails. Current regulations are not adequate to eliminate impacts from these activities. We address issues related to the high‐density of 3D trails compared to 2D methods, with larger crews, more camps, and more vehicles. We focus on consequences to the hilly landscapes, including microtopography, snow, vegetation, hydrology, active layers, and permafrost. Based on studies of 2D‐seismic trails created in 1984–1985 in the same area by similar types of vehicles, under similar regulations, approximately 122 km2 would likely sustain direct medium‐ to high‐level disturbance from the proposed exploration, with possibly expanded impacts through permafrost degradation and hydrological connectivity. Strong winds are common, and snow cover necessary to minimize impacts from vehicles is windblown and inadequate to protect much of the area. Studies of 2D‐seismic impacts have shown that moist vegetation types, which dominate the area, sustain longer‐lasting damage than wet or dry types, and that the heavy vehicles used for mobile camps caused the most damage. The permafrost is ice rich, which combined with the hilly topography, makes it especially susceptible to thermokarst and erosion triggered by winter vehicle traffic. The effects of climate warming will exacerbate the impacts of winter travel due to warmer permafrost and a shift of precipitation from snow to rain. The cumulative impacts of 3D‐seismic traffic in tundra areas need to be better assessed, together with the effects of climate change and the industrial development that would likely follow. Current data needs include studies of the impacts of 3D‐seismic exploration, better climate records for the Arctic National Wildlife Refuge, especially for wind and snow; and high‐resolution maps of topography, ground ice, hydrology, and vegetation.
Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence

Abstract BREX (for BacteRiophage EXclusion) is a superfamily of common bacterial and archaeal defence systems active against diverse bacteriophages. While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by BrxX (PglX) methyltransferase. Here, we report that T7 bacteriophage Ocr, a DNA mimic protein that protects the phage from the defensive action of type I restriction–modification systems, is also active against BREX. In contrast to the wild–type phage, which is resistant to BREX defence, T7 lacking Ocr is strongly inhibited by BREX, and its ability to overcome the defence could be complemented by Ocr provided in trans. We further show that Ocr physically associates with BrxX methyltransferase. Although BREX+ cells overproducing Ocr have partially methylated BREX sites, their viability is unaffected. The result suggests that, similar to its action against type I R–M systems, Ocr associates with as yet unidentified BREX system complexes containing BrxX and neutralizes their ability to both methylate and exclude incoming phage DNA.
Duration of untreated illness and depression severity are associated with cognitive impairment in mood disorders

Abstract Introduction: In this study we estimated the rate and the trajectory of cognitive impairment in a naturalistic sample of outpatients with major depressive disorder (MDD) and bipolar disorder (BD) and its correlation with different variables. Materials and methods: An overall sample of 109 outpatients with MDD or BD was assessed for multiple clinical variables, including duration of untreated illness (DUI), and tested using the Montreal Cognitive Assessment (MoCA) during Major Depressive Episodes (MDE) and after remission. Correlations between MoCA scores and the clinical variables were then computed. Results: About 50% of patients with MDD and BD showed mild cognitive impairment during MDE. Improvement of cognitive function between depression and remission was significant, even though residual symptoms were observed especially in the most impaired patients. Of note, cognitive performance during depression was negatively associated with depression severity and DUI. Discussion: Present findings confirm available evidence about patterns of cognitive impairment in mood disorders, in terms of prevalence and persistence beyond remission in most severe cases. Moreover, a longer DUI was associated with worse cognitive performance during depression, and consequently with poorer outcome, underlining the importance of prompt treatment of these disorders also in light of a cognitive perspective. Keypoints Although distinct entities, unipolar and bipolar depression determine similar patterns of cognitive impairment in terms of severity and types of altered domains. Depression (but not anxiety) severity is associated with cognitive performance in depression. Prolonged duration of untreated illness is associated with more severe cognitive impairment during depression, particularly but not specifically in bipolar disorder.
Pilot service evaluation of a brief psychological therapy for self-harm in an emergency department: Hospital Outpatient Psychotherapy Engagement Service.

