Knowledge, Attitude, and Practice toward Skin Cancer among Patients of Dermatology Clinics and Medical Students/General Practitioners.

This cross-sectional study assessed the knowledge, attitude, and practices (KAP) regarding skin cancer among dermatology clinic patients, medical students, and general practitioners (GPs) in Tehran, Iran. The researchers collected data using a validated questionnaire administered online, measuring KAP on scales of 0-31, 0-16, and 0-28, respectively, with scores above 16, 8, and 14 indicating "good" levels. Of 2243 participants (mean age 28 years), 59.4% had good knowledge, 19.8% had good attitudes, 31.8% had good practices, and 29.8% had good overall KAP. Medical students/GPs scored higher on knowledge and attitudes, while patients scored better on practices. Knowledge, attitudes, and practices were positively correlated in professionals but inversely correlated in patients. The findings suggest that while knowledge was moderate, attitudes and behaviors remained poor, particularly among patients. Immediate interventions are needed to improve attitudes and prevention practices, as public health initiatives must focus on positively influencing both to translate knowledge into meaningful action and find the reasons why good knowledge may not always lead to good practice. These findings underline the need for targeted interventions to bridge the gap between knowledge and preventive behaviors, to effectively reduce the burden of skin cancer in the population.

Impacts of SARS-CoV-2 on brain renin angiotensin system related signaling and its subsequent complications on brain: A theoretical perspective.

Cellular ACE2 (cACE2), a vital component of the renin-angiotensin system (RAS), possesses catalytic activity to maintain AngII and Ang 1-7 balance, which is necessary to prevent harmful effects of AngII/AT2R and promote protective pathways of Ang (1-7)/MasR and Ang (1-7)/AT2R. Hemostasis of the brain-RAS is essential for maintaining normal central nervous system (CNS) function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral disease that causes multi-organ dysfunction. SARS-CoV-2 mainly uses cACE2 to enter the cells and cause its downregulation. This, in turn, prevents the conversion of Ang II to Ang (1-7) and disrupts the normal balance of brain-RAS. Brain-RAS disturbances give rise to one of the pathological pathways in which SARS-CoV-2 suppresses neuroprotective pathways and induces inflammatory cytokines and reactive oxygen species. Finally, these impairments lead to neuroinflammation, neuronal injury, and neurological complications. In conclusion, the influence of RAS on various processes within the brain has significant implications for the neurological manifestations associated with COVID-19. These effects include sensory disturbances, such as olfactory and gustatory dysfunctions, as well as cerebrovascular and brain stem-related disorders, all of which are intertwined with disruptions in the RAS homeostasis of the brain.

Additive effect of histamine and muscimol upon induction of antinociceptive and antidepressant effects in mice.

We investigated the effects of histamine and GABA A receptor agents on pain and depression-like behaviors and their interaction using a tail-flick test and the forced swimming test (FST) in male mice. Our data revealed that intraperitoneal administration of muscimol (0.12 and 0.25 mg/kg) increased the percentage of maximum possible effect (%MPE) and area under the curve (AUC) of %MPE, indicating an antinociceptive response. Intraperitoneal injection of bicuculline (0.5 and 1 mg/kg) decreased %MPE and AUC of %MPE, suggesting hyperalgesia. Moreover, muscimol by reducing the immobility time of the FST elicited an antidepressant-like response but bicuculline by enhancing the immobility time of the FST caused a depressant-like response. Intracerebroventricular (i.c.v.) microinjection of histamine (5 µg/mouse) enhanced %MPE and AUC of %MPE. i.c.v. infusion of histamine (2.5 and 5 µg/mouse) decreased immobility time in the FST. Co-administration of different doses of histamine along with a sub-threshold dose of muscimol potentiated antinociceptive and antidepressant-like responses produced by histamine. Cotreatment of different doses of histamine plus a noneffective dose of bicuculline reversed antinociception and antidepressant-like effects elicited by histamine. Cotreatment of histamine, muscimol, and bicuculline reversed antinociceptive and antidepressant-like behaviors induced by the drugs. The results demonstrated additive antinociceptive and antidepressant-like effects between histamine and muscimol in mice. In conclusion, our results indicated an interaction between the histaminergic and GABAergic systems in the modulation of pain and depression-like behaviors.

The integrative role of orexin-1 and orexin-2 receptors within the hippocampal dentate gyrus in the modulation of the stress-induced antinociception in the formalin pain test in the rat.

