Upper extremity vascular injuries: Etiology, management and outcome.

BACKGROUND: Vascular injuries of the upper extremities are considered relatively rare injuries affecting mostly the young population. They often are complex injuries accompanied by other musculoskeletal trauma or trauma in other anatomic locations. Their management is challenging since they can lead to disabilities with major socioeconomic effects. AIM: To analyze data about the mechanism of injury, the management algorithm and functional outcomes of vascular injuries of the upper extremity. METHODS: One hundred and fifteen patients (96 males and 19 females) with arterial injuries of the upper extremity treated in a tertiary trauma center from January 2003 to December 2022 was conducted. Mean patients' age was 33.7 years and the mean follow up time was 7.4 years. Patients with Mangled Extremity Severity Score ≥ 7 and Injury Severity Score ≥ 20, previous upper limb surgery or major trauma and any neuromuscular or psychiatric disease were excluded, from the study. RESULTS: A penetrating trauma was the most common cause of injury. The radial artery was the artery injured in most of the cases (37.4%) followed by the ulnar (29.5%), the brachial (12.1%) and the axillary (6%). A simultaneous injury of both of the forearm's arteries was in 15.6% of the cases. In 93% of the cases there were other concomitant musculoskeletal injuries of the extremity. Tendon lacerations were the most common, followed by nerve injuries. The postoperative functional scores (full Disabilities of the Arm, Shoulder, and Hand and VAS) had very satisfactory values. CONCLUSION: Although vascular injuries of the upper extremity are rare, they may occur in the context of major combined musculoskeletal trauma. Although a multidisciplinary approach is essential to optimize outcome, the ability of trained hand surgeons to repair all injuries in combined vascular and musculoskeletal upper extremity trauma, excluding isolated vascular injuries, ensures shorter operative times and better functional outcomes.

Pediatric Knee Injury: A Unique Case of Intra-articular Osteochondral Fracture Following Penetrating Trauma.

Penetrating injuries to the musculoskeletal system pose common challenges for orthopedic surgeons in emergency departments (EDs). The complexity escalates when a joint is affected, increasing the risk of severe complications such as infection and post-traumatic arthritis. Given the potential importance of these injuries, early diagnosis and a meticulous treatment plan are crucial. In this paper, we present a unique case of penetrating trauma, resulting in an intra-articular defect on the lateral femoral condyle of an adolescent girl. This case underscores the importance of tailored interventions in managing complex musculoskeletal injuries.

Pectoralis major rupture in body builders: a case series including anabolic steroid use.

BACKGROUND: Rupture of the pectoralis major (PM) muscle is a rare injury, with increasing incidence over the last decades, mainly due to participation in weightlifting and contact sports. Surgical management of PM injuries has been related with superior functional outcome, faster return to activities, better cosmesis and higher level of patients' satisfaction. The aim of the study is to present our experience in the management of this rare clinical entity and to correlate the use of anabolic steroids in the occurrence of the injury and the impact of type of injury, method of reconstruction and anabolic steroids on the post-operative outcome. CASES: We present a series of six male bodybuilding athletes who sustained PM rupture during weightlifting. We recorded the location & type of injury, the history and type of anabolic steroids use, the method of repair and the post-operative outcome. TREATMENT AND OUTCOMES: The mean follow-up period was 16 (12-24) months. All patients treated surgically had excellent results according to Bak criteria and returned to full activity within 5.4 (5-7) months following surgical reconstruction. No post-operative complications were recorded, despite the continued use of anabolic steroids, however one patient died from myocardial infarction within a year of surgical treatment. CONCLUSIONS: PM rupture is an injury with increasing incidence within bodybuilding athletes probably not related to the dominance of the limb. Fixation of the tendon with suture anchors results in excellent clinical outcome and patient's satisfaction postoperatively regardless the chronicity of the repair. Our observations in these cases suggest that anabolic steroids use may contribute to the injury due to an excessive upward adjustment of the athlete's goals in lifting weights and moreover the continuation of administration even in the recovery period does not seem to have a negative effect either on the time or on the level of adequate functional recovery postoperatively.

