IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway.

BACKGROUND: Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated. METHODS: Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan-Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry. RESULTS: Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin-a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes-reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin. CONCLUSIONS: The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.

The Cleft Lip Education with Augmented Reality (CLEAR) VR Phase 2 Trial: A Pilot Randomized Crossover Trial of a Novel Patient Information Leaflet.

BACKGROUND: The Cleft Lip Education with Augmented Reality (CLEAR) project centers around the use of augmented reality (AR) in patient leaflets, as a visual means to overcome the "health literacy" gap. This trial followed Virtual Reality (VR CORE) guidelines for VR Phase 2 (Pilot) trials. METHODS: Participants included families of children treated for Cleft Lip and Palate at the Royal Hospital for Children, Glasgow. Interventions were AR leaflet or Traditional Leaflet. Objectives were to calculate sample sizes, assess outcome instruments, trial design, and acceptability to patients. Primary outcome measure was Mental Effort Rating Scale, and secondary outcomes were Patient Satisfaction (Visual Analogue Scale), Usefulness Scale for Patient Information Material (USE) scale, and Instructional Materials Motivation Survey (IMMS). Randomization was by block randomization. The trial was single blinded with assessors blinded to group assignment. RESULTS: 12 Participants were randomized, with crossover design permitting analysis of 12 per group. Primary outcome with Mental Effort Rating Scale indicated higher mental effort with Traditional compared to AR Leaflet (4.75 vs 2.00, P = .0003). Secondary outcomes for Satisfaction were Traditional 54.50 versus AR 93.50 (P = .0001); USE scale 49.42 versus 74.08 (P = .0011); and IMMS 112.50 versus 161.75 (P = .0003). Subjective interviews noted overwhelmingly positive patient comments regarding the AR leaflet. Outcome instruments and trial design were acceptable to participants. No harms were recorded. CONCLUSIONS: The CLEAR pilot trial provides early evidence of clinical efficacy of AR leaflets in patient education. It is hoped that this will provide a future paradigm shift in the way patient education is delivered.

Food and beverage advertising in Hong Kong mass transit railway stations.

OBJECTIVES: To examine the extent and characteristics of food and beverage (F&B) promotion in Hong Kong mass transit railway (MTR) stations in districts with different socioeconomic statuses (SES) and school density. DESIGN: All advertisements located in the eight selected MTR stations were recorded by photographs or videos, and classified into F&B and non-F&B. The percentage of F&B advertisements and unhealthy F&B being promoted, and common persuasive marketing strategies used in F&B advertisements were compared between low v. high SES districts and school zones v. non-school zones. SETTING: MTR stations in Hong Kong. PARTICIPANTS: Not applicable. RESULTS: Of the 8064 advertisements documented, 861 (10·7 %) were F&B advertisements, promoting 1860 F&B items. More than half of the these were unhealthy foods. Stations in high SES districts or school zones tend to advertise more unhealthy items (high v. low SES: 55·8 v. 50·8 %, P = 0·049; school v. non-school: 60·8 v. 49·3 %, P < 0·001). More than one-third of the F&B advertisements recorded did not utilise any of those persuasive marketing techniques that were examined, and using models (13·9 %) or providing discounts (8·8 %) were the two most frequently used non-festival-related persuasive marketing strategies. CONCLUSIONS: Unhealthy F&B advertising in MTR stations is prevalent regardless of SES and school density, and persuasive marketing strategies were infrequently used. These suggest that a ban on unhealthy F&B advertising around schools or the use of persuasive marketing strategies alone would be ineffective in Hong Kong. To align with the recommendation from WHO, a universal ban of junk food advertising should be enacted.

Free vascularised medial femoral condyle periosteal flaps in recalcitrant long bone non-union: a systematic review.

