A Fumonisin Prevention Tool for Targeting and Ranking Agroclimatic Conditions Favoring Exposure in French Maize-Growing Areas

The levels of fumonisins (FUMO)—mycotoxins produced by Fusarium verticillioides—in maize for food and feed are subject to European Union regulations. Compliance with the regulations requires the targeting of, among others, the agroclimatic factors influencing fungal contamination and FUMO production. Arvalis-Institut du végétal has created a national, multiyear database for maize, based on field survey data collected since 2003. This database contains information about agricultural practices, climatic conditions and FUMO concentrations at harvest for 738 maize fields distributed throughout French maize-growing regions. A linear mixed model approach highlights the presence of borers and the use of a late variety, high temperatures in July and October, and a water deficit during the maize cycle as creating conditions favoring maize contamination with Fusarium verticillioides. It is thus possible to target a combination of risk factors, consisting of this climatic sequence associated with agricultural practices of interest. The effects of the various possible agroclimatic combinations can be compared, grouped and classified as promoting very low to high FUMO concentrations, possibly exceeding the regulatory threshold. These findings should facilitate the creation of a national, informative and easy-to-use prevention tool for producers and agricultural cooperatives to manage the sanitary quality of their harvest.     

Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road

Glutamatergic transmission is widely implicated in neuropsychiatric disorders, and the discovery that ketamine elicits rapid-acting antidepressant effects by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) signaling has spurred a resurgence of interest in the field. This review explores agents in various stages of development for neuropsychiatric disorders that positively modulate AMPARs, both directly and indirectly. Despite promising preclinical research, few direct and indirect AMPAR positive modulators have progressed past early clinical development. Challenges such as low potency have created barriers to effective implementation. Nevertheless, the functional complexity of AMPARs sets them apart from other drug targets and allows for specificity in drug discovery. Additional effective treatments for neuropsychiatric disorders that work through positive AMPAR modulation may eventually be developed.     

Gall Bladder Carcinoma Presenting with Spinal Metastasis: A Rare Phenomenon

Skeletal metastasis as a primary presentation of gall bladder carcinoma is rare. A 50-year-old lady presented with neck pain and weakness in her right upper limb of 3 months duration. Clinical and imaging work-up suggested locally advanced gall bladder carcinoma with metastasis to cervical vertebra and sternum. Only one case till date has been reported where the patient presented with neurological symptoms due to pathological fracture secondary to metastasis from an occult gall bladder carcinoma. Although rare, an occult gall bladder cancer may present with neurological symptoms due to pathological fracture of spine secondary to metastasis. We present a brief review of literature of patients who presented with skeletal metastases in clinically silent gall bladder malignancy. Palliative care issues in advanced gall bladder carcinoma have also been discussed.     

Nano-engineered microcapsules boost the treatment of persistent pain

Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments.     

Evaluation of nosocomial infection risk using APACHE II scores in the neurological intensive care unit

To evaluate the feasibility and accuracy of using the Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) scoring system for predicting the risk of nosocomial infection in the neurological intensive care unit (NICU), 216 patients transferred to NICU within 24 hours of admission were retrospectively evaluated. Based on admission APACHE II scores, they were classified into three groups, with higher APACHE II scores representing higher infectious risk. The device utilization ratios and device-associated infection ratios of NICU patients were analyzed and compared with published reports on patient outcome. Statistical analysis of nosocomial infection ratios showed obvious differences between the high-risk, middle-risk and low-risk groups (p < 0.05). The area under the receiver operating characteristic curve of the APACHE II model in predicting the risk of nosocomial infection was 0.81, which proved to be reliable and consistent with the expectation. In addition, we found statistical differences in the duration of hospital stay (patient-days) and device utilization (device-days) between different risk groups (p < 0.05). Thus the APACHE II scoring system was validated in predicting the risk of nosocomial infection, duration of patient-days and device-days, and providing accurate assessment of patients’ condition, so that appropriate prevention strategies can be implemented based on admission APACHE II scores.     

IL-1β、IL-6、TNF-α与注意缺陷多动障碍的相关性

目的:探讨注意缺陷多动障碍(ADHD)儿童体内IL-1β、IL-6、TNF-α含量变化及可能的发病机制;分析IL-1β、IL-6、TNF-α与ADHD症状特征及行为问题的关系。方法:对35例符合DSM-Ⅳ诊断标准的ADHD和25例正常儿童进行血清IL-1β、IL-6、TNF-α浓度测定,选用Achenbach儿童行为量表(CBCL)进行行为评定,比较两组IL-1β、IL-6、TNF-α浓度水平,并与DSM-Ⅳ诊断标准和CBCL得分进行相关分析。结果:ADHD儿童IL-1β较对照组增高,差异有统计学意义(χ2=4.239,P=0.041;Z=2.051,P=0.040);IL-6较对照组增高,但差异不具统计学意义(χ2=3.138,P=0.074;Z=1.892,P=0.058);TNF-α较对照组降低,差异有统计学意义(χ2=5.173,P=0.023;Z=2.792,P=0.005);TNF-α与注意缺陷因子、多动/冲动因子负相关(r=-0.377,P=0.003;r=-0.274,P=0.034);IL-1β与注意缺陷因子正相关(r=0.273,P=0.035);TNF-α与CBCL注意问题、违纪行为、攻击行为、外向性、行为问题总分负相关(r=-0.325,P=0.011;r=-0.396,P=0.002;r=-0.306,P=0.017;r=-0.324,P=0.011;r=-0.346,P=0.007)。结论:ADHD儿童存在高水平的IL-1β和低水平的TNF-α;IL-1β尤其是TNF-α与ADHD注意缺陷症状及某些行为问题间存在关联性。     

Radiographer reporting of neurological magnetic resonance imaging examinations of the head and cervical spine: Findings of an accredited postgraduate programme

IntroductionTo analyse the objective structured examination (OSE) results of the first cohorts of radiographers (n = 13) who successfully completed an accredited postgraduate programme in clinical reporting of neurological magnetic resonance imaging (MRI) examinations of the head and cervical spine.MethodsForty MRI examinations were used in the OSE which included a range of abnormal cases (prevalence of abnormal examinations approximated 50%) and included: haemorrhage, infarction, demyelination disease, abscess, mass lesions (metastatic deposits, meningioma, glioma, astrocytoma); and disc disease, cord compression, stenosis, ligament rupture, syringomyelia appearances on patients referred from a range of referral sources. Normal variants and incidental findings were also included. True/false positive and negative fractions were used to mark the responses which were also scored for agreement with the previously agreed expected answers based on agreement between three consultant radiologists' reports.ResultsThe mean sensitivity, specificity and agreement rates for all head and cervical spine investigations (n = 520) combined were 98.86%, 98.08% and 88.37%, respectively. The highest scoring cases were cases which included astrocytoma, disc protrusion with cord compression and glioma. The most common errors were related to syringomyelia, ligament rupture and vertebral fracture.ConclusionsThese OSE results suggest that in an academic setting, and following an accredited postgraduate education programme, this group of radiographers has the ability to correctly identify normal MRI examinations of the head/cervical spine and are able to provide a report on the abnormal appearances to a high standard. Further work is required to confirm the clinical application of these findings.