Polydactyly: Clinical and molecular manifestations.

Polydactyly is a malformation during the development of the human limb, which is characterized by the presence of more than the normal number of fingers or toes. It is considered to be one of the most common inherited hand disorders. It can be divided into two major groups: Non-syndromic polydactyly or syndromic polydactyly. According to the anatomical location of the duplicated digits, polydactyly can be generally subdivided into pre-, post-axial, and mesoaxial forms. Non-syndromic polydactyly is often inherited with an autosomal dominant trait and defects during the procedure of anterior-posterior patterning of limb development are incriminated for the final phenotype of the malformation. There are several forms of polydactyly, including hand and foot extra digit manifestations. The deformity affects upper limbs with a higher frequency than the lower, and the left foot is more often involved than the right. The treatment is always surgical. Since the clinical presentation is highly diverse, the treatment combines single or multiple surgical operations, depending on the type of polydactyly. The research attention that congenital limb deformities have recently attracted has resulted in broadening the list of isolated gene mutations associated with the disorders. Next generation sequencing technologies have contributed to the correlation of phenotype and genetic profile of the multiple polydactyly manifestations and have helped in early diagnosis and screening of most non-syndromic and syndromic disorders.

Leptin-depended NLRP3 inflammasome activation in osteoarthritic chondrocytes is mediated by ROS.

Leptin and ROS are implicated in the regulation of inflammatory pathways including NLRP3-inflammasome. We investigated the functional link between leptin, ROS and NLRP3-inflammasome formation/activation in osteoarthritis (OA), an age-related disease. We found that inflammasome components' (NLRP3, ASC, Caspase-1 and cleaved Caspase-1) protein expression were increased in OA cartilage biopsies and chondrocytes compared to healthy cartilage and chondrocytes. Immunofluorescence showed increased co-localization of NLRP3/ASC and NLRP3/Caspase-1, ASC-specks formation and ROS levels in OA compared to normal chondrocytes. NOX4 mRNA expression and IL-1ß/IL-18 secretion levels were also elevated in OA chondrocytes. Furthermore, NLRP3-siRNA in OA chondrocytes revealed significant MMP-9/MMP-13 downregulation. To elucidate leptin/ROS/NLRP3-inflammasome interactions, OA chondrocytes were treated with ROS-inhibitor NAC, NOXs-inhibitor DPI, NOX4-inhibitor GLX351322 and leptin-siRNA, while normal chondrocytes were incubated with leptin with or without DPI or GLX351322. We observed attenuated ROS levels and NLRP3-inflammasome formation/activation in NAC-, DPI- or GLX351322-treated OA chondrocytes, while the same effect was shown after transfection with leptin-siRNA. Furthermore, incubation of normal chondrocytes with leptin enhanced ROS production and inflammasome formation/activation, while pretreatment with DPI or GLX351322 abolished leptin's stimulatory effects confirming leptin-NOX4-ROS-inflammasome regulatory axis. Overall, our findings provide novel evidence indicating that leptin-induced NLRP3-inflammasome formation/activation in OA chondrocytes is mediated by NOX4-dependent ROS production.

Tibial Nerve Palsy: An Atypical Presentation of a Popliteal Cyst.

Popliteal cysts represent one of the commonest knee pathologies in the adult population. The vast majority of cases may be treated conservatively as symptoms tend to resolve spontaneously. However, few patients may experience persistent pain and nerve-related symptoms not responding to conservative management. We present a case of a 46-year-old patient who suffered from tibial nerve palsy due to a popliteal cyst that was treated successfully with combined open and arthroscopic procedure. It is important to understand that popliteal cysts rarely may lead to tibial nerve entrapment and in selected cases operative management may be indicated.