INTRODUCTION: In adults, treatment of recalcitrant long bone non-union is extremely challenging, with poorly vascularised and atrophic defects unresponsive to standard non-vascularised bone graft treatment. Recent studies have documented the use of free vascularised periosteal flaps to achieve union in refractory long bone fracture non-union, yet its use is not well established. This systematic review aims to assess the evidence for free vascularised periosteal flaps in recalcitrant long bone non-union. MATERIALS AND METHODS: The MEDLINE®/PubMed® and Embase databases were searched for the Medical Subject Heading (MeSH) terms periosteal flap/vascularised flap/long bone/non-union/non united fracture in accordance with the PRISMA guidelines. Bibliographies were scrutinised for additional articles. RESULTS: Pooled data from 14 studies met the inclusions criteria, comprising 137 cases of non-union, with 117 relating to long bone non-union. Pooled data indicated an overall 99% (116/117) successful union rate. All studies were of mid- to low-level evidence (Level III, IV and V). Only one study directly compared vascularised periosteal flaps to non-vascularised bone grafts, showing union rates of 100% versus 80% and faster time to union (2 versus 5.5 months). CONCLUSIONS: Free vascularised periosteal flaps are promising with pooled data showing a 99% success rate in achieving union in refractory long bone non-union. This compares favourably with standard orthopaedic care consisting of revision fixation and non-vascularised bone graft union rates of approximately 80%. However, study design flaws should be addressed by validated outcome measures plus adequate blinding, and further comparative studies with greater patient numbers are required.

The importance of early flap coverage in deep sternal wounds.

BACKGROUND: Chronic or persistent wound infection is one of the key outcome measures after flap reconstruction in deep sternal wound infection (DSWI). This study aimed to assess potentially modifiable factors associated with chronic infection in patients undergoing flap reconstruction. MATERIALS AND METHODS: An analysis of a prospective database of 5239 median sternotomies performed during a 5-year period was carried out. Seventy-seven cases of DSWI were recorded, of which 23 cases proceeded to flap reconstruction. The flap-reconstructed patients were placed into groups according to the primary outcome measure of those who experienced chronic infection and those who remained infection free. RESULTS: Of the flap-reconstructed patients, 22% experienced subsequent chronic infection, whereas 78% remained infection free. The only 2 variables that were associated with chronic infection were the timing of flap reconstruction; median time 29.5 days (vs 12 days in the infection-free group), P=0.011 and time taken from diagnosis of wound infection/dehiscence to referral to the plastic surgical team; median 21 days (vs median 8 days in the infection free group), P=0.02. Each day of delay from the diagnosis of clinical infection to flap cover equated to an increase in risk of chronic infection of 1.2 times per day (OR=1.205, P=0.039). CONCLUSIONS: This study suggests that chronic infection after flap reconstruction in DSWI is associated with late flap cover. We suggest the need for a consensus agreement on the combined care and early management of DSWI.

Differential impact of cytoplasmic vs. nuclear RAD51 expression on breast cancer progression and patient prognosis.

RAD51 recombinase is one of the DNA damage repair proteins associated with breast cancer risk. Apart from its function to maintain genomic integrity within the cell nucleus, RAD51 localized to the cytoplasm has also been implicated in breast malignancy. However, limited information exists on the roles of cytoplasmic vs. nuclear RAD51 in breast cancer progression and patient prognosis. In the present study, the association of cytoplasmic and nuclear RAD51 with clinical outcomes of patients with breast cancer was analyzed, revealing that elevated cytoplasmic RAD51 expression was associated with breast cancer progression, including increased cancer stage, grade, tumor size, lymph node metastasis and chemoresistance, along with reduced patient survival. By contrast, elevated nuclear RAD51 expression largely had the inverse effect. Results from in vitro investigations supported the cancer­promoting effect of RAD51, showing that overexpression of RAD51 promoted breast cancer cell growth, chemoresistance and metastatic ability, while knockdown of RAD51 repressed these malignant behaviors. The current data suggest that differential expression of subcellular RAD51 had a distinct impact on breast cancer progression and patient survival. Specifically, cytoplasmic RAD51 in contrast to nuclear RAD51 was potentially an adverse marker in breast cancer.

Ghana 3D Telemedicine International MDT: A proof-of-concept study.