BACKGROUND Brief psychological therapies may be helpful for people who have recently self-harmed. The current paper reports on a service evaluation of a novel brief therapy service based within an Emergency Department, Hospital Outpatient Psychotherapy Engagement (HOPE) Service. This service combines elements of psychodynamic interpersonal and cognitive analytic therapy to help people who present with self-harm-related difficulties. The primary aim of this service evaluation was to ascertain the feasibility of HOPE in terms of attendance rates. The study also examined variables associated with engagement, and change over time in psychological distress for those attending the service. METHOD The HOPE service was evaluated over a ten-month period. Consenting patients completed measures of psychological distress and working alliance across four therapy sessions and one follow-up session. Measures of emotion regulation style and self-harm function were also completed at the point of referral. RESULTS Eight-nine patients were referred to the service (83 eligible referrals). Fifty-three (64%) attended at least one therapy session. Baseline variables did not distinguish people who attended and people who did not. Psychological distress decreased significantly across the sessions. Most people reported a good working alliance with their therapist. CONCLUSIONS The results of this service evaluation support the feasibility of the HOPE service, demonstrating good engagement rates given the complexity of the population and context. Whilst there was evidence of reductions in distress, randomized controlled trials are needed to determine if HOPE has clinical efficacy. PRACTITIONER POINTS Rates of engagement with HOPE suggest the service is feasible in an Emergency Department context Working alliance scores were positive for the majority of patients The HOPE service shows promise as a brief intervention for people who self-harm but requires further evaluation Randomized controlled trials are needed to determine the clinical efficacy of the HOPE service.
Medication Use for ADHD and the Risk of Driving Citations and Crashes Among Teenage Drivers: A Population-Based Cohort Study

Objectives: To evaluate the real-world effectiveness of ADHD medications on adverse driving outcomes in teenage drivers with ADHD. Method: We retrospectively followed 15- to 20-year-old ADHD patients with valid driver’s license to compare the risk for crashes and citations between periods with and without ADHD medication use, using Florida Medicaid records linked to Department of Motor Vehicles data from 1999 to 2004. Patient-level demographic, clinical, and driver licensing characteristics as well as county-level crash and traffic statistics were adjusted in Cox models. Results: A total of 2,049 patients had 67 crashes and 319 citations. Adjusted hazard ratios comparing ADHD medication use versus no use were 1.22 (95% confidence interval [CI] = [0.66, 1.90]) and 0.89 (95% CI = [0.69, 1.13]) for crashes and citations, respectively. Conclusion: Our study showed no evidence that ADHD medication use was associated with a reduced risk of adverse driving outcomes among teenage drivers enrolled in Medicaid programs. Limitations in interpreting this finding are presented.
Prevalence and incidence of clinical outcomes in patients presenting to secondary mental health care with mood instability and sleep disturbance

Abstract Background. Mood instability and sleep disturbance are common symptoms in people with mental illness. Both features are clinically important and associated with poorer illness trajectories. We compared clinical outcomes in people presenting to secondary mental health care with mood instability and/or sleep disturbance with outcomes in people without either mood instability or sleep disturbance. Methods. Data were from electronic health records of 31,391 patients ages 16–65 years presenting to secondary mental health services between 2008 and 2016. Mood instability and sleep disturbance were identified using natural language processing. Prevalence of mood instability and sleep disturbance were estimated at baseline. Incidence rate ratios were estimates for clinical outcomes including psychiatric diagnoses, prescribed medication, and hospitalization within 2-years of presentation in persons with mood instability and/or sleep disturbance compared to individuals without either symptom. Results. Mood instability was present in 9.58%, and sleep disturbance in 26.26% of patients within 1-month of presenting to secondary mental health services. Compared with individuals without either symptom, those with mood instability and sleep disturbance showed significantly increased incidence of prescription of any psychotropic medication (incidence rate ratios [IRR] = 7.04, 95% confidence intervals [CI] 6.53–7.59), and hospitalization (IRR = 5.32, 95% CI 5.32, 4.67–6.07) within 2-years of presentation. Incidence rates of most clinical outcomes were considerably increased among persons with both mood instability and sleep disturbance, relative to persons with only one symptom. Conclusions. Mood instability and sleep disturbance are present in a wide range of mental disorders, beyond those in which they are conventionally considered to be symptoms. They are associated with poor outcomes, particularly when they occur together. The poor prognosis associated with mood instability and sleep disorder may be, in part, because they are often treated as secondary symptoms. Mood instability and sleep disturbance need better recognition as clinical targets for treatment in their own right.
Differences in Discriminability and Response Bias on Rey Auditory Verbal Learning Test Delayed Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer’s Disease