Overview of fracture liaison services in the UK and Europe: standards, model of care, funding, and challenges.

Fragility fractures represent a growing global problem, including in the United Kingdom and European countries. Reports demonstrate the benefits of national guidance and organized fragility fracture programs through fracture liaison services to deliver care to patients who sustain these injuries. The challenge of assembling multidisciplinary teams, providing routine screening of appropriate patients, and monitoring therapies where there is a known compliance problem, remains an obstacle to the success of fragility fracture treatment programs to all. Efforts should continue to introduce and maintain fracture liaison services through coordinated national approaches and advanced systems.

Update in combined musculoskeletal and vascular injuries of the extremities.

Combined musculoskeletal and vascular injuries of the extremities are conditions in which a multidisciplinary approach is a sine qua non to ensure life initially and limb viability secondarily. Vascular injuries as part of musculoskeletal trauma are usually the result of the release of a high energy load in the wound site so that the prognosis is determined by the degree of soft-tissue damage, duration of limb ischemia, patient's medical status and presence of associated injuries. The management of these injuries is challenging and requires a specific algorithm of action, because they are usually characterized by increased morbidity, amputation rate, infection, neurological and functional deficits, and they could be life threatening. Although vascular injuries are rare and occur either isolated or in the context of major combined musculoskeletal trauma, the high index of suspicion, imaging control, and timely referral of the patient to organized trauma centers ensure the best functional outcome of the extremity in such challenging cases. Even after a successful initial treatment of a combined trauma pattern, long-term follow-up is crucial to prevent and detect early possible complications. The purpose of this manuscript is to provide an update on diagnosis and treatment of combined musculoskeletal and vascular injuries of the extremities, from an orthopedic point of view.

Medico-legal risks associated to hand and wrist trauma.

BACKGROUND: Acute hand and wrist injuries are common and may lead to long-term disability if not managed adequately. Claims for negligence have been increasing in medical practice over the past few decades, with hand and wrist injuries and their treatment representing a significant percentage of orthopedic surgery lawsuits. There is no available literature regarding medical malpractice claims in hand and wrist injuries and surgery in Greece. AIM: To identify claims related to hand and wrist trauma and surgery and to define the reasons of successful litigations. METHODS: We performed a retrospective study of all legal claims of negligence for hand and upper extremity surgery that went to a trial, attributed to all surgical specialties, in Greece for a 20-year period. Data was further analyzed to identify claims related to hand and wrist trauma and surgery. RESULTS: There were six malpractice claims related to hand and wrist trauma that ended in a trial. A missed diagnosis, which resulted in failure of initial management of the injury, was the main reason for a claim. Three of the six cases resulted in complete or partial loss of a finger. Two cases are still open, requiring an expert witness's report, two cases were closed in favor of the defendant, and two cases were closed in favor of the plaintiff with a mean compensation of €2000 (€1000-€3000). CONCLUSION: Missed diagnosis was the main reason for a malpractice claim. Better understanding of factors leading to successful claims will help surgeons improve their practice to minimize legal implications and litigation.

Postacute sequelae of SARS-CoV-2 infection. Osteonecrosis must not be overlooked.

Recovery from COVID-19 is not always uneventful, especially in critically ill hospitalized patients. Persistent symptoms including fatigue/ weakness, shortness of breath, anxiety, and depression have been described at one-year follow-up. Furthermore, symptoms from the musculoskeletal system like joint pain or stiffness are underreported in studies with long-term follow-up of up to one year. Infection with SARS-CoV-2 itself has been associated with endothelial damage, and together with high-dose corticosteroid treatment, it is predisposed to the dissemination of microthrombi and the development of femoral head osteonecrosis (FHOn), as it has been shown during the previous (2003-2004) coronavirus outbreaks. A resurgence of FHOn cases is anticipated but this is not reflected in the existing studies with long-term follow-up. Prompt diagnosis is critical for early treatment and possibly for the hip joint preservation. Patients with COVID-19 treated with corticosteroids should be screened for avascular necrosis early after discharge from the hospital. Every healthcare worker involved in the management of these patients should maintain a high level of suspicion and should be alert when patients report symptoms such as vague aches at the buttocks, hip area, adductors, and/or above the knee. Studies are needed to identify risk factors for FHOn including disease severity, type of steroid, cumulative dose, and duration of treatment.

