A prospective study of risk factors for hamstring injury in Australian football league players.

This study aimed to explore the association between hamstring strength, age and lower limb soft tissue injury history and subsequent hamstring injury among Australian Football League (AFL) players. This prospective cohort study recruited 125 players from three professional AFL teams. Eccentric knee flexor strength was assessed while performing the Nordic hamstring exercise in pre-season, and injury data were collected retrospectively (hamstring, groin, calf, quadriceps and knee), and prospectively (hamstring injuries) for one AFL playing season. Fourteen players (11%) sustained a hamstring injury in the subsequent playing season. Nordic strength was not significantly associated with future hamstring injury (Odds Ratio (OR) 1.9, p = 0.36), whereas player age greater than 25 years (OR = 2.9, p < 0.05), report of a hamstring injury within the previous year (OR = 3.7, p = 0.01), or greater than 1-year (OR = 3.6, p = 0.01), a previous groin (OR = 8.6, p < 0.01) or calf injury (OR = 4.6, p = 0.01) were factors significantly associated with subsequent hamstring injury. Based on these findings, increasing age and previous hamstring, groin and calf injury are all associated with an elevated risk of subsequent hamstring injury in AFL players.

Hospital Outbreak of Pulmonary and Cutaneous Zygomycosis due to Contaminated Linen Items From Substandard Laundry.

BACKGROUND: Healthcare laundry-related infection is rare, and pulmonary zygomycosis due to contaminated hospital linens has never been reported. METHODS: We reported an outbreak investigation of zygomycosis in a university-affiliated teaching hospital. Air samplers, sponge swabs and Replicate Organism Detection and Counting (RODAC) contact plates were used for environmental sampling. The fungal isolates from clinical and environmental samples were identified by morphology, MALDI-TOF MS, and ITS1-5.8S-ITS2 rRNA gene cluster sequencing. RESULTS: From 2 June 2015 to 18 July 2015, 6 immunosuppressed patients developed pulmonary (n = 4) and/or cutaneous (n = 3) infection by a spore-forming mold, Rhizopus microsporus, through direct inhalation and skin contact of contaminated linen items supplied by a designated laundry. Seventy (27.8%) of 252 freshly laundered clothing and 15 (3.4%) of 443 nonclothing laundered linen items (pillow case, bed sheet, draw sheet) were contaminated by R. microsporus, which was significantly higher than those from other hospital laundries (0%, n = 451; P < .001) supplying linen to hospitals with no cases of zygomycosis reported during the same period. The fungal isolates from patients and linens were phylogenetically related. In sum, 61% of environmental samples and 100% of air samples at the designated laundry were also positive for zygomycetes, suggesting heavy environmental contamination. RODAC contact plates revealed mean total viable bacteria counts of freshly laundered items (1028 ± 611 CFU/100 cm(2)) far exceeded the "hygienically clean" standard of 20 CFU/100 cm(2) set by the US healthcare textile certification requirement. CONCLUSIONS: Suboptimal conditions of washing, drying, and storage contributed to the massive linen contamination and the outbreak of zygomycosis.

Disseminated Infections with Talaromyces marneffei in Non-AIDS Patients Given Monoclonal Antibodies against CD20 and Kinase Inhibitors.

Infections with the fungus Talaromyces (formerly Penicillium) marneffei are rare in patients who do not have AIDS. We report disseminated T. marneffei infection in 4 hematology patients without AIDS who received targeted therapy with monoclonal antibodies against CD20 or kinase inhibitors during the past 2 years. Clinicians should be aware of this emerging complication, especially in patients from disease-endemic regions.

Subcutaneous phaeohyphomycosis in a patient with IgG4-related sclerosing disease caused by a novel ascomycete, Hongkongmyces pedis gen. et sp. nov.: first report of human infection associated with the family Lindgomycetaceae.

