Skull Flexure as a Contributing Factor in the Mechanism of Injury in the Rat when Exposed to a Shock Wave

The manner in which energy from an explosion is transmitted into the brain is currently a highly debated topic within the blast injury community. This study was conducted to investigate the injury biomechanics causing blast-related neurotrauma in the rat. Biomechanical responses of the rat head under shock wave loading were measured using strain gauges on the skull surface and a fiber optic pressure sensor placed within the cortex. MicroCT imaging techniques were applied to quantify skull bone thickness. The strain gauge results indicated that the response of the rat skull is dependent on the intensity of the incident shock wave; greater intensity shock waves cause greater deflections of the skull. The intracranial pressure (ICP) sensors indicated that the peak pressure developed within the brain was greater than the peak side-on external pressure and correlated with surface strain. The bone plates between the lambda, bregma, and midline sutures are probable regions for the greatest flexure to occur. The data provides evidence that skull flexure is a likely candidate for the development of ICP gradients within the rat brain. This dependency of transmitted stress on particular skull dynamics for a given species should be considered by those investigating blast-related neurotrauma using animal models.     

One-year outcomes of tension-free vaginal tape (TVT) mid-urethral slings in overweight and obese women

Introduction  The purpose of this study was to assess the impact of body mass index (BMI) on tension-free vaginal tape (TVT) success rates, patient satisfaction, and complications 1 year following surgery. Methods  Baseline and 1-year postsurgery outcomes were abstracted, including Urogenital Distress Inventory (UDI-6) scores, Incontinence Impact Questionnaire (IIQ-7) scores, and patient satisfaction ratings. Multivariable logistic and linear regression analyses were performed to examine relationships between outcomes and BMI. Results  Subjects (N = 195) with a mean age of 59.3 ± 12.6 were included. There was significant improvement within each group (all p values <0.01) in total UDI-6 and IIQ-7 scores from baseline to 1 year postsurgery; all groups had high patient satisfaction. No differences in improvement or complications rates were observed among the BMI cohorts (all p values >0.05). Conclusion  Differential counseling of overweight or obese women regarding outcomes of the TVT procedure is not supported by these results; longer follow-up is warranted. Poster presentation Annual Meeting of the Society of Gynecologic Surgeons, April 2009. Partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases DK068389 to HER.     

Genetic and environmental determinants on bone loss in postmenopausal Caucasian women: a 14-year longitudinal twin study

Summary  This longitudinal twin study documented that genetic factors explain 44–56% of the between-individual variance in bone loss at femoral neck, lumbar spine, and forearm in postmenopausal Caucasian women, providing a rationale for identifying the specific genes involved. Introduction  Although there is a significant genetic effect on peak BMD, until recently, no substantive studies on heritability of bone loss in human were available. The aim of the study was to estimate the heritability of the bone loss at multiple sites in postmenopausal Caucasian women. Methods  Postmenopausal female monozygotic (MZ) and dizygotic (DZ) twins aged 40 or above at baseline were selected from the TwinsUK registry and followed up for an average of 8 years (range 5–14 years). All twins were noncurrent hormone replacement therapy users and not on any osteoporosis treatment. They had dual-energy X-ray absorptiometry (DXA) scans of their hip, lumbar spine, and forearm several times (range 2–9) during the follow-up period. Individual bone losses at femoral neck, lumbar spine, and forearm were estimated by linear regression modeling. Structural equation modeling was utilized to estimate the heritability of the bone loss. Results  A total of 712 postmenopausal Caucasian female twins (152 MZ and 204 DZ pairs) were included. MZ twins were older and had slightly lower BMD at all sites than DZ twins. DZ twins had slightly higher bone loss at lumbar spine, but similar at femoral neck and forearm compared to MZ twins. Intraclass correlation coefficients (ICC) for the bone loss at all sites were significantly higher in MZ than DZ twin pairs (p = 0.0045, 0.0003, and 0.0007 for femoral neck, lumbar spine, and forearm, respectively), indicating a significant genetic influence on bone loss at these sites. After adjustment for age at baseline and weight change during the follow-up, the heritability estimate was 47% (95% CI 27–63%) for bone loss at femoral neck, 44% (95% CI 27–58%) for lumbar spine, and 56% (95% CI 44–65%) for forearm. Conclusions  Our data suggest that up to 56% of the between-individual variance in bone loss is due to genes, providing a rationale to identify specific genetic factors for bone loss.     