Surgical management of upper limb lipoma arborescens: a systematic review.

BACKGROUND: Lipoma arborescens (LA) is a rare benign synovial tumour characterized by the proliferation of mature adipocytes within the synovial cells. Given its rarity, current evidence is mainly based on case reports and case series, and no guidelines are available. The present study investigated the current surgical management and related outcomes of LA in the upper limb. METHODS: This systematic review was conducted following the PRISMA guidelines. PubMed, Scopus, and Virtual Health Library were accessed in September 2021. Clinical studies evaluating patients with LA undergoing surgical treatment were considered eligible for this systematic review. Only studies which reported data on LA located in the upper limb with histopathological confirmation were considered. Articles that reported data from nonsurgical management were not considered. RESULTS: A total of 21 studies reporting 22 lesions in 21 patients were assessed. The mean age of the patients was 48.48 years (range 22-77). Most studies evaluated the restoration of range of motion and symptom resolution for the functional outcome assessment. Open or arthroscopic excision and synovectomy were the most common surgical procedures for LA. The concomitant lesions were treated in a single-stage procedure. All patients had satisfactory outcomes after open or arthroscopic excision and synovectomy without recurrence at a mean follow-up of 21.14 months (range 2-60). One patient developed postoperative cellulitis (4.55%). CONCLUSION: Open and arthroscopic excision combined with synovectomy should be considered the standard treatment option of upper limb LA. Concomitant pathologies can be addressed in a one-stage procedure. Although LA was recognized as a clinical entity decades ago, there is a lack of evidence based guidelines and long term outcome data are unavailable.

Should We Routinely Exclude Retroperitoneal Abscess in Cases of Hip Periprosthetic Joint Infections?

Hip periprosthetic joint infections (PJIs) with concomitant retroperitoneal abscesses may not be common clinical situations but they can be easily misdiagnosed affecting the effectiveness of infection control and eradication interventions. We present the case of a 75-year-old female patient with a late hip PJI complicated with iliopsoas abscess that was barely discovered intraoperatively. Literature review supports our recommendation of a high index of suspicion in cases of hip PJI and even routinely imaging examination of pelvis and abdomen for retroperitoneal involvement exclusion.

Spaghetti wrist: Transverse injury, axial incision, layered microsurgical reconstruction.

INTRODUCTION: Among various patterns of complex injuries of the wrist and forearm, "spaghetti wrist" refers to an extensive volar forearm laceration, in which several of the 12 tendons, 2 major nerves and 2 major arteries are transected, leading to lifelong disability and psychological, social and economic consequences. The aim of the study is to emphasize the keynote principles for the management of these injuries through retrospective review of a large group of patients treated by a team of experienced hand surgeons. MATERIAL-METHODS: Data were retrospectively obtained for 61 patients (49 males and 12 females with average age of 34.7 years) treated for spaghetti wrist lacerations and followed for a minimum period of two years, in two accredited Orthopaedic / Hand-Upper Extremity Surgery and Microsurgery Departments in Greece. All patients were treated within 16 hours of injury and underwent primary, layered reconstruction of all injured structures through an axial forearm exposure. RESULTS: The most frequent mechanism of injury was glass-related lacerations. Overall, 541 structures were reconstructed, of which 417 were tendons, 76 nerves, and 48 arteries. An average of 8.86 structures were injured per patient, including 6.83 tendons, 1.24 nerves, and 0.79 arteries. The majority of the patients (28/61) had ≥10 structures injured (45.9%), while 32.7% (20/61) and 21.3% (13/61) of patients had 6-9 and 3-5 injured structures respectively. Almost 80% (49/61) of patients had excellent/good grading in all six tests used for the functional assessment post-operatively. DISCUSSION: Spaghetti wrist injuries usually occur in a transverse wound pattern and necessitate timely and definitive operative reconstruction of all injured structures in layers, through an axial approach, by experienced hand surgeons to maximize outcome and to avoid complications. The most important prognostic factor of functional recovery is not the number of transected tendons, but the involvement of ulnar and/or median nerve injury.