No members of the freshwater ascomycetes family Lindgomycetaceae have been associated with human infections. We isolated a mould (HKU35(T)) from the biopsy specimen of a patient with invasive foot infection and underlying immunoglobulin G4-related sclerosing disease. Histology showed florid, suppurative, granulomatous inflammation in the dermis, with central microabscess formation surrounded by epithelioid histiocytes, scattered giant cells, and a small number of lymphocytes. A Grocott stain revealed fungal elements in the center of the lesion. On Sabouraud glucose agar, HKU35(T) grew as gray and velvety colonies. Among the members of the family Lindgomycetaceae, HKU35(T) was the only strain that grew at 37°C. Microscopically, only sterile mycelia, but no fruiting bodies, were observed. HKU35(T) was susceptible to itrazonazole, voriconazole, and posaconazole, which was in line with the patient's clinical response to itraconazole treatment. Internal transcribed spacer and partial 18S nuclear rDNA (nrDNA), 28S nrDNA, ß-tubulin gene, and EF1α gene sequencing showed that HKU35(T) occupied a unique phylogenetic position, most closely related to but distinct from members of the genera Clohesyomyces and Lindgomyces. We propose a new genus and species, Hongkongmyces pedis gen. et sp. nov., to describe this fungus, which belongs to the family Lindgomycetaceae in the orderPleosporales of class Dothideomycetes. This case also represents the first report of human infection associated with the family Lindgomycetaceae.

Evaluation of Corrosion Performance of AZ31 Mg Alloy in Physiological and Highly Corrosive Solutions.

Resorbable Mg and Mg alloys have gained significant interest as promising biomedical materials. However, corrosion of these alloys can lead to premature reduction in their mechanical properties, and therefore their corrosion rate needs to be controlled. The aim of this study is to select an appropriate environment where the effects of coatings on the corrosion rate of the underlying Mg alloy can be discerned and measured in a relatively short time period. The corrosion resistance of uncoated AZ31 alloy in different solutions [Hank's Balanced Salt Solution, 1× phosphate buffered solution (PBS), 4× PBS, 0.9%, 3.5%, and 5 M sodium chloride (NaCl)] was determined by measuring the weight loss over a 2 week period. Upon exposure to physiological solutions, the uncoated AZ31 alloys exhibited a variable weight increase of 0.4 ± 0.4%. 3.5% and 5 M NaCl solutions led to 0.27 and 9.7 mm/year corrosion rates, respectively, where the compositions of corrosion products from AZ31 in all saline solutions were similar. However, the corrosion of the AZ31 alloy when coated by electrochemical oxidation with two phosphate coatings, one containing fluorine (PF) and another containing both fluorine and silica (PFS), showed 0.3 and 0.25 mm/year corrosion rates, respectively. This is more than 30 times lower than that of the uncoated alloy (7.8 mm/year), making them promising candidates for corrosion protection in severe corrosive environments. Cross-sections of the samples showed that the coatings protected the alloy from corrosion by preventing access of saline to the alloy surface, and this was further reinforced by corrosion products from both the alloy and the coatings forming an additional barrier. The information in this paper provides a methodology for evaluating the effects of coatings on the rate of corrosion of magnesium alloys.

Comparison of four in vitro test methods to assess nucleus pulposus replacement device expulsion risk.

Background: Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula-hoop (Protocol 1), adapted hula-hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing. Methods: Nucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols. Results: NRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response. Conclusions: Adapted hula-hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.

Mycobacterium abscessus bacteremia after receipt of intravenous infusate of cytokine-induced killer cell therapy for body beautification and health boosting.

