Release the Kratom: Post-Acute Withdrawal Syndrome in a 70 Year Old Male

Centuries in Eastern medicine.. Kratom has been commonly used for chronic pain and opiate withdrawal symptoms with first reported cases in the United States in the early 2000s. It is a plant that consists of psychoactive alkaloids that target opioid receptors with different affinity. Effects from Kratom are dose-dependent, at lower doses, it acts as a stimulant, while at higher doses produces analgesia and euphoria. Although Kratom is legal and easily accessible over the counter, there have been increasing reports of potential for addiction and toxicity. Cessation of Kratom can result in withdrawal symptoms similar to opiate withdrawal. Here we discuss a case of a 71 year old male with inadvertent Kratom dependence, who had prolonged withdrawal weeks after cessation and required management of dysphoric mood and insomnia symptoms persisting after withdrawal

A Terrible Prank Gone Horribly Wrong the Development of Delusional Infestation as an Adjustment Reaction to a Traumatic Hoax

Delusional infestation (DI) is a somatic type delusional disorder, characterized by a fixed belief that one is infested by living or nonliving pathogens (1,3) . DI is a relatively rare disorder (4,5), with an estimated 20-80 cases per million people annually (6). Effective management of patients suffering from DI is crucial, as patients may cause significant harm to themselves in their attempts to remove the pathogens (7,8). Regarding treatment options, antipsychotic medications such as pimozide and risperidone have been promising (8,10). However, there remain many barriers to care (11), and patients are hardly ever seen in psychiatry as they preferably seek other specialists such as dermatologists (7,11). It is important for psychiatrists to understand this devastating disorder and properly manage and treat patients with DI when the opportunity arises

Seizure to Drug Induced Schizophrenia: A Rare Case of Keppra-Induced Psychosis

Levetiracetam is a broad-spectrum antiseizure medication and is approved as adjunctive therapy to treat focal-onset seizures in children and adults with epilepsy. Levetiracetam has a wide margin of safety and patient-friendly pharmacokinetics that distinguish it from other currently available antiepileptic drugs. Most common side effects are fatigue, somnolence, dizziness, and upper respiratory infection. Neuropsychiatric symptoms are reported. Psychotic symptoms, paranoid ideation, hallucinations, and behavioral problems may occur in adult and pediatric patients. Among all adverse effects, the rate of psychosis is very low and ranges from less than 1% to 1.4%. A retrospective study showed that this rate is higher in older patients than in the younger population. Although the current literature provides cases of levetiracetam-induced psychosis, the onset of psychotic symptoms is one-week post drug administration. This case highlights that it is essential for psychiatrists to consider drug induced psychosis even when the onset of symptoms is not acutely after drug administration

Intraoperative radiotherapy electron boost in advanced and recurrent epithelial ovarian carcinoma: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Relapses of epithelial ovarian carcinoma (EOC) have a poor prognosis and are almost always fatal. The aim of this study was to evaluate the clinical outcome and toxicity of intraoperative electron beam radiation therapy (IOERT) in advanced and recurrent EOC.</p> <p>Methods</p> <p>Forty-five women with EOC were treated with IOERT. Twenty-five patients had primary disease (PD) without distant metastasis at IOERT, and 20 patients had an isolated local recurrence (ILR) after surgery. All 45 patients in this series underwent optimal cytoreductive (≤ 1 cm) surgery. The whole pelvic (WP) radiotherapy was intraoperatively delivered using 12 Mev electron beam; 43 patients received 18-20 Gy and two patients received 10 Gy. Thirty-three patients received postoperateive intraperitoneal (IP) chemotherapy, while seven patients received intravenous (IV) chemotherapy. Five patients refused concurrent chemotherapy. Overall survival (OS) rates were analyzed using the Kaplan-Meier method.</p> <p>Results</p> <p>Tumor recurrence and metastasis were observed in 16 patients (35.6%). Of those, 14 patients (31.1%) relapsed and two patients (4.4%) had distant metastasis alone. Eight of 25 (32%) local failures were observed in the PD group, as compared to 6/20 (30%) in the ILR group (<it>P </it>= 0.885). Actuarial local control at five year follow-up was 31/45 (68.9%). Seventeen of the total 45 (37.8%) patients died. Nine of 25 (36%) in the PD group died, as compared to 8 of 20 (40%) in the ILR group. The 5-year OS and disease-free survival (DFS) rates were 28/45 (62.2%) and 25/45 (55.6%), respectively. In the PD group, the 5-year OS and DFS rates were 16/25 (64%) and 14/25 (56%) (<it>P </it>> 0.05, <it>vs</it>. the ILR group at 12/20 and 11/20, respectively). The OS and DFS in the IOERT plus IP group were 25/33 (75.8%) and 23/33 (69.7%), respectively, which were superior to the rates achieved with IOERT plus IV chemotherapy (<it>P </it>< 0.05, 2/7 and 1/7, respectively). The major complication of IOERT was neuropathy. Five (11.1%) patients developed peripheral neurotoxicity.</p> <p>Conclusions</p> <p>IOERT may be feasible and effective as a boosting technique for advanced and recurrent ovarian cancer. IOERT plus IP chemotherapy may achieve high locoregional disease control and survival benefit with a low risk of toxicity. Peripheral nerves in the IOERT field are dose-limiting structures requiring nerve protection policies or a dose compromise to ensure against severe neurological damage.</p

Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study

Abstract Background Knee osteoarthritis (OA) is a debilitating condition affecting human body biomechanics and quality of life. Current standard care for knee OA leads to trivial improvement and entails multiple adverse effects or complications. Recently, investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee OA receiving intra-articular injections of BMAC vs PRP. Methods Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function. The repeated-measures general linear model with Sidak test for pairwise comparisons was used to investigate the influence of the treatment on the score evolution within groups (between baseline and each time point) and between groups (overall). Results The BMAC group (n = 26 knees) significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale (P < .002, P < .01, P < .011, respectively). Conclusions Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee OA to a greater extent than PRP injections. Graphical abstract Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy

Humoral Immunity to Allogeneic Immunoproteasome-Expressing Mesenchymal Stromal Cells Requires Efferocytosis by Endogenous Phagocytes

The extensive use of mesenchymal stromal cells (MSCs) over the last decade has revolutionized modern medicine. From the delivery of pharmacological proteins to regenerative medicine and immune modulation, these cells have proven to be highly pleiotropic and responsive to their surrounding environment. Nevertheless, their role in promoting inflammation has been fairly limited by the questionable use of interferon-gamma, as this approach has also been proven to enhance the cells&rsquo; immune-suppressive abilities. Alternatively, we have previously shown that de novo expression of the immunoproteasome (IPr) complex instills potent antigen cross-presentation capabilities in MSCs. Interestingly, these cells were found to express the major histocompatibility class (MHC) II protein, which prompted us to investigate their ability to stimulate humoral immunity. Using a series of in vivo studies, we found that administration of allogeneic ovalbumin (OVA)-pulsed MSC-IPr cells elicits a moderate antibody titer, which was further enhanced by the combined use of pro-inflammatory cytokines. The generated antibodies were functional as they blocked CD4 T-cell activation following their co-culture with OVA-pulsed MSC-IPr and mitigated E.G7 tumor growth in vivo. The therapeutic potency of MSC-IPr was, however, dependent on efferocytosis, as phagocyte depletion prior to vaccination abrogated MSC-IPr-induced humoral responses while promoting their survival in the host. In contrast, antibody-mediated neutralization of CD47, a potent &ldquo;do not eat me signal&rdquo;, enhanced antibody titer levels. These observations highlight the major role played by myeloid cells in supporting antibody production by MSC-IPr and suggest that the immune outcome is dictated by a net balance between efferocytosis-stimulating and -inhibiting signals

Effect of silica nanoparticles on kidney of albino rats with the potential ameliorative efficacy of liposomal curcumin

Silica nanoparticles (SiO2-NPs) are widely used commercially in various biomedical and industrial applications. However, their potential toxicity on human and animal health hasattracted particular attention. Liposomal curcumin (LP-Cur) has effective antioxidant and anti-inflammatory defense mechanism.So, this study was achieved toassess the potential ameliorative effect of (LP-Cur) on (SiO2-NPs) induced nephrotoxicity in rats. Twenty four adult male albino  rats of the same weight  were divided into four groups: (Gp I) negative control group (received single intraperitoneal injection of 0.9% saline, standard diet and distilled water), (Gp II) SiO2-NPs  exposed group  (received 200 mg/kg body weight intraperitoneally), (Gp III) SiO2-NPs and LP-Cur co-treated  group  (received 200 mg/kg body weight SiO2-NPsintraperitoneally + 80 mg/kg body weight LP-Cur orally), and (Gp IV) LP-Cur treated group (received 80 mg/kg body weight orally) for 30 days. At the end of experiment, the rats were euthanized by inhalation of 2% isoflurane (0.10 ml) in internal volume of chamber. Blood and kidney samples were collected from all rats for biochemical, histopathological and immunohistochemical analyses. SiO2-NPssignificantly increased blood urea nitrogen (BUN), serum creatinine levels and malondialdehyde. Whereas they substantially reduced the glutathione levels. SiO2-NPs also caused dilatation, congestion ofmost glomeruli in addition to, some atrophied ones. Also, most renal tubulesshowed degenerative changes and marked interstitial hemorrhage. A significant increase in the immunoreactions of caspase-3 of SiO2-NPs exposed rats. Conversely, the administration of LP-Cur ameliorated the detrimental toxic effects caused by SiO2-NPs.In conclusion, antiapoptotic and antioxidant actions of LP-Cur ameliorate the nephrotoxic effect induced by SiO2-NP

LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response

Mesenchymal stromal cells (MSCs) are commonly known for their immune-suppressive abilities. However, our group provided evidence that it is possible to convert MSCs into potent antigen presenting cells (APCs) using either genetic engineering or pharmacological means. Given the capacity of UM171a to trigger APC-like function in MSCs, and the recent finding that this drug may modulate the epigenome by inhibiting the lysine-specific demethylase 1 (LSD1), we explored whether the direct pharmacological inhibition of LSD1 could instill APC-like functions in MSCs akin to UM171a. The treatment of MSCs with the LSD1 inhibitor tranylcypromine (TC) elicits a double-stranded (ds)RNA stress response along with its associated responsive elements, including pattern recognition receptors (PRRs), Type-I interferon (IFN), and IFN-stimulated genes (ISGs). The net outcome culminates in the enhanced expression of H2-Kb, and an increased stability of the cell surface peptide: MHCI complexes. As a result, TC-treated MSCs stimulate CD8 T-cell activation efficiently, and elicit potent anti-tumoral responses against the EG.7 T-cell lymphoma in the context of prophylactic vaccination. Altogether, our findings reveal a new pharmacological protocol whereby targeting LSD1 in MSCs elicits APC-like capabilities that could be easily exploited in the design of future MSC-based anti-cancer vaccines

UM171A-induced ROS promote antigen cross-presentation of immunogenic peptides by bone marrow-derived mesenchymal stromal cells

Abstract Background Mesenchymal stromal cells (MSCs) have been extensively used in the clinic due to their exquisite tissue repair capacity. However, they also hold promise in the field of cellular vaccination as they can behave as conditional antigen presenting cells in response to interferon (IFN)-gamma treatment under a specific treatment regimen. This suggests that the immune function of MSCs can be pharmacologically modulated. Given the capacity of the agonist pyrimido-indole derivative UM171a to trigger the expression of various antigen presentation-related genes in human hematopoietic progenitor cells, we explored the potential use of UM171a as a means to pharmacologically instill and/or promote antigen presentation by MSCs. Methods Besides completing a series of flow-cytometry-based phenotypic analyses, several functional antigen presentation assays were conducted using the SIINFEKL-specific T-cell clone B3Z. Anti-oxidants and electron transport chain inhibitors were also used to decipher UM171a’s mode of action in MSCs. Finally, the potency of UM171a-treated MSCs was evaluated in the context of therapeutic vaccination using immunocompetent C57BL/6 mice with pre-established syngeneic EG.7T-cell lymphoma. Results Treatment of MSCs with UM171a triggered potent increase in H2-Kb cell surface levels along with the acquisition of antigen cross-presentation abilities. Mechanistically, such effects occurred in response to UM171a-mediated production of mitochondrial-derived reactive oxygen species as their neutralization using anti-oxidants or Antimycin-A mitigated MSCs’ ability to cross-present antigens. Processing and presentation of the immunogenic ovalbumin-derived SIINFEKL peptide was caused by de novo expression of the Psmb8 gene in response to UM171a-triggered oxidative stress. When evaluated for their anti-tumoral properties in the context of therapeutic vaccination, UM171a-treated MSC administration to immunocompetent mice with pre-established T-cell lymphoma controlled tumor growth resulting in 40% survival without the need of additional supportive therapy and/or standard-of-care. Conclusions Altogether, our findings reveal a new immune-related function for UM171a and clearly allude to a direct link between UM171a-mediated ROS induction and antigen cross-presentation by MSCs. The fact that UM171a treatment modulates MSCs to become antigen-presenting cells without the use of IFN-gamma opens-up a new line of investigation to search for additional agents capable of converting immune-suppressive MSCs to a cellular tool easily adaptable to vaccination. Graphical abstrac