Effects of Sex and Age on Quadriceps and Hamstring Strength and Flexibility in High School Basketball Athletes

BackgroundEccentric hamstring strength and hamstring/quadriceps strength ratios have been identified as modifiable risk factors of hamstring strains. Additionally, those strength and flexibility characteristics are commonly used as clinical tests to monitor progress of athletes with acute or chronic hamstring strains. Although hamstring strains are common among basketball athletes, normative values of knee strength and flexibility characteristics are scarce. Normative values for these athletes would be important in prevention and management of hamstring strains.PurposeTo establish quadriceps and hamstring isokinetic strength and flexibility values among high school basketball athletes and examine the effects of sex and age.Study DesignCross-sectional researchMethodsIsokinetic knee muscular strength (concentric quadriceps [QuadC], concentric hamstring [HamC], eccentric hamstring [HamE], and strength ratios ([HamC/QuadC and HamE/Quad]), flexibility of hip flexors and quadriceps during a Modified Thomas test, and flexibility of hip extensors and hamstring during passive straight leg raise (SLR) and passive knee extension (PKE) tests were measured. Effects of sex and age were analyzed using t-tests and analysis of variance, respectively with Bonferroni corrected post hoc tests (p≤0.01).ResultsA total of 172 high school basketball athletes (64 males/108 females; mean age (range): 15.7 (14-18) years old) participated in the study. Male athletes were significantly stronger than female athletes (QuadC: p<0.001; HamC: p<0.001) while no differences were observed in strength ratio (HamC/QuadC: p=0.759-0.816; HamE/QuadC: p=0.022-0.061). Among male athletes, a significant effect of age on quadriceps and hamstring strength was observed: older male athletes were stronger than younger male athletes. Contrarily, there were no effects of age on strength among female athletes. There were significant sex differences in quadriceps flexibility, SLR, and PKE (female athletes were more flexible; p=0.001-0.005) while no sex differences were found in hip flexor flexibility (p=0.105-0.164). There were no effects of age for any flexibility variables within male and female athletes (p=0.151-0.984).ConclusionThe current results provide normative values for hamstring strength and flexibility in high school basketball athletes. These normative values may further assist sports medicine specialists to develop screening tests, interventions, and return-to-sport criteria in this population.Level of Evidence3B     

Clinical outcome data for symptomatic breast cancer: the breast cancer clinical outcome measures (BCCOM) project

Background:

Data collection for screen-detected breast cancer in the United Kingdom is fully funded, which has led to improvements in clinical practice. However, data on symptomatic cancer are deficient, and the aim of this project was to monitor the current practice.

Methods:

A data set was designed together with surrogate outcome measures to reflect best practice. Data from cancer registries initially required the consent of clinicians, but in the third year anonymised data were available.

Results:

The quality of data improved, but this varied by region and only a third of the cases were validated by clinicians. Regional variations in mastectomy rates were identified, and one-third of patients who underwent conservative surgery for the treatment invasive breast cancer were not recorded as receiving radiotherapy.

Conclusion:

National data are essential to ensure that all patients receive appropriate treatment for breast cancer, but variations still exist in the United Kingdom and further improvement in data capture is required.     

Recombinant human VEGF165b protein is an effective anti-cancer agent in mice

Tumour growth is dependent on angiogenesis, the key mediator of which is vascular endothelial growth factor-A (VEGF-A). VEGF-A exists as two families of alternatively spliced isoforms - pro-angiogenic VEGF(xxx) generated by proximal, and anti-angiogenic VEGF(xxx)b by distal splicing of exon 8. VEGF(165)b inhibits angiogenesis and is downregulated in tumours. Here, we show for the first time that administration of recombinant human VEGF(165)b inhibits colon carcinoma tumour growth and tumour vessel density in nude mice, with a terminal plasma half-life of 6.2h and directly inhibited angiogenic parameters (endothelial sprouting, orientation and structure formation) in vitro. Intravenous injection of (125)I-VEGF(165)b demonstrated significant tumour uptake lasting at least 24h. No adverse effects on liver function or haemodynamics were observed. These results indicate that injected VEGF(165)b was taken up into the tumour as an effective anti-angiogenic cancer therapy, and provide proof of principle for the development of this anti-angiogenic growth factor splice isoform as a novel cancer therapy.     