BACKGROUND: We report the first series of Mycobacterium abscessus bacteremia after cytokine-induced killer cell therapy for body beautification and health boosting. METHODS: The clinical manifestations, laboratory and radiological investigations, cytokine/chemokine profiles, and outcomes were described and analyzed. RESULTS: Four patients were admitted, and 3 patients had septic shock. Chest radiographs showed pulmonary infiltrates in all patients. Three patients developed peripheral gangrene, and 1 patient required lower limb and finger amputations. Patient 1 also developed disseminated infection including meningitis and urinary tract infection. Postmortem examination of patient 1 showed focal areas of pulmonary hemorrhage and diffuse alveolar damage, splenic infarct, adrenal necrosis, and hemorrhage, and acid-fast bacilli (AFB) were seen in the lung, liver, kidney, and adrenal gland. Patient 2 developed inguinal granulomatous lymphadenitis about 40 days after onset of lower limb gangrene. Wedge-shaped pulmonary infarcts were found in patient 3, and retinitis and subcutaneous lesions developed in patient 4. Patients in septic shock had dysregulated cytokine/chemokine profiles. Patient 4 with relatively milder presentation had increasing levels of interleukin 17 and cytokines in the interferon-γ/interleukin 12 pathway. All survivors required prolonged intravenous antibiotics. Blood cultures grew M. abscessus for all patients, and admission peripheral blood smear revealed AFB for 3 patients. Mycobacterium abscessus was also isolated from respiratory specimens (2 patients), urine (1 patient), and cerebrospinal fluid (1 patient). Time to initial blood culture positivity (patients 1, 2, and 3: ≤52 hours; patient 4: 83 hours) appeared to correlate with disease severity. CONCLUSIONS: Empirical coverage for rapidly growing mycobacteria should be considered in patients with sepsis following cosmetic procedures.

Reactive and infective dermatoses associated with adult-onset immunodeficiency due to anti-interferon-gamma autoantibody: Sweet's syndrome and beyond.

Immunodeficiency due to anti-interferon-gamma autoantibody (anti-IFN-γ autoAb) is an emerging adult-onset immunodeficiency syndrome predominantly found in Southeast Asians. It is associated with severe or disseminated infections caused by non-tuberculous mycobacteria (NTM) and other opportunistic pathogens. We describe 3 patients with anti-IFN-γ autoAb who developed reactive and infective dermatoses, and thoroughly review the existing literature on dermatoses associated with the immunodeficiency syndrome. Case 1 developed Sweet's syndrome associated with Mycobacterium chelonae lymphadenitis and penicilliosis. Case 2 suffered from multiple episodes of lobular panniculitis during recurrent infections by NTM, Penicillium marneffei and Burkholderia pseudomallei. Both cases responded to immunomodulating agents including corticosteroid and non-steroidal anti-inflammatory drugs. Case 3 had direct skin invasion by M. chelonae and responded to prolonged anti-mycobacterial therapy. A novel working algorithm is proposed for the diagnosis and treatment of these patients who may be encountered by the dermatologist and histopathologist in clinical practice.

An in vitro comparison of three nucleus pulposus removal techniques for partial intervertebral disc replacement: An ultra-high resolution MRI study.

Background: Nuclectomy, also known as nucleotomy, is a percutaneous surgical procedure performed to remove nucleus material from the center of the disc. Multiple techniques have been considered to perform a nuclectomy, however, the advantages and disadvantages of each are not well understood. Aims: This in vitro biomechanical investigation on human cadaveric specimens aimed to quantitatively compare three nuclectomy techniques performed using an automated shaver, rongeurs, and laser. Material & Methods: Comparisons were made in terms of mass, volume and location of material removal, changes in disc height, and stiffness. Fifteen vertebra-disc-vertebra lumbar specimens were acquired from six donors (40 ± 13 years) and split into three groups. Before and after nucleotomy axial mechanical tests were performed and T2-weighted 9.4T MRIs were acquired for each specimen. Results: When using the automated shaver and rongeurs similar volumes of disc material were removed (2.51 ± 1.10% and 2.76 ± 1.39% of the total disc volume, respectively), while considerably less material was removed using the laser (0.12 ± 0.07%). Nuclectomy using the automated shaver and rongeurs significantly reduced the toe-region stiffness (p = 0.036), while the reduction in the linear region stiffness was significant only for the rongeurs group (p = 0.011). Post-nuclectomy, 60% of the rongeurs group specimens showed changes in the endplate profile while 40% from the laser group showed subchondral marrow changes. Discussion: From the MRIs, homogeneous cavities were seen in the center of the disc when using the automated shaver. When using rongeurs, material was removed non-homogeneously both from the nucleus and annulus regions. Laser ablation formed small and localized cavities suggesting that the technique is not suitable to remove large volumes of material unless it is developed and optimized for this application. Conclusion: The results demonstrate that both rongeurs and automated shavers can be used to remove large volumes of NP material but the reduced risk of collateral damage to surrounding tissues suggests that the automated shaver may be more suitable.

Quantifying internal intervertebral disc strains to assess nucleus replacement device designs: a digital volume correlation and ultra-high-resolution MRI study.

Introduction: Nucleus replacement has been proposed as a treatment to restore biomechanics and relieve pain in degenerate intervertebral discs (IVDs). Multiple nucleus replacement devices (NRDs) have been developed, however, none are currently used routinely in clinic. A better understanding of the interactions between NRDs and surrounding tissues may provide insight into the causes of implant failure and provide target properties for future NRD designs. The aim of this study was to non-invasively quantify 3D strains within the IVD through three stages of nucleus replacement surgery: intact, post-nuclectomy, and post-treatment. Methods: Digital volume correlation (DVC) combined with 9.4T MRI was used to measure strains in seven human cadaveric specimens (42 ± 18 years) when axially compressed to 1 kN. Nucleus material was removed from each specimen creating a cavity that was filled with a hydrogel-based NRD. Results: Nucleus removal led to loss of disc height (12.6 ± 4.4%, p = 0.004) which was restored post-treatment (within 5.3 ± 3.1% of the intact state, p > 0.05). Nuclectomy led to increased circumferential strains in the lateral annulus region compared to the intact state (-4.0 ± 3.4% vs. 1.7 ± 6.0%, p = 0.013), and increased maximum shear strains in the posterior annulus region (14.6 ± 1.7% vs. 19.4 ± 2.6%, p = 0.021). In both cases, the NRD was able to restore these strain values to their intact levels (p ≥ 0.192). Discussion: The ability of the NRD to restore IVD biomechanics and some strain types to intact state levels supports nucleus replacement surgery as a viable treatment option. The DVC-MRI method used in the present study could serve as a useful tool to assess future NRD designs to help improve performance in future clinical trials.

A novel Dirofilaria species causing human and canine infections in Hong Kong.

Dirofilariasis is globally the commonest manifestation of zoonotic filariasis. We report the detection of a novel canine species causing human and canine dirofilariasis in Hong Kong. Three human cases occurring over 10 months were identified, one presenting with cervical lymphadenopathy, one with an abdominal subcutaneous mass, and one with a subconjunctival nodule. Transected worms recovered from the resected abdominal subcutaneous mass were morphologically compatible with Dirofilaria. The cox1 gene sequences of the three human isolates were identical; however, they were only 96.2% and 89.3% identical to the cox1 gene of Dirofilaria repens and Dirofilaria immitis, respectively. Sequencing of the 18S-ITS1-5.8S gene cluster was successful in the intact worm, and the nucleotide sequences were 94.0% and 94.9% identical to those of D. repens and D. immitis, respectively. Screening of the blood samples from 200 dogs and 100 cats showed the presence of the novel Dirofilaria species in 3% (6/200) of the dogs' but none of the cats' blood samples. Nucleotide sequences of the cox1 gene and 18S-ITS1-5.8S gene clusters of the dogs' samples were identical to those in the human samples. The sera of canines infected by this novel Dirofilaria species were negative when tested with the SNAP 4Dx D. immitis detection kit, except in the case of dogs with a mixed infection with D. immitis as detected by PCR. The results from this study suggest that this novel Dirofilaria species is a cause of filarial infection in humans and dogs in Hong Kong. We propose to name this Dirofilaria species "Candidatus Dirofilaria hongkongensis."

17q12 microdeletion syndrome: three patients illustrating the phenotypic spectrum.

