Very early signs of autism reported by parents include many concerns not specific to autism criteria

This study assessed parents’ first concerns about their autistic child. This information was categorized so that it could help healthcare professionals improve early detection of autism. We designed a questionnaire using an open-ended format, and 459 questionnaires were completed by parents to assess difficulties encountered in obtaining a diagnosis for their child. Answers about their first motive of concerns were categorized and compared with regards to age, gender, birth order, age of onset, delay in seeking professional advice, and delay in diagnosis. Concerns about social development or autistic behaviors were frequent, but not exclusive. Parents were divided into three clusters of concerns: (a) an “early awareness group”: which included motor problems and passivity (14.6 months); (b) “intermediate awareness group”: included emotional, hyperactivity, and sleep problems (15.3 months); and (c) a “later awareness group”: which included communication problems, poor social interaction, and autistic-type behaviors (22.3 months). Parents who noticed general concerns not specific to autism were worried earlier, but received a later diagnosis. We suggest that motor problems, and/or emotional problems, and/or the level of a child's activity should encourage frontline professionals to seek autistic symptoms in infants.     

Chronic Cancer-Related Pain: Continuous Perineural Infusion of Local Anesthetics as Alternative to Systemic Analgesic Drugs

Pain is a major concern for patients suffering from cancer. Although opioid drugs remain the gold standard for treatment of pain, little is known about the interest of continuous analgesia techniques as alternative. The aim of the present article is to detail the feasibility and to present the diversity of continuous perineural infusion of local anesthetic. A series of five patients suffering from different cancer-related pain is presented. A continuous perineural block was proposed to patients presenting with unbearable pain in an area innervated by a plexus or a nerve despite parenteral analgesic pharmacotherapy. All blocks were performed in a surgical theatre under sterile conditions. An initial bolus dose with 3.75 mg/mL ropivacaine was injected followed by a continuous infusion of 2 mg/mL of ropivacaine. Patient-controlled perineural analgesia was started at home by a nursing network. The technique, the efficacy, and the side effects were reported. Complete pain relief was noted 15 minutes after local anesthetic injection in the five cases, and efficacy was maintained during the following days at home, with no other analgesic treatment required. One patient restarted working a few weeks after catheter insertion. The catheter duration lasted for 12 to 110 days. One catheter was removed because of local anesthetic leak at the puncture point. Some paresthesia was noted in one patient. No other side effect was noted. No infection was reported. In selected patients, continuous perineural infusion of local anesthetics appears to be an attractive alternative to parenteral opioids for cancer-related pain. Further investigation is warranted to better define the place of these techniques in the armamentarium of cancer-related pain treatment.     

Using Intraindividual Variability to Detect Malingering in Cognitive Performance

The utility of measures for detecting malingering was evaluated using a simulation design in which half the participants were encouraged to do their best and half were asked to feign head injury. Particular attention was focused on the utility of repeated assessment (intraindividual variability) in discriminating the groups. Participants were tested on three occasions on measures commonly used to detect malingering including a specific symptom validity test (SVT). The results indicated that multiple measures of malingering obtained in single assessment (occasion one) discriminated the groups effectively. In addition, however, intraindividual variability in performance, particularly of indicators from the SVT, provided unique information beyond level of performance. The results suggest that response inconsistency across testing sessions may be a clinically useful measure for the detection of malingering.     

PACE4 inhibitors and their peptidomimetic analogs block prostate cancer tumor progression through quiescence induction,increased apoptosis and impaired neovascularisation

Prostate cancer is the leading cancer in North American men. Current pharmacological treatments are limited to anti-androgen strategies and the development of new therapeutic approaches remains a challenge. As a fundamentally new approach, we propose the inhibition of PACE4, a member of the proprotein convertases family of enzymes, as a therapeutic target in prostate cancer. We developed an inhibitor named the Multi-Leu peptide, with potent in vitro anti-proliferative effects. However, the Multi-Leu peptide has not been tested under in vivo conditions and its potency under such conditions is most likely limited, due to the labile characteristics of peptides in general. Using a peptidomimetic approach, we modified the initial scaffold, generating the analog Ac-[DLeu]LLLRVK-Amba, which demonstrates increased inhibitory potency and stability. The systemic administration of this peptidomimetic significantly inhibits tumor progression in the LNCaP xenograft model of prostate cancer by inducing tumor cell quiescence, increased apoptosis and neovascularization impairment. Pharmacokinetic and biodistribution profiles of this inhibitor confirm adequate tumor delivery properties of the compound. We conclude that PACE4 peptidomimetic inhibitors could result in stable and potent drugs for a novel therapeutic strategy for prostate cancer.