A real-time 3D Telemedicine system - leveraging Microsoft's Holoportation™ communication technology - enabled an international multidisciplinary team meeting (MDT) to consult with complex reconstructive patients before, during, and after an overseas surgical collaboration. METHODS: A proof-of-concept international 3D MDT clinic took place in November 2022, between the Canniesburn Plastic Surgery Unit, UK, and the National Reconstructive Plastic Surgery and Burns Centre, Korle Bu Teaching Hospital, Ghana. The 3D system was utilised 1) previsit to assess patients and enable logistical planning, 2) on-site in Ghana to further allow patients to see themselves and proposed operations in 3D, and 3) post visit to debrief the team and patients. RESULTS: Four Ghana patients were followed through their patient journey (mandibular ameloblastoma, sarcoma thigh, maxillary tumour, sarcoma back). Thirteen participants (four patients, four Ghana clinicians, and five UK clinicians) completed feedback on the 3D MDT. Outcome measures were rated highly with satisfaction 84.31/100, perceived benefit 4.54/5, overall quality 127.3/147 (Telehealth Usability Questionnaire), and usability 83.2/100 (System Usability Scale). These data show close alignment with that previously published on high-income countries. CONCLUSIONS: This novel technology has the potential to enhance the delivery of overseas surgical visits to low-to-middle-income countries, by improving planning, informed discussion with patients, expert consensus on complex cases, and fostering engagement with professionals who may be thousands of miles away. This is the first demonstration that real-time 3D Telemedicine can both work, and enhance care within an international MDT clinic, and may thus enable change in the approach to overseas surgical collaborations.

Lc3 over-expression improves survival and attenuates lung injury through increasing autophagosomal clearance in septic mice.

OBJECTIVE: To clarify the role of autophagy in sepsis-induced lung injury. BACKGROUND: The role of autophagy as a protective or maladaptive response in lung cells during sepsis has not yet been determined. The lack of specificity of the autophagic process has driven the development of new approaches that assess autophagosomes from formation to fusion with lysosomes. METHODS: Sepsis was induced by cecal ligation and puncture (CLP). The autophagic process was manipulated using the pharmacological inhibitors of the autophagy pathway. Green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic mice were further used to determine the role of autophagy. RESULTS: The formation of autophagosomal protein LC3-II progressively accumulated in the lungs over 24 hours after CLP, with the Lc3 gene expression returning to baseline levels at 24 hours. Autophagosome-lysosome fusion, however, gradually decreased from 8 to 24 hours after CLP, suggesting impaired clearance of autophagosomes rather than upregulation of autophagy in the septic lung. In contrast, transgenic mice overexpressing the Lc3 gene exhibited increased clearance of autophagosomes and improved survival after CLP. This protective effect was also seen in decreased cell death, inflammatory responses, neutrophil accumulation, albumin leakage, and edema formation. However, blockade of autophagosome-lysosome fusion with bafilomycin A1 abolished the protective effects in transgenic mice. This indicates that Lc3 transgene attenuates lung injury/inflammation in sepsis, possibly through increasing the clearance of autophagosomes. CONCLUSIONS: Autophagy in the septic lung represents a protective response. However, autophagy, by virtue of excessive autophagosome accumulation, may play a maladaptive role in the late stage of sepsis, leading to acute lung injury.

In search of the ideal periosteal flap for bone non-union: The chimeric fibula-periosteal flap.