The stressful experiences, by triggering a cascade of hormonal and neural changes, can produce antinociception commonly referred to as stress-induced antinociception (SIA). Orexin neuropeptides have an essential role in stress responses and pain modulation. The dentate gyrus receives orexinergic projections and has been shown to be involved in pain processing. The current study investigated the possible role of orexin-1 and orexin-2 receptors (OX1r and OX2r, respectively) within the dentate gyrus in SIA in a rat model of formalin-induced pain behavior in one hind paw. Male Wistar rats weighing 230-250 g underwent stereotaxic surgery and a cannula was implanted in their brains, above the dentate gyrus region. Either SB334867 or TCS OX2 29 (OX1r and OX2r antagonists, respectively) was microinjected into the dentate gyrus region at a range of doses at 1, 3, 10, and 30 nmol (control group received DMSO 12% as vehicle), 5 min before the forced swim stress (FSS) exposure. The formalin test was performed to assess pain-related behaviors. The results indicated that FSS exposure relieves pain-related behavior in the early and late phases of the formalin test. Blockade of intra-dentate gyrus OX1 or OX2 receptors reduced the antinociceptive responses induced by FSS in the formalin test, with more impact during the late phase. Our findings support the potential role of intra-dentate gyrus orexin receptors as target sites of orexin neurons in painful and stressful situations. Therefore, understanding the exact mechanisms of SIA and the role of the orexinergic system in this phenomenon can lead to identifying the strategies to guide future research and offer a new approach to discovering new pain therapeutic agents.

Orexin receptors in the hippocampal dentate gyrus modulated the restraint stress-induced analgesia in the animal model of chronic pain.

Previous studies have shown that stressful stimuli induced an adaptive response of reduced nociception, known as stress-induced analgesia (SIA). Since orexin neuropeptides are involved in pain modulation, and orexin neurons, primarily located in the lateral hypothalamus (LH), project to various hippocampal regions, such as the dentate gyrus (DG), the current study aimed to examine the role of orexin receptors within the DG region in the restraint SIA in the animal model of chronic pain. One hundred-thirty adult male Wistar rats (230-250 g) were unilaterally implanted with a cannula above the DG region. Animals were given SB334867 or TCS OX2 29 (1, 3, 10, and 30 nmol, 0.5 µl/rat) into the DG region as orexin-1 receptor (OX1r) and orexin-2 receptor (OX2r) antagonists, respectively, five min before exposure to a 3-hour restraint stress (RS) period. Animals were then undergone the formalin test to assess pain-related behaviors as the animal model of chronic pain. The results showed that RS produces an analgesic response during the early and late phases of the formalin test. However, intra-DG microinjection of OX1r and OX2r antagonists attenuated the restraint SIA. OX2r antagonist was more potent than OX1r antagonist in the early phase of the formalin test, while OX1r antagonist was little more effective in the late phase. Predominantly, it could be concluded that the orexinergic system in the DG region might act as a potential endogenous pain control system and a novel target for treating stress-related disorders.

GABA-ergic agents modulated the effects of histamine on the behaviour of male mice in the elevated plus maze test.

NEW FINDINGS: What is the central question of this study? Is there an interaction between histamine and the GABAergic system in modulation of anxiety in mice? What is the main finding and its importance? There is a synergistic anxiogenic effect between histamine and bicuculline in mice. This effect may be due to a direct or an indirect effect of the histaminergic system on the GABAergic system. ABSTRACT: It has been documented that both histaminergic and GABAergic systems participate in the neurobiology of anxiety behaviour. In the current research, we investigated the effects of the histaminergic system and GABAA receptor agents on anxiety-related behaviours and their interaction using the elevated plus maze test in mice. Intraperitoneal (i.p.) administration of muscimol (0.12 and 0.25 mg/kg) increased the open arm time (OAT) (P < 0.001) without affecting the open arm entries (OAE) and locomotor activity, showing an anxiolytic effect. i.p. injection of bicuculline (0.5 and 1 mg/kg) decreased OAT (P < 0.001) but not OAE and locomotor activity, suggesting an anxiogenic behaviour. Intracerebroventricular (i.c.v.) microinjection of histamine (2.5 and 5 µg/mouse) resulted in a decline in OAT (P < 0.001) but not OAE and locomotor activity, indicating an anxiogenic response. Co-administration of histamine with GABAergic agents, muscimol (0.06 mg/kg; i.p.) and bicuculline (0.25 mg/kg; i.p.), decreased (P < 0.001) and increased (P < 0.05), respectively, the anxiogenic-like response to the effective dose (5 µg/mouse; i.c.v.) of histamine. In addition, co-treatment of effective doses of histamine (2.5 and 5 µg/mouse;i.c.v.) with an effective dose of muscimol (0.12 mg/kg; i.p.) and a non-effective dose of bicuculline (0.25 mg/kg; i.p.) significantly decreased OAT (P < 0.001), suggesting a likely interaction between the histaminergic and GABAergic systems in the regulation of anxiety. The results demonstrated a synergistic anxiogenic-like effect between histamine and bicuculline in mice. In conclusion, our results present an interaction between the histaminergic and GABAergic systems in anxiolytic/anxiogenic-like behaviours in the elevated plus maze test.