Vascular endothelial growth factor (VEGF)-A165b is a weak in vitro agonist for VEGF receptor-2 due to lack of coreceptor binding and deficient regulation of kinase activity

Vascular endothelial growth factor (VEGF)-A165b is a COOH-terminal splice variant of VEGF-A that has been implicated in negative regulation of angiogenesis. We compared the properties of VEGF-A165b with those of VEGF-A121, VEGF-A145, and VEGF-A165. Induction of tyrosine phosphorylation sites in VEGFR-2 differed between the VEGF ligands as determined by tryptic phosphopeptide mapping and by use of phosphosite-specific antibodies. VEGF-A165b was considerably poorer in inducing phosphorylation of the positive regulatory site Y1052 in VEGFR-2. Whereas this did not affect activation of VEGFR-2 in vitro, we show that VEGF-A165b failed to induce vasculogenesis and sprouting angiogenesis in differentiating embryonic stem cells and vascularization of s.c. Matrigel plugs. In addition, the ability of the different VEGF ligands to induce angiogenesis correlated with their abilities to bind the VEGF coreceptor neuropilin 1 (NRP1). Our data indicate that loss of VEGFR-2/NRP1 complex formation and Y1052 phosphorylation contribute to the lack of angiogenic properties of VEGF-A165b.     

The Ubiquitin-Proteasome Reporter GFPu Does Not Accumulate in Neurons of the R6/2 Transgenic Mouse Model of Huntington's Disease

Impairment of the ubiquitin-proteasome system (UPS) has long been considered an attractive hypothesis to explain the selective dysfunction and death of neurons in polyglutamine disorders such as Huntington's disease (HD). The fact that inclusion bodies in HD mouse models and patient brains are rich in ubiquitin and proteasome components suggests that the UPS may be hindered directly or indirectly by inclusion bodies or their misfolded monomeric or oligomeric precursors. However, studies into UPS function in various polyglutamine disease models have yielded conflicting results, suggesting mutant polyglutamine tracts may exert different effects on the UPS depending on protein context, expression level, subcellular localisation and cell-type. To investigate UPS function in a well-characterised mouse model of HD, we have crossed R6/2 HD mice with transgenic UPS reporter mice expressing the GFPu construct. The GFPu construct comprises GFP fused to a constitutive degradation signal (CL-1) that promotes its rapid degradation under conditions of a healthy UPS. Using a combination of immunoblot analysis, fluorescence and immunofluorescence microscopy studies, we found that steady-state GFPu levels were not detectably different between R6/2 and non-R6/2 brain. We observed no correlation between inclusion body formation and GFPu accumulation, suggesting no direct relationship between protein aggregation and global UPS inhibition in R6/2 mice. These findings suggest that while certain branches of the UPS can be impaired by mutant polyglutamine proteins, such proteins do not necessarily cause total blockade of UPS-dependent degradation. It is therefore likely that the relationship between mutant polyglutamine proteins and the UPS is more complex than originally anticipated.     

Health Care Equity in the Use of Advanced Analytics and Artificial Intelligence Technologies in Primary Care

The integration of advanced analytics and artificial intelligence (AI) technologies into the practice of medicine holds much promise. Yet, the opportunity to leverage these tools carries with it an equal responsibility to ensure that principles of equity are incorporated into their implementation and use. Without such efforts, tools will potentially reflect the myriad of ways in which data, algorithmic, and analytic biases can be produced, with the potential to widen inequities by race, ethnicity, gender, and other sociodemographic factors implicated in disparate health outcomes. We propose a set of strategic assertions to examine before, during, and after adoption of these technologies in order to facilitate healthcare equity across all patient population groups. The purpose is to enable generalists to promote engagement with technology companies and co-create, promote, or support innovation and insights that can potentially inform decision-making and health care equity.