Factors predisposing to thrombosis after major joint arthroplasty.

BACKGROUND: Total joint arthroplasty is one of the most common options for end stage osteoarthritis of major joints. However, we must take into account that thrombosis after hip/knee arthroplasty may be related to mutations in genes encoding for blood coagulation factors and immune reactions to anticoagulants [heparin-induced thrombocytopenia (HIT)/thrombosis]. Identifying and characterizing genetic risk should help to develop diagnostic strategies or modify anticoagulant options in the search for etiological mechanisms that cause thrombophilia following major orthopedic surgery. AIM: To evaluate the impact of patients' coagulation profiles and to study specific pharmacologic factors in the development of post-arthroplasty thrombosis. METHODS: In 212 (51 male and 161 female) patients that underwent primary total hip arthroplasty (100) or total knee arthroplasty (112) due to osteoarthritis during a period of 1 year, platelet counts and anti-platelet factor 4 (PF4)/heparin antibodies were evaluated pre/postoperatively, and antithrombin III, methylenetetrahydrofolate reductase, factor V and prothrombin gene mutations were evaluated preoperatively. In a minimum follow-up of 3 years, 196 patients receiving either low-molecular-weight heparins (173) or fondaparinux (23) were monitored for the development of thrombocytopenia, anti-PF4/heparin antibodies, HIT, and thrombosis. RESULTS: Of 196 patients, 32 developed thrombocytopenia (nonsignificant correlation between anticoagulant type and thrombocytopenia, P = 0134.) and 18 developed anti-PF4/heparin antibodies (12/173 for low-molecular-weight heparins and 6/23 for fondaparinux; significant correlation between anticoagulant type and appearance of antibodies, P = 0.005). Odds of antibody emergence: 8.2% greater in patients receiving fondaparinux than low-molecular-weight heparins. Gene mutations in factor II or V (two heterozygotes for both factor V and II) were identified in 15 of 196 patients. Abnormal low protein C and/or S levels were found in 3 of 196 (1.5%) patients, while all patients had normal levels of von Willebrand factor, lupus anticoagulant, and antithrombin III. Four patients developed HIT (insignificant correlation between thrombocytopenia and antibodies) and five developed thrombosis (two had positive antibodies and two were heterozygotes for both factor II & V mutations). Thrombosis was not significantly correlated to platelet counts or HIT. The correlation of thrombosis to antibodies, factor II, factor V was P = 0.076, P = 0.043, P = 0.013, respectively. CONCLUSION: Screening of coagulation profile, instead of platelet monitoring, is probably the safest way to minimize the risk of post-arthroplasty thrombosis. In addition, fondaparinux can lead to the formation of anti-PF4/heparin antibodies or HIT.

A Tumor-Like Lump in the Palm Caused by an Inconspicuous-for 75 Years-Bullet.

CASE: An unusual case of a foreign body in the hand is described here. Excision of a tumor-like soft tissue mass revealed a 75-year-old World War II bullet fragment of which patient was unaware. CONCLUSION: Differential diagnosis of hand lumps and inflammatory reaction must always include retained foreign bodies even after a very long period of posttraumatic quiescence or patient's inability to provide a relative injury case history.

Nanographene oxide-TiO2 photonic films as plasmon-free substrates for surface-enhanced Raman scattering.

