312 research outputs found

    The Single Leg Squat Test: A “Top-Down” or “Bottom-Up” Functional Performance Test?

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    # Background Medial knee deviation (MKD) during the single leg squat test (SLST) is a common clinical finding that is often attributed to impairments of proximal muscular structures. Investigations into the relationship between MKD and the foot and ankle complex have provided conflicting results, which may impact clinicians’ interpretation of the SLST. # Purpose The purpose of this study was to compare ankle dorsiflexion range of motion (ROM) and foot posture in subjects that perform the SLST with MKD (fail) versus without MKD (pass). # Hypothesis There will be a difference in ankle dorsiflexion ROM and/or foot posture between healthy individuals that pass and fail the SLST for MKD. # Study Design Cross-sectional study. # Methods Sixty-five healthy, active volunteers (sex = 50 female, 15 male; age = 25.2 +/- 5.6 years; height = 1.7 +/- .1 m; weight = 68.5 +/- 13.5 kg) who demonstrated static balance and hip abductor strength sufficient for performance of the SLST participated in the study. Subjects were divided into pass and fail groups based on visual observation of MKD during the SLST. Foot Posture Index (FPI-6) scores and measures of non-weight bearing and weight bearing active ankle dorsiflexion (ROM) were compared. # Results There were 33 individuals in the pass group and 32 in the fail group. The groups were similar on age (p = .899), sex (p = .341), BMI (p = .818), and Tegner Activity Scale score (p = .456). There were no statistically significant differences between the groups on the FPI-6 (pass group mean = 2.5 +/- 3.9; fail group mean = 2.3 +/- 3.5; p = .599), or any of the measures of dorsiflexion range of motion (non-weight bearing dorsiflexion with knee extended: pass group = 6.9^o^ +/- 3.7^o^, fail group = 7.8^o^ +/- 3.0^o^; non-weight bearing dorsiflexion with knee flexed: pass group = 13.5^o^ +/- 5.6^o^, fail group = 13.9^o^ +/- 5.3^o^; weight bearing dorsiflexion: pass group = 42.7^o^ +/- 6.0^o^, 42.7^o^ +/- 8.3^o^, p = .611). # Conclusions Failure on the SLST is not related to differences in clinical measures of active dorsiflexion ROM or foot posture in young, healthy individuals. These findings suggest that clinicians may continue using the SLST to assess neuromuscular performance of the trunk, hip, and knee without ankle dorsiflexion ROM or foot posture contributing to results. # Level of Evidence Level 3

    Return to Hanging Rock: Lost Children in a Gothic Landscape

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    Using the philosophical position of phenomenology this article examines the ways in which ideas of wildness combine with Australian Gothic tropes such as the white colonial lost child and the bush as a haunted locale to compose key features of an Australian Ecogothic. Joan Lindsay’s enigmatic novel Picnic at Hanging Rock (1967) has prompted scholars such as Lesley Kathryn Hawkes to describe how in Australian literature for both adults and children ‘the environment is far more than a setting or backdrop against which the plot takes place’ (Hawkes, 2011,67). On St Valentine’s Day in 1900 three young Australian girls and their teacher disappear from a school picnic at the ancient site of Mount Macedon in Victoria. The analysis, which focuses on Lindsay’s posthumously published chapter eighteen (1987) examines how elements of the material, sensing world combine with the mythological or sacred to connect the human protagonists with the gothic landscape they inhabit. The resulting intersubjectivity problematizes colonial ideology and unsettles notions of national identity. Using the philosophical position of phenomenology this article examines the ways in which ideas of wildness combine with Australian Gothic tropes such as the white colonial lost child and the bush as a haunted locale to compose key features of an Australian Ecogothic. Joan Lindsay’s enigmatic novel Picnic at Hanging Rock (1967) has prompted scholars such as Lesley Kathryn Hawkes to describe how in Australian literature for both adults and children ‘the environment is far more than a setting or backdrop against which the plot takes place’ (Hawkes, 2011,67). On St Valentine’s Day in 1900 three young Australian girls and their teacher disappear from a school picnic at the ancient site of Mount Macedon in Victoria. The analysis, which focuses on Lindsay’s posthumously published chapter eighteen (1987) examines how elements of the material, sensing world combine with the mythological or sacred to connect the human protagonists with the gothic landscape they inhabit. The resulting intersubjectivity problematizes colonial ideology and unsettles notions of national identity

