A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits

Background

Mild traumatic brain injury (TBI) is a serious public health concern affecting more than 1.7 million people in the United States annually. Mild TBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition.

Methods

We subjected mice to a mild TBI (mTBI-1 or mTBI-2) induced by a weight drop model. We assessed brain injury histologically and biochemically, the latter by serum neuron-specific enolase and glial fibrillary acidic protein. Systemic and brain inflammation were measured by cytokine array. We determined blood–brain barrier integrity by cerebral vascular leakage of micromolecular and macromolecular fluorescent molecules. We evaluated mice using a rotarod device and novel object recognition to measure motor coordination and cognition, respectively.

Results

Mice undergoing mTBI-1 or mTBI-2 had significant deficits in motor coordination and cognition for several days after injury compared with controls. Furthermore, both mTBI-1 and mTBI-2 caused micromolecular leakage in the blood–brain barrier, whereas only mTBI-2 caused macromolecular leakage. Serum neuron-specific enolase and glial fibrillary acidic protein were elevated acutely and corresponded to the degree of injury, but returned to baseline within 24 h. Serum cytokines interleukin-6 and keratinocyte-derived chemokine were significantly increased within 90 min of TBI. Interleukin-6 levels correlated with the degree of injury.

Conclusions

The current study provides a reproducible model of mild TBI in mice that exhibits pathologic features of mild TBI in humans. Furthermore, our data suggest that serum cytokines, such as IL-6, may be effective biomarkers for severity of head injury.     

The Harrington reconstruction for advanced periacetabular metastatic destruction: Good outcome in 32 patients

We report the outcome in 32 patients operated on for advanced periacetabular metastatic destruction, where all but 2 had Harrington class III destruction. The patients were operated on using the Harrington reconstruction technique, where threaded pins and cement and a total hip replacement are used to reconstruct the acetabulum and ilium. The median survival was 11 (0-106+) months. 13 patients lived for a year or more. At follow-up after 1 year, 10 of the 13 were free of pain at rest and weight-bearing, 6 were walking with and 7 without support, and 11 lived outside a health care facility. 2 patients died within 2 weeks of surgery, both of excessive peroperative bleeding. 2 patients had dislocations, 1 developed a deep infection, and 2 patients deep vein thrombosis. There were no complications caused by erroneous pin placement or intraoperative thromboembolic incidents. There were no mechanical failures, or radiographic signs of loosening, of the pelvic components. The Harrington reconstruction technique is an effective and long-lasting method to relieve pain and restore function in patients with advanced periacetabular metastatic destruction.     

Risk factors for hip fracture in very old people: a population-based study

Summary

Knowledge of risk factors for hip fracture among very old people is limited. Walking indoors with help from ≤1 person, Parkinson’s disease, currently smoking, delirium in the previous month, underweight, and age were associated with increased risk of hip fracture and could be important for preventive strategy development.

Introduction

The purpose of this study is to investigate risk factors for hip fracture among a representative sample of very old people.

Methods

In total, 953 participants from the Umeå 85+/Gerontological Regional Database population-based cohort study were interviewed and assessed during home visits. Associations of baseline characteristics with hip fracture during the maximum 5-year follow-up period were analyzed using Cox proportional hazards regression.

Results

Participants had a mean age of 89.3?±?4.7 years; 65.8 % were women, 36.8 % lived in residential care facilities, 33.6 % had dementia, and 20.4 % had histories of hip fracture. During a mean follow-up period of 2.7 years, 96 (10.1 %) individuals sustained hip fracture. Walking indoors with help from no more than one person (hazard ratio [HR]?=?8.57; 95 % confidence interval [CI], 1.90–38.71), Parkinson’s disease (HR?=?5.12; 95 % CI, 1.82–14.44), currently smoking (HR?=?4.38; 95 % CI 2.06–9.33), delirium in the previous month (HR?=?2.01; 95 % CI, 1.15–3.49), underweight (body mass index <22; HR?=?1.74, 95 % CI, 1.09–2.77), and age (HR?=?1.09; 95 % CI, 1.04–1.14) were associated independently with an increased risk of hip fracture. Hip prosthesis at baseline decreased the risk of hip fracture (HR?=?0.37; 95 % CI, 0.15–0.91), but only for those with bilateral hip prostheses.

Conclusions

Seven factors were associated independently with incident hip fracture during follow-up in this sample of very old people. These factors could have important clinical implications in identifying persons at high risk of hip fracture, as well as in the development of effective preventive strategies.

     

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" is a distinct cytologic category: histologic outcomes and HPV prevalence

We examined the histologic outcomes and prevalence of high-risk human papillomavirus (HR-HPV) in women with liquid-based Papanicolaou (Pap) tests interpreted as "low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) compared with the 2001 Bethesda System (TBS 2001) cytologic categories of LSIL, high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A computer search identified 426 LSIL, 86 ASC-H, 81 LSIL-H, and 110 HSIL cytologic interpretations during a 1-year period, each with up to 2 years of histologic follow-up. The risk of histologic cervical intraepithelial neoplasia (CIN) 2 or worse (CIN 2+) associated with LSIL-H (32/81 [40%]) was intermediate between LSIL (46/426 [10.8%]) and HSIL (72/110 [65.5%]), but not significantly different from ASC-H (23/86 [27%]). However, LSIL-H was more frequently associated with a definitive histologic diagnosis of any CIN (CIN 1+) than ASC-H (53/81 [65%] vs 35/86 [41%]). Moreover, the prevalence of HR-HPV was significantly greater in patients with LSIL-H than in patients with ASC-H (15/15 [100%] vs 43/73 [59%]). The histologic outcomes and HR-HPV prevalence associated with LSIL-H differ significantly from the established categories of TBS 2001 and provide evidence to support the recognition of LSIL-H as a distinct cytologic category.