Abstract Objective: Episodic memory is impaired in Alzheimer’s disease (AD) dementia but thought to be relatively spared in behavioral variant frontotemporal dementia (bvFTD). This view is challenged by evidence of memory impairment in bvFTD. This study investigated differences in recognition memory performance between bvFTD and AD. Method: We performed a retrospective analysis on the recognition trial of the Rey Auditory Verbal Learning Test in patients with bvFTD (n = 85), AD (n = 55), and control participants (n = 59). Age- and education-adjusted between-group analysis was performed on the total score and indices of discriminative ability and response bias. Correlations between recognition and measures of memory, language, executive functioning, and construction were examined. Results: Patients with AD had a significantly lower total recognition score than patients with bvFTD (control 28.8 ± 1.5; bvFTD 24.8 ± 4.5; AD 23.4 ± 3.6, p < .01). Both bvFTD and AD had worse discriminative ability than controls (A’ control 0.96 ± 0.03; bvFTD 0.87 ± 0.03; AD 0.84 ± 0.10, p < .01), but there was no difference in response bias (B” control 0.9 ± 0.2; bvFTD 1.6 ± 1.47; AD 1.4± 1.4, p < .01). AD had worse discriminability than bvFTD (p < .05). Discriminability was associated with memory for both patient groups (median correlation coefficient r = .34) and additionally associated with language (r = .31), but not executive functioning (r = −.03) in bvFTD. Response bias was unrelated to other cognitive functions (r = −.02). Conclusions: Discriminability, but not response bias, differentiated patients with bvFTD from AD. The presence of an impaired discrimination index suggests a “pure” (recognition) memory deficit in bvFTD.
Racial Capitalism: A Fundamental Cause of Novel Coronavirus (COVID-19) Pandemic Inequities in the United States

Racial capitalism is a fundamental cause of the racial and socioeconomic inequities within the novel coronavirus pandemic (COVID-19) in the United States. The overrepresentation of Black death reported in Detroit, Michigan is a case study for this argument. Racism and capitalism mutually construct harmful social conditions that fundamentally shape COVID-19 disease inequities because they (a) shape multiple diseases that interact with COVID-19 to influence poor health outcomes; (b) affect disease outcomes through increasing multiple risk factors for poor, people of color, including racial residential segregation, homelessness, and medical bias; (c) shape access to flexible resources, such as medical knowledge and freedom, which can be used to minimize both risks and the consequences of disease; and (d) replicate historical patterns of inequities within pandemics, despite newer intervening mechanisms thought to ameliorate health consequences. Interventions should address social inequality to achieve health equity across pandemics.
Geographic and Seasonal Variation of Vitamin D: A Retrospective Study in Two Centers of Nepal.

BACKGROUND Vitamin D deficiency is a common problem in many countries throughout the world. This study aimed at understanding the status of vitamin D deficiency in relation to age, gender, geography and season among relatively bigger numbers of population residing in central and western regions of Nepal. METHODS This retrospective cross-sectional study was carried out by reviewing the records of vitamin D tests in two centers of Nepal- namely united reference laboratories at Pokhara and Chitwan Medical College at Chitwan. A total of 3320 individuals who were tested for clinical suspicion of vitamin D deficiency over a period of one year were included in the study. RESULTS Mean vitamin D level was 18.7 ng/mL. Majority of subjects tested for vitamin D were females (71.36 %) with female to male ratio of 2.49:1. Hypovitaminosis D (≤ 30 ng/mL) was found in 84.5% subjects and was moderate to severely deficit (less than 10 ng/mL) in 25.9% of subjects. Status of hypovitaminosis D was found to be less in ≥50 years (79.9%) than the younger subjects (89.9% in ≤18 years and 87.0% in 19-49 years age group). Vitamin D deficiency was found lower in hills districts (80.8% vs 89.7% in the plains), which was found to be more pronounced during winter through summer seasons as compared to fall season. CONCLUSIONS Population residing in plain areas and summer, spring and winter season are found to have increased problem of Hypovitaminosis D. It is also found to be common among younger children and female of reproductive age group. We have also found out the increased problem of hypovitaminosis D among population residing in the plain areas than in the hills especially in the summer, spring and winter season.