    Cognitive function prior to systemic therapy and subsequent well‐being in older breast cancer survivors: Longitudinal findings from the Thinking and Living with Cancer Study

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    ObjectiveTo investigate the relationships between self‐reported and objectively measured cognitive function prior to systemic therapy and subsequent well‐being outcomes over 24 months in older breast cancer survivors.MethodsData were from 397 women aged 60 to 98 diagnosed with non‐metastatic breast cancer in the Thinking and Living with Cancer Study recruited from 2010‐2016. Cognitive function was measured at baseline (following surgery, prior to systemic therapy) using neuropsychological assessments of attention, processing speed, and executive function (APE), learning and memory (LM), and the self‐reported FACT‐Cog scale. Well‐being was measured using the FACT‐G functional, physical, social, and emotional well‐being domain scales at baseline and 12 and 24 months later, scaled from 0 (low) to 100 (high). Linear mixed‐effects models assessed the relationships between each of baseline APE, LM, and FACT‐Cog quartiles with well‐being scores over 24 months, adjusted for confounding variables.ResultsAt baseline, older survivors in the lowest APE, LM, and FACT‐Cog score quartiles experienced poorer global well‐being than those in the highest quartiles. At 24 months, older survivors tended to improve in well‐being, and there were no differences according to baseline APE or LM scores. At 24 months, mean global well‐being was 80.3 (95% CI: 76.2‐84.3) among those in the lowest vs 86.6 (95% CI: 83.1‐90.1) in the highest FACT‐cog quartile, a clinically meaningful difference of 6.3 points (95% CI: 1.5‐11.1).ConclusionsAmong older breast cancer survivors, self‐reported, but not objective cognitive impairments, were associated with lower global well‐being over the first 2 years of survivorship.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155908/1/pon5376.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155908/2/pon5376_am.pd

    MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma

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    Renal carcinoma is a common and aggressive malignancy whose histopathogenesis is incompletely understood and that is largely resistant to cytotoxic chemotherapy. We present two mouse models of kidney cancer that recapitulate the genomic alterations found in human papillary (pRCC) and clear cell RCC (ccRCC), the most common RCC subtypes. MYC activation results in highly penetrant pRCC tumours (MYC), while MYC activation, when combined with Vhl and Cdkn2a (Ink4a/Arf) deletion (VIM), produce kidney tumours that approximate human ccRCC. RNAseq of the mouse tumours demonstrate that MYC tumours resemble Type 2 pRCC, which are known to harbour MYC activation. Furthermore, VIM tumours more closely simulate human ccRCC. Based on their high penetrance, short latency, and histologic fidelity, these models of papillary and clear cell RCC should be significant contributions to the field of kidney cancer research

    Evaluation of Pyridoacridine Alkaloids in a Zebrafish Phenotypic Assay

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    Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1–6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 ÎŒM. No phenotype other than death was observed for compounds 1–3, 5, 6

    Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring

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    Understanding the effects of environmental exposures on germline mutation rates has been a decades-long pursuit in genetics. We used next-generation sequencing and comparative genomic hybridization arrays to investigate genome-wide mutations in the offspring of male mice exposed to benzo(a)pyrene (BaP), a common environmental pollutant. We demonstrate that offspring developing from sperm exposed during the mitotic or post-mitotic phases of spermatogenesis have significantly more de novo single nucleotide variants (1.8-fold; P < 0.01) than controls. Both phases of spermatogenesis are susceptible to the induction of heritable mutations, although mutations arising from post-fertilization events are more common after post-mitotic exposure. In addition, the mutation spectra in sperm and offspring of BaP-exposed males are consistent. Finally, we report a significant increase in transmitted copy number duplications (P = 0.001) in BaP-exposed sires. Our study demonstrates that germ cell mutagen exposures induce genome-wide mutations in the offspring that may be associated with adverse health outcomes

    Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

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    Purpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (Δ4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores (P = .05) and those initiating hormonal therapy having lower LM scores at 12 months (P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only Δ4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant (P = .14), but scores were significantly lower for Δ4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than Δ4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures (P < .001); frailty was associated with baseline APE and self-reported decline (P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years

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    Background An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials. Objective To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling. Methods Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years. Results Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3–6 months. Interpretation Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting individuals with persisting impairment
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