Distinct ERP profiles for auditory processing in infants at-risk for autism and language impairment.

Early identification of autism spectrum disorder (ASD) is crucial for the formulation of effective intervention programs. Language deficits may be a hallmark feature of ASD and language delay observed in ASD shows striking similarities to that observed in children with language impairment (LI). Auditory processing deficits are seen in both LI and ASD, however, they have not previously been compared directly using Event-Related Potentials (ERPs) in the two at-risk populations. This study aims to characterize infants at-risk for ASD (HR-ASD) at the electrophysiological level and to compare them with infants at-risk for LI (HR-LI) and controls, to find specific markers with predictive value. At 12-month-old, auditory processing in HR-ASD, HR-LI and controls was characterized via ERP oddball paradigm. All infants were then evaluated at 20 months, to investigate the associations between auditory processing and language/ASD-related outcomes. In both HR-ASD and HR-LI, mismatch response latency was delayed compared to controls, whereas only HR-ASD showed overall larger P3 amplitude compared to controls. Interestingly, these ERP measures correlated with later expressive vocabulary and M-CHAT critical items in the whole sample. These results may support the use of objective measurement of auditory processing to delineate pathophysiological mechanisms in ASD, as compared to LI.

Metformin use and gynecological cancers: A novel treatment option emerging from drug repositioning.

Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition. This drug leads to activation of the cellular energy-sensing liver kinase B1 [LKB1]/AMPK pathway. LKB1 is implicated as a tumor suppressor gene in molecular pathogenesis of different malignancies. AMPK is a serine/threonine protein kinase that acts as an ultra-sensitive cellular energy sensor maintaining the energy balance within the cell. AMPK activation inhibits mRNA translation and proliferation in cancer cells via down-regulation of PI3K/Akt/mTOR pathway. Moreover, metformin decreases the production of insulin, insulin-like growth factor, inflammatory cytokines and vascular endothelial growth factor, and therefore it exerts anti-mitotic, anti-inflammatory and anti-angiogenetic effects. Recent in vitro and experimental data suggest that metformin electively targets cancer stem cells, and acts together with chemotherapy to block tumor growth in different cancers. Several epidemiological studies and meta-analysis have shown that metformin use is associated with decreased cancer risk and/or reduced cancer mortality for different malignancies. The present review analyzes the recent biological and clinical data suggesting a possible growth-static effect of metformin also in gynecological cancers. The large majority of available clinical data on the anti-cancer potential of metformin are based on observational studies. Therefore long-term phase II-III clinical trials are strongly warranted to further investigate metformin activity in gynecological cancers.

Treatment of climacteric symptoms in survivors of gynaecological cancer.

Different treatments (surgery, radiotherapy, chemotherapy) for gynaecological cancers may cause ovarian failure or increase menopausal symptoms. There is a widespread reluctance among physicians to prescribe hormone replacement therapy (HRT) to the survivors of gynaecological cancer. This review analyses the use of HRT and of alternative therapies in such women. Squamous cervical cancer is not estrogen dependent and thus HRT is not contraindicated. While a cautious approach to hormone-dependent cancer is warranted, for women treated for non-hormone-related tumours alternative treatments for menopausal symptoms should be given due consideration, as any reluctance to prescribe HRT for them has neither a biological nor a clinical basis. In studies of HRT for survivors of endometrial and ovarian cancer, for instance, no evidence of increased risk was found, although no definitive conclusions can yet be formulated. The positive effect of HRT on quality of life seems to outweigh the unfounded suspicion of an increased risk of recurrence of non-hormone-related tumours. Effective non-hormonal alternatives for vasomotor symptoms are selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors.

Evaluation of a ketamine-propofol drug combination with or without dexmedetomidine for intravenous anesthesia in cats undergoing ovariectomy.

OBJECTIVE: To evaluate the use of a ketamine-propofol combination, with or without dexmedetomidine, in cats undergoing ovariectomy and to assess Heinz body formation following administration of these drugs. DESIGN: Randomized clinical trial. ANIMALS: 15 client-owned female cats. PROCEDURES: Anesthesia was induced with a ketamine (2.0 mg/kg [0.91 mg/lb])-propofol (2.0 mg/kg) combination with (n = 7) or without (8) dexmedetomidine (0.003 mg/kg [0.0013 mg/lb]) and was maintained via continuous IV infusion of a 1:1 ketamine-propofol combination (administration rate for each drug, 10.0 mg/kg/h [4.54 mg/lb/h]). Cats underwent ovariectomy; duration of infusion was 25 minutes. Physiologic variables were measured at predetermined time points. Heinz bodies were quantified via examination of blood smears. Numeric scales were used to assess quality of recovery, degree of sedation, and signs of pain after surgery. RESULTS: The ketamine-propofol group had a significantly higher mean heart rate at several time points during drug infusion, a significantly shorter time from the end of infusion to extubation (7 vs 29 minutes), and significantly lower sedation scores for the first hour after surgery than did the ketamine-propofol-dexmedetomidine group. Other variables were similar between groups; recovery was smooth, and anesthesia and postoperative analgesia were deemed adequate for all cats. The number of RBCs with Heinz bodies was not increased after surgery, compared with values immediately after anesthetic induction. CONCLUSIONS AND CLINICAL RELEVANCE: Total IV anesthesia with a ketamine-propofol combination, with or without dexmedetomidine, appeared to be effective in healthy cats. These short-term infusions produced smooth recovery and adequate analgesia during the postoperative period.

Pharmacokinetics and efficacy of intravenous and extradural tramadol in dogs.

Tramadol is a synthetic opioid agonist used extensively in human and, to a lesser extent, veterinary medicine throughout the world. The clinical efficacy and pharmacokinetic profile of intravenous (i.v.) and extradural (e.d.) tramadol (2 mg/kg) and its o-desmethyl metabolite were studied in dogs undergoing tibial plateau levelling osteotomy (TPLO). Intra-operative cardiorespiratory variables were monitored and post-operative pain was assessed using the short form of the Glasgow Composite Pain Scale. A rapid (<5 min) and effective production of o-desmethyl tramadol was recorded. The pharmacokinetic profile was similar for tramadol and its metabolite irrespective of the route of administration. E.d. tramadol provided sufficient intra- and post-operative analgesia without significant clinical side-effects, but the post-operative analgesia was comparable to that following i.v. administration and the e.d. route could therefore not be considered a practical alternative to the i.v. route.