Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6 mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

Postoperative Patient Pain Severity and Its Association With Anxiety, Depression, and Sleep Quality.

Introduction The experience of pain is a complex phenomenon. A patient in the acute postsurgical pain setting may feel a constant bombardment of nociceptive input from the surgical site; this in turn influences psychological factors that determine the overall emotional experience of pain, which is significant. The aim of our study was to investigate the severity of pain in postsurgical patients three days after surgery using the 100 mm visual analog scale (VAS). Methods This was a cross-sectional assessment of postoperative pain. Participants were patients between 18 and 64 years of age who had undergone a surgical procedure (laparoscopic or open surgery), three days prior to the data collection and who were admitted or discharged postoperatively at the Al Salmaniya Complex, Manama, Bahrain. Participants were asked demographic questions about whether they had laparoscopic or open surgeries and completed self-reporting scales. Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for both the presence and severity of depression; Generalized Anxiety Disorder 7-item (GAD-7) was administered to screen for anxiety; the Insomnia Severity Index (ISI) was used to evaluate insomnia; and the VAS was used to evaluate pain.  Results Sixty-seven patients were recruited, with a mean age of 61.53 years (SD = 7.37). Twenty-nine (43%) were females, 38 (57%) were males, 36 (54%) underwent elective surgery, 31 (46%) underwent emergency surgery, 31 (46%) underwent laparoscopic surgery, and 36 (54%) underwent open surgery. The average score on the Brief Pain Inventory Short Form (BPISF) was 8.12 (SD = 1.16), indicating a moderate level of pain. Twenty-six (43%) patients had moderate-severe insomnia, 21 participants (31%) had no insomnia, 17 participants (25%) had subthreshold insomnia, 28 (42%) had moderate depression, five (7%) had moderate-severe depression, and 34 (51%) had severe depression. Eighteen participants (27%) had mild anxiety, 46 (69%) had moderate anxiety, and 3 (4%) had severe anxiety. Six of the participants (9%) reported moderate pain, while 61 participants (91%) reported severe pain.

Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm.

Cytokine storm can result from cancer immunotherapy or certain infections, including COVID-19. Though short-term immune-related adverse events are routinely described, longer-term immune consequences and sequential immune monitoring are not as well defined. In 2006, six healthy volunteers received TGN1412, a CD28 superagonist antibody, in a first-in-man clinical trial and suffered from cytokine storm. After the initial cytokine release, antibody effect-specific immune monitoring started on Day + 10 and consisted mainly of evaluation of dendritic cell and T-cell subsets and 15 serum cytokines at 21 time-points over 2 years. All patients developed problems with concentration and memory; three patients were diagnosed with mild-to-moderate depression. Mild neutropenia and autoantibody production was observed intermittently. One patient suffered from peripheral dry gangrene, required amputations, and had persistent Raynaud's phenomenon. Gastrointestinal irritability was noted in three patients and coincided with elevated γδT-cells. One had pruritus associated with elevated IgE levels, also found in three other asymptomatic patients. Dendritic cells, initially undetectable, rose to normal within a month. Naïve CD8+ T-cells were maintained at high levels, whereas naïve CD4+ and memory CD4+ and CD8+ T-cells started high but declined over 2 years. T-regulatory cells cycled circannually and were normal in number. Cytokine dysregulation was especially noted in one patient with systemic symptoms. Over a 2-year follow-up, cognitive deficits were observed in all patients following TGN1412 infusion. Some also had signs or symptoms of psychological, mucosal or immune dysregulation. These observations may discern immunopathology, treatment targets, and long-term monitoring strategies for other patients undergoing immunotherapy or with cytokine storm.