Functional recreation of age-related CD8 T cells in young mice identifies drivers of aging- and human-specific tissue pathology.

Mitigating effects of aging on human health remains elusive because aging impacts multiple systems simultaneously, and because experimental animals exhibit critical aging differences relative to humans. Separation of aging into discrete processes may identify targetable drivers of pathology, particularly when applied to human-specific features. Gradual homeostatic expansion of CD8 T cells dominantly alters their function in aging humans but not in mice. Injecting T cells into athymic mice induces rapid homeostatic expansion, but its relevance to aging remains uncertain. We hypothesized that homeostatic expansion of T cells injected into T-deficient hosts models physiologically relevant CD8 T cell aging in young mice, and aimed to analyze age-related T cell phenotype and tissue pathology in such animals. Indeed, we found that such injection conferred uniform age-related phenotype, genotype, and function to mouse CD8 T cells, heightened age-associated tissue pathology in young athymic hosts, and humanized amyloidosis after brain injury in secondary wild-type recipients. This validates a model conferring a human-specific aging feature to mice that identifies targetable drivers of tissue pathology. Similar examination of independent aging features should promote systematic understanding of aging and identify additional targets to mitigate its effects on human health.

Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation.

The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding.

Automatic detection of periods of slow wave sleep based on intracranial depth electrode recordings.

BACKGROUND: An automated process for sleep staging based on intracranial EEG data alone is needed to facilitate research into the neural processes occurring during slow wave sleep (SWS). Current manual methods for sleep scoring require a full polysomnography (PSG) set-up, including electrooculography (EOG), electromyography (EMG), and scalp electroencephalography (EEG). This set-up can be technically difficult to place in the presence of intracranial EEG electrodes. There is thus a need for a method for sleep staging based on intracranial recordings alone. NEW METHOD: Here we show a reliable automated method for the detection of periods of SWS solely based on intracranial EEG recordings. The method utilizes the ratio of spectral power in delta, theta, and spindle frequencies relative to alpha and beta frequencies to classify 30-s segments as SWS or not. RESULTS: We evaluated this new method by comparing its performance against visually scored patients (n=9), in which we also recorded EOG and EMG simultaneously. Our method had a mean positive predictive value of 64% across all nights. Also, an ROC analysis of the performance of our algorithm compared to manually labeled nights revealed a mean average area under the curve of 0.91 across all nights. COMPARISON WITH EXISTING METHOD: Our method had an average kappa score of 0.72 when compared to visual sleep scoring by an independent blinded sleep scorer. CONCLUSION: This shows that this simple method is capable of differentiating between SWS and non-SWS epochs reliably based solely on intracranial EEG recordings.

Limit Crystalloid Resuscitation after Traumatic Brain Injury.

Patients with traumatic brain injury (TBI) are often resuscitated with crystalloids in the emergency department (ED) to maintain cerebral perfusion. The purpose of this study was to evaluate whether crystalloid resuscitation volume impacts mortality in TBI patients. This was a retrospective study of trauma patients with head abbreviated injury scale score ≥2, who received crystalloids during ED resuscitation between 2004 and 2013. Clinical characteristics and volume of crystalloids received in the ED were collected. Patients who received <2 L of crystalloids were categorized as low volume (LOW), whereas those who received ≥2 L were considered high volume (HIGH). Mortality and outcomes were compared. Multivariable regression analysis was used to determine the odds of mortality while controlling for confounders. Over 10 years, 875 patients met inclusion criteria. Overall mortality was 12.5 per cent. Seven hundred and forty-two (85%) were in the LOW cohort and 133 (15%) in the HIGH cohort. Gender and age were similar between the groups. The HIGH cohort had lower admission systolic blood pressure (128 vs 138 mm Hg, P = 0.001), lower Glasgow coma scale score (10 vs 12, P < 0.001), higher head abbreviated injury scale (3.8 vs 3.3, P < 0.001), and higher injury severity score (25 vs 18, P < 0.001). The LOW group had a lower unadjusted mortality (10 vs 26%, P < 0.001). Multivariable analysis adjusting for confounders demonstrated that those resuscitated with ≥2 L of crystalloids had increased odds of mortality (adjusted odds ratio 2.25, P = 0.005). Higher volume crystalloid resuscitation after TBI is associated with increased mortality, thus limited resuscitation for TBI patients may be indicated.

Clinical experience with a high definition exoscope system for surgery of pineal region lesions.