Primary care has a critical role to play in ensuring that mission-driven values aimed at eliminating health care disparities are prioritized in the development, selection, clinical implementation, and use of advanced analytics and AI technologies. Because the application of these technologies in primary care is in its infancy, primary care professionals have a unique opportunity to guide the growth of fair, transparent, and ethical AI and analytics applications that embody health equity principles that meet the needs of diverse populations.Today, clinical decision-making in primary care is influenced by the ongoing integration of advanced analytics and AI technologies into the practice of medicine.¹ Examples include patient risk stratification, predictive modeling for disease progression,^2,3 decision-support applications,^4,5 and population health management tools for cancer screenings,^6,7 diabetes,^8,9 cardiovascular disease,^10–12 and other chronic disease conditions.¹³ These and other similar tools may or may not explicitly address the needs of diverse patient populations in primary care. Unless explicit strategies are used to promote equity, advanced analytics may inadvertently perpetuate inequities in primary care delivery, such as the use of algorithms that erroneously treat race categories as biological rather than social attributes in clinical decision making.¹⁴The importance of articulating equity as a specific goal for integrating AI into care is described in the 2019 National Academy of Medicine (NAM) report, Artificial Intelligence in Health Care: The Hope, The Hype, The Promise, The Peril. The report describes a quintuple aim to improve population health, reduce costs, improve the patient experience, promote care team well-being and achieve health care equity.¹⁵ Specifically, the report suggests that embracing health care equity would challenge a siloed approach to health care by addressing the diversity of patient needs using varied sources of data that include social determinants of health and psychosocial risk factors (Fig. ​(Fig.1).1). Equity, integral to the quintuple aim, would also require engaging diverse stakeholders to inform the design of AI applications and to monitor the impact of these technologies. The NAM report underscores the need for explicit strategies to actively embrace health care equity; without such strategies, AI applications are likely to reflect human biases in ways that will widen inequities by race/ethnicity, gender identity, sexual orientation, disability status, age, social class, geography, and other dimensions of social identity.^15,16 Open in a separate windowFigure 1Building on the quintuple aims of equity and inclusion in health and healthcare (National Academy of Medicine).¹⁴Indifference to technology and passive acceptance of biased tools pose risks to health care equity among diverse groups. To prevent this, we must be willing to articulate the priorities for successful AI and advanced analytics implementation and adopt strategies and processes that lead to equitable outcomes. To further these aims, we propose the following series of questions that should be considered before and during the adoption of an AI technology or advanced analytic strategy into practice. First, what needs of diverse patient populations can be better served by applying advanced analytics and AI technology? How can novel and diverse data sources be leveraged to enhance equity in AI implementations? How can patients and community members engage with stakeholders involved in shaping the use of AI in the delivery of health care? And finally, how are principles of diversity and inclusion reflected among those who are involved in the development, selection, and use of technology solutions to enable equitable health care?     

Practical approach to determining costs and frequency of adverse drug events in a health care network.

The frequency, preventability, severity, root causes, and projected costs of adverse drug events (ADEs) occurring after or causing admission to a four-hospital integrated academic health network were studied. The sample included all admissions during a 53-day study period. Events were identified through daily record review of a random patient sample, computerized flags, and self-reporting. A case review committee validated the occurrence, classification, and root causes of the events. Additional length of stay and costs associated with ADEs were analyzed by using a case-control, multiple linear regression model. The estimated ADE rate during hospitalization was 4.2 events per 100 admissions, with a cost of $2162 per ADE. In addition, 3.2% of admissions were caused by ADEs, with an associated cost of $6685 per event. Fifteen percent of hospital ADEs and 76% of ADEs causing admission were judged preventable. The annual cost to the organization for events occurring during hospitalization was $1.7 million, and the cost of preventable ADEs was $260,000, while the projected costs of preventable ADEs causing admission were $3.8 million. The rate of admissions to the mental health center caused by ADEs was higher than for other settings at 13.6%, with a cost of preventable ADEs of $1.3 million. Patient noncompliance was judged to be the cause of the 69% of the ADEs causing admission. Seventy-one percent of the serious medication errors occurred at the prescribing stage of the medication-use process. ADEs were frequent, costly, and often preventable and resulted in many admissions to a mental health center.     

A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-kinase/Akt in colon carcinoma cells.

A major obstacle to successful treatment of colorectal cancer is chemotherapy resistance. Enhanced expression of variant CD44 isoforms has been associated with aggressive tumor behavior, prompting the question of whether signaling from this receptor might modulate drug sensitivity. Activation of variant CD44 in colon carcinoma cell lines triggered resistance to the drug 1,3-bis(2-chloroethyl)-1-nitrosurea. Resistance was induced by monoclonal antibodies directed against epitopes independent of the hyaluronate-binding region but was not triggered by identical treatment of a carcinoma line expressing the standard CD44 isoform. We observed that variant CD44 produced activation of the src-family tyrosine kinase lyn. Moreover, overexpression of dominant-active lyn recapitulated chemoresistance via a pathway shown to involve activation of phosphoinositide 3-kinase and Akt. These results establish a novel role for CD44 in determining survival of colon carcinoma cells through lyn kinase and Akt. The ability to suppress apoptosis might play a critical role in the onset and development of colorectal malignancies.