The lesional and epileptogenic consequences of lithium-pilocarpine-induced status epilepticus are affected by previous exposure to isolated seizures: effects of amygdala kindling and maximal electroshocks

In temporal lobe epilepsy, the occurrence of seizures seems to correlate with the presence of lesions underlying the establishment of a hyperexcitable circuit. However, in the lithium-pilocarpine model of epilepsy, neuronal damage occurs both in the structures belonging to the circuit of initiation and maintenance of the seizures (forebrain limbic system) as in the propagation areas (cortex and thalamus) and in the circuit of remote control of seizures (substantia nigra pars reticulata). To determine whether or not we could protect the brain from lesions and epileptogenesis induced by status epilepticus and identify cerebral structures involved in the genesis of epilepsy, we studied the effects of the chronic exposure to non-deleterious seizures, either focalized with secondary generalization (amygdala kindling, kindled-pilocarpine rats), or primary generalized (ear-clip electroshocks, electroshock-pilocarpine rats) on neuronal damage and epileptogenesis induced by lithium-pilocarpine status epilepticus. These animals were compared to rats subjected to status epilepticus but not pretreated with seizures (sham-kindled-pilocarpine or sham-electroshock-pilocarpine rats). Compared to sham-pilocarpine rats, neuronal damage was prevented in the limbic system of the kindled-pilocarpine rats, except in the hilus of the dentate gyrus and the entorhinal cortex, while it was enhanced in rats pretreated with electroshocks, mainly in the entorhinal and perirhinal cortices. Most sham-kindled- and sham-electroshock-pilocarpine rats (92-100%) developed recurrent seizures after a silent period of 40-54days. Likewise, all kindled-pilocarpine rats developed spontaneous seizures after the same latency as their sham controls, while only two of 10 electroshock-pilocarpine rats became epileptic after a delay of 106-151days.The present data show that the apparent antiepileptic properties of electroshocks correlate with extensive damage in midbrain cortical regions, which may prevent the propagation of seizures from the hippocampus and inhibit their motor expression. Conversely, the extensive neuroprotection of the limbic system but not the hilus and entorhinal cortex provided by amygdala kindling does not prevent epileptogenesis. Thus, the hilus, the entorhinal and/or perirhinal cortex may be key structure(s) for the establishment of epilepsy.     

Role of Drosophila IKK gamma in a toll-independent antibacterial immune response

We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.     

Remote Echography between a Ground Control Center and the International Space Station Using a Tele-operated Echograph with Motorized Probe

Echography is the most appropriate imaging modality for investigating astronauts. Unfortunately, it requires a great deal of training to perform ultrasound examinations, which can be difficult and time consuming, especially if the astronaut does not have a medical background. We designed a new echography system with motorized probes that allows for the majority of exam functions to be controlled by a ground-based sonographer. Using tele-operation, the sonographer controls the orientation of the transducer (tilt, rotation) and echograph settings (gain, depth, freeze) and triggers ultrasound functions (pulsed wave color Doppler, 3-D capture, radiofrequency data collection, elastography). With this system, astronauts are required to hold the motorized probe only at the locations indicated, with the remainder of the exam being conducted by the ground-based sonographer. During spaceflight, ultrasound imaging of the carotid artery, jugular vein, thyroid, liver, gallbladder, biliary tract and portal vein (2-D, 3-D, color, pulsed wave, radiofrequency) were successfully performed.     

Development and validation of the Workplace Interruptions Measure

In 3 studies, we developed and tested the first comprehensive, self‐report measure of workplace interruptions. The Workplace Interruptions Measure (WIM) is based on a typology of interruptions that included intrusions, distractions, discrepancy detections, and breaks. The four‐factor structure was reduced to a 12‐item measure in Study 1 (N = 317) and confirmed in a diverse sample of employees in Study 2 (N = 160). Study 3 (N = 323) further examined the psychometric properties of the WIM in a sample of university faculty and staff. Studies 2 and 3 demonstrated that both effort‐enhancing interruptions (intrusions, distractions, and discrepancy detections) and recovery‐enhancing interruptions (breaks) were associated with stressors and strains. Distractions, discrepancy detections, and breaks uniquely predicted strain outcomes beyond other workplace stressors (i.e., quantitative workload, interpersonal conflict, and role conflict). We discuss implications of the WIM for the theory and practice of interruptions research.     

Understanding Population-Based Site-Specific Cancer Incidence Rates in the USA

As compared with conventionally reported national population-based incidence rates, incidence rates better represent the ??burden?? of disease if they remove prevalent cases from the denominator. In order to reflect the ??risk?? in a disease-free population, rates should both exclude prevalent cases from the denominator and second or later diagnosed cases at the same site from the numerator. Five common cancers were evaluated through a correction method using 2005?C2007 Surveillance, Epidemiology, and End Results Program data to determine the extent of difference between conventional and corrected incidence rates. These corrections lowered the incidence rates 4.0?C5.8% for female breast cancer, 4.6?C7.6% for melanoma, 3.0?C4.0% for colorectal cancer, and 2.1?C2.5% for lung and bronchus cancer. Corrected incidence rates for prostate cancer were 9.9?C13.7% higher. In cancers with either high prevalence and/or high occurrence of multiple primaries at the same site, corrected population-based incidence rates are warranted.     

Dermoscopy to Identify Dermal Thinning

Biopsying of children is often difficult to accomplish and traumatic. Consequently, techniques that avert biopsy are welcome in children. We describe the use of handheld dermoscopy for confirmation of the diagnosis of lesions with dermal thinning, including focal dermal hypoplasia, aplasia cutis, and striae. The major advantage of this technique is rapid diagnosis in the absence of a surgical procedure.     

Role of the vulnerable elders survey-13 screening tool in predicting treatment plan modification for older adults with cancer

Background: The Vulnerable Elders Survey (VES-13) is commonly used to identify older patients who may benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cut point of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive VES-13 scores (7–10)have a higher likelihood of a change in treatment compared to low positive scores (3–6).Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment in an academic geriatric oncology clinic from June 2015 to June 2019. Various VES-13 cut points were analyzed to identify those individuals whose treatment was modified after CGA. Area under the curve (AUC) was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by treatment modality.Results: We included 386 patients with mean age 81, 58% males. Gastrointestinal cancer was the most common site (31%) and 60% were planned to receive curative treatment. The final treatment plan was modified in 59% overall, with 52.7% modified with VES-13 scores 7–10, 50.8% with scores 3–6 and 28.1% with scores <3 (P = 0.002). VES-13 performance in predicting treatment modification was similar for cut points 3 (AUC 0.58), 4 (0.59), 5 (0.59), and 6 (0.59) and in those considering local treatment vs. chemotherapy.Conclusions: A positive VES-13 score was associated with final oncologic treatment plan modification. A high positive score was not superior to the conventional cut point of ≥3.