Deletions of 17q12 are associated with renal cysts and maturity onset diabetes of the young, and have also been identified in women with reproductive tract anomalies due to Mullerian aplasia. Although initially identified in patients with normal cognitive ability, some patients with this recurrent microdeletion syndrome have learning problems. We identified a 17q12 microdeletion in three patients with renal cystic disease by array comparative genomic hybridization and the phenotypic spectrum of the 17q12 microdeletion syndrome is illustrated by the description of these patients. Of two patients who are old enough to be assessed, one has significant speech delay, autism spectrum disorder, and mild learning difficulty, while the other patient has only mild speech delay. This highlights the variability of cognitive involvement in this condition. The third patient presented with Alagille syndrome-like features in the neonatal period. All three patients had transient hypercalcemia in the neonatal period, a finding that has not previously been described in this condition. Moreover, two patients have mild or no dysmorphism, while one displays striking facial dysmorphism in addition to minor congenital anomalies. We suggest that while patients with 17q12 microdeletion syndrome can present with type 2 diabetes or renal cysts without any dysmorphic features, a subgroup may have dysmorphic features or present with neonatal cholestasis. Transient neonatal hypercalcemia may be a feature of this microdeletion syndrome.

Nordic strength and history of hamstring injury in Australian Football League players.

OBJECTIVES: Compare hamstring strength between Australian Football League (AFL) players with and without a prior hamstring injury and determine the effect of the number of previous hamstring injuries, time since the last injury, and injury severity, on hamstring strength. DESIGN: Cross-sectional, retrospective. SETTING: AFL clubs. PARTICIPANTS: 124 AFL players. MAIN OUTCOME MEASURES: Bilateral hamstring strength was assessed on a Nordbord (Vald Performance) during the Nordic Hamstring Exercise. Self-reported questionnaires were used to record previous hamstring injuries. Players were categorized into No Injury or Hamstring Injury groups. Previously injured players were subgrouped based on number of prior hamstring injuries (single or multiple), time since the last hamstring injury (≤1 or > 1-year ago), and hamstring injury severity (≤3 or > 3 matches missed). RESULTS: 19 hamstring injuries were reported. Hamstring strength was not different between players with and without a history of hamstring injury when assessed in absolute (N) or relative (i.e., N.kg-1) terms. No differences in strength were detected between hamstring injury subgroups when assessed in absolute or relative terms. CONCLUSIONS: AFL players that experienced a previous hamstring injury did not exhibit deficits in hamstring strength relative to their uninjured limb or players without a previous hamstring injury.

The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS).

By careful analysis of experimental X-ray ligand crystallographic protein data across several inhibitor series we have discovered a novel, potent and selective series of iNOS inhibitors exemplified by compound 8.

Lower limb joint position sense and prospective hamstring injury.

BACKGROUND: The hamstrings remain the most injured muscle group within the Australian Football League (AFL). OBJECTIVE: To investigate preseason measures of hip and knee joint position sense (JPS) and prospective hamstring injury in AFL players. DESIGN: Prospective cohort study. METHODS: A total of 116 AFL players were recruited for this study. JPS was assessed with 3-D sensors using mono-articular hip (45° flexion and 0°) and knee (90° and 45° flexion) joint reproduction tests conducted in the preseason. Hamstring injury data were collected prospectively in the following AFL season. Wilcoxon-signed rank tests were used to assess between the subsequently injured and uninjured limbs. Mann-Whitney U tests were used to assess between group differences and odds ratio (OR) were used to predict players at risk of hamstring injury. RESULTS: Eight players with JPS data sustained a season hamstring injury and 108 players did not. JPS was not significantly different between the subsequently injured and uninjured limbs (all P values > 0.05). No significant differences for any JPS measure were found between the subsequently injured and uninjured players (all p's > 0.05). ORs did not achieve significance for AE (2.7, p = 0.21) or for RMSE (OR = 1.9, p = 0.44). CONCLUSION: Lower limb JPS measures were not predictive of hamstring injury in AFL players.

Guaraná's Journey from Regional Tonic to Aphrodisiac and Global Energy Drink.

