Genital HSV-2 Infection Induces Short-Term NK Cell Memory

NK cells are known as innate immune cells that lack immunological memory. Recently, it has been shown that NK cells remember encounters with chemical haptens that induce contact hypersensitivity and cytomegalovirus infection. Here, we show the existence of NK cell memory following HSV-2 infection. Stimulation with HSV-2 Ags led to higher IFNγ production in NK cells that were exposed 30 days previously to HSV-2, compared to NK cells from naïve mice. More importantly, this increased production of IFNγ in NK cells was independent of B- and T- lymphocytes and specific for the HSV-2 Ags. We also showed that previously exposed NK cells in a B- and T-lymphocyte free environment mediate protection against HSV-2 infection and they are necessary for the protection of mice against HSV-2 infection. Collectively, NK cells remember prior HSV-2 encounters independent of B- and T- lymphocytes leading to protection against HSV-2 mediated morbidity and mortality upon re-exposure

Induction of Innate Immunity against Herpes Simplex Virus Type 2 Infection via Local Delivery of Toll-Like Receptor Ligands Correlates with Beta Interferon Production

Toll-like receptors (TLRs) constitute a family of innate receptors that recognize and respond to a wide spectrum of microorganisms, including fungi, bacteria, viruses, and protozoa. Previous studies have demonstrated that ligands for TLR3 and TLR9 induce potent innate antiviral responses against herpes simplex virus type 2 (HSV-2). However, the factor(s) involved in this innate protection is not well-defined. Here we report that production of beta interferon (IFN-β) but not production of IFN-α, IFN-γ, or tumor necrosis factor alpha (TNF-α) strongly correlates with innate protection against HSV-2. Local delivery of poly(I:C) and CpG oligodeoxynucleotides induced significant production of IFN-β in the genital tract and provided complete protection against intravaginal (IVAG) HSV-2 challenge. There was no detectable IFN-β in mice treated with ligands for TLR4 or TLR2, and these mice were not protected against subsequent IVAG HSV-2 challenge. There was no correlation between levels of TNF-α or IFN-γ in the genital tract and protection against IVAG HSV-2 challenge following TLR ligand delivery. Both TNF-α(−/−) and IFN-γ(−/−) mice were protected against IVAG HSV-2 challenge following local delivery of poly(I:C). To confirm that type I interferon, particularly IFN-β, mediates innate protection, mice unresponsive to type I interferons (IFN-α/βR(−/−) mice) and mice lacking IFN regulatory factor-3 (IRF-3(−/−) mice) were treated with poly(I:C) and then challenged with IVAG HSV-2. There was no protection against HSV-2 infection following poly(I:C) treatment of IFN-α/βR(−/−) or IRF-3(−/−) mice. Local delivery of murine recombinant IFN-β protected C57BL/6 and IRF-3(−/−) mice against IVAG HSV-2 challenge. Results from these in vivo studies clearly suggest a strong correlation between IFN-β production and innate antiviral immunity against HSV-2

Social media as an emerging tool for reducing prescription opioid misuse risk factors

Interventions are urgently needed to reduce prescription opioid misuse risk factors, including anxiety and concomitant use of sedatives. However, only a limited number of randomized controlled opioid intervention trials have been conducted. We sought to determine whether an online behavior change/support community, compared to a control Facebook group, could reduce anxiety and opioid misuse among chronic pain patients. 51 high-risk non-cancer chronic pain patients were randomly assigned to either a Harnessing Online Peer Education (HOPE) peer-led online behavior change intervention or a control group (no peer leaders) on Facebook for 12 weeks. Inclusion criteria were: 18 years or older, a UCLA Health System patient, prescribed an opioid for non-cancer chronic pain between 3 and 12 months ago, and a score of ≥9 on the Current Opioid Misuse Measure (COMM) and/or concomitant use of benzodiazepines. Participation in the online community was voluntary. Patients completed baseline and follow-up assessments on Generalized Anxiety Disorder screener (GAD-7), COMM, and frequency of social media discussions about pain and opioid use. Compared to control group participants, intervention participants showed a baseline-to-follow-up decrease in anxiety, and more frequently used social media to discuss pain, prescription opioid use, coping strategies, places to seek help, and alternative therapies for pain. Both groups showed a baseline to follow-up decrease in COMM score. Preliminary results support the use an online community interventions as a low-cost tool to decrease risk for prescription opioid misuse and its complications

“ICE” – A rare cause for coagulopathy in a case of massive post-partum hemorrhage

A case of massive post-partum hemorrhage in East-Malaysia, associated with 3-4 methylene-dioxy-methamphetamine (MDMA) abuse otherwise known as Ecstasy or locally as “ICE”, injected by the patient as a means to suppress labor pains prior to hospital presentation. We report a rare case of substance abuse that lead to life threatening hemorrhage in a maternal patient of productive age group. Presenting to the labor suite in second stage of labor in breech presentation, exhibiting active neuropsychiatric symptoms of intoxication like euphoria, drowsiness, mydriasis but able to obey commands. A rapid response by the Obstetric on-call team proceeded with an assisted-breech delivery. Post-delivery, a baby girl with poor Apgar score was born and intubated. The mother was then posted for an Examination Under Anesthesia as she was noted to have slow blood oozing per-vaginally using a single shot spinal as she exhibited features of difficult intubation and high risk of aspiration. During the procedure, she tipped into massive PPH complicated with DIVC, and was rushed into the intensive care unit for stabilization and back into the operation theatre, needing a total abdominal hysterectomy (TAH) as definitive bleeding control. She required large scale resuscitative efforts peri-operatively including continuous veno-venous hemofiltration (CVVH) as well as regional intensive care consultation. We describe, chronologically the anesthetic challenges faced in managing a patient in acute substance intoxication at presentation to our district hospital during twilight hours. We then explain the pharmacodynamics of MDMA in provoking coagulopathy. No reports of similar cases in the South-East Asia region

Feasibility of a social media/online community support group intervention among chronic pain patients on opioid therapy.

Aims: Assess whether the Harnessing Online Peer Education (HOPE) social media-based support group can engage patients on opioids at risk for misuse/overdose to discuss risk reduction strategies. Methods: Fifty-one patients on chronic opioid therapy and risk factors for aberrant medication-taking behaviors were randomized to a HOPE intervention or control (Facebook) group. Results: Compared to control group participants, intervention participants had almost 10 times higher posting engagement (n = 411 posts versus 45; 73% versus 52% of participants). Participants discussed coping, pain, medication and non-medication treatments, and other opioid and addiction-related topics. Discussion: Results suggest that a HOPE online community might serve as an effective behavioral intervention tool among chronic pain patients on opioid therapy