The development of nanostructured semiconductors with tailored morphology and electronic properties for surface-enhanced Raman scattering (SERS) has been attracting significant attention as a promising alternative to conventional coinage metal SERS substrates. In this work, functionalized TiO2 photonic crystals by graphene oxide nanocolloids (nanoGO) are demonstrated as highly sensitive, recyclable, plasmon-free SERS substrates that combine slow-photon amplification effects with the high adsorption capacity and surface reactivity of GO nanosheets. Comparative evaluation of photonic band gap engineered nanoGO-TiO2 inverse opal films was performed on methylene blue SERS detection under different laser excitations in combination with rigorous theoretical simulations of the photonic band structure. A very low detection limit of 6 × 10-7 M and an enhancement factor of 5 × 104 along with excellent self-cleaning performance and reusability could be achieved by the interplay of slow-photon effects assisted by interfacial charge transfer between the analyte and the nanoGO-TiO2 semiconducting substrate. Slow-photon management in combination with judicious engineering of chemical enhancement in photonic nanostructures is accordingly proposed as an advanced approach for the design of efficient dielectric SERS substrates.

Vascular endothelial growth factor for the treatment of femoral head osteonecrosis: An experimental study in canines.

AIM: To evaluate the treatment of osteonecrosis of the femoral head (ONFH) with the use of vascular endothelial growth factor (VEGF). METHODS: In 30 mature beagles (6 groups of 5 beagles) ONFH was induced cryosurgically and one of the following solutions was administered locally in the femoral head (FH) in each group: Single injection of 500 µg VEGF (t-VEGFµ group); single injection of 500 ng VEGF (t-VEGFn group); continuous delivery of 500 µg VEGF through osmotic micropump (t-VEGFpump-µ group); continuous delivery of 500 ng VEGF through osmotic micropump (t-VEGFpump-n group); single injection of 0.9% sodium chloride (t-NS group), while one group that served as control group did not receive any local solution (No-t group). FHs were retrieved 12 wk postoperatively, underwent decalcification and hematoxylin/eosin and toluidine blue staining. In two canines per group, one half of FH was processed without decalcification and stained with modified Masson Trichrome. Histological sections were observed by light microscopy and measured with a semi-automatized bone histomorphometry system and Bone Volume/Total Volume (BV/TV), Marrow Volume/Total Volume (MaV/TV), and Trabecular Thickness (TbTh) were assessed. Standard and robust tests (Welch, Brown Forsythe) of analysis of variance along with multiple comparisons, were carried out among the categories. RESULTS: The untreated (No-t) group had signs of osteonecrosis, whereas the VEGF groups revealed reversal of the osteonecrosis. Statistical analysis of the decalcified specimens revealed a significantly better BV/TV ratio and a higher TbTh between the VEGF treatment groups (except the t-VEGFn group) and the No-t group or the control t-NS group. Single dose 500 µgVEGF group had significantly better BV/TV ratio and higher TbTh when compared to the No-t group (50.45 ± 6.18 vs 29.50 ± 12.27, P = 0.002 and 151.44 ± 19.07 vs 107.77 ± 35.15, P = 0.161 respectively) and the control t-NS group (50.45 ± 6.18 vs 30.9 ± 6.67, P = 0.004 and 151.44 ± 19.07 vs 107.14 ± 35.71, P = 0.151 respectively). Similar differences were found for the prolonged VEGF delivery/pump groups of 500 µg and 500 ng. Analysis of the totality of specimens (decalcified/non-decalcified) enhanced the aforementioned differences and additionally revealed significant differences in the comparison of the TbTh. CONCLUSION: In an experimental model of ONFH in canines it was found that local treatment with VEGF leads to bone tissue remodeling and new bone formation.

Molecular fluorescence enhancement in plasmonic environments: exploring the role of nonlocal effects.