VITOM-90 (Karl Storz Endoscopy, Tuttlingen, Germany) is a new technology that can be used as an alternative to the operating microscope. We have found that this device substantially improves surgeon comfort during infra-tentorial supracerebellar approaches to pineal region masses, and now report our experiences. The VITOM-90 is a specially designed scope that is attached to a high definition (HD) digital camera and displayed on a HD video monitor. This system was utilized in five patients undergoing infratentorial supracerebellar approaches for pineal region lesions. Surgical outcomes and pathologies are described. The device was used by three surgeons during five procedures. Three patients underwent surgery in the sitting position and two in the modified prone (Concorde) position. Pathologies included pineocytoma, lipoma, and germinoma. Total resection was achieved in three patients and subtotal in two patients. Surgeon assessment was positive; surgeons indicated that surgery with the VITOM-90 was more comfortable than with the operating microscope. Lack of stereopsis was considered a minor drawback. The VITOM-90 permitted a natural head and neck position. Operating room personnel and residents reported improved visualization of the anatomy. Using the VITOM-90 benefited surgeons during pineal region surgery by reducing strain and allowing the surgeon to operate from a comfortable position without increased operative time or complications. The improved comfort levels may translate into safer, more accurate surgeries in this complex area.

Survival and prognostic factors of anaplastic gliomas.

BACKGROUND: The prognosis of patients with anaplastic glioma tumors is relatively favorable compared with patients with glioblastoma multiforme. OBJECTIVE: To estimate survival differences between anaplastic astrocytoma (AA) and anaplastic oligodendroglioma (AO) patients and factors associated with survival prognosis. METHODS: A nationwide cohort of grade III glioma patients diagnosed between 1990 and 2008 was studied using the Surveillance, Epidemiology, and End Results registry. Multivariate Cox proportional hazard models evaluated the role of patient and clinical characteristics on overall survival. RESULTS: A total of 1766 patients with AA and 570 patients with AO were studied. The median overall survival was 15 and 42 months among AA and AO patients, respectively. Age increments of 10 years implicated a 50% increase in mortality hazards among AA (hazard ratio [HR], 1.49; P < .001) and AO (HR, 1.51; P < .001) patients. Among AA patients, radiation (HR, 0.62; P < .001), surgery (vs biopsy; HR, 0.73; P < .001), female sex (HR, 0.87; P = .02), and married status (HR, 0.87; P = .02) were associated with a reduction in the hazard of mortality. Longer survival if diagnosed in 2000 relative to 1990 was observed (HR, 0.84; P = .004) in AA patients. Although surgery did not significantly improve survival among AO patients, gross total resection increased the median survival from 40 to 61 months (P = .001) in this cohort. CONCLUSION: First-course radiation, younger age, female sex, treatment in recent years, and surgery were associated with improved survival in AA patients. In contrast, age was the most prominent predictor of survival in AO patients. Surgery alone did not seem to benefit AO patients, and gross total resection improved survival by 21 months.

Direct lateral interbody fusion (DLIF) at the lumbosacral junction L5-S1.

The direct lateral interbody fusion (DLIF), a minimally invasive lateral approach for placement of an interbody fusion device, does not require nerve root retraction or any contact with the great vessels and can lead to short operative times with little blood loss. Due to anatomical restrictions, this procedure has not been used at the lumbosacral (L5-S1) junction. Lumbosacral transitional vertebrae (LSTV), a structural anomaly of the lumbosacral spine associated with low back pain, can result in a level being wrongly identified pre-operatively due to misnumbering of the vertebral levels. To our knowledge, use of the DLIF graft in this patient is the first report of an interbody fusion graft being placed at the disc space between the LSTV and S1 via the transpsoas route. We present a review of the literature regarding the LSTV variation as well as the lateral placement of interbody fusion grafts at the lumbosacral junction.

An effective nonchemical treatment for head lice: a lot of hot air.

OBJECTIVES: Head lice (Pediculus humanus capitis) are a major irritant to children and their parents around the world. Each year millions of children are infested with head lice, a condition known as pediculosis, which is responsible for tens of millions of lost school days. Head lice have evolved resistance to many of the currently used pediculicides; therefore, an effective new treatment for head lice is needed. In this study we examined the effectiveness of several methods that use hot air to kill head lice and their eggs. METHODS: We tested 6 different treatment methods on a total of 169 infested individuals. Each method delivers hot air to the scalp in a different way. We evaluated how well these methods kill lice and their eggs in situ. We also performed follow-up inspections to evaluate whether the sixth, most successful, method can cure head louse infestations. RESULTS: All 6 methods resulted in high egg mortality (> or = 88%), but they showed more-variable success in killing hatched lice. The most successful method, which used a custom-built machine called the LouseBuster, resulted in nearly 100% mortality of eggs and 80% mortality of hatched lice. The LouseBuster was effective in killing lice and their eggs when operated at a comfortable temperature, slightly cooler than a standard blow-dryer. Virtually all subjects were cured of head lice when examined 1 week after treatment with the LouseBuster. There were no adverse effects of treatment. CONCLUSIONS: Our findings demonstrate that one 30-minute application of hot air has the potential to eradicate head lice infestations. In summary, hot air is an effective, safe treatment and one to which lice are unlikely to evolve resistance.