Vascularised periosteal flaps may increase the union rates in recalcitrant long bone non-union. The fibula-periosteal chimeric flap utilises the periosteum raised on an independent periosteal vessel. This allows the periosteum to be inset freely around the osteotomy site, thereby facilitating bone consolidation. PATIENTS AND METHODS: Ten patients underwent fibula-periosteal chimeric flaps (2016-2022) at the Canniesburn Plastic Surgery Unit, UK. Preceding non-union 18.6 months, with mean bone gap of 7.5 cm. Patients underwent preoperative CT angiography to identify the periosteal branches. A case-control approach was used. Patients acted as their own controls, with one osteotomy covered by the chimeric periosteal flap and one without, although in two patients both the osteotomies were covered using a long periosteal flap. RESULTS: A chimeric periosteal flap was used in 12 of the 20 osteotomy sites. Periosteal flap osteotomies had a primary union rate of 100% (11/11) versus those without flaps at 28.6% (2/7) (p = 0.0025). Union occurred in the chimeric periosteal flaps at 8.5 months versus 16.75 months in the control group (p = 0.023). One case was excluded from primary analysis due to recurrent mycetoma. The number needed to treat = 2, indicating that 2 patients would require a chimeric periosteal flap to avoid one non-union. Survival curves with a hazard ratio of 4.1 were observed, equating to a 4 times higher chance of union with periosteal flaps (log-rank p = 0.0016). CONCLUSIONS: The chimeric fibula-periosteal flap may increase the consolidation rates in difficult cases of recalcitrant non-union. This elegant modification of the fibula flap uses periosteum that is normally discarded, and this adds to the accumulating data supporting the use of vascularised periosteal flaps in non-union.

[Plastic-surgical reconstruction of the lower extremity in senior patients]. / Plastisch-chirurgische Rekonstruktion der unteren Extremität bei alten Patienten.

The proportion of patients in the population beyond the 7th decade of life is increasing worldwide, especially in highly developed countries. Consequently, there is also an increasing need for complex lower extremity reconstructions after trauma, tumors, or infections in this age group. The reconstruction of soft tissue defects of the lower extremity should be performed according to the principle of the plastic-reconstructive ladder or elevator. The goal of reconstruction is to restore anatomy and function of the lower extremity to enable pain-free and stable standing and walking; however, for older patients in particular, a careful preoperative multidisciplinary planning, detailed preoperative assessment and optimization of comorbidities, such as diabetes, malnutrition or pathological vascular alterations, as well an age-adapted perioperative management are necessary. By implementing these principles, older and very old patients can maintain their mobility and autonomy, which are crucial for a high quality of life.

Tenosynovial giant cell tumor: a case report.

BACKGROUND: This case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients' knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma. CASE PRESENTATION: A 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment. CONCLUSIONS: Tenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.

Effect of differing flap reconstruction strategies in perineal closure following advanced pelvic oncological resection: a retrospective cohort study.

INTRODUCTION: Advancing approaches to locally invasive pelvic malignancy creates a large tissue defect resulting in perineal wound complications, dehiscence, and perineal hernia. Use of reconstructive flaps such as vertical rectus abdominus myocutaneous (VRAM) flap, gracilis, anterolateral thigh and gluteal flaps have been utilised in our institution to address perineal closure. The authors compared outcomes using different flap techniques along with primary perineal closure in advanced pelvic oncological resection. METHODS: A prospectively maintained database of patients undergoing advanced pelvic oncological resection in a single tertiary hospital was retrospectively analysed. This study included consecutive patients between 2014 and 2021 according to the Strengthening The Reporting of Cohort Studies in Surgery (STROCSS) criteria. Primary outcome measures were the frequency of postoperative perineal complications between primary closure, VRAM, gluteal and thigh (anterolateral thigh and gracilis) reconstruction. RESULTS: One hundred twenty-two patients underwent advanced pelvic resection with perineal closure. Of these, 40 patients underwent extra-levator abdominoperineal resection, and 70 patients underwent pelvic exenteration. Sixty-four patients received reconstructive flap closure, which included VRAM (22), gluteal (21) and thigh flaps (19). Perineal infection and dehiscence rates were low. Infection rates were lower in the flap group despite a higher rate of radiotherapy ( P <0.050). Reoperation rates were infrequent (<10%) but specific for each flap, such as donor-site hernia following VRAM and flap dehiscence after thigh flap reconstruction. CONCLUSIONS: In patients who are at high risk of postoperative perineal infections, reconstructive flap closure offers acceptable outcomes. VRAM, gluteal and thigh flaps offer comparable outcomes and can be tailored to the individual patient.

Participatory development of a 3D telemedicine system during COVID: The future of remote consultations.