Molecular spontaneous emission and fluorescence depend strongly on the emitter local environment. Plasmonic nanoparticles provide excellent templates for tailoring fluorophore emission, as they exhibit potential for both fluorescence enhancement and quenching, depending on emitter positioning in the nanoparticle vicinity. Here we explore the influence of hitherto disregarded nonclassical effects on the description of emitter-plasmon hybrids, focusing on the roles of the metal nonlocal response and especially size-dependent plasmon damping. Through extensive modelling of metallic nanospheres and nanoshells coupled to dipole emitters, we show that within a purely classical description a remarkable fluorescence enhancement can be achieved. However, once departing from the local-response approximation, and particularly by implementing the recent generalised nonlocal optical response theory, which provides a more complete physical description combining electron convection and diffusion, we show that not only are fluorescence rates dramatically reduced compared to the predictions of the local description and the common hydrodynamic Drude model, but the optimum emitter-nanoparticle distance is also strongly affected. In this respect, experimental measurements of fluorescence, the theoretical description of which requires a precise concurrent evaluation of far- and near-field properties of the system, constitute a novel, more sensitive probe for assessing the validity of state-of-the-art nonclassical theories.

Synergy of leptin/STAT3 with HER2 receptor induces tamoxifen resistance in breast cancer cells through regulation of apoptosis-related genes.

PURPOSE: Tamoxifen is a major treatment modality for estrogen receptor positive breast cancer, but the occurrence of resistance remains a problem. Recently, obesity-related leptin has been found to interfere with tamoxifen in breast cancer MCF-7 cells. In the present study we investigated the effect of leptin on three tamoxifen-treated breast cancer cell types (i.e., MDA-MB-231, MCF-7 and MCF-7/HER2). METHODS: The effect of tamoxifen/leptin treatment was evaluated using a MTT cell viability assay. mRNA expression was assessed by real time PCR and protein expression by Western blotting. WWOX, Survivin and BCL2 gene promoter activities were evaluated by chromatin immunoprecipitation. RESULTS: Cell viability assays revealed that estrogen receptor negative MDA-MB-231 cells were resistant, that estrogen receptor positive MCF-7 cells were sensitive and that MCF-7/HER2 cells were relatively resistant to tamoxifen, while leptin co-administration 'rescued' MCF-7 and, especially, MCF-7/HER2 cells from the anti-proliferative effect of tamoxifen. The cell lines also exhibited a different phosphorylation status of STAT3, a transcription factor that is activated by the obesity related leptin receptor b (Ob-Rb). Most importantly, chromatin immunoprecipitation assays revealed differential STAT3 binding to the anti-apoptotic BCL2 and pro-apoptotic WWOX gene promoters in MCF-7 and MCF-7/HER2 cells, leading to concomitant modifications of its mRNA/protein expression levels, thus providing a selective advantage to HER2 over-expressing MCF-7/HER2 cells after treatment with tamoxifen and tamoxifen plus leptin. CONCLUSIONS: Our study provides novel evidence indicating that synergy between the leptin/Ob-Rb/STAT3 signalling pathway and the HER2 receptor protects tamoxifen-treated HER2 over-expressing cells from the inhibitory effect of tamoxifen through differential regulation of apoptosis-related genes.

Breakdown of the linear acousto-optic interaction regime in phoxonic cavities.

The limits of validity of the linear photoelastic model are investigated in a one-dimensional dual photonic-phononic cavity, formed by alternating layers of a chalcogenide glass and a polymer homogeneous and isotropic material, which supports both optical and acoustic resonant modes localized in the same region. It is shown that the linear-response regime breaks down when either the acoustic excitation increases or the first-order acousto-optic interaction coupling element vanishes by symmetry, giving rise to the manifestation of multiphonon absorption and emission processes by a photon. Our results provide a consistent interpretation of different aspects of the underlying physics relating to nonlinear acousto-optic interactions that can occur in such cavities.