Flowering of kiwifruit (Actinidia deliciosa) is reduced by long photoperiods

Mature kiwifruit (Actinidia deliciosa ‘Hayward’) vines grown under standard orchard management were exposed to 16-h photoperiods from the longest day in summer until after leaf fall in autumn. Photoperiod extension was achieved with tungsten halogen lamps that produced 2–8 µmols m–2 s–1 photosynthetically active radiation. Long day treatments did not affect fruit dry matter or fruit weight at harvest during the growing season that the treatments were applied or during the following growing season. However, flowering was reduced by 22% during the spring following treatment application. As this reduction in flowering was not accompanied by a decrease in budbreak, the long day effect is not consistent with a delay in the onset of winter chilling. It is suggested therefore, that the observed reduction in flowering may be because of a diminution of floral evocation

Management of chronic lateral instability due to lateral collateral ligament deficiency after total knee arthroplasty: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lateral instability following total knee arthroplasty (TKA) is a rare condition with limited report of treatment options. The objective of this case presentation is to demonstrate the outcomes of different surgical procedures performed in a single patient with lateral collateral ligament (LCL) deficiency.</p> <p>Case presentation</p> <p>We present a case of chronic lateral instability due to LCL deficiency after primary TKA in a 47-year-old Caucasian woman with an obesity problem. Multiple treatment options have been performed in order to manage this problem, including the following: ligament reconstruction; combined ligament reconstruction and constrained implant; and rotating-hinge knee prosthesis that was the most recent surgery. All ligament reconstruction procedures failed within one year. The varus-valgus constrained prosthesis provided stability for six years.</p> <p>Conclusions</p> <p>Ligament reconstruction alone cannot provide enough stability for the treatment of chronic lateral instability in patients with obesity problems and LCL deficiency. When the reconstruction fails, a salvage procedure with rotating-hinge knee is still available.</p

Catheter Balloon Adjustment of the Pulmonary Artery Band: Feasibility and Safety

The study aimed to assess the feasibility and safety of increasing pulmonary artery band (PAB) diameter by catheter-based PAB balloon dilation (PABBD). Eight dilations were performed between October 2006 and December 2008. Hemoclips were used to fix PABs surgically in a procedure designed to permit progressive clip dislodgment in a controlled manner. The PABBD resulted in gradual band loosening until the desired physiologic state was achieved. At time of PABBD, the patients had a mean age of 6 months (range 3–14 months) and a mean weight of 5 kg (range 2.6–7.3 kg). The median time from PAB placement until PABBD was 4.5 months (range 1–9 months). The single-balloon technique was used in seven cases (serial dilations in 5 cases) and the double-balloon technique in one case. The PABBDs were successful for all the patients, who experienced a mean saturation increase of 75–89% (P = 0.01) (mean increase of 20%), a mean PAB gradient decrease from 69 to 36 mmHg (P = 0.002) (mean decrease of 49%), and a mean band site diameter increase from 4.1 to 6.1 mm (P = 0.01) (mean increase of 45%). The only complication was transient pulmonary edema in one patient. The PABBD procedure is a feasible and safe method for increasing pulmonary blood flow in a staged manner and may eliminate the need for surgical band removal in some cases

Varus distal femoral osteotomy in young adults with valgus knee

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders specially knee osteoarthritis are the most common causes of morbidity in old patients. Disturbance of the mechanical axis of the lower extremity is one of the most important causes in progression of knee osteoarthritis. The purpose of the present study was to analyze the surgical results of distal femoral varus osteotomy in patients with genu valgum.</p> <p>Methods</p> <p>In this study, after recording history and physical examination, appropriate radiographs were taken. We did varus distal femoral osteotomy by standard medial subvastus approach and 90-angle blade plate fixation then followed the patients clinically and radiographically.</p> <p>Results</p> <p>This study was done on 23 knees (16 patients) age 23.3 years (range, 17 to 41 years). The mean duration of following up was 16.3 months (range, 8 to 25 months). Based on paired T test, there were statistically significant difference between pre- and postoperative tibiofemoral and congruence angles (p < 0.001, t = 21.3 and p < 0.001, t = 10.1 respectively). Pearson correlation between the amount of tibiofemoral and congruence angle correction was also statistically significant (p = 0.02 and r = 0.46).</p> <p>Conclusion</p> <p>Distal femoral varus osteotomy with blade plate fixation can be a reliable procedure for the treatment of valgus knee deformity. In this procedure, with more tibiofemoral angle correction, more congruence angle correction can be achieved. Therefore, along with genu valgum correction, the patella should be stabilized simultaneously.</p

SMAC Mimetic BV6 Induces Cell Death in Monocytes and Maturation of Monocyte-Derived Dendritic Cells

Background: Compounds mimicking the inhibitory effect of SMAC / DIABLO on X-linked inhibitor of apoptosis (XIAP) have been developed with the aim to achieve sensitization for apoptosis of tumor cells resistant due to deregulated XIAP expression. It turned out that SMAC mimetics also have complex effects on the NFkB system and TNF signaling. In view of the overwhelming importance of the NFkB transcription factors in the immune system, we analyzed here the effects of the SMAC mimetic BV6 on immune cells. Principal Findings: BV6 induced apoptotic and necrotic cell death in monocytes while T-cells, dendritic cells and macrophages were largely protected against BV6-induced cell death. In immature dendritic cells BV6 treatment resulted in moderate activation of the classical NFkB pathway, but it also diminished the stronger NFkB-inducing effect of TNF and CD40L. Despite its inhibitory effect on TNF- and CD40L signaling, BV6 was able to trigger maturation of immature DCs as indicated by upregulation of CD83, CD86 and IL12. Significance: The demonstrated effects of SMAC mimetics on immune cells may complicate the development of tumor therapeutic concepts based on these compounds but also arise the possibility to exploit them for the development of immune stimulatory therapies