BACKGROUND: The COVID pandemic brought the need for more realistic remote consultations into focus. 2D Telemedicine solutions fail to replicate the fluency or authenticity of in-person consultations. This research reports on an international collaboration on the participatory development and first validated clinical use of a novel, real-time 360-degree 3D Telemedicine system worldwide. The development of the system - leveraging Microsoft's Holoportation™ communication technology - commenced at the Canniesburn Plastic Surgery Unit, Glasgow, in March 2020. METHODS: The research followed the VR CORE guidelines on the development of digital health trials, placing patients at the heart of the development process. This consisted of three separate studies - a clinician feedback study (23 clinicians, Nov-Dec 2020), a patient feedback study (26 patients, Jul-Oct 2021), and a cohort study focusing on safety and reliability (40 patients, Oct 2021-Mar 2022). "Lose, Keep, and Change" feedback prompts were used to engage patients in the development process and guide incremental improvements. RESULTS: Participatory testing demonstrated improved patient metrics with 3D in comparison to 2D Telemedicine, including validated measures of satisfaction (p<0.0001), realism or 'presence' (Single Item Presence scale, p<0.0001), and quality (Telehealth Usability Questionnaire, p = 0.0002). The safety and clinical concordance (95%) of 3D Telemedicine with a face-to-face consultation were equivalent or exceeded estimates for 2D Telemedicine. CONCLUSIONS: One of the ultimate goals of telemedicine is for the quality of remote consultations to get closer to the experience of face-to-face consultations. These data provide the first evidence that Holoportation™ communication technology brings 3D Telemedicine closer to this goal than a 2D equivalent.

Risk stratification in oral cavity squamous cell carcinoma by preoperative CRP and SCC antigen levels.

BACKGROUND: Squamous cell carcinoma antigen (SCC-Ag) level and C-reactive protein (CRP) have been shown to be associated with tumor invasion, lymph node metastasis, staging and survival in patients with oral squamous cell carcinoma (OSCC). The purpose of the present study was to analyze the relationship between preoperative levels of both SCC-Ag and CRP, with clinicopathologic factors and prognosis in OSCC patients. METHODS: A retrospective study was performed on 142 OSCC patients between March 2008 and March 2011. Their serum SCC-Ag and CRP levels were measured preoperatively. RESULTS: SCC-Ag level of ≥2.0 ng/ml and CRP level ≥5.0 mg/L were significantly associated with pathologic tumor status (P < 0.001), pathologic nodal metastasis (P = 0.001), tumor depth (≥10 mm vs. <10 mm, P < 0.001), disease-free survival (P ≤ 0.001) and overall survival (P ≤ 0.001). The influence of SCC-Ag and CRP level on disease-free survival (hazard ratio 4.046, 95 % confidence interval 1.698-9.692) and overall survival (hazard ratio 3.655, 95 % confidence interval 1.464-9.130) still existed after adjusting for tumor status, lymph node metastasis and tumor cell differentiation. CONCLUSIONS: Concurrent high levels of both preoperative SCC-Ag and CRP levels act as a predictor for lymph node metastasis, advanced tumor stage and tumor recurrence. It therefore has significant potential as a biomarker for risk stratification in OSCC.

Resistin expression in breast cancer tissue as a marker of prognosis and hormone therapy stratification.

OBJECTIVE: Adipocytokines are adipocyte-derived hormones and well documented to be involved in carcinogenesis. The expression of resistin, a newly discovered adipocytokine, in breast cancer tissues was determined and correlated with patient clinicopathological variables. METHODS: Resistin expression in breast cancer tissues and the normal adjacent breast tissues was analyzed by immunohistochemistry and was correlated with clinicopathological variables as well as recurrence rates by the chi-square test. The prognostic value of resistin for disease-free and overall survival was determined by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. RESULTS: High resistin expression was predominantly observed in breast cancer tissues but not the adjacent normal breast tissues. High resistin expression in breast cancer tissues was correlated significantly with tumor stage, tumor size, lymph node metastasis and estrogen receptor status. Hormone therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in patients with high resistin expression. While high resistin expression was associated with poor disease-free and overall survival, Cox regression analysis also revealed that resistin was an independent predictor of disease-free and overall survival. CONCLUSIONS: High resistin expression in breast cancer tissue is associated with a more malignant clinicopathological status as well as poor patient survival. Resistin may therefore hold promise as an independent prognosis predictor for breast cancer, as a marker for hormone therapy stratification and as a potential therapeutic target.

Functional quadriceps reconstruction: 3D gait analysis, EMG and environmental simulator outcomes.

OBJECT: Limited objective evidence exists on the benefits of functional muscle transfers following quadriceps resection in sarcoma. In particular, no studies have compared patients with functional transfers to those without. In this study, objective and subjective assessments were performed with 3D Gait Analysis, Environmental Simulator, Electromyography (EMG) and Patient-Reported Outcomes. METHODS: Thirty-four patients at the Scottish Sarcoma Network Glasgow Centre/ Canniesburn Plastic Surgery Unit underwent quadriceps resection for sarcoma between 2009 - 2019, including 24 patients with functional reconstruction and 10 without. Both groups were equivalent for the extent of quadriceps resection (2.58 versus 2.85 components, p=0.47). Primary outcome measure was 3D Gait Analysis and Gait Profile Score (GPS), and secondary outcome was the Toronto Extremity Salvage Score (TESS) score. Ancillary analyses included environmental simulation with the Motek CAREN system and EMG of transferred muscles. RESULTS: Outcomes measures were better in functional reconstruction patients when compared to those without - the GPS score was 8.04 versus 10.2 (p=0.0019), and the TESS score was 81.85 versus 71.17 (p=0.028). Environmental simulator tasks found that functional reconstruction patients could complete activities of daily living including shopping and collision avoidance tasks, without significantly slowing their walking speed. Patients without a functional reconstruction could not complete weighted shopping tasks. EMG showed that transferred hamstrings co-activated with the ipsilateral rectus femoris during the gait cycle. CONCLUSIONS: These are the first objective data demonstrating the superiority of muscle transfers for functional restoration in quadriceps resection versus patients without functional transfers. Critically, these also provide answers to patient-oriented questions relating to the recovery of function and activities of daily living.

ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model.

The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy.

Evaluation of CLSI agar dilution method and Trek Sensititre broth microdilution panel for determining antimicrobial susceptibility of Streptococcus pneumoniae.

Both the CLSI agar dilution method and Trek Sensititre broth microdilution panel for Streptococcus pneumoniae antimicrobial susceptibility testing were evaluated against the reference CLSI broth microdilution method using the most recently published CLSI breakpoints. While agar dilution was not an optimal method, the commercial panel appeared to be an acceptable method, with minor errors encountered for ceftriaxone, penicillin, and meropenem.

Research of the Holiday kind: Tabulating Ingestion of Mocha Solution (TIMS): a longitudinal prospective cohort study.

The annual "Roll Up the Rim to Win" contest at Tim Hortons restaurants provides customers the opportunity to win prizes. This study investigated win ratios, prize types and patterns of coffee consumption.

MRE11 as a molecular signature and therapeutic target for cancer treatment with radiotherapy.

MRE11, the core of the MRE11/RAD50/NBS1 complex, is one of key DNA damage response proteins. Increasing evidence suggests that its expression in cancer cells is critical to developing radioresistance; as such, MRE11 is an emerging marker for targeted radiosensitization strategies. Elevated MRE11 in tumor tissues has been associated with poor survival in patients undergoing radiotherapy, although in some cancer types, the opposite has been noted. The recent discovery of ionizing radiation-induced truncation of MRE11, which decreases its efficacy, may explain some of these paradoxical findings. The progress of research on the biological modulation of MRE11 expression is also discussed, with the potential application of small molecule or large molecule inhibitors of MRE11 for enhancing radiosensitivity. Current research has further highlighted both nuclease and non-nuclease activities of MRE11 in cancer cells treated with ionizing radiation, and differentiation between these is essential to verify the targeting effects of radiosensitizing agents. These updates clarify our understanding of how MRE11 expression may be utilized in future stratification of cancer patients for radiotherapy, and how it may be leveraged in shaping novel radiosensitization strategies.