Guaraná (Paullinia cupana H.B.K., Sapindaceae) is a rainforest vine that was domesticated in the Amazon for its caffeine-rich fruits. Guaraná has long been used as a tonic and to treat various disorders in Brazil and abroad and became a national soda in Brazil about a century ago. In the last two decades or so, guaraná has emerged as a key ingredient in various 'sports' and energy drinks as well as concoctions that allegedly boost one's libido. For some time, guaraná's high caffeine content was thought to be a detriment because of health concerns about excessive intake of caffeine-rich drinks. But it is precisely this quality, and the fact that it has a mysterious name and comes from an exotic land, that has propelled guaraná into a global beverage.

Profiling of Circulating Free DNA Using Targeted and Genome-wide Sequencing in Patients with SCLC.

INTRODUCTION: SCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option for patient stratification and response monitoring. METHODS: We applied whole genome next-generation sequencing to circulating free DNA (cfDNA) from 39 patients with limited-stage (LS) SCLC and 30 patients with extensive-stage SCLC to establish genome-wide copy number aberrations and also performed targeted mutation analysis of 110 SCLC associated genes. Quantitative metrics were calculated for copy number aberrations, including percent genome amplified (PGA [the percentage of genomic regions amplified]), Z-score (a measure of standard deviation), and Moran's I (a measure of spatial autocorrelation). In addition CellSearch, an epitope-dependent enrichment platform, was used to enumerate circulating tumor cells (CTCs) from a parallel blood sample. RESULTS: Genome-wide and targeted cfDNA sequencing data identified tumor-related changes in 94% of patients with LS SCLC and 100% of patients with extensive-stage SCLC. Parallel analysis of CTCs based on at least 1 CTC/7.5 mL of blood increased tumor detection frequencies to 95% for LS SCLC. Both CTC counts and cfDNA readouts correlated with disease stage and overall survival. CONCLUSIONS: We demonstrate that a simple cfDNA genome-wide copy number approach provides an effective means of monitoring patients through treatment and show that targeted cfDNA sequencing identifies potential therapeutic targets in more than 50% of patients. We are now incorporating this approach into additional studies and trials of targeted therapies.

Automated, scalable culture of human embryonic stem cells in feeder-free conditions.

Large-scale manufacture of human embryonic stem cells (hESCs) is prerequisite to their widespread use in biomedical applications. However, current hESC culture strategies are labor-intensive and employ highly variable processes, presenting challenges for scaled production and commercial development. Here we demonstrate that passaging of the hESC lines, HUES7, and NOTT1, with trypsin in feeder-free conditions, is compatible with complete automation on the CompacT SelecT, a commercially available and industrially relevant robotic platform. Pluripotency was successfully retained, as evidenced by consistent proliferation during serial passage, expression of stem cell markers (OCT4, NANOG, TRA1-81, and SSEA-4), stable karyotype, and multi-germlayer differentiation in vitro, including to pharmacologically responsive cardiomyocytes. Automation of hESC culture will expedite cell-use in clinical, scientific, and industrial applications.

Analysis of circulating cell-free DNA identifies KRAS copy number gain and mutation as a novel prognostic marker in Pancreatic cancer.

Serial biopsy of pancreatic ductal adenocarcinoma (PDAC), to chart tumour evolution presents a significant challenge. We examined the utility of circulating free DNA (cfDNA) as a minimally invasive approach across a cohort of 55 treatment-naïve patients with PDAC; 31 with metastatic and 24 with locally advanced disease. Somatic mutations in cfDNA were detected using next generation sequencing in 15/24 (62.5%) and 27/31 (87%) of patients with locally advanced and metastatic disease, respectively. Copy number changes were detected in cfDNA of 10 patients of whom 7 exhibited gain of chromosome 12p harbouring KRAS as well as a canonical KRAS codon 12 mutation. In multivariable Cox Regression analysis, we show for the first time that patients with KRAS copy number gain and KRAS mutation have significantly worse outcomes, suggesting that this may be linked to PDAC progression. The simple cfDNA assay we describe will enable determination of the presence of KRAS copy number gain and KRAS mutations in larger studies and clinical trials.