Molecular determinants of Smac mimetic induced degradation of cIAP1 and cIAP2

The inhibitors of apoptosis (IAP) proteins cIAP1 and cIAP2 have recently emerged as key ubiquitin-E3 ligases regulating innate immunity and cell survival. Much of our knowledge of these IAPs stems from studies using pharmacological inhibitors of IAPs, dubbed Smac mimetics (SMs). Although SMs stimulate auto-ubiquitylation and degradation of cIAPs, little is known about the molecular determinants through which SMs activate the E3 activities of cIAPs. In this study, we find that SM-induced rapid degradation of cIAPs requires binding to tumour necrosis factor (TNF) receptor-associated factor 2 (TRAF2). Moreover, our data reveal an unexpected difference between cIAP1 and cIAP2. Although SM-induced degradation of cIAP1 does not require cIAP2, degradation of cIAP2 critically depends on the presence of cIAP1. In addition, degradation of cIAP2 also requires the ability of the cIAP2 RING finger to dimerise and to bind to E2s. This has important implications because SM-mediated degradation of cIAP1 causes non-canonical activation of NF-κB, which results in the induction of cIAP2 gene expression. In the absence of cIAP1, de novo synthesised cIAP2 is resistant to the SM and suppresses TNFα killing. Furthermore, the cIAP2-MALT1 oncogene, which lacks cIAP2's RING, is resistant to SM treatment. The identification of mechanisms through which cancer cells resist SM treatment will help to improve combination therapies aimed at enhancing treatment response

A Real-Time PCR Antibiogram for Drug-Resistant Sepsis

Current molecular diagnostic techniques for susceptibility testing of septicemia rely on genotyping for the presence of known resistance cassettes. This technique is intrinsically vulnerable due to the inability to detect newly emergent resistance genes. Traditional phenotypic susceptibility testing has always been a superior method to assay for resistance; however, relying on the multi-day growth period to determine which antimicrobial to administer jeopardizes patient survival. These factors have resulted in the widespread and deleterious use of broad-spectrum antimicrobials. The real-time PCR antibiogram, described herein, combines universal phenotypic susceptibility testing with the rapid diagnostic capabilities of PCR. We have developed a procedure that determines susceptibility by monitoring pathogenic load with the highly conserved 16S rRNA gene in blood samples exposed to different antimicrobial drugs. The optimized protocol removes heme and human background DNA from blood, which allows standard real-time PCR detection systems to be employed with high sensitivity (<100 CFU/mL). Three strains of E. coli, two of which were antimicrobial resistant, were spiked into whole blood and exposed to three different antibiotics. After real-time PCR-based determination of pathogenic load, a ΔCt<3.0 between untreated and treated samples was found to indicate antimicrobial resistance (P<0.01). Minimum inhibitory concentration was determined for susceptible bacteria and pan-bacterial detection was demonstrated with 3 Gram-negative and 2 Gram-positive bacteria. Species identification was performed via analysis of the hypervariable amplicons. In summary, we have developed a universal diagnostic phenotyping technique that assays for the susceptibility of drug-resistant septicemia with the speed of PCR. The real-time PCR antibiogram achieves detection, susceptibility testing, minimum inhibitory concentration determination, and identification in less than 24 hours

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.</p> <p>Methods</p> <p>This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.</p> <p>Results</p> <p>We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.</p> <p>Conclusions</p> <p>Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas.</p

SMG1 and NIK regulate apoptosis induced by Smac mimetic compounds

Smac mimetic compounds (SMCs) are experimental small molecules that induce tumour necrosis factor alpha (TNFα)-dependent cancer cell death by targeting the inhibitor of apoptosis proteins. However, many cancer cell lines are resistant to SMC-mediated apoptosis despite the presence of TNFα. To add insight into the mechanism of SMC-resistance, we used functional siRNA-based kinomic and focused chemical screens and identified suppressor of morphogenesis in genitalia-1 (SMG1) and NF-κB-inducing kinase (NIK) as novel protective factors. Both SMG1 and NIK prevent SMC-mediated apoptosis likely by maintaining FLICE inhibitory protein (c-FLIP) levels to suppress caspase-8 activation. In SMC-resistant cells, the accumulation of NIK upon SMC treatment enhanced the activity of both the classical and alternative nuclear factor-κB pathways, and increased c-FLIP mRNA levels. In parallel, persistent SMG1 expression in SMC-resistant cells repressed SMC-mediated TNFα-induced JNK activation and c-FLIP levels were sustained. Importantly, SMC-resistance is overcome by depleting NIK and SMG1, which appear to facilitate the downregulation of c-FLIP in response to SMC and TNFα treatment, leading to caspase-8-dependent apoptosis. Collectively, these data show that SMG1 and NIK function as critical repressors of SMC-mediated apoptosis by potentially converging on the regulation of c-FLIP metabolism