A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary

The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition that CCCs respond poorly to conventional chemotherapy there are efforts to initiate clinical trials for CCC, making accurate diagnosis critical. The purpose of this study was to test and validate a set of antibodies that could aid in the diagnosis of CCC, using a series of cases from different centers in North America. Using a test set of 133 CCCs, we identified the following markers: Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1beta, Ki-67, p21, p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs. For validation, these markers were characterized on an independent set of 104 CCCs from 3 other centers. There were no significant differences in expression of these 7 markers between the independent test and validation sets of CCC. Combining all CCC cases (N=237), HNF-1beta showed the highest sensitivity (82.5%) and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%, specificity: 97.4%). A diagnostic panel consisting of WT1, ER, and HNF-1beta demonstrated nearly identical performance as a panel using all 7 markers in distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three percent of cases were misclassified and 13% carried an uninformative triple negative immunophenotype. CCCs show a distinct, reproducible immunophenotype, compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic aid in problematic cases.     

Measuring Electronic Health Record Use in the Pediatric ICU Using Audit-Logs and Screen Recordings

Background  Time spent in the electronic health record (EHR) has been identified as an important unit of measure for health care provider clinical activity. The lack of validation of audit-log based inpatient EHR time may have resulted in underuse of this data in studies focusing on inpatient patient outcomes, provider efficiency, provider satisfaction, etc. This has also led to a dearth of clinically relevant EHR usage metrics consistent with inpatient provider clinical activity. Objective  The aim of our study was to validate audit-log based EHR times using observed EHR-times extracted from screen recordings of EHR usage in the inpatient setting. Methods  This study was conducted in a 36-bed pediatric intensive care unit (PICU) at Lucile Packard Children''s Hospital Stanford between June 11 and July 14, 2020. Attending physicians, fellow physicians, hospitalists, and advanced practice providers with ≥0.5 full-time equivalent (FTE) for the prior four consecutive weeks and at least one EHR session recording were included in the study. Citrix session recording player was used to retrospectively review EHR session recordings that were captured as the provider interacted with the EHR. Results  EHR use patterns varied by provider type. Audit-log based total EHR time correlated strongly with both observed total EHR time ( r  = 0.98, p  < 0.001) and observed active EHR time ( r  = 0.95, p  < 0.001). Each minute of audit-log based total EHR time corresponded to 0.95 (0.87–1.02) minutes of observed total EHR time and 0.75 (0.67–0.83) minutes of observed active EHR time. Results were similar when stratified by provider role. Conclusion  Our study found inpatient audit-log based EHR time to correlate strongly with observed EHR time among pediatric critical care providers. These findings support the use of audit-log based EHR-time as a surrogate measure for inpatient provider EHR use, providing an opportunity for researchers and other stakeholders to leverage EHR audit-log data in measuring clinical activity and tracking outcomes of workflow improvement efforts longitudinally and across provider groups.     

Randomized double‐blind study of botulinum toxin type B for sialorrhea in als patients

Twenty ALS patients with sialorrhea refractory to medical therapy were enrolled in this double‐blind, randomized study to receive either 2,500 U of botulinum toxin type B (BTxb) or placebo into the bilateral parotid and submandibular glands using electromyographic guidance. Patients who received BTxb reported a global impression of improvement of 82% at 2 weeks compared to 38% of those who received placebo (P < 0.05). This significant effect was sustained at 4 weeks. At 12 weeks, 50% of patients who received BTxb continued to report improvement compared to 14% of those who received placebo. There were no significant adverse events, including dysphagia, in the BTxb group, and there was no significant increase in the rate of decline of vital capacity. Muscle Nerve 39: 137–143, 2009     

The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus)

We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat (Myrmecobius fasciatus). Surprisingly, both of our thylacine sequences differ by 11